The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety by modifying the CONSORT statement.

PubMed

O'Connor, A M; Sargeant, J M; Gardner, I A; Dickson, J S; Torrence, M E; Dewey, C E; Dohoo, I R; Evans, R B; Gray, J T; Greiner, M; Keefe, G; Lefebvre, S L; Morley, P S; Ramirez, A; Sischo, W; Smith, D R; Snedeker, K; Sofos, J; Ward, M P; Wills, R

2010-03-01

The conduct of randomized controlled trials in livestock with production, health and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A 2-day consensus meeting was held on 18-19 November 2008 in Chicago, IL, USA, to achieve the objective. Prior to the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock-production specialists, journal editors, assistant editors and associate editors. Prior to the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety and 22-item checklist. Fourteen items were modified from the CONSORT checklist and an additional sub-item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health and food-safety outcomes.

The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety.

PubMed

O'Connor, A M; Sargeant, J M; Gardner, I A; Dickson, J S; Torrence, M E; Dewey, C E; Dohoo, I R; Evans, R B; Gray, J T; Greiner, M; Keefe, G; Lefebvre, S L; Morley, P S; Ramirez, A; Sischo, W; Smith, D R; Snedeker, K; Sofos, J N; Ward, M P; Wills, R

2010-01-01

The conduct of randomized controlled trials in livestock with production, health, and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A two-day consensus meeting was held on November 18-19, 2008 in Chicago, Ill, United States of America, to achieve the objective. Prior to the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock production specialists, journal editors, assistant editors, and associate editors. Prior to the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety (LFS) and 22-item checklist. Fourteen items were modified from the CONSORT checklist, and an additional sub-item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health, and food-safety outcomes.

Defining standardized protocols for determining the efficacy of a postmilking teat disinfectant following experimental exposure of teats to mastitis pathogens.

PubMed

Schukken, Y H; Rauch, B J; Morelli, J

2013-04-01

The objective of this paper was to define standardized protocols for determining the efficacy of a postmilking teat disinfectant following experimental exposure of teats to both Staphylococcus aureus and Streptococcus agalactiae. The standardized protocols describe the selection of cows and herds and define the critical points in performing experimental exposure, performing bacterial culture, evaluating the culture results, and finally performing statistical analyses and reporting of the results. The protocols define both negative control and positive control trials. For negative control trials, the protocol states that an efficacy of reducing new intramammary infections (IMI) of at least 40% is required for a teat disinfectant to be considered effective. For positive control trials, noninferiority to a control disinfectant with a published efficacy of reducing new IMI of at least 70% is required. Sample sizes for both negative and positive control trials are calculated. Positive control trials are expected to require a large trial size. Statistical analysis methods are defined and, in the proposed methods, the rate of IMI may be analyzed using generalized linear mixed models. The efficacy of the test product can be evaluated while controlling for important covariates and confounders in the trial. Finally, standards for reporting are defined and reporting considerations are discussed. The use of the defined protocol is shown through presentation of the results of a recent trial of a test product against a negative control. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Selective outcome reporting and sponsorship in randomized controlled trials in IVF and ICSI.

PubMed

Braakhekke, M; Scholten, I; Mol, F; Limpens, J; Mol, B W; van der Veen, F

2017-10-01

Are randomized controlled trials (RCTs) on IVF and ICSI subject to selective outcome reporting and is this related to sponsorship? There are inconsistencies, independent from sponsorship, in the reporting of primary outcome measures in the majority of IVF and ICSI trials, indicating selective outcome reporting. RCTs are subject to bias at various levels. Of these biases, selective outcome reporting is particularly relevant to IVF and ICSI trials since there is a wide variety of outcome measures to choose from. An established cause of reporting bias is sponsorship. It is, at present, unknown whether RCTs in IVF/ICSI are subject to selective outcome reporting and whether this is related with sponsorship. We systematically searched RCTs on IVF and ICSI published between January 2009 and March 2016 in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed. We analysed 415 RCTs. Per included RCT, we extracted data on impact factor of the journal, sample size, power calculation, and trial registry and thereafter data on primary outcome measure, the direction of trial results and sponsorship. Of the 415 identified RCTs, 235 were excluded for our primary analysis, because the sponsorship was not reported. Of the 180 RCTs included in our analysis, 7 trials did not report on any primary outcome measure and 107 of the remaining 173 trials (62%) reported on surrogate primary outcome measures. Of the 114 registered trials, 21 trials (18%) provided primary outcomes in their manuscript that were different from those in the trial registry. This indicates selective outcome reporting. We found no association between selective outcome reporting and sponsorship. We ran additional analyses to include the trials that had not reported sponsorship and found no outcomes that differed from our primary analysis. Since the majority of the trials did not report on sponsorship, there is a risk on sampling bias. IVF and ICSI trials are subject, to a large extent, to selective outcome reporting. Readers should be aware of this to avoid implementation of false or misleading results in clinical practice. No funding received and there are no conflicts of interest. N/A. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

PubMed

Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

2014-07-16

To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

Quality of surgical randomized controlled trials for acute cholecystitis: assessment based on CONSORT and additional check items.

PubMed

Shikata, Satoru; Nakayama, Takeo; Yamagishi, Hisakazu

2008-01-01

In this study, we conducted a limited survey of reports of surgical randomized controlled trials, using the consolidated standards of reporting trials (CONSORT) statement and additional check items to clarify problems in the evaluation of surgical reports. A total of 13 randomized trials were selected from two latest review articles on biliary surgery. Each randomized trial was evaluated according to 28 quality measures that comprised items from the CONSORT statement plus additional items. Analysis focused on relationships between the quality of each study and the estimated effect gap ("pooled estimate in meta-analysis" -- "estimated effect of each study"). No definite relationships were found between individual study quality and the estimated effect gap. The following items could have been described but were not provided in almost all the surgical RCT reports: "clearly defined outcomes"; "details of randomization"; "participant flow charts"; "intention-to-treat analysis"; "ancillary analyses"; and "financial conflicts of interest". The item, "participation of a trial methodologist in the study" was not found in any of the reports. Although the quality of reporting trials is not always related to a biased estimation of treatment effect, the items used for quality measures must be described to enable readers to evaluate the quality and applicability of the reporting. Further development of an assessment tool is needed for items specific to surgical randomized controlled trials.

Authors of clinical trials reported individual and financial conflicts of interest more frequently than institutional and nonfinancial ones: a methodological survey.

PubMed

Hakoum, Maram B; Jouni, Nahla; Abou-Jaoude, Eliane A; Hasbani, Divina Justina; Abou-Jaoude, Elias A; Lopes, Luciane Cruz; Khaldieh, Mariam; Hammoud, Mira Z; Al-Gibbawi, Mounir; Anouti, Sirine; Guyatt, Gordon; Akl, Elie A

2017-07-01

Conflicts of interest (COIs) are increasingly recognized as important to disclose and manage in health research. The objective of this study was to assess the reporting of both financial and nonfinancial COI by authors of randomized controlled trials published in a representative sample of clinical journals. We searched Ovid Medline and included a random sample of 200 randomized controlled trials published in 2015 in one of the 119 Core Clinical Journals. We classified COI using a comprehensive framework that includes the following: individual COIs (financial, professional, scholarly, advocatory, personal) and institutional COIs (financial, professional, scholarly, and advocatory). We conducted descriptive and regression analyses. Of the 200 randomized controlled trials, 188 (94%) reported authors' COI disclosures that were available in the main document (92%) and as International Committee of Medical Journal Editors forms accessible online (12%). Of the 188 trials, 57% had at least one author reporting at least one COI; in all these trials, at least one author reported financial COI. Institutional COIs (11%) and nonfinancial COIs (4%) were less commonly reported. References to COI disclosure statements for editors (1%) and medical writers (0%) were seldom present. Regression analyses showed positive associations between reporting individual financial COI and higher journal impact factor (odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.02-1.10), larger number of authors (OR = 1.10, 95% CI 1.02-1.20), affiliation with an institution from a high-income country (OR = 16.75, 95% CI 3.38-82.87), and trials reporting on pharmacological interventions (OR = 2.28, 95% CI 1.13-4.62). More than half of published randomized controlled trials report that at least one author has a COI. Trial authors report financial COIs more often than nonfinancial COIs and individual COIs more frequently than institutional COIs. Copyright © 2017 Elsevier Inc. All rights reserved.

Quality of radiotherapy reporting in randomized controlled trials of prostate cancer.

PubMed

Soon, Yu Yang; Chen, Desiree; Tan, Teng Hwee; Tey, Jeremy

2018-06-07

Good radiotherapy reporting in clinical trials of prostate radiotherapy is important because it will allow accurate reproducibility of radiotherapy treatment and minimize treatment variations that can affect patient outcomes. The aim of our study is to assess the quality of prostate radiotherapy (RT) treatment reporting in randomized controlled trials in prostate cancer. We searched MEDLINE for randomized trials of prostate cancer, published from 1996 to 2016 and included prostate RT as one of the intervention arms. We assessed if the investigators reported the ten criteria adequately in the trial reports: RT dose prescription method; RT dose-planning procedures; organs at risk (OAR) dose constraints; target volume definition, simulation procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance (QA) as well as presence or absence of deviations in RT treatment planning and delivery. We performed multivariate logistic regression to determine the factors that may influence the quality of reporting. We found 59 eligible trials. There was significant variability in the quality of reporting. Target volume definition, total RT dose and fractionation schedule were reported adequately in 97% of included trials. OAR constraints, simulation procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in 30% of included trials. Twenty-four trials (40%) reported seven criteria or more adequately. Multivariable logistic analysis showed that trials that published their quality assurance results and cooperative group trials were more likely to have adequate quality in reporting in at least seven criteria. There is significant variability in the quality of reporting on prostate radiotherapy treatment in randomized trials of prostate cancer. We need to have consensus guidelines to standardize the reporting of radiotherapy treatment in randomized trials.

A systematic review of randomised control trials of sexual health interventions delivered by mobile technologies.

PubMed

Burns, Kara; Keating, Patrick; Free, Caroline

2016-08-12

Sexually transmitted infections (STIs) pose a serious public health problem globally. The rapid spread of mobile technology creates an opportunity to use innovative methods to reduce the burden of STIs. This systematic review identified recent randomised controlled trials that employed mobile technology to improve sexual health outcomes. The following databases were searched for randomised controlled trials of mobile technology based sexual health interventions with any outcome measures and all patient populations: MEDLINE, EMBASE, PsycINFO, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, NHS Health Technology Assessment Database, and Web of Science (science and social science citation index) (Jan 1999-July 2014). Interventions designed to increase adherence to HIV medication were not included. Two authors independently extracted data on the following elements: interventions, allocation concealment, allocation sequence, blinding, completeness of follow-up, and measures of effect. Trials were assessed for methodological quality using the Cochrane risk of bias tool. We calculated effect estimates using intention to treat analysis. A total of ten randomised trials were identified with nine separate study groups. No trials had a low risk of bias. The trials targeted: 1) promotion of uptake of sexual health services, 2) reduction of risky sexual behaviours and 3) reduction of recall bias in reporting sexual activity. Interventions employed up to five behaviour change techniques. Meta-analysis was not possible due to heterogeneity in trial assessment and reporting. Two trials reported statistically significant improvements in the uptake of sexual health services using SMS reminders compared to controls. One trial increased knowledge. One trial reported promising results in increasing condom use but no trial reported statistically significant increases in condom use. Finally, one trial showed that collection of sexual health information using mobile technology was acceptable. The findings suggest interventions delivered by SMS interventions can increase uptake of sexual health services and STI testing. High quality trials of interventions using standardised objective measures and employing a wider range of behavioural change techniques are needed to assess if interventions delivered by mobile phone can alter safer sex behaviours carried out between couples and reduce STIs.

"Every Child Counts": Testing Policy Effectiveness Using a Randomised Controlled Trial, Designed, Conducted and Reported to CONSORT Standards

ERIC Educational Resources Information Center

Torgerson, Carole; Wiggins, Andy; Torgerson, David; Ainsworth, Hannah; Hewitt, Catherine

2013-01-01

We report a randomised controlled trial evaluation of an intensive one-to-one numeracy programme--"Numbers Count"--which formed part of the previous government's numeracy policy intervention--"Every Child Counts." We rigorously designed and conducted the trial to CONSORT guidelines. We used a pragmatic waiting list design to…

Controlled trials in children: quantity, methodological quality and descriptive characteristics of pediatric controlled trials published 1948-2006.

PubMed

Thomson, Denise; Hartling, Lisa; Cohen, Eyal; Vandermeer, Ben; Tjosvold, Lisa; Klassen, Terry P

2010-09-30

The objective of this study was to describe randomized controlled trials (RCTs) and controlled clinical trials (CCTs) in child health published between 1948 and 2006, in terms of quantity, methodological quality, and publication and trial characteristics. We used the Trials Register of the Cochrane Child Health Field for overall trends and a sample from this to explore trial characteristics in more detail. We extracted descriptive data on a random sample of 578 trials. Ninety-six percent of the trials were published in English; the percentage of child-only trials was 90.5%. The most frequent diagnostic categories were infectious diseases (13.2%), behavioural and psychiatric disorders (11.6%), neonatal critical care (11.4%), respiratory disorders (8.9%), non-critical neonatology (7.9%), and anaesthesia (6.5%). There were significantly fewer child-only studies (i.e., more mixed child and adult studies) over time (P = 0.0460). The proportion of RCTs to CCTs increased significantly over time (P<0.0001), as did the proportion of multicentre trials (P = 0.002). Significant increases over time were found in methodological quality (Jadad score) (P<0.0001), the proportion of double-blind studies (P<0.0001), and studies with adequate allocation concealment (P<0.0001). Additionally, we found an improvement in reporting over time: adequate description of withdrawals and losses to follow-up (P<0.0001), sample size calculations (P<0.0001), and intention-to-treat analysis (P<0.0001). However, many trials still do not describe their level of blinding, and allocation concealment was inadequately reported in the majority of studies across the entire time period. The proportion of studies with industry funding decreased slightly over time (P = 0.003), and these studies were more likely to report positive conclusions (P = 0.028). The quantity and quality of pediatric controlled trials has increased over time; however, much work remains to be done, particularly in improving methodological issues around conduct and reporting of trials.

The handsearching of 2 medical journals of Bahrain for reports of randomized controlled trials.

PubMed

Al-Hajeri, Amani A; Fedorowicz, Zbigniew; Amin, Fawzi A; Eisinga, Anne

2006-04-01

To identify reports of randomized trials by handsearching 2 Bahrain medical journals, which are indexed in the biomedical database EMBASE and to determine any added value of the handsearching by comparing the reports found by handsearching with what would have been found by searching EMBASE to examine (i) the precision and sensitivity of the EMBASE index term Randomized Controlled Trial (RCT) and (ii) The Cochrane Collaboration's systematic electronic search of EMBASE (which uses 4 index terms and 9 free-text terms). All issues of the Bahrain Medical Bulletin (BMB) (1979-2004) and the Journal of the Bahrain Medical Society (JBMS) (1989-2004) were handsearched in February 2005 for reports of RCTs or Controlled Clinical Trials (CCTs), according to Cochrane eligibility criteria. Out of 395 articles in BMB we found reports of 12 RCTs and 4 CCTs. Distribution by country of corresponding author: Jordan (4 RCTs, one CCT), Bahrain (one RCT, one CCT), India (3 RCTs, one CCT), Kuwait (one CCT), Saudi Arabia (2 RCTs), USA/Bahrain (one RCT), and Oman (one RCT); and by specialty: Anesthesia (8), Surgery (1) Pediatrics (1), Radiotherapy (1), Community Medicine (1), Sports Medicine (1), Obstetrics/Gynecology (3). The Journal of the Bahrain Medical Society included reports of 14 RCTs and 3 CCTs, out of 97 articles. Distribution by country of corresponding author: Jordan (9 RCTs, 2 CCTs), Bahrain (3 RCTs), Egypt (one RCT), Kuwait (one RCT), and Saudi Arabia (one RCT); and by specialty: Anesthesia (7), General Surgery (3), Obstetrics/Gynecology (1), Radiotherapy (1), Pediatrics (1), Orthopaedic Surgery (1), Education (1) Ear Nose and Throat (1) Ophthalmology (1). Overall, of the 33 reports of trials found by handsearching both journals, only 23 were included in EMBASE of which only 6 had been indexed with the term RCT. Of the 23 reports of trials included in EMBASE, 16 had been identified in the Collaboration s systematic search of EMBASE. Two reports of trials could have been retrieved by this search but there was insufficient information in the title and abstract to code these as trials. The EMBASE records for the remaining 5 reports of trials did not contain terms currently used by The Cochrane Collaboration to identify reports of randomized trials in this database. The handsearching of these journals will help minimize publication bias by locating randomized trials not previously identified and, through their inclusion in the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, will ensure reports of randomized trials will not remain buried through indexing bias.

Benefits and challenges of using the cohort multiple randomised controlled trial design for testing an intervention for depression.

PubMed

Viksveen, Petter; Relton, Clare; Nicholl, Jon

2017-07-06

Trials which test the effectiveness of interventions compared with the status quo frequently encounter challenges. The cohort multiple randomised controlled trial (cmRCT) design is an innovative approach to the design and conduct of pragmatic trials which seeks to address some of these challenges. In this article, we report our experiences with the first completed randomised controlled trial (RCT) using the cmRCT design. This trial-the Depression in South Yorkshire (DEPSY) trial-involved comparison of treatment as usual (TAU) with TAU plus the offer of an intervention for people with self-reported long-term moderate to severe depression. In the trial, we used an existing large population-based cohort: the Yorkshire Health Study. We discuss our experiences with recruitment, attrition, crossover, data analysis, generalisability of results, and cost. The main challenges in using the cmRCT design were the high crossover to the control group and the lower questionnaire response rate among patients who refused the offer of treatment. However, the design did help facilitate efficient and complete recruitment of the trial population as well as analysable data that were generalisable to the population of interest. Attrition rates were also smaller than those reported in other depression trials. This first completed full trial using the cmRCT design testing an intervention for self-reported depression was associated with a number of important benefits. Further research is required to compare the acceptability and cost effectiveness of standard pragmatic RCT design with the cmRCT design. ISRCTN registry: ISRCTN02484593 . Registered on 7 Jan 2013.

Analgesic effects of treatments for non-specific low back pain: a meta-analysis of placebo-controlled randomized trials.

PubMed

Machado, L A C; Kamper, S J; Herbert, R D; Maher, C G; McAuley, J H

2009-05-01

Estimates of treatment effects reported in placebo-controlled randomized trials are less subject to bias than those estimates provided by other study designs. The objective of this meta-analysis was to estimate the analgesic effects of treatments for non-specific low back pain reported in placebo-controlled randomized trials. Medline, Embase, Cinahl, PsychInfo and Cochrane Central Register of Controlled Trials databases were searched for eligible trials from earliest records to November 2006. Continuous pain outcomes were converted to a common 0-100 scale and pooled using a random effects model. A total of 76 trials reporting on 34 treatments were included. Fifty percent of the investigated treatments had statistically significant effects, but for most the effects were small or moderate: 47% had point estimates of effects of <10 points on the 100-point scale, 38% had point estimates from 10 to 20 points and 15% had point estimates of >20 points. Treatments reported to have large effects (>20 points) had been investigated only in a single trial. This meta-analysis revealed that the analgesic effects of many treatments for non-specific low back pain are small and that they do not differ in populations with acute or chronic symptoms.

CONSORT item reporting quality in the top ten ranked journals of critical care medicine in 2011: a retrospective analysis.

PubMed

Stevanovic, Ana; Schmitz, Sabine; Rossaint, Rolf; Schürholz, Tobias; Coburn, Mark

2015-01-01

Reporting randomised controlled trials is a key element in order to disseminate research findings. The CONSORT statement was introduced to improve the reporting quality. We assessed the adherence to the CONSORT statement of randomised controlled trials published 2011 in the top ten ranked journals of critical care medicine (ISI Web of Knowledge 2011, Thomson Reuters, London UK). Design. We performed a retrospective cross sectional data analysis. Setting. This study was executed at the University Hospital of RWTH, Aachen. Participants. We selected the following top ten listed journals according to ISI Web of Knowledge (Thomson Reuters, London, UK) critical care medicine ranking in the year 2011: American Journal of Respiratory and Critical Care Medicine, Critical Care Medicine, Intensive Care Medicine, CHEST, Critical Care, Journal of Neurotrauma, Resuscitation, Pediatric Critical Care Medicine, Shock and Minerva Anestesiologica. Main outcome measures. We screened the online table of contents of each included journal, to identify the randomised controlled trials. The adherence to the items of the CONSORT Checklist in each trial was evaluated. Additionally we correlated the citation frequency of the articles and the impact factor of the respective journal with the amount of reported items per trial. We analysed 119 randomised controlled trials and found, 15 years after the implementation of the CONSORT statement, that a median of 61,1% of the checklist-items were reported. Only 55.5% of the articles were identified as randomised trials in their titles. The citation frequency of the trials correlated significantly (rs = 0,433; p<0,001 and r = 0,331; p<0,001) to the CONSORT statement adherence. The impact factor showed also a significant correlation to the CONSORT adherence (r = 0,386; p<0,001). The reporting quality of randomised controlled trials in the field of critical care medicine remains poor and needs considerable improvement.

[Systematic Review of the Application of Complementary and Alternative Medicine and their Potential Therapeutic Benefits in the Treatment of Ophthalmology Patients].

PubMed

Welte, A K; Hahn, U; Büssing, A; Krummenauer, F

2017-05-01

Purpose A systematic review was carried out of the reported therapeutic effects of complementary and alternative medicine methods as supplementary or primary treatments for patients suffering from glaucoma, cataract or age-related macular degeneration (AMD). Material and Methods For the years 1990 to 2013, the following databases were screened for reports of the application of complementary and alternative treatments: PubMed, Cochrane Library, EMBASE, CAMbase and AMED. Both randomised and prospective non-randomised patient trials were included in the review; results were evaluated in the following classes: "phytotherapy", "acupuncture/acupressure", "biofeedback" and "other alternative treatments". The studies were evaluated by measures of clinical effect, statistical significance (p value and/or confidence interval) and the underlying trial design. Results 30 clinical trials were included, including 13 on glaucoma, 5 on cataract and 12 on AMD patients. These trials were based on patient numbers of 6 - 332, 27 - 157 and 6 - 328 patients, respectively. Phytotherapy was applied in 14 trials, including 6 on glaucoma patients (all 6 with a controlled design, and 3 of which reporting statistically significant results); 5 trials were on cataract patients (3 with a controlled design and 2 with a significant result) and 3 on AMD patients (only 1 with a controlled design, with a significant result). Acupuncture/acupressure was investigated in 9 trials, 5 on glaucoma patients (3 with a controlled design, 1 with a significant result); no acupuncture/acupressure trial was found in cataract patients, but 4 trials in AMD patients (none with a controlled design). Biofeedback was studied in 4 trials, all on AMD patients (only one with a controlled design, without statistically significant findings). Conclusion Despite its rigorous inclusion criteria, this review identified several clinical trials on complementary and alternative medicine in ophthalmological patients. Phytotherapeutic methods gave significant results in half of the reported controlled trials, whereas there were few significant benefits with acupuncture or acupressure. Georg Thieme Verlag KG Stuttgart · New York.

A Systematic Review of Randomized Controlled Trials Examining Psychological Interventions for Needle-related Procedural Pain and Distress in Children and Adolescents: An Abbreviated Cochrane Review*

PubMed Central

Chambers, Christine T.; McGrath, Patrick J.; Kisely, Stephen

2008-01-01

Objective To report the results of a systematic review of randomized controlled trials (RCTs) of psychological interventions for children and adolescents undergoing needle-related procedures. Methods A variety of cognitive-behavioral psychological interventions for managing procedural pain and distress in children and adolescents between 2 and 19 years of age were examined. Outcome measures included pain and distress as assessed by self-report, observer report, behavioral/observational measures, and physiological correlates. Results Twenty-eight trials met the criteria for inclusion in the review and provided the data necessary for pooling the results. Together, the trials included 1,039 participants in treatment conditions and 951 in control conditions. The largest effect sizes for treatment improvement over control conditions were found for distraction, combined cognitive-behavioral interventions, and hypnosis, with promising but limited evidence for several other psychological interventions. Conclusions Recommendations for conducting future RCTs are provided, and particular attention to the quality of trial design and reporting is highlighted. PMID:18387963

Control groups in recent septic shock trials: a systematic review.

PubMed

Pettilä, Ville; Hjortrup, Peter Buhl; Jakob, Stephan M; Wilkman, Erika; Perner, Anders; Takala, Jukka

2016-12-01

The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care. Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.

Components of effective randomized controlled trials of hydrotherapy programs for fibromyalgia syndrome: A systematic review.

PubMed

Perraton, Luke; Machotka, Zuzana; Kumar, Saravana

2009-11-30

Previous systematic reviews have found hydrotherapy to be an effective management strategy for fibromyalgia syndrome (FMS). The aim of this systematic review was to summarize the components of hydrotherapy programs used in randomized controlled trials. A systematic review of randomized controlled trials was conducted. Only trials that have reported significant FMS-related outcomes were included. Data relating to the components of hydrotherapy programs (exercise type, duration, frequency and intensity, environmental factors, and service delivery) were analyzed. Eleven randomized controlled trials were included in this review. Overall, the quality of trials was good. Aerobic exercise featured in all 11 trials and the majority of hydrotherapy programs included either a strengthening or flexibility component. Great variability was noted in both the environmental components of hydrotherapy programs and service delivery. Aerobic exercise, warm up and cool-down periods and relaxation exercises are common features of hydrotherapy programs that report significant FMS-related outcomes. Treatment duration of 60 minutes, frequency of three sessions per week and an intensity equivalent to 60%-80% maximum heart rate were the most commonly reported exercise components. Exercise appears to be the most important component of an effective hydrotherapy program for FMS, particularly when considering mental health-related outcomes.

Cognitive Science Program: Processes in the Resolution of Ambiguous Words: Towards a Model of Selective Inhibition.

DTIC Science & Technology

1986-05-01

NUMBERS Department of Psychology NR 667-523 University of Oregon II. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE May 1, 1986 13. NUMBER OF PAGES 21...14. MONITORING AGENCY NAME & ADDRSWI ’ dillsrat from Controlling Office) 15. SECURITY CLASS. (of this report) Unclassified IS. DECLASSIFICATION...trial n+It naming latencies were longer in trial n+1 thar in a control condition where there was no relation between successive trials. Neill proposed

Effectiveness of a Parent Health Report in Increasing Fruit and Vegetable Consumption Among Preschoolers and Kindergarteners.

PubMed

Hunsaker, Sanita L; Jensen, Chad D

2017-05-01

To determine the effectiveness of a parent health report on fruit and vegetable consumption among preschoolers and kindergarteners. Pre-post open design trial and a randomized controlled trial. A university-sponsored preschool and kindergarten. A total of 63 parents of preschool and kindergarten students participated in the pre-post open design trial and 65 parents participated in the randomized controlled trial. Parents in intervention groups were given a parent health report providing information about their child's fruit and vegetable intake as well as recommendations for how to increase their child's fruit and vegetable consumption. Change in fruit and vegetable consumption. Latent growth curve modeling with Bayesian estimation. Vegetable consumption increased by 0.3 servings/d in the open trial and 0.65 servings/d in the randomized trial. Fruit consumption did not increase significantly in either study. Results from both an open trial and a randomized controlled trial suggested that the parent health report may be a beneficial tool to increase vegetable consumption in preschoolers and kindergarteners. Increases in vegetable consumption can lead to the establishment of lifelong habits of healthy vegetable intake and decrease risk for chronic diseases. Copyright © 2017 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Aloe vera herbal dentifrices for plaque and gingivitis control: a systematic review.

PubMed

Dhingra, K

2014-04-01

To evaluate the effectiveness of aloe vera containing herbal dentifrices in improving plaque control and gingival health. A manual and electronic literature (MEDLINE and Cochrane Central Register of Controlled Trials) search was performed up to July 2012, for randomized controlled trials presenting clinical, microbiological, immunological, and patient-centered data for the efficacy of aloe vera herbal dentifrices for controlling plaque and gingival inflammation in patients with gingivitis. From 79 titles and abstracts, eight full-text articles were screened and finally two randomized controlled trials were selected. These randomized controlled trials reported that aloe vera dentifrices were similar in efficacy to control dentifrices in effectively reducing plaque and gingival inflammation in gingivitis patients based on the assessment of clinical, microbiological, and patient-centered treatment outcomes. However, many important details (composition and characteristics of aloe vera and control dentifrices along with appropriate randomization, blinding, and outcomes assessed) were lacking in these trials, and therefore, the quality of reporting and methods was generally flawed with high risk of bias. Even though there are some promising results, the clinical effectiveness of aloe vera herbal dentifrices is not sufficiently defined at present and warrants further investigations based on reporting guidelines of herbal CONSORT statement. © 2013 John Wiley & Sons A/S.

Vascular Access Outcomes Reported in Maintenance Hemodialysis Trials: A Systematic Review.

PubMed

Viecelli, Andrea K; O'Lone, Emma; Sautenet, Benedicte; Craig, Jonathan C; Tong, Allison; Chemla, Eric; Hooi, Lai-Seong; Lee, Timmy; Lok, Charmaine; Polkinghorne, Kevan R; Quinn, Robert R; Vachharajani, Tushar; Vanholder, Raymond; Zuo, Li; Irish, Ashley B; Mori, Trevor A; Pascoe, Elaine M; Johnson, David W; Hawley, Carmel M

2018-03-01

Many randomized controlled trials have been performed with the goal of improving outcomes related to hemodialysis vascular access. If the reported outcomes are relevant and measured consistently to allow comparison of interventions across trials, such trials can inform decision making. This study aimed to assess the scope and consistency of vascular access outcomes reported in contemporary hemodialysis trials. Systematic review. Adults requiring maintenance hemodialysis. All randomized controlled trials and trial protocols reporting vascular access outcomes identified from ClinicalTrials.gov, Embase, MEDLINE, and the Cochrane Kidney and Transplant Specialized Register from January 2011 to June 2016. Any hemodialysis-related intervention. The frequency and characteristics of vascular access outcome measures were analyzed and classified. From 168 relevant trials, 1,426 access-related outcome measures were extracted and classified into 23 different outcomes. The 3 most common outcomes were function (136 [81%] trials), infection (63 [38%]), and maturation (31 [18%]). Function was measured in 489 different ways, but most frequently reported as "mean access blood flow (mL/min)" (37 [27%] trials) and "number of thromboses" (30 [22%]). Infection was assessed in 136 different ways, with "number of access-related infections" being the most common measure. Maturation was assessed in 44 different ways at 15 different time points and most commonly characterized by vein diameter and blood flow. Patient-reported outcomes, including pain (19 [11%]) and quality of life (5 [3%]), were reported infrequently. Only a minority of trials used previously standardized outcome definitions. Restricted sampling frame for feasibility and focus on contemporary trials. The reporting of access outcomes in hemodialysis trials is very heterogeneous, with limited patient-reported outcomes and infrequent use of standardized outcome measures. Efforts to standardize outcome reporting for vascular access are critical to optimizing the comparability, reliability, and value of trial evidence to improve outcomes for patients requiring hemodialysis. Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.

A systematic review of randomised controlled trials in rheumatoid arthritis: the reporting and handling of missing data in composite outcomes.

PubMed

Ibrahim, Fowzia; Tom, Brian D M; Scott, David L; Prevost, Andrew Toby

2016-06-02

Most reported outcome measures in rheumatoid arthritis (RA) trials are composite, whose components comprise single measures that are combined into one outcome. The aims of this review were to assess the range of missing data rates in primary composite outcomes and to document the current practice for handling and reporting missing data in published RA trials compared to the Consolidated Standards of Reporting Trials (CONSORT) recommendations. A systematic search for randomised controlled trials was conducted for RA trials published between 2008 and 2013 in four rheumatology and four high impact general medical journals. A total of 51 trials with a composite primary outcome were identified, of which 38 (75 %) used the binary American College of Rheumatology responder index and 13 (25 %) used the Disease Activity Score for 28 joints (DAS28). Forty-four trials (86 %) reported on an intention-to-treat analysis population, while 7 trials (14 %) analysed according to a modified intention-to-treat population. Missing data rates for the primary composite outcome ranged from 2-53 % and were above 30 % in 9 trials, 20-30 % in 11 trials, 10-20 % in 18 trials and below 10 % in 13 trials. Thirty-eight trials (75 %) used non-responder imputation and 10 (20 %) used last observation carried forward to impute missing composite outcome data at the primary time point. The rate of dropout was on average 61 % times higher in the placebo group compared to the treatment group in the 34 placebo controlled trials (relative rate 1.61, 95 % CI: 1.29, 2.02). Thirty-seven trials (73 %) did not report the use of sensitivity analyses to assess the handling of missing data in the primary analysis as recommended by CONSORT guidelines. This review highlights an improvement in rheumatology trial practice since the revision of CONSORT guidelines, in terms of power calculation and participant's flow diagram. However, there is a need to improve the handling and reporting of missing composite outcome data and their components in RA trials. In particular, sensitivity analyses need to be more widely used in RA trials because imputation is widespread and generally uses single imputation methods, and in this area the missing data rates are commonly differentially higher in the placebo group.

Post-licence driver education for the prevention of road traffic crashes: a systematic review of randomised controlled trials.

PubMed

Ker, Katharine; Roberts, Ian; Collier, Timothy; Beyer, Fiona; Bunn, Frances; Frost, Chris

2005-03-01

The effectiveness of post-licence driver education for preventing road traffic crashes was quantified using a systematic review and meta-analyses of randomised controlled trials. Searches of appropriate electronic databases, the Internet and reference lists of relevant papers were conducted. The searches were not restricted by language or publication status. Data were pooled from 21 randomised controlled trials, including over 300,000 full licence-holding drivers of all ages. Nineteen trials reported subsequent traffic offences, with a pooled relative risk of 0.96 (95% confidence interval 0.94, 0.98). Fifteen trials reported traffic crashes with a pooled relative risk of 0.98 (0.96, 1.01). Four trials reported injury crashes with a pooled relative risk of 1.12 (0.88, 1.41). The results provide no evidence that post-licence driver education is effective in preventing road injuries or crashes. Although the results are compatible with a small reduction in the occurrence of traffic crashes, this may be due to selection biases or bias in the included trials.

Controlled Trials in Children: Quantity, Methodological Quality and Descriptive Characteristics of Pediatric Controlled Trials Published 1948-2006

PubMed Central

Thomson, Denise; Hartling, Lisa; Cohen, Eyal; Vandermeer, Ben; Tjosvold, Lisa; Klassen, Terry P.

2010-01-01

Background The objective of this study was to describe randomized controlled trials (RCTs) and controlled clinical trials (CCTs) in child health published between 1948 and 2006, in terms of quantity, methodological quality, and publication and trial characteristics. We used the Trials Register of the Cochrane Child Health Field for overall trends and a sample from this to explore trial characteristics in more detail. Methodology/Principal Findings We extracted descriptive data on a random sample of 578 trials. Ninety-six percent of the trials were published in English; the percentage of child-only trials was 90.5%. The most frequent diagnostic categories were infectious diseases (13.2%), behavioural and psychiatric disorders (11.6%), neonatal critical care (11.4%), respiratory disorders (8.9%), non-critical neonatology (7.9%), and anaesthesia (6.5%). There were significantly fewer child-only studies (i.e., more mixed child and adult studies) over time (P = 0.0460). The proportion of RCTs to CCTs increased significantly over time (P<0.0001), as did the proportion of multicentre trials (P = 0.002). Significant increases over time were found in methodological quality (Jadad score) (P<0.0001), the proportion of double-blind studies (P<0.0001), and studies with adequate allocation concealment (P<0.0001). Additionally, we found an improvement in reporting over time: adequate description of withdrawals and losses to follow-up (P<0.0001), sample size calculations (P<0.0001), and intention-to-treat analysis (P<0.0001). However, many trials still do not describe their level of blinding, and allocation concealment was inadequately reported in the majority of studies across the entire time period. The proportion of studies with industry funding decreased slightly over time (P = 0.003), and these studies were more likely to report positive conclusions (P = 0.028). Conclusions/Significance The quantity and quality of pediatric controlled trials has increased over time; however, much work remains to be done, particularly in improving methodological issues around conduct and reporting of trials. PMID:20927344

Clinical Trial Registries Are of Minimal Use for Identifying Selective Outcome and Analysis Reporting

ERIC Educational Resources Information Center

Norris, Susan L.; Holmer, Haley K.; Fu, Rongwei; Ogden, Lauren A.; Viswanathan, Meera S.; Abou-Setta, Ahmed M.

2014-01-01

Objective: This study aimed to examine selective outcome reporting (SOR) and selective analysis reporting (SAR) in randomized controlled trials (RCTs) and to explore the usefulness of trial registries for identifying SOR and SAR. Study Design and Setting: We selected one "index outcome" for each of three comparative effectiveness reviews…

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials.

PubMed

Cooper, Cindy L; Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-04-01

External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland-Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was -4.4% with limits of agreement of -37.1% to 28.2%. Limits of agreement for randomisation rates were -47.8% to 77.5%. Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate.

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials

PubMed Central

Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-01-01

Background/aims: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Methods: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland–Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Results: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was −4.4% with limits of agreement of −37.1% to 28.2%. Limits of agreement for randomisation rates were −47.8% to 77.5%. Conclusion: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate. PMID:29361833

Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials.

PubMed

Dechartres, Agnes; Bond, Elizabeth G; Scheer, Jordan; Riveros, Carolina; Atal, Ignacio; Ravaud, Philippe

2016-11-30

Publication bias and other reporting bias have been well documented for journal articles, but no study has evaluated the nature of results posted at ClinicalTrials.gov. We aimed to assess how many randomized controlled trials (RCTs) with results posted at ClinicalTrials.gov report statistically significant results and whether the proportion of trials with significant results differs when no treatment effect estimate or p-value is posted. We searched ClinicalTrials.gov in June 2015 for all studies with results posted. We included completed RCTs with a superiority hypothesis and considered results for the first primary outcome with results posted. For each trial, we assessed whether a treatment effect estimate and/or p-value was reported at ClinicalTrials.gov and if yes, whether results were statistically significant. If no treatment effect estimate or p-value was reported, we calculated the treatment effect and corresponding p-value using results per arm posted at ClinicalTrials.gov when sufficient data were reported. From the 17,536 studies with results posted at ClinicalTrials.gov, we identified 2823 completed phase 3 or 4 randomized trials with a superiority hypothesis. Of these, 1400 (50%) reported a treatment effect estimate and/or p-value. Results were statistically significant for 844 trials (60%), with a median p-value of 0.01 (Q1-Q3: 0.001-0.26). For the 1423 trials with no treatment effect estimate or p-value posted, we could calculate the treatment effect and corresponding p-value using results reported per arm for 929 (65%). For 494 trials (35%), p-values could not be calculated mainly because of insufficient reporting, censored data, or repeated measurements over time. For the 929 trials we could calculate p-values, we found statistically significant results for 342 (37%), with a median p-value of 0.19 (Q1-Q3: 0.005-0.59). Half of the trials with results posted at ClinicalTrials.gov reported a treatment effect estimate and/or p-value, with significant results for 60% of these. p-values could be calculated from results reported per arm at ClinicalTrials.gov for only 65% of the other trials. The proportion of significant results was much lower for these trials, which suggests a selective posting of treatment effect estimates and/or p-values when results are statistically significant.

Blood pressure control for diabetic retinopathy

PubMed Central

Do, Diana V; Wang, Xue; Vedula, Satyanarayana S; Marrone, Michael; Sleilati, Gina; Hawkins, Barbara S; Frank, Robert N

2015-01-01

Background Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Simultaneous blood pressure control has been advocated for the same purpose, but findings reported from individual studies have supported varying conclusions regarding the ocular benefit of interventions on blood pressure. Objectives The primary aim of this review was to summarize the existing evidence regarding the effect of interventions to control or reduce blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs. A secondary aim was to compare classes of anti-hypertensive medications with respect to the same outcomes. Search methods We searched a number of electronic databases including CENTRAL as well as ongoing trial registries. We last searched the electronic databases on 25 April 2014. We also reviewed reference lists of review articles and trial reports selected for inclusion. In addition, we contacted investigators of trials with potentially pertinent data. Selection criteria We included in this review randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to intense versus less intense blood pressure control, to blood pressure control versus usual care or no intervention on blood pressure, or to different classes of anti-hypertensive agents versus placebo. Data collection and analysis Pairs of review authors independently reviewed titles and abstracts from electronic and manual searches and the full text of any document that appeared to be relevant. We assessed included trials independently for risk of bias with respect to outcomes reported in this review. We extracted data regarding trial characteristics, incidence and progression of retinopathy, visual acuity, quality of life, and cost-effectiveness at annual intervals after study entry whenever provided in published reports and other documents available from included trials. Main results We included 15 RCTs, conducted primarily in North America and Europe, that had enrolled 4157 type 1 and 9512 type 2 diabetic participants, ranging from 16 to 2130 participants in individual trials. In 10 of the 15 RCTs, one group of participants was assigned to one or more anti-hypertensive agents and the control group received placebo. In three trials, intense blood pressure control was compared to less intense blood pressure control. In the remaining two trials, blood pressure control was compared with usual care. Five of the 15 trials enrolled type 1 diabetics, and 10 trials enrolled type 2 diabetics. Six trials were sponsored entirely by pharmaceutical companies, seven trials received partial support from pharmaceutical companies, and two studies received support from government-sponsored grants and institutional support. Study designs, populations, interventions, and lengths of follow-up (range one to nine years) varied among the included trials. Overall, the quality of the evidence for individual outcomes was low to moderate. For the primary outcomes, incidence and progression of retinopathy, the quality of evidence was downgraded due to inconsistency and imprecision of estimates from individual studies and differing characteristics of participants. For primary outcomes among type 1 diabetics, one of the five trials reported incidence of retinopathy and one trial reported progression of retinopathy after 4 to 5 years of treatment and follow-up; four of the five trials reported a combined outcome of incidence and progression over the same time interval. Among type 2 diabetics, 5 of the 10 trials reported incidence of diabetic retinopathy and 3 trials reported progression of retinopathy; one of the 10 trials reported a combined outcome of incidence and progression during a 4-to 5-year follow-up period. One trial in which type 2 diabetics participated had reported no primary (or secondary) outcome targeted for this review. The evidence from these trials supported a benefit of more intensive blood pressure control intervention with respect to 4- to 5-year incidence of diabetic retinopathy (estimated risk ratio (RR) 0.80; 95% confidence interval (CI) 0.71 to 0.92) and the combined outcome of incidence and progression (estimated RR 0.78; 95% CI 0.63 to 0.97). The available evidence provided less support for a benefit with respect to 4- to 5-year progression of diabetic retinopathy (point estimate was closer to 1 than point estimates for incidence and combined incidence and progression, and the CI overlapped 1; estimated RR 0.88; 95% CI 0.73 to 1.05). The available evidence regarding progression to proliferative diabetic retinopathy or clinically significant macular edema or moderate to severe loss of best-corrected visual acuity did not support a benefit of intervention on blood pressure: estimated RRs and 95% CIs 0.95 (0.83 to 1.09) and 1.06 (0.85 to 1.33), respectively, after 4 to 5 years of follow-up. Findings within subgroups of trial participants (type 1 and type 2 diabetics; participants with normal blood pressure levels at baseline and those with elevated levels) were similar to overall findings. The adverse event reported most often (7 of 15 trials) was death, yielding an estimated RR 0.86 (95% CI 0.64 to 1.14). Hypotension was reported from three trials; the estimated RR was 2.08 (95% CI 1.68 to 2.57). Other adverse ocular events were reported from single trials. Authors’ conclusions Hypertension is a well-known risk factor for several chronic conditions in which lowering blood pressure has proven to be beneficial. The available evidence supports a beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to 4 to 5 years. However, the lack of evidence to support such intervention to slow progression of diabetic retinopathy or to prevent other outcomes considered in this review, along with the relatively modest support for the beneficial effect on incidence, weakens the conclusion regarding an overall benefit of intervening on blood pressure solely to prevent diabetic retinopathy. PMID:25637717

Analysis and interpretation of cost data in randomised controlled trials: review of published studies

PubMed Central

Barber, Julie A; Thompson, Simon G

1998-01-01

Objective To review critically the statistical methods used for health economic evaluations in randomised controlled trials where an estimate of cost is available for each patient in the study. Design Survey of published randomised trials including an economic evaluation with cost values suitable for statistical analysis; 45 such trials published in 1995 were identified from Medline. Main outcome measures The use of statistical methods for cost data was assessed in terms of the descriptive statistics reported, use of statistical inference, and whether the reported conclusions were justified. Results Although all 45 trials reviewed apparently had cost data for each patient, only 9 (20%) reported adequate measures of variability for these data and only 25 (56%) gave results of statistical tests or a measure of precision for the comparison of costs between the randomised groups. Only 16 (36%) of the articles gave conclusions which were justified on the basis of results presented in the paper. No paper reported sample size calculations for costs. Conclusions The analysis and interpretation of cost data from published trials reveal a lack of statistical awareness. Strong and potentially misleading conclusions about the relative costs of alternative therapies have often been reported in the absence of supporting statistical evidence. Improvements in the analysis and reporting of health economic assessments are urgently required. Health economic guidelines need to be revised to incorporate more detailed statistical advice. Key messagesHealth economic evaluations required for important healthcare policy decisions are often carried out in randomised controlled trialsA review of such published economic evaluations assessed whether statistical methods for cost outcomes have been appropriately used and interpretedFew publications presented adequate descriptive information for costs or performed appropriate statistical analysesIn at least two thirds of the papers, the main conclusions regarding costs were not justifiedThe analysis and reporting of health economic assessments within randomised controlled trials urgently need improving PMID:9794854

Systematic review of universal school-based resilience interventions targeting adolescent tobacco, alcohol or illicit drug use: review protocol

PubMed Central

Hodder, Rebecca Kate; Freund, Megan; Wolfenden, Luke; Bowman, Jenny; Gillham, Karen; Dray, Julia; Wiggers, John

2014-01-01

Introduction Tobacco, alcohol and illicit drug use contribute significantly to global rates of morbidity and mortality. Despite evidence suggesting interventions designed to increase adolescent resilience may represent a means of reducing adolescent substance use, and schools providing a key opportunity to implement such interventions, existing systematic reviews assessing the effectiveness of school-based interventions targeting adolescent substance use have not examined this potential. Methods and analysis The aim of the systematic review is to determine whether universal interventions focused on enhancing the resilience of adolescents are effective in reducing adolescent substance use. Eligible studies will: include participants 5–18 years of age; report tobacco use, alcohol consumption or illicit drug use as outcomes; and implement a school-based intervention designed to promote internal (eg, self-esteem) and external (eg, school connectedness) resilience factors. Eligible study designs include randomised controlled trials, cluster randomised controlled trials, staggered enrolment trials, stepped wedged trials, quasi-randomised trials, quasi-experimental trials, time series/interrupted time-series trials, preference trials, regression discontinuity trials and natural experiment studies with a parallel control group. A search strategy including criteria for participants, study design, outcome, setting and intervention will be implemented in various electronic databases and information sources. Two reviewers will independently screen studies to assess eligibility, as well as extract data from, and assess risk of bias of included studies. A third reviewer will resolve any discrepancies. Attempts will be made to quantify trial effects by meta-analysis. Binary outcomes will be pooled and effect size reported using ORs. For continuous data, effect size of trials will be reported using a mean difference where trial outcomes report the same outcome using a consistent measure, or standardised mean difference where trials report a comparable measure. Otherwise, trial outcomes will be described narratively. Dissemination Review findings will be disseminated via peer-reviewed journals and conferences. PMID:24861548

The influence of industry sponsorship on the reporting of subgroup analyses within phase III randomised controlled trials in gastrointestinal oncology.

PubMed

Barton, Sarah; Peckitt, Clare; Sclafani, Francesco; Cunningham, David; Chau, Ian

2015-12-01

Correct interpretation of subgroup analyses (SGA) is important as it influences selection of therapeutic interventions for patient subsets. The primary aim of our study was to compare reporting of SGA between industry and non-industry sponsored trials. We performed a systematic literature review and extracted data from journal articles (JA) and conference abstracts (CA) published over a decade reporting SGA results of phase III randomised controlled gastrointestinal (GI) oncology trials with patient participants of ≥150. In JA, SGA was reported in 100/145 (69%) trials: 41/54 industry sponsored (76%; 95% confidence interval [CI]: 63-86%) and 59/91 non-industry sponsored (65%; 95% CI: 55-74%) trials (p = 0.16). In CA, SGA was reported in 86/204 (42%) trials: 43/83 industry sponsored (52%; 95% CI: 41-62%) and 43/121 non-industry sponsored (36%; 95% CI: 28-44%) trials (p = 0.02). Number of SGA performed per trial was significantly larger for industry compared to non-industry sponsored trials in both JA (median 6 versus 2, p = 0.003) and CA (median 1 versus 0, p = 0.023). Claims of subgroup effect were made in 52% of trials in JA and 50% in CA, with significant test of interaction evident in only 25% of JA and 16% of CA, with no difference between industry and non-industry trials. Industry sponsored trials with a significant primary end-point reported more SGA (p < 0.001 JA; p = 0.046 CA). Industry sponsored trials reported more SGA. Claimed subgroup effects were often not accompanied by significant interaction test; thus circumspection should be adopted when using SGA to deviate from standard therapeutic decision-making in GI oncology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reporting Randomized Controlled Trials in Education

ERIC Educational Resources Information Center

Mayo-Wilson, Evan; Grant, Sean; Montgomery, Paul

2014-01-01

Randomized controlled trials (RCTs) are increasingly used to evaluate programs and interventions in order to inform education policy and practice. High quality reports of these RCTs are needed for interested readers to understand the rigor of the study, the interventions tested, and the context in which the evaluation took place (Mayo-Wilson et…

Components of effective randomized controlled trials of hydrotherapy programs for fibromyalgia syndrome: A systematic review

PubMed Central

Perraton, Luke; Machotka, Zuzana; Kumar, Saravana

2009-01-01

Aim Previous systematic reviews have found hydrotherapy to be an effective management strategy for fibromyalgia syndrome (FMS). The aim of this systematic review was to summarize the components of hydrotherapy programs used in randomized controlled trials. Method A systematic review of randomized controlled trials was conducted. Only trials that have reported significant FMS-related outcomes were included. Data relating to the components of hydrotherapy programs (exercise type, duration, frequency and intensity, environmental factors, and service delivery) were analyzed. Results Eleven randomized controlled trials were included in this review. Overall, the quality of trials was good. Aerobic exercise featured in all 11 trials and the majority of hydrotherapy programs included either a strengthening or flexibility component. Great variability was noted in both the environmental components of hydrotherapy programs and service delivery. Conclusions Aerobic exercise, warm up and cool-down periods and relaxation exercises are common features of hydrotherapy programs that report significant FMS-related outcomes. Treatment duration of 60 minutes, frequency of three sessions per week and an intensity equivalent to 60%–80% maximum heart rate were the most commonly reported exercise components. Exercise appears to be the most important component of an effective hydrotherapy program for FMS, particularly when considering mental health-related outcomes. PMID:21197303

Endorsement of the CONSORT guidelines, trial registration, and the quality of reporting randomised controlled trials in leading nursing journals: A cross-sectional analysis.

PubMed

Jull, Andrew; Aye, Phyu Sin

2015-06-01

To establish the reporting quality of trials published in leading nursing journals and investigate associations between CONSORT Statement or trial registration endorsment and reporting of design elements. The top 15 nursing journals were searched using Medline for randomised controlled trials published in 2012. Journals were categorised as CONSORT and trial registration promoting based on requirements of submitting authors or the journal's webpage as at January 2014. Data on sequence generation, allocation concealment, follow up, blinding, baseline equivalence and sample size calculation were extracted by one author and independently verified by the second author against source data. Seven journals were CONSORT promoting and three of these journals were also trial registration promoting. 114 citations were identified and 83 were randomised controlled trials. Eighteen trials (21.7%) were registered and those published in trial registration promoting journals were more likely to be registered (RR 2.64 95%CI 1.14-6.09). We assessed 68.7% of trials to be low risk of bias for sequence generation, 20.5% for allocation concealment, 38.6% for blinding, 55.4% for completeness of follow up and 79.5% for baseline equivalence. Trials published in CONSORT promoting journals were more likely to be at low risk of bias for blinding (RR 2.33, 95%CI 1.01-5.34) and completeness of follow up (RR 1.77, 95%CI 1.02-3.10), but journal endorsement of the CONSORT Statement or trial registration otherwise had no significant effect. Trials published in CONSORT and trial registration promoting journals were more likely to have high quality sample size calculations (RR 2.91, 95%CI 1.18-7.19 and RR 1.69, 95%CI 1.08-2.64, respectively). Simple endorsement of the CONSORT Statement and trials registration is insufficient action to encourage improvement of the quality of trial reporting across the most important of trial design elements. Copyright © 2014 Elsevier Ltd. All rights reserved.

Registration status and methodological reporting of randomized controlled trials in obesity research: A review.

PubMed

Byrne, Jillian L S; Yee, Tamara; O'Connor, Kathleen; Dyson, Michele P; Ball, Geoff D C

2017-04-01

To assess registration and reporting details of randomized controlled trials (RCTs) published from 2011 to 2016 across four obesity journals. All issues from four leading obesity journals were searched systematically for RCTs from January 2011 to June 2016. Data on registration status were extracted from manuscripts, online trial registries, and a trial database; corresponding authors were contacted for registration details, when necessary. The methodological reporting of RCTs was assessed on specific criteria from the Consolidated Standards of Reporting Trials. A total of 223 RCTs were reviewed. Three-quarters (n = 170) were registered publicly; 94 (55.3%) reported registration details in the manuscript, and 82 (48.2%) were registered prospectively. Newer RCTs were more likely to be registered prospectively than older RCTs (2014-2016: 57.3% vs. 2011-2013: 39.2%; c 2  = 5.5, P = 0.02). Assessment on the Consolidated Standards of Reporting Trials demonstrated that less than half of all studies reported data collection dates (n = 108; 48.4%) or included "randomized trial" in the title (n = 89; 39.9%). The methodological reporting of RCTs published in obesity journals is suboptimal, despite current guidelines and policies. To complement existing standards, editorial boards should incorporate mandatory fields within the online manuscript submission process to enhance the quality, transparency, and comprehensiveness of reporting RCTs in obesity journals. © 2017 The Obesity Society.

Impact of a web-based tool (WebCONSORT) to improve the reporting of randomised trials: results of a randomised controlled trial.

PubMed

Hopewell, Sally; Boutron, Isabelle; Altman, Douglas G; Barbour, Ginny; Moher, David; Montori, Victor; Schriger, David; Cook, Jonathan; Gerry, Stephen; Omar, Omar; Dutton, Peter; Roberts, Corran; Frangou, Eleni; Clifton, Lei; Chiocchia, Virginia; Rombach, Ines; Wartolowska, Karolina; Ravaud, Philippe

2016-11-28

The CONSORT Statement is an evidence-informed guideline for reporting randomised controlled trials. A number of extensions have been developed that specify additional information to report for more complex trials. The aim of this study was to evaluate the impact of using a simple web-based tool (WebCONSORT, which incorporates a number of different CONSORT extensions) on the completeness of reporting of randomised trials published in biomedical publications. We conducted a parallel group randomised trial. Journals which endorsed the CONSORT Statement (i.e. referred to it in the Instruction to Authors) but do not actively implement it (i.e. require authors to submit a completed CONSORT checklist) were invited to participate. Authors of randomised trials were requested by the editor to use the web-based tool at the manuscript revision stage. Authors registering to use the tool were randomised (centralised computer generated) to WebCONSORT or control. In the WebCONSORT group, they had access to a tool allowing them to combine the different CONSORT extensions relevant to their trial and generate a customised checklist and flow diagram that they must submit to the editor. In the control group, authors had only access to a CONSORT flow diagram generator. Authors, journal editors, and outcome assessors were blinded to the allocation. The primary outcome was the proportion of CONSORT items (main and extensions) reported in each article post revision. A total of 46 journals actively recruited authors into the trial (25 March 2013 to 22 September 2015); 324 author manuscripts were randomised (WebCONSORT n = 166; control n = 158), of which 197 were reports of randomised trials (n = 94; n = 103). Over a third (39%; n = 127) of registered manuscripts were excluded from the analysis, mainly because the reported study was not a randomised trial. Of those included in the analysis, the most common CONSORT extensions selected were non-pharmacologic (n = 43; n = 50), pragmatic (n = 20; n = 16) and cluster (n = 10; n = 9). In a quarter of manuscripts, authors either wrongly selected an extension or failed to select the right extension when registering their manuscript on the WebCONSORT study site. Overall, there was no important difference in the overall mean score between WebCONSORT (mean score 0.51) and control (0.47) in the proportion of CONSORT and CONSORT extension items reported pertaining to a given study (mean difference, 0.04; 95% CI -0.02 to 0.10). This study failed to show a beneficial effect of a customised web-based CONSORT checklist to help authors prepare more complete trial reports. However, the exclusion of a large number of inappropriately registered manuscripts meant we had less precision than anticipated to detect a difference. Better education is needed, earlier in the publication process, for both authors and journal editorial staff on when and how to implement CONSORT and, in particular, CONSORT-related extensions. ClinicalTrials.gov: NCT01891448 [registered 24 May 2013].

On the Reporting of Experimental and Control Therapies in Stroke Rehabilitation Trials: A Systematic Review.

PubMed

Lohse, Keith R; Pathania, Anupriya; Wegman, Rebecca; Boyd, Lara A; Lang, Catherine E

2018-03-01

To use the Centralized Open-Access Rehabilitation database for Stroke to explore reporting of both experimental and control interventions in randomized controlled trials for stroke rehabilitation (including upper and lower extremity therapies). The Centralized Open-Access Rehabilitation database for Stroke was created from a search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Cumulative Index of Nursing and Allied Health from the earliest available date to May 31, 2014. A total of 2892 titles were reduced to 514 that were screened by full text. This screening left 215 randomized controlled trials in the database (489 independent groups representing 12,847 patients). Using a mixture of qualitative and quantitative methods, we performed a text-based analysis of how the procedures of experimental and control therapies were described. Experimental and control groups were rated by 2 independent coders according to the Template for Intervention Description and Replication criteria. Linear mixed-effects regression with a random effect of study (groups nested within studies) showed that experimental groups had statistically more words in their procedures (mean, 271.8 words) than did control groups (mean, 154.8 words) (P<.001). Experimental groups had statistically more references in their procedures (mean, 1.60 references) than did control groups (mean, .82 references) (P<.001). Experimental groups also scored significantly higher on the total Template for Intervention Description and Replication checklist (mean score, 7.43 points) than did control groups (mean score, 5.23 points) (P<.001). Control treatments in stroke motor rehabilitation trials are underdescribed relative to experimental treatments. These poor descriptions are especially problematic for "conventional" therapy control groups. Poor reporting is a threat to the internal validity and generalizability of clinical trial results. We recommend authors use preregistered protocols and established reporting criteria to improve transparency. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Medication adherence in randomized controlled trials evaluating cardiovascular or mortality outcomes in dialysis patients: A systematic review.

PubMed

Murali, Karumathil M; Mullan, Judy; Chen, Jenny H C; Roodenrys, Steven; Lonergan, Maureen

2017-01-31

Medication non-adherence is common among renal dialysis patients. High degrees of non-adherence in randomized controlled trials (RCTs) can lead to failure to detect a true treatment effect. Cardio-protective pharmacological interventions have shown no consistent benefit in RCTs involving dialysis patients. Whether non-adherence contributes to this lack of efficacy is unknown. We aimed to investigate how medication adherence and drug discontinuation were assessed, reported and addressed in RCTs, evaluating cardiovascular or mortality outcomes in dialysis patients. Electronic database searches were performed in MEDLINE, EMBASE & Cochrane CENTRAL for RCTs published between 2005-2015, evaluating self-administered medications, in adult dialysis patients, which reported clinical cardiovascular or mortality endpoints, as primary or secondary outcomes. Study characteristics, outcomes, methods of measuring and reporting adherence, and data on study drug discontinuation were analyzed. Of the 642 RCTs in dialysis patients, 22 trials (12 placebo controlled), which included 19,322 patients, were eligible. The trialed pharmacological interventions included anti-hypertensives, phosphate binders, lipid-lowering therapy, cardio-vascular medications, homocysteine lowering therapy, fish oil and calcimimetics. Medication adherence was reported in five trials with a mean of 81% (range: 65-92%) in the intervention arm and 84.5% (range: 82-87%) in the control arm. All the trials that reported adherence yielded negative study outcomes for the intervention. Study-drug discontinuation was reported in 21 trials (mean 33.2%; 95% CI, 22.0 to 44.5, in intervention and 28.8%; 95% CI, 16.8 to 40.8, in control). Trials with more than 20% study drug discontinuation, more often yielded negative study outcomes (p = 0.018). Non-adherence was included as a contributor to drug discontinuation in some studies, but the causes of discontinuation were not reported consistently between studies, and non-adherence was listed under different categories, thereby potentiating the misclassification of adherence. Reporting of medication adherence and study-drug discontinuation in RCTs investigating cardiovascular or mortality endpoints in dialysis patients are inconsistent, making it difficult to compare studies and evaluate their impact on outcomes. Recommendations for consistent reporting of non-adherence and causes of drug discontinuation in RCTs will therefore help to assess their impact on clinical outcomes.

Reporting of harm and safety results in randomized controlled trials published in 5 dermatology journals.

PubMed

Haddad, Cynthia; Sigha, Odette Berline; Lebrun-Vignes, Bénédicte; Chosidow, Olivier; Fardet, Laurence

2017-07-01

Randomized controlled trials (RCTs) are considered the gold standard for assessing efficacy and short-term harm of medicines. However, several studies have come to the conclusion that harm is less well reported than efficacy outcomes. To describe harm reporting in publications on dermatological RCTs and assess parameters that could influence the quality of harm reporting. Methodologic systematic review of dermatologic RCTs published from 2010 to 2014 in 5 dermatological journals. Among 110 assessed publications on RCTs, 80 (73%) adequately reported harm and 52% adequately reported its severity. Overall, 40% of the assessed manuscripts perfectly reported and discussed harm. The adequate reporting of harm was significantly associated with the type of trial (odds ratio [OR] 4.41, 95% confidence interval [CI] 1.60-12.35 for multicenter compared with monocentric trials) and having a predefined method for collecting harm data (OR 5.93, 95% CI 2.26-15.56). Reporting of harm severity was better in pharmacologic trials (OR 6.48, 95% CI 2.00-21.0) compared with nonpharmacologic trials and in trials for which a method for collecting harm (OR 5.65, 95% CI 2.00-16.4) and its severity (OR 3.60, 95% CI 1.00-12.8) was defined before the study onset. Assessment was restricted to RCTs and 5 dermatological journals. Harm is quite well reported in dermatologic journals. Efforts should be made on reporting severity of harm. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Corticosteroids for the common cold.

PubMed

Hayward, Gail; Thompson, Matthew J; Perera, Rafael; Del Mar, Chris B; Glasziou, Paul P; Heneghan, Carl J

2015-10-13

The common cold is a frequent illness, which, although benign and self limiting, results in many consultations to primary care and considerable loss of school or work days. Current symptomatic treatments have limited benefit. Corticosteroids are an effective treatment in other upper respiratory tract infections and their anti-inflammatory effects may also be beneficial in the common cold. This updated review has included one additional study. To compare corticosteroids versus usual care for the common cold on measures of symptom resolution and improvement in children and adults. We searched Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 4), which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects (DARE) (2015, Issue 2), NHS Health Economics Database (2015, Issue 2), MEDLINE (1948 to May week 3, 2015) and EMBASE (January 2010 to May 2015). Randomised, double-blind, controlled trials comparing corticosteroids to placebo or to standard clinical management. Two review authors independently extracted data and assessed trial quality. We were unable to perform meta-analysis and instead present a narrative description of the available evidence. We included three trials (353 participants). Two trials compared intranasal corticosteroids to placebo and one trial compared intranasal corticosteroids to usual care; no trials studied oral corticosteroids. In the two placebo-controlled trials, no benefit of intranasal corticosteroids was demonstrated for duration or severity of symptoms. The risk of bias overall was low or unclear in these two trials. In a trial of 54 participants, the mean number of symptomatic days was 10.3 in the placebo group, compared to 10.7 in those using intranasal corticosteroids (P value = 0.72). A second trial of 199 participants reported no significant differences in the duration of symptoms. The single-blind trial in children aged two to 14 years, who were also receiving oral antibiotics, had inadequate reporting of outcome measures regarding symptom resolution. The overall risk of bias was high for this trial. Mean symptom severity scores were significantly lower in the group receiving intranasal steroids in addition to oral amoxicillin. One placebo-controlled trial reported the presence of rhinovirus in nasal aspirates and found no differences. Only one of the three trials reported on adverse events; no differences were found. Two trials reported secondary bacterial infections (one case of sinusitis, one case of acute otitis media; both in the corticosteroid groups). A lack of comparable outcome measures meant that we were unable to combine the data. Current evidence does not support the use of intranasal corticosteroids for symptomatic relief from the common cold. However, there were only three trials, one of which was very poor quality, and there was limited statistical power overall. Further large, randomised, double-blind, placebo-controlled trials in adults and children are required to answer this question.

Effectiveness of Azadirachta indica (neem) mouthrinse in plaque and gingivitis control: a systematic review.

PubMed

Dhingra, K; Vandana, K L

2017-02-01

The aim of this systematic review was to evaluate the effectiveness of Azadirachta indica (neem)-based herbal mouthrinse in improving plaque control and gingival health. Literature search was accomplished using electronic databases (PubMed, Cochrane Central Register of Controlled Trials and EMBASE) and manual searching, up to February 2015, for randomized controlled trials (RCTs) presenting clinical data for efficacy of neem mouthrinses when used alone or as an adjunct to mechanical oral hygiene as compared to chlorhexidine mouthrinses for controlling plaque and gingival inflammation in patients with gingivitis. Of the total 206 articles searched, three randomized controlled trials evaluating neem-based herbal mouthrinses were included. Due to marked heterogeneity observed in study characteristics, meta-analysis was not performed. These studies reported that neem mouthrinse was as effective as chlorhexidine mouthrinse when used as an adjunct to toothbrushing in reducing plaque and gingival inflammation in gingivitis patients. However, the quality of reporting and evidence along with methods of studies was generally flawed with unclear risk of bias. Despite the promising results shown in existing randomized controlled trials, the evidence concerning the clinical use of neem mouthrinses is lacking and needs further reinforcement with high-quality randomized controlled trials based on the reporting guidelines of herbal CONSORT statement. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evidence for compliance with long-term medication: a systematic review of randomised controlled trials.

PubMed

King, Michelle A; Pryce, Rebecca L

2014-02-01

Pharmacists play a pivotal role in optimising medication use which often includes actions to maximise compliance with long-term medication. The best evidence to support medication use is derived from randomised controlled trials (RCTs). It is often assumed that 100 % compliance is required to obtain the outcomes identified in the trial. This assumption needs to be examined. To systematically review the reporting of compliance in RCTs of long-term medications. RCTs published in the New England Journal of Medicine, Journal of the American Medical Association, Lancet and BMJ in 2012, were reviewed to identify trials of medications for long-term use in adults. These trials were examined to evaluate the reporting of compliance. The proportion of trials reporting compliance data, the methods used, and the proportion of trials using more than one method to determine compliance. Of the 289 RCTs published in 2012, 25 assessed long-term medications in adults. Compliance was reported in 12 (48 %) studies and only 2 (8 %) studies used more than one method to measure compliance. Pill count was the most commonly reported method for measuring compliance, with patient reports and blood levels also being used. The reporting of compliance in RCTs is poor and the methodology inconsistent. The methods used overestimate compliance. If compliance in a clinical trial is low, the evidence for the effectiveness and most importantly safety of the medication(s) is questionable. Two or more methods, one of which is standardised, should be used to measure compliance in clinical trials. The requirement to report compliance should be included in publication guidelines.

The Quality of Reporting of Abstracts in Physical Therapy Literature is Suboptimal: Cross-Sectional, Bibliographic Analysis.

PubMed

Richter, Randy R; Sebelski, Chris A; Austin, Tricia M

2016-09-01

The quality of abstract reporting in physical therapy literature is unknown. The purpose of this study was to provide baseline data for judging the future impact of the 2010 Consolidated Standards of Reporting Trials statement specifically referencing the 2008 Consolidated Standards of Reporting Trials statement for reporting of abstracts of randomized controlled trials across and between a broad sample and a core sample of physical therapy literature. A cross-sectional, bibliographic analysis was conducted. Abstracts of randomized controlled trials from 2009 were retrieved from PubMed, PEDro, and CENTRAL. Eligibility was determined using PEDro criteria. For outcomes measures, items from the Consolidated Standards of Reporting Trials statement for abstract reporting were used for assessment. Raters were not blinded to citation details. Using a computer-generated set of random numbers, 150 abstracts from 112 journals comprised the broad sample. A total of 53 abstracts comprised the core sample. Fourteen of 20 Consolidated Standards of Reporting Trials items for both samples were reported in less than 50% of the abstracts. Significantly more abstracts in the core sample reported (% difference core - broad; 95% confidence interval) title (28.4%; 12.9%-41.2%), blinding (15.2%; 1.6%-29.8%), setting (47.6%; 32.4%-59.4%), and confidence intervals (13.1%; 5.0%-25.1%). These findings provide baseline data for determining if continuing efforts to improve abstract reporting are heeded.

Accounting for correlation in network meta-analysis with multi-arm trials.

PubMed

Franchini, A J; Dias, S; Ades, A E; Jansen, J P; Welton, N J

2012-06-01

Multi-arm trials (trials with more than two arms) are particularly valuable forms of evidence for network meta-analysis (NMA). Trial results are available either as arm-level summaries, where effect measures are reported for each arm, or as contrast-level summaries, where the differences in effect between arms compare with the control arm chosen for the trial. We show that likelihood-based inference in both contrast-level and arm-level formats is identical if there are only two-arm trials, but that if there are multi-arm trials, results from the contrast-level format will be incorrect unless correlations are accounted for in the likelihood. We review Bayesian and frequentist software for NMA with multi-arm trials that can account for this correlation and give an illustrative example of the difference in estimates that can be introduced if the correlations are not incorporated. We discuss methods of imputing correlations when they cannot be derived from the reported results and urge trialists to report the standard error for the control arm even if only contrast-level summaries are reported. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd.

Quality of reporting of modern randomized controlled trials in medical oncology: a systematic review.

PubMed

Péron, Julien; Pond, Gregory R; Gan, Hui K; Chen, Eric X; Almufti, Roula; Maillet, Denis; You, Benoit

2012-07-03

The Consolidated Standards of Reporting Trials (CONSORT) guidelines were developed in the mid-1990s for the explicit purpose of improving clinical trial reporting. However, there is little information regarding the adherence to CONSORT guidelines of recent publications of randomized controlled trials (RCTs) in oncology. All phase III RCTs published between 2005 and 2009 were reviewed using an 18-point overall quality score for reporting based on the 2001 CONSORT statement. Multivariable linear regression was used to identify features associated with improved reporting quality. To provide baseline data for future evaluations of reporting quality, RCTs were also assessed according to the 2010 revised CONSORT statement. All statistical tests were two-sided. A total of 357 RCTs were reviewed. The mean 2001 overall quality score was 13.4 on a scale of 0-18, whereas the mean 2010 overall quality score was 19.3 on a scale of 0-27. The overall RCT reporting quality score improved by 0.21 points per year from 2005 to 2009. Poorly reported items included method used to generate the random allocation (adequately reported in 29% of trials), whether and how blinding was applied (41%), method of allocation concealment (51%), and participant flow (59%). High impact factor (IF, P = .003), recent publication date (P = .008), and geographic origin of RCTs (P = .003) were independent factors statistically significantly associated with higher reporting quality in a multivariable regression model. Sample size, tumor type, and positivity of trial results were not associated with higher reporting quality, whereas funding source and treatment type had a borderline statistically significant impact. The results show that numerous items remained unreported for many trials. Thus, given the potential impact of poorly reported trials, oncology journals should require even stricter adherence to the CONSORT guidelines.

Trial Registration: Understanding and Preventing Reporting Bias in Social Work Research

ERIC Educational Resources Information Center

Harrison, Bronwyn A.; Mayo-Wilson, Evan

2014-01-01

Randomized controlled trials are considered the gold standard for evaluating social work interventions. However, published reports can systematically overestimate intervention effects when researchers selectively report large and significant findings. Publication bias and other types of reporting biases can be minimized through prospective trial…

Meta-analysis: aerobic exercise for the treatment of anxiety disorders.

PubMed

Bartley, Christine A; Hay, Madeleine; Bloch, Michael H

2013-08-01

This meta-analysis investigates the efficacy of exercise as a treatment for DSM-IV diagnosed anxiety disorders. We searched PubMED and PsycINFO for randomized, controlled trials comparing the anxiolytic effects of aerobic exercise to other treatment conditions for DSM-IV defined anxiety disorders. Seven trials were included in the final analysis, totaling 407 subjects. The control conditions included non-aerobic exercise, waitlist/placebo, cognitive-behavioral therapy, psychoeducation and meditation. A fixed-effects model was used to calculate the standardized mean difference of change in anxiety rating scale scores of aerobic exercise compared to control conditions. Subgroup analyses were performed to examine the effects of (1) comparison condition; (2) whether comparison condition controlled for time spent exercising and (3) diagnostic indication. Aerobic exercise demonstrated no significant effect for the treatment of anxiety disorders (SMD=0.02 (95%CI: -0.20-0.24), z = 0.2, p = 0.85). There was significant heterogeneity between trials (χ(2) test for heterogeneity = 22.7, df = 6, p = 0.001). The reported effect size of aerobic exercise was highly influenced by the type of control condition. Trials utilizing waitlist/placebo controls and trials that did not control for exercise time reported large effects of aerobic exercise while other trials report no effect of aerobic exercise. Current evidence does not support the use of aerobic exercise as an effective treatment for anxiety disorders as compared to the control conditions. This remains true when controlling for length of exercise sessions and type of anxiety disorder. Future studies evaluating the efficacy of aerobic exercise should employ larger sample sizes and utilize comparison interventions that control for exercise time. Copyright © 2013. Published by Elsevier Inc.

Reporting funding source or conflict of interest in abstracts of randomized controlled trials, no evidence of a large impact on general practitioners' confidence in conclusions, a three-arm randomized controlled trial.

PubMed

Buffel du Vaure, Céline; Boutron, Isabelle; Perrodeau, Elodie; Ravaud, Philippe

2014-04-28

Systematic reporting of funding sources is recommended in the CONSORT Statement for abstracts. However, no specific recommendation is related to the reporting of conflicts of interest (CoI). The objective was to compare physicians' confidence in the conclusions of abstracts of randomized controlled trials of pharmaceutical treatment indexed in PubMed. We planned a three-arm parallel-group randomized trial. French general practitioners (GPs) were invited to participate and were blinded to the study's aim. We used a representative sample of 75 abstracts of pharmaceutical industry-funded randomized controlled trials published in 2010 and indexed in PubMed. Each abstract was standardized and reported in three formats: 1) no mention of the funding source or CoI; 2) reporting the funding source only; and 3) reporting the funding source and CoI. GPs were randomized according to a computerized randomization on a secure Internet system at a 1:1:1 ratio to assess one abstract among the three formats. The primary outcome was GPs' confidence in the abstract conclusions (0, not at all, to 10, completely confident). The study was planned to detect a large difference with an effect size of 0.5. Between October 2012 and June 2013, among 605 GPs contacted, 354 were randomized, 118 for each type of abstract. The mean difference (95% confidence interval) in GPs' confidence in abstract findings was 0.2 (-0.6; 1.0) (P = 0.84) for abstracts reporting the funding source only versus no funding source or CoI; -0.4 (-1.3; 0.4) (P = 0.39) for abstracts reporting the funding source and CoI versus no funding source and CoI; and -0.6 (-1.5; 0.2) (P = 0.15) for abstracts reporting the funding source and CoI versus the funding source only. We found no evidence of a large impact of trial report abstracts mentioning funding sources or CoI on GPs' confidence in the conclusions of the abstracts. ClinicalTrials.gov identifier: NCT01679873.

Are reports of randomized controlled trials improving over time? A systematic review of 284 articles published in high-impact general and specialized medical journals.

PubMed

To, Matthew J; Jones, Jennifer; Emara, Mohamed; Jadad, Alejandro R

2013-01-01

Inadequate reporting undermines findings of randomized controlled trials (RCTs). This study assessed and compared articles published in high-impact general medical and specialized journals. Reports of RCTs published in high-impact general and specialized medical journals were identified through a search of MEDLINE from January to March of 1995, 2000, 2005, and 2010. Articles that provided original data on adult patients diagnosed with chronic conditions were included in the study. Data on trial characteristics, reporting of allocation concealment, quality score, and the presence of a trial flow diagram were extracted independently by two reviewers, and discrepancies were resolved by consensus or independent adjudication. Descriptive statistics were used for quantitative variables. Comparisons between general medical and specialized journals, and trends over time were performed using Chi-square tests. Reports of 284 trials were analyzed. There was a significantly higher proportion of RCTs published with adequate reporting of allocation concealment (p = 0.003), presentation of a trial flow diagram (p<0.0001) and high quality scores (p = 0.038) over time. Trials published in general medical journals had higher quality scores than those in specialized journals (p = 0.001), reported adequate allocation concealment more often (p = 0.013), and presented a trial flow diagram more often (p<0.001). We found significant improvements in reporting quality of RCTs published in high-impact factor journals over the last fifteen years. These improvements are likely attributed to concerted international efforts to improve reporting quality such as CONSORT. There is still much room for improvement, especially among specialized journals.

Incidence and impact of withdrawal of life-sustaining therapies in clinical trials of severe traumatic brain injury: A systematic review.

PubMed

Leblanc, Guillaume; Boutin, Amélie; Shemilt, Michèle; Lauzier, François; Moore, Lynne; Potvin, Véronique; Zarychanski, Ryan; Archambault, Patrick; Lamontagne, François; Léger, Caroline; Turgeon, Alexis F

2018-06-01

Background Most deaths following severe traumatic brain injury follow decisions to withdraw life-sustaining therapies. However, the incidence of the withdrawal of life-sustaining therapies and its potential impact on research data interpretation have been poorly characterized. The aim of this systematic review was to assess the reporting and the impact of withdrawal of life-sustaining therapies in randomized clinical trials of patients with severe traumatic brain injury. Methods We searched Medline, Embase, Cochrane Central, BIOSIS, and CINAHL databases and references of included trials. All randomized controlled trials published between January 2002 and August 2015 in the six highest impact journals in general medicine, critical care medicine, and neurocritical care (total of 18 journals) were considered for eligibility. Randomized controlled trials were included if they enrolled adult patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) and reported data on mortality. Our primary objective was to assess the proportion of trials reporting the withdrawal of life-sustaining therapies in a publication. Our secondary objectives were to describe the overall mortality rate, the proportion of deaths following the withdrawal of life-sustaining therapies, and to assess the impact of the withdrawal of life-sustaining therapies on trial results. Results From 5987 citations retrieved, we included 41 randomized trials (n = 16,364, ranging from 11 to 10,008 patients). Overall mortality was 23% (range = 3%-57%). Withdrawal of life-sustaining therapies was reported in 20% of trials (8/41, 932 patients in trials) and the crude number of deaths due to the withdrawal of life-sustaining therapies was reported in 17% of trials (7/41, 884 patients in trials). In these trials, 63% of deaths were associated with the withdrawal of life-sustaining therapies (105/168). An analysis carried out by imputing a 4% differential rate in instances of withdrawal of life-sustaining therapies between study groups yielded different results and conclusions in one third of the trials. Conclusion Data on the withdrawal of life-sustaining therapies are incompletely reported in randomized controlled trials of patients with severe traumatic brain injury. Given the high proportion of deaths due to the withdrawal of life-sustaining therapies in severe traumatic brain injury patients, and the potential of this medical decision to influence the results of clinical trials, instances of withdrawal of life-sustaining therapies should be systematically reported in clinical trials in this group of patients.

Herbal Medicine for Xerostomia in Cancer Patients: A Systematic Review of Randomized Controlled Trials.

PubMed

Park, Bongki; Noh, Hyeonseok; Choi, Dong-Jun

2018-06-01

Xerostomia (dry mouth) causes many clinical problems, including oral infections, speech difficulties, and impaired chewing and swallowing of food. Many cancer patients have complained of xerostomia induced by cancer therapy. The aim of this systematic review is to assess the efficacy of herbal medicine for the treatment of xerostomia in cancer patients. Randomized controlled trials investigating the use of herbal medicines to treat xerostomia in cancer patients were included. We searched the following 12 databases without restrictions on time or language. The risk of bias was assessed using the Cochrane Risk of Bias Tool. Twenty-five randomized controlled trials involving 1586 patients met the inclusion criteria. A total of 24 formulas were examined in the included trials. Most of the included trials were insufficiently reported in the methodology section. Five formulas were shown to significantly improve the salivary flow rate compared to comparators. Regarding the grade of xerostomia, all formulas with the exception of a Dark Plum gargle solution with normal saline were significantly effective in reducing the severity of dry mouth. Adverse events were reported in 4 trials, and adverse effects of herbal medicine were reported in 3 trials. We found herbal medicines had potential benefits for improving salivary function and reducing the severity of dry mouth in cancer patients. However, methodological limitations and a relatively small sample size reduced the strength of the evidence. More high-quality trials reporting sufficient methodological data are warranted to enforce the strength of evidence regarding the effectiveness of herbal medicines.

The Consolidated Standards of Reporting Trials (CONSORT) Statement applied to allergen-specific immunotherapy with inhalant allergens: a Global Allergy and Asthma European Network (GA(2)LEN) article.

PubMed

Bousquet, Philippe J; Calderón, Moisés A; Demoly, Pascal; Larenas, Désirée; Passalacqua, Giovanni; Bachert, Claus; Brozek, Jan; Canonica, G Walter; Casale, Thomas; Fonseca, Joao; Dahl, Ronald; Durham, Stephen R; Merk, Hans; Worm, Margitta; Wahn, Ulrich; Zuberbier, Torsten; Schünemann, Holger J; Bousquet, Jean

2011-01-01

Randomized trials provide evidence to inform treatment decisions. The Consolidated Standards of Reporting Trials (CONSORT) Statement is a set of recommendations for the reporting of trials. We sought to assess the quality of reporting allergen-specific immunotherapy trials according to CONSORT criteria. The reporting of the procedure, randomization, dropouts, strict conduct of intention-to-treat (ITT) analysis, and sample size calculation according to CONSORT were assessed in the 46 subcutaneous and 48 sublingual immunotherapy (SLIT) blind, placebo-controlled randomized trials published between 1996 and 2009 in English. One subcutaneous immunotherapy (2.2%) and 3 SLIT (6.6%) trials met CONSORT Statement criteria. These were used for the registration of sublingual tablets to the European Medicines Agency. In subcutaneous immunotherapy, 16 (35%) studies reported a CONSORT flow chart, and 12 (26%) provided a description of dropouts. Adequate randomization was reported in 9 (35%) studies, and incomplete randomization was reported in 15 (33%). Power analysis was reported in 15 (33%) studies. In SLIT, 20 (42%) studies reported a CONSORT flow chart, and 16 (32%) a description of dropouts. ITT analysis was carried out in 1 (2.2%) SLIT study, and a modified ITT analysis was used in 1 (2.2%) subcutaneous immunotherapy study and 2 (4.4%) SLIT studies. Adequate randomization was reported in 6 (12%) studies, and incomplete randomization was reported in 16 (32%). Power analysis was reported in 15 (27%) studies. As in other areas of medicine, the quality of reporting of most immunotherapy trials is low, and only 4.2% of SLIT randomized controlled trials met all of the criteria of the CONSORT Statement. Use of the CONSORT criteria should be encouraged. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Vitex agnus-castus extracts for female reproductive disorders: a systematic review of clinical trials.

PubMed

van Die, M Diana; Burger, Henry G; Teede, Helena J; Bone, Kerry M

2013-05-01

Vitex agnus-castus L. (chaste tree; chasteberry) is a popular herbal treatment, predominantly used for a range of female reproductive conditions in Anglo-American and European practice. The objective of this systematic review was to evaluate the evidence for the efficacy and safety of Vitex extracts from randomised, controlled trials investigating women's health.Eight databases were searched using Latin and common names for Vitex and phytotherapeutic preparations of the herb as a sole agent, together with filters for randomised, controlled trials or clinical trials. Methodological quality was assessed according to the Cochrane risk of bias and Jadad scales, as well as the proposed elaboration of CONSORT for reporting trials on herbal interventions.Thirteen randomised, controlled trials were identified and twelve are included in this review, of which eight investigated premenstrual syndrome, two premenstrual dysphoric disorder, and two latent hyperprolactinaemia. For premenstrual syndrome, seven of eight trials found Vitex extracts to be superior to placebo (5 of 6 studies), pyridoxine (1), and magnesium oxide (1). In premenstrual dysphoric disorder, one study reported Vitex to be equivalent to fluoxetine, while in the other, fluoxetine outperformed Vitex. In latent hyperprolactinaemia, one trial reported it to be superior to placebo for reducing TRH-stimulated prolactin secretion, normalising a shortened luteal phase, increasing mid-luteal progesterone and 17β-oestradiol levels, while the other found Vitex comparable to bromocriptine for reducing serum prolactin levels and ameliorating cyclic mastalgia. Adverse events with Vitex were mild and generally infrequent. The methodological quality of the included studies varied, but was generally moderate-to-high. Limitations include small sample sizes in some studies, heterogeneity of conditions being treated, and a range of reference treatments.Despite some methodological limitations, the results from randomised, controlled trials to date suggest benefits for Vitex extracts in the treatment of premenstrual syndrome, premenstrual dysphoric disorder and latent hyperprolactinaemia. Further research is recommended, and greater transparency in reporting for future trials. Georg Thieme Verlag KG Stuttgart · New York.

Chinese herbal medicine for diabetic peripheral neuropathy.

PubMed

Chen, Wei; Zhang, Yin; Liu, Jian Ping

2011-06-15

Chinese herbal medicine is frequently used for treating diabetic peripheral neuropathy in China. Many controlled trials have been undertaken to investigate its efficacy. To assess the beneficial effects and harms of Chinese herbal medicine for people with diabetic peripheral neuropathy. We searched the Cochrane Neuromuscular Disease Group Specialized Register (15 June 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2010 in The Cochrane Library), MEDLINE (January 1966 to June 2010), EMBASE (January 1980 to June 2010), AMED (January 1985 to June 2010), Chinese Biomedical Database (CBM) (1979 to June 2010), Chinese National Knowledge Infrastructure Database (CNKI) (1979 to June 2010), and VIP Chinese Science and Technique Journals Database (1989 to June 2010). We searched for unpublished literature in the Chinese Conference Papers Database and Chinese Dissertation Database (from inception to March 2010). No language or publication restrictions were used. We included randomized controlled trials of Chinese herbal medicine (with a minimum of four weeks treatment duration) for people with diabetic peripheral neuropathy compared with placebo, no intervention, or conventional interventions. Trials of herbal medicine plus a conventional drug versus the drug alone were also included. Two authors independently extracted data and evaluated trial quality. We contacted study authors for additional information. The data analyses were carried out using Review Manager 5.1 (Cochrane software). Thirty-nine randomized trials involving 2890 participants were included. All trials were conducted and published in China. Thirty different herbal medicines were tested in these trials, including four single herbs (extracts from a single herb), eight traditional Chinese patent medicines, and 18 self-concocted Chinese herbal compound prescriptions. The trials reported on global symptom improvement (including improvement in numbness or pain) and changes in nerve conduction velocity. There was inadequate reporting on adverse events in the included trials. Most of the trials did not mention whether they monitored adverse effects at all. Only two trials reported adverse events: one occurred in the control group in one trial and in which group was unclear in the other trial . Conclusions cannot be drawn from this review about the safety of herbal medicines due to inadequate reporting. Most of the trials were of low methodological quality and therefore the interpretation of any positive findings for the efficacy of the included Chinese herbal medicines for treating diabetic peripheral neuropathy should be made with caution. Based on this systematic review, there is no evidence to support the objective effectiveness and safety of Chinese herbal medicines for diabetic peripheral neuropathy. No well designed, randomized placebo controlled trial with objective outcome measures has been conducted.

Inadequate safety reporting in pre-eclampsia trials: a systematic evaluation.

PubMed

Duffy, Jmn; Hirsch, M; Pealing, L; Showell, M; Khan, K S; Ziebland, S; McManus, R J

2018-06-01

Randomised trials and their syntheses in meta-analyses offer a unique opportunity to assess the frequency and severity of adverse reactions. To assess safety reporting in pre-eclampsia trials. Systematic search using bibliographic databases, including Cochrane Central Register of Controlled Trials, Embase, and MEDLINE, from inception to August 2017. Randomised trials evaluating anticonvulsant or antihypertensive medication for pre-eclampsia. Descriptive statistics appraising the adequacy of adverse reaction and toxicity reporting. We included 60 randomised trials. Six trials (10%) were registered with the International Clinical Trials Registry Platform, two registry records referred to adverse reactions, stating 'safety and toleration' and 'possible side effects' would be collected. Twenty-six trials (43%) stated the frequency of withdrawals within each study arm, and five trials (8%) adequately reported these withdrawals. Adverse reactions were inconsistently reported across eligible trials: 24 (40%) reported no serious adverse reactions and 36 (60%) reported no mild adverse reactions. The methods of definition or measurement of adverse reactions were infrequently reported within published trial reports. Pre-eclampsia trials regularly omit critical information related to safety. Despite the paucity of reporting, randomised trials collect an enormous amount of safety data. Developing and implementing a minimum data set could help to improve safety reporting, permitting a more balanced assessment of interventions by considering the trade-off between the benefits and harms. National Institute for Health Research (DRF-2014-07-051), UK; Maternity Forum, Royal Society of Medicine, UK. Developing @coreoutcomes could help to improve safety reporting in #preeclampsia trials. @NIHR_DC. © 2017 Royal College of Obstetricians and Gynaecologists.

External validity of randomized controlled trials in older adults, a systematic review.

PubMed

van Deudekom, Floor J; Postmus, Iris; van der Ham, Danielle J; Pothof, Alexander B; Broekhuizen, Karen; Blauw, Gerard J; Mooijaart, Simon P

2017-01-01

To critically assess the external validity of randomized controlled trials (RCTs) it is important to know what older adults have been enrolled in the trials. The aim of this systematic review is to study what proportion of trials specifically designed for older patients report on somatic status, physical and mental functioning, social environment and frailty in the patient characteristics. PubMed was searched for articles published in 2012 and only RCTs were included. Articles were further excluded if not conducted with humans or only secondary analyses were reported. A random sample of 10% was drawn. The current review analyzed this random sample and further selected trials when the reported mean age was ≥ 60 years. We extracted geriatric assessments from the population descriptives or the in- and exclusion criteria. In total 1396 trials were analyzed and 300 trials included. The median of the reported mean age was 66 (IQR 63-70) and the median percentage of men in the trials was 60 (IQR 45-72). In 34% of the RCTs specifically designed for older patients somatic status, physical and mental functioning, social environment or frailty were reported in the population descriptives or the in- and exclusion criteria. Physical and mental functioning was reported most frequently (22% and 14%). When selecting RCTs on a mean age of 70 or 80 years the report of geriatric assessments in the patient characteristics was 46% and 85% respectively but represent only 5% and 1% of the trials. Somatic status, physical and mental functioning, social environment and frailty are underreported even in RCTs specifically designed for older patients published in 2012. Therefore, it is unclear for clinicians to which older patients the results can be applied. We recommend systematic to transparently report these relevant characteristics of older participants included in RCTs.

The prevalence of patient engagement in published trials: a systematic review.

PubMed

Fergusson, Dean; Monfaredi, Zarah; Pussegoda, Kusala; Garritty, Chantelle; Lyddiatt, Anne; Shea, Beverley; Duffett, Lisa; Ghannad, Mona; Montroy, Joshua; Hassan Murad, M; Pratt, Misty; Rader, Tamara; Shorr, Risa; Yazdi, Fatemeh

2018-01-01

With the growing movement to engage patients in research, questions are being asked about who is engaging patients and how they are being engaged. Internationally, research groups are supporting and funding patient-oriented research studies that engage patients in the identification of research priorities and the design, conduct and uptake of research. As we move forward, we need to know what meaningful patient engagement looks like, how it benefits research and clinical practice, and what are the barriers to patient engagement?We conducted a review of the published literature looking for trials that report engaging patients in the research. We included both randomized controlled trials and non-randomized comparative trials. We looked at these trials for important study characteristics, including how patients were engaged, to better understand the practices used in trials. Importantly, we also discuss the number of trials reporting patient engagement practices relative to all published trials. We found that very few trials report any patient engagement activities even though it is widely supported by many major funding organizations. The findings of our work will advance patient-oriented research by showing how patients can be engaged and by stressing that patient engagement practices need to be better reported. Patient-Oriented Research (POR) is research informed by patients and is centred on what is of importance to them. A fundamental component of POR is that patients are included as an integral part of the research process from conception to dissemination and implementation, and by extension, across the research continuum from basic research to pragmatic trials [J Comp Eff Res 2012, 1:181-94, JAMA 2012, 307:1587-8]. Since POR's inception, questions have been raised as to how best to achieve this goal.We conducted a systematic review of randomized controlled trials and non-randomized comparative trials that report engaging patients in their research. Our main goal was to describe the characteristics of published trials engaging patients in research, and to identify the extent of patient engagement activities reported in these trials. The MEDLINE®, EMBASE®, Cinahl, PsycINFO, Cochrane Methodology Registry, and Pubmed were searched from May 2011 to June 16th, 2016. Title, abstract and full text screening of all reports were conducted independently by two reviewers. Data were extracted from included trials by one reviewer and verified by a second. All trials that report patient engagement for the purposes of research were included. Of the 9490 citations retrieved, 2777 were reviewed at full text, of which 23 trials were included. Out of the 23 trials, 17 were randomized control trials, and six were non-randomized comparative trials. The majority of these trials (83%, 19/23) originated in the United States and United Kingdom. The trials engaged a range of 2-24 patients/ community representatives per study. Engagement of children and minorities occurred in 13% (3/23) and 26% (6/23) of trials; respectively. Engagement was identified in the development of the research question, the selection of study outcomes, and the dissemination and implementation of results. The prevalence of patient engagement in patient-oriented interventional research is very poor with 23 trials reporting activities engaging patients. Research dedicated to determining the best practice for meaningful engagement is still needed, but adequate reporting measures also need to be defined.

Computer Enabled Neuroplasticity Treatment: A Clinical Trial of a Novel Design for Neurofeedback Therapy in Adult ADHD

PubMed Central

Cowley, Benjamin; Holmström, Édua; Juurmaa, Kristiina; Kovarskis, Levas; Krause, Christina M.

2016-01-01

Background: We report a randomized controlled clinical trial of neurofeedback therapy intervention for ADHD/ADD in adults. We focus on internal mechanics of neurofeedback learning, to elucidate the primary role of cortical self-regulation in neurofeedback. We report initial results; more extensive analysis will follow. Methods: Trial has two phases: intervention and follow-up. The intervention consisted of neurofeedback treatment, including intake and outtake measurements, using a waiting-list control group. Treatment involved ~40 h-long sessions 2–5 times per week. Training involved either theta/beta or sensorimotor-rhythm regimes, adapted by adding a novel “inverse-training” condition to promote self-regulation. Follow-up (ongoing) will consist of self-report and executive function tests. Setting: Intake and outtake measurements were conducted at University of Helsinki. Treatment was administered at partner clinic Mental Capital Care, Helsinki. Randomization: We randomly allocated half the sample then adaptively allocated the remainder to minimize baseline differences in prognostic variables. Blinding: Waiting-list control design meant trial was not blinded. Participants: Fifty-four adult Finnish participants (mean age 36 years; 29 females) were recruited after screening by psychiatric review. Forty-four had ADHD diagnoses, 10 had ADD. Measurements: Symptoms were assessed by computerized attention test (T.O.V.A.) and self-report scales, at intake and outtake. Performance during neurofeedback trials was recorded. Results: Participants were recruited and completed intake measurements during summer 2012, before assignment to treatment and control, September 2012. Outtake measurements ran April-August 2013. After dropouts, 23 treatment and 21 waiting-list participants remained for analysis. Initial analysis showed that, compared to waiting-list control, neurofeedback promoted improvement of self-reported ADHD symptoms, but did not show transfer of learning to T.O.V.A. Comprehensive analysis will be reported elsewhere. Trial Registration: “Computer Enabled Neuroplasticity Treatment (CENT),” ISRCTN13915109. PMID:27242472

Adjudication-related processes are underreported and lack standardization in clinical trials of venous thromboembolism: a systematic review.

PubMed

Stuck, Anna K; Fuhrer, Evelyn; Limacher, Andreas; Méan, Marie; Aujesky, Drahomir

2014-03-01

Although the use of an adjudication committee (AC) for outcomes is recommended in randomized controlled trials, there are limited data on the process of adjudication. We therefore aimed to assess whether the reporting of the adjudication process in venous thromboembolism (VTE) trials meets existing quality standards and which characteristics of trials influence the use of an AC. We systematically searched MEDLINE and the Cochrane Library from January 1, 2003, to June 1, 2012, for randomized controlled trials on VTE. We abstracted information about characteristics and quality of trials and reporting of adjudication processes. We used stepwise backward logistic regression model to identify trial characteristics independently associated with the use of an AC. We included 161 trials. Of these, 68.9% (111 of 161) reported the use of an AC. Overall, 99.1% (110 of 111) of trials with an AC used independent or blinded ACs, 14.4% (16 of 111) reported how the adjudication decision was reached within the AC, and 4.5% (5 of 111) reported on whether the reliability of adjudication was assessed. In multivariate analyses, multicenter trials [odds ratio (OR), 8.6; 95% confidence interval (CI): 2.7, 27.8], use of a data safety-monitoring board (OR, 3.7; 95% CI: 1.2, 11.6), and VTE as the primary outcome (OR, 5.7; 95% CI: 1.7, 19.4) were associated with the use of an AC. Trials without random allocation concealment (OR, 0.3; 95% CI: 0.1, 0.8) and open-label trials (OR, 0.3; 95% CI: 0.1, 1.0) were less likely to report an AC. Recommended processes of adjudication are underreported and lack standardization in VTE-related clinical trials. The use of an AC varies substantially by trial characteristics. Copyright © 2014 Elsevier Inc. All rights reserved.

Developing a Reporting Guideline for Social and Psychological Intervention Trials

ERIC Educational Resources Information Center

Grant, Sean; Montgomery, Paul; Hopewell, Sally; Macdonald, Geraldine; Moher, David; Mayo-Wilson, Evan

2013-01-01

Social and psychological interventions are often complex. Understanding randomized controlled trials (RCTs) of these complex interventions requires a detailed description of the interventions tested and the methods used to evaluate them; however, RCT reports often omit, or inadequately report, this information. Incomplete and inaccurate reporting…

Lack of diversity in orthopaedic trials conducted in the United States.

PubMed

Somerson, Jeremy S; Bhandari, Mohit; Vaughan, Clayton T; Smith, Christopher S; Zelle, Boris A

2014-04-02

Several orthopaedic studies have suggested patient race and ethnicity to be important predictors of patient functional outcomes. This issue has also been emphasized by federal funding sources. However, the reporting of race and ethnicity has gained little attention in the orthopaedic literature. The objective of this study was to determine the percentage of orthopaedic randomized controlled clinical trials in the United States that included race and ethnicity data and to record the racial and ethnic distribution of patients enrolled in these trials. A systematic review of orthopaedic randomized controlled trials published from 2008 to 2011 was performed. The studies were identified through a manual search of thirty-two scientific journals, including all major orthopaedic journals as well as five leading medical journals. Only trials from the United States were included. The publication date, journal impact factor, orthopaedic subspecialty, ZIP code of the primary research site, number of enrolled patients, type of funding, and race and ethnicity of the study population were extracted from the identified studies. A total of 158 randomized controlled trials with 37,625 enrolled patients matched the inclusion criteria. Only thirty-two studies (20.3%) included race or ethnicity with at least one descriptor. Government funding significantly increased the likelihood of reporting these factors (p < 0.05). The percentages of Hispanic and African-American patients were extractable for studies with 7648 and 6591 enrolled patients, respectively. In those studies, 4.6% (352) of the patients were Hispanic and 6.2% (410) were African-American; these proportions were 3.5-fold and twofold lower, respectively, than those represented in the 2010 United States Census. Few orthopaedic randomized controlled trials performed in the United States reported data on race or ethnicity. Among trials that did report demographic race or ethnicity data, the inclusion of minority patients was substantially lower than would be expected on the basis of census demographics. Failure to represent the true racial diversity may result in decreased generalizability of trial conclusions across clinical populations.

[Report quality of randomized controlled trials of moxibustion for knee osteoarthritis based on CONSORT and STRICTOM].

PubMed

Xiong, Jun; Zhu, Daocheng; Chen, Rixin; Ye, Wenguo

2015-08-01

The report quality of randomized controlled trials (RCTs) of moxibustion for knee osteoarthritis (KOA) in China was evaluated by Consolidated Standards for Reporting of Trials (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Moxibustion (STRICTOM). Computer and manual retrieval was used. Four databases of China National Knowledge Infrastructure (CNKD, China Biomedicine (CBM), VIP and WNFANG were searched in combination with manual retrieval for relevant journals to screen the literature that: met the inclusive criteria, and CONSORT and STRICTOM were used to assess the report quality. A total of 52 RCTs were included. It was found that unclear description of random methods, low use of blind methods, no allocation concealment, no sample size calculation, no intention-to-treat analysis,inadequate report of moxibustion details and no mention of practitioners background existed in the majority of the RCTs. Although the quality of RCTs of moxibustion for KOA was generally low, reducing the reliability and homogeneous comparability of the reports ,the quality of heat-sensitive moxibustion RCTs was high. It was believed that in order to improve the reliability and quality of RCTs of moxibustion, CONSORT and STRICTOM should be introduced into the RCT design of moxibustion and be strictly performed.

Topical non-steroidal anti-inflammatory drugs for analgesia in traumatic corneal abrasions.

PubMed

Wakai, Abel; Lawrenson, John G; Lawrenson, Annali L; Wang, Yongjun; Brown, Michael D; Quirke, Michael; Ghandour, Omar; McCormick, Ryan; Walsh, Cathal D; Amayem, Ahmed; Lang, Eddy; Harrison, Nick

2017-05-18

Traumatic corneal abrasions are relatively common and there is a lack of consensus about analgesia in their management. It is therefore important to document the clinical efficacy and safety profile of topical ophthalmic non-steroidal anti-inflammatory drugs (NSAIDs) in the management of traumatic corneal abrasions. To identify and evaluate all randomised controlled trials (RCTs) comparing the use of topical NSAIDs with placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions (including corneal abrasions arising from foreign body removal), to reduce pain, and its effects on healing time. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 30 March 2017), Embase Ovid (1947 to 30 March 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 30 March 2017), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/); searched 30 March 2017, ZETOC (1993 to 30 March 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 30 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 30 March 2017 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 30 March 2017. We did not use any date or language restrictions in the electronic searches for trials.We checked the reference lists of identified trials to search for further potentially relevant studies. RCTs comparing topical NSAIDs to placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions. Two review authors independently performed data extraction and assessed risks of bias in the included studies. We rated the certainty of the evidence using GRADE. We included nine studies that met the inclusion criteria, reporting data on 637 participants.The studies took place in the UK, USA, Israel, Italy, France and Portugal. These studies compared five types of topical NSAIDs (0.1% indomethacin, 0.03% flurbiprofen, 0.5% ketorolac, 1% indomethacin, 0.1% diclofenac) to control (consisting of standard care and in four studies used placebo eye drops). Overall, the studies were at an unclear or high risk of bias (particularly selection and reporting bias). None of the included studies reported the primary outcome measures of this review, namely participant-reported pain intensity reduction of 30% or more or 50% or more at 24 hours. Four trials, that included data on 481 participants receiving NSAIDs or control (placebo/standard care), reported on the use of 'rescue' analgesia at 24 hours as a proxy measure of pain control. Topical NSAIDs were associated with a reduction in the need for oral analgesia compared with control (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.34 to 0.61; low-certainty evidence). Approximately 4 out of 10 people in the control group used rescue analgesia at 24 hours. No data were available on the use of analgesia at 48 or 72 hours.One trial (28 participants) reported on the proportion of abrasions healed after 24 and 48 hours. These outcomes were similar in both arms of the trial. (at 24 hours RR 1.00 (0.81 to 1.23); at 48 hours RR 1.00 (0.88 to 1.14); low-certainty evidence). In the control group nine out of 10 abrasions were healed within 24 hours and all were healed by 48 hours. Complications of corneal abrasions were reported in 6 studies (609 participants) and were infrequently reported (4 complications, 1 in NSAID groups (recurrent corneal erosion) and 3 in control groups (2 recurrent corneal erosions and 1 corneal abscess), very low-certainty evidence). Possible drug-related adverse events (AEs) were reported in two trials (163 participants), with the number of adverse events low (4 AEs, 3 in NSAID group, including discomfort/photophobia on instillation, conjunctival hyperaemia and urticaria, and 1 in the control group, corneal abscess) very low-certainty evidence. The findings of the included studies do not provide strong evidence to support the use of topical NSAIDs in traumatic corneal abrasions. This is important, since NSAIDs are associated with a higher cost compared to oral analgesics. None of the trials addressed our primary outcome measure of participant-reported pain intensity reduction of 30% or more or 50% or more at 24 hours.

Quality of full and final publications reporting acute stroke trials: a systematic review.

PubMed

Bath, F J; Owen, V E; Bath, P M

1998-10-01

Several studies have shown that the quality of reporting of trials throughout medicine is variable and often poor. We report on the quality of the final reports of randomized controlled trials (RCTs) of drug therapies assessed in acute stroke. English-language reports published up to the end of 1996 relating to completed RCTs in acute stroke were identified from electronic searches of the Cochrane Stroke Review Group database of stroke trials and the Cochrane Controlled Trials Register (CD-ROM issue 1, 1997, of the Cochrane Library). Report quality was assessed with the 33 criteria of the CONSORT statement and 53 additional factors relevant to acute stroke or trials in general. Trial quality was also assessed with a 7-point scale. Up to 1996, 114 RCTs were published which involved 20 536 patients (median, 80; range, 16 to 1267 per trial); 39 (35.5%) of these were published in Stroke. The median total report quality was 40/86 (range, 15 to 61) for all criteria and 19/33 (range, 9 to 29) for the CONSORT criteria alone. Although adequate information was given in the introduction and discussion sections of most reports, insufficient details were given on methods, assignment of patients to treatment groups, statistical analyses, the prevalence of risk factors, and assessment of outcomes. Report quality has improved between 1956 and 1996 (Spearman correlation coefficient [rs], 0.575; 95% confidence interval [CI], 0. 439 to 0.685) and was superior in large trials (rs=0.434; 95% CI, 0. 274 to 0.571). Although report quality was related to trial quality (rs=0.675; 95% CI, 0.563 to 0.763), it was not related to journal impact factor (rs=0.170; 95% CI, -0.015 to 0.344). Trials with a positive outcome tended to be less well reported than those with a neutral or negative outcome (rs=-0.192; 95% CI, -0.351 to -0.011). The overall quality of study reports for parallel group RCTs in acute stroke is poor but appears to be improving with time and in parallel with an increase in trial size. Reports often lack detailed information on the methods of randomization, concealment of allocation, and statistical analysis, all factors which can, if undertaken poorly, affect trial results and validity. It is vital that future trials are adequately reported; we believe that authors should follow the CONSORT guidelines and that referees and editors should ensure this happens.

Risk of bias assessment of randomised controlled trials in high-impact ophthalmology journals and general medical journals: a systematic review.

PubMed

Joksimovic, Lazar; Koucheki, Robert; Popovic, Marko; Ahmed, Yusuf; Schlenker, Matthew B; Ahmed, Iqbal Ike K

2017-10-01

Evidence-based treatments in ophthalmology are often based on the results of randomised controlled trials. Biased conclusions from randomised controlled trials may lead to inappropriate management recommendations. This systematic review investigates the prevalence of bias risk in randomised controlled trials published in high-impact ophthalmology journals and ophthalmology trials from general medical journals. Using Ovid MEDLINE, randomised controlled trials in the top 10 high-impact ophthalmology journals in 2015 were systematically identified and critically appraised for the prevalence of bias risk. Included randomised controlled trials were assessed in all domains of bias as defined by the Cochrane Collaboration. In addition, the prevalence of conflict of interest and industry sponsorship was investigated. A comparison with ophthalmology articles from high-impact general medical journals was performed. Of the 259 records that were screened from ophthalmology-specific journals, 119 trials met all inclusion criteria and were critically appraised. In total, 29.4% of domains had an unclear risk, 13.8% had a high risk and 56.8% had a low risk of bias. In comparison, ophthalmology articles from general medical journals had a lower prevalence of unclear risk (17.1%), higher prevalence of high risk (21.9%) and a higher prevalence of low risk domains (61.9%). Furthermore, 64.7% of critically appraised trials from ophthalmology-specific journals did not report any conflicts of interest, while 70.6% did not report an industry sponsor of their trial. In closing, it is essential that authors, peer reviewers and readers closely follow published risk of bias guidelines. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Assessing treatment-as-usual provided to control groups in adherence trials: Exploring the use of an open-ended questionnaire for identifying behaviour change techniques.

PubMed

Oberjé, Edwin J M; Dima, Alexandra L; Pijnappel, Frank J; Prins, Jan M; de Bruin, Marijn

2015-01-01

Reporting guidelines call for descriptions of control group support in equal detail as for interventions. However, how to assess the active content (behaviour change techniques (BCTs)) of treatment-as-usual (TAU) delivered to control groups in trials remains unclear. The objective of this study is to pre-test a method of assessing TAU in a multicentre cost-effectiveness trial of an HIV-treatment adherence intervention. HIV-nurses (N = 21) completed a semi-structured open-ended questionnaire enquiring about TAU adherence counselling. Two coders independently coded BCTs. Completeness and clarity of nurse responses, inter-coder reliabilities and the type of BCTs reported were examined. The clarity and completeness of nurse responses were adequate. Twenty-three of the 26 identified BCTs could be reliably coded (mean κ = .79; mean agreement rate = 96%) and three BCTs scored below κ = .60. Total number of BCTs reported per nurse ranged between 7 and 19 (M = 13.86, SD = 3.35). This study suggests that the TAU open-ended questionnaire is a feasible and reliable tool to capture active content of support provided to control participants in a multicentre adherence intervention trial. Considerable variability in the number of BCTs provided to control patients was observed, illustrating the importance of reliably collecting and accurately reporting control group support.

Can wireless text messaging improve adherence to preventive activities? Results of a randomised controlled trial.

PubMed

Cocosila, Mihail; Archer, Norm; Haynes, R Brian; Yuan, Yufei

2009-04-01

To determine the effectiveness of cell phone wireless text messaging for improving adherence to a healthy behaviour. A randomised, unblinded, controlled trial was conducted with 102 subjects, 18 years or older, each having a cell phone and willing to take 1 vitamin C pill per day for 1 month for preventive reasons. Intervention group participants received text messaging reminders and were asked to acknowledge receiving their messages after taking the vitamins, whereas control group subjects had no text messaging activity. Self-reported adherence and the number of participant text messages acknowledging vitamins taken. Both groups reported an increased adherence after the trial: by 246% for the intervention group and by 131% for the control group. There was a non-significant difference between the two groups at endpoint: an average difference of 0.8 between the number of pills missed in the last week of the trial (2.5 out of 7 in the intervention and 3.3 out of 7 in the control group) with a power of 0.54. The study revealed a significant correlation (coefficient=-0.352, sig.=0.01) between the average number of text messaging acknowledgements sent by the intervention group participants and the number of pills they reported missed during the last week of the trial. This was a small randomised controlled trial with inconclusive but encouraging results. It suggests a new approach in addressing insufficient adherence in outpatient conditions and shows that the use of information technology tools for compliance warrants further research.

Randomized controlled trials in children's heart surgery in the 21st century: a systematic review.

PubMed

Drury, Nigel E; Patel, Akshay J; Oswald, Nicola K; Chong, Cher-Rin; Stickley, John; Barron, David J; Jones, Timothy J

2018-04-01

Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children's heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28-82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). The recent literature in children's heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice.

Randomized controlled trials in children’s heart surgery in the 21st century: a systematic review

PubMed Central

Drury, Nigel E; Patel, Akshay J; Oswald, Nicola K; Chong, Cher-Rin; Stickley, John; Barron, David J; Jones, Timothy J

2018-01-01

Abstract OBJECTIVES Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children’s heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. METHODS We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. RESULTS We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28–82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). CONCLUSIONS The recent literature in children’s heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice. PMID:29186478

Methods to decrease blood loss and transfusion requirements for liver transplantation.

PubMed

Gurusamy, Kurinchi Selvan; Pissanou, Theodora; Pikhart, Hynek; Vaughan, Jessica; Burroughs, Andrew K; Davidson, Brian R

2011-12-07

Excessive blood loss and increased blood transfusion requirements may have significant impact on the short-term and long-term outcomes after liver transplantation. To compare the potential benefits and harms of different methods of decreasing blood loss and blood transfusion requirements during liver transplantation. We searched The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and metaRegister of Controlled Trials until September 2011. We included all randomised clinical trials that were performed to compare various methods of decreasing blood loss and blood transfusion requirements during liver transplantation. Two authors independently identified the trials and extracted the data. We analysed the data with both the fixed-effect and the random-effects model using RevMan Analysis. For each outcome we calculated the risk ratio (RR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals (CI) based on available data analysis. We also conducted network meta-analysis. We included 33 trials involving 1913 patients. The sample size in the trials varied from 8 to 209 participants. The interventions included pharmacological interventions (aprotinin, tranexamic acid, epsilon amino caproic acid, antithrombin 3, recombinant factor (rFvIIa), oestrogen, prostaglandin, epinephrine), blood substitutes (blood components rather than whole blood, hydroxy-ethyl starch, thromboelastography), and cardiovascular interventions (low central venous pressure). All the trials were of high risk of bias. Primary outcomes were reported in at least two trials for the following comparisons: aprotinin versus control, tranexamic acid versus control, recombinant factor VIIa (rFVIIa) versus control, and tranexamic acid versus aprotinin. There were no significant differences in the 60-day mortality (3 trials; 6/161 (3.7%) in the aprotinin group versus 8/119 (6.7%) in the control group; RR 0.52; 95% CI 0.18 to 1.45), primary graft non-function (2 trials; 0/128 (0.0%) in the aprotinin group versus 4/89 (4.5%) in the control group; RR 0.15; 95% CI 0.02 to 1.25), retransplantation (3 trials; 2/256 (0.8%) in the aprotinin group versus 12/178 (6.7%) in the control group; RR 0.21; 95% CI 0.02 to 1.79), or thromboembolic episodes (3 trials; 4/161 (2.5%) in the aprotinin group versus 5/119 (4.2%) in the control group; RR 0.59; 95% CI 0.19 to 1.84) between the aprotinin and control groups. There were no significant differences in the 60-day mortality (3 trials; 4/83 (4.8%) in the tranexamic acid group versus 5/56 (8.9%) in the control group; RR 0.55; 95% CI 0.17 to 1.76), retransplantation (2 trials; 3/41 (7.3%) in the tranexamic acid group versus 3/36 (8.3%) in the control group; RR 0.79; 95% CI 0.18 to 3.48), or thromboembolic episodes (5 trials; 5/103 (4.9%) in the tranexamic acid group versus 1/76 (1.3%) in the control group; RR 2.20; 95% CI 0.38 to 12.64) between the tranexamic acid and control groups. There were no significant differences in the 60-day mortality (3 trials; 8/195 (4.1%) in the recombinant factor VIIa (rFVIIa) group versus 2/91 (2.2%) in the control group; RR 1.51; 95% CI 0.33 to 6.95), thromboembolic episodes (2 trials; 24/185 (13.0%) in the rFVIIa group versus 8/81 (9.9%) in the control group; RR 1.38; 95% CI 0.65 to 2.91), or serious adverse events (2 trials; 90/185 (48.6%) in the rFVIIa group versus 30/81 (37.0%) in the control group; RR 1.30; 95% CI 0.94 to 1.78) between the rFVIIa and control groups. There were no significant differences in the 60-day mortality (2 trials; 6/91 (6.6%) in the tranexamic acid group versus 1/87 (1.1%) in the aprotinin group; RR 4.12; 95% CI 0.71 to 23.76) or thromboembolic episodes (2 trials; 4/91 (4.4%) in the tranexamic acid group versus 2/87 (2.3%) in the aprotinin group; RR 1.97; 95% CI 0.37 to 10.37) between the tranexamic acid and aprotinin groups. The remaining outcomes in the above comparisons and the remaining comparisons included only only trial under the primary outcome or the outcome was not reported at all in the trials. There were no significant differences in the mortality, primary graft non-function, graft failure, retransplantation, thromboembolic episodes, or serious adverse events in any of these comparisons. However, the confidence intervals were wide, and it is not possible to reach any conclusion on the safety of the interventions. None of the trials reported the quality of life in patients.Secondary outcomes were reported in at least two trials for the following comparisons - aprotinin versus control, tranexamic acid versus control, rFVIIa versus control, thromboelastography versus control, and tranexamic acid versus aprotinin. There was significantly lower allogeneic blood transfusion requirements in the aprotinin group than the control group (8 trials; 185 patients in aprotinin group and 190 patients in control group; SMD -0.61; 95% CI -0.82 to -0.40). There were no significant differences in the allogeneic blood transfusion requirements between the tranexamic acid and control groups (4 trials; 93 patients in tranexamic acid group and 66 patients in control group; SMD -0.27; 95% CI -0.59 to 0.06); rFVIIa and control groups (2 trials; 141 patients in rFVIIa group and 80 patients in control group; SMD -0.05; 95% CI -0.32 to 0.23); thromboelastography and control groups (2 trials; 31 patients in thromboelastography group and 31 patients in control group; SMD -0.73; 95% CI -1.69 to 0.24); or between the tranexamic acid and aprotinin groups (3 trials; 101 patients in tranexamic acid group and 97 patients in aprotinin group; SMD -0.09; 95% CI -0.36 to 0.19). The remaining outcomes in the above comparisons and the remaining comparisons included only only trial under the primary outcome or the outcome was not reported at all in the trials. There were no significant differences in the blood loss, transfusion requirements, hospital stay, or intensive care unit stay in most of the comparisons. Aprotinin, recombinant factor VIIa, and thromboelastography groups may potentially reduce blood loss and transfusion requirements. However, risks of systematic errors (bias) and risks of random errors (play of chance) hamper the confidence in this conclusion. We need further well-designed randomised trials with low risk of systematic error and low risk of random errors before these interventions can be supported or refuted.

Methodological reporting of randomized controlled trials in major hepato-gastroenterology journals in 2008 and 1998: a comparative study

PubMed Central

2011-01-01

Background It was still unclear whether the methodological reporting quality of randomized controlled trials (RCTs) in major hepato-gastroenterology journals improved after the Consolidated Standards of Reporting Trials (CONSORT) Statement was revised in 2001. Methods RCTs in five major hepato-gastroenterology journals published in 1998 or 2008 were retrieved from MEDLINE using a high sensitivity search method and their reporting quality of methodological details were evaluated based on the CONSORT Statement and Cochrane Handbook for Systematic Reviews of interventions. Changes of the methodological reporting quality between 2008 and 1998 were calculated by risk ratios with 95% confidence intervals. Results A total of 107 RCTs published in 2008 and 99 RCTs published in 1998 were found. Compared to those in 1998, the proportion of RCTs that reported sequence generation (RR, 5.70; 95%CI 3.11-10.42), allocation concealment (RR, 4.08; 95%CI 2.25-7.39), sample size calculation (RR, 3.83; 95%CI 2.10-6.98), incomplete outecome data addressed (RR, 1.81; 95%CI, 1.03-3.17), intention-to-treat analyses (RR, 3.04; 95%CI 1.72-5.39) increased in 2008. Blinding and intent-to-treat analysis were reported better in multi-center trials than in single-center trials. The reporting of allocation concealment and blinding were better in industry-sponsored trials than in public-funded trials. Compared with historical studies, the methodological reporting quality improved with time. Conclusion Although the reporting of several important methodological aspects improved in 2008 compared with those published in 1998, which may indicate the researchers had increased awareness of and compliance with the revised CONSORT statement, some items were still reported badly. There is much room for future improvement. PMID:21801429

Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials.

PubMed

Sun, Xin; Briel, Matthias; Busse, Jason W; Akl, Elie A; You, John J; Mejza, Filip; Bala, Malgorzata; Diaz-Granados, Natalia; Bassler, Dirk; Mertz, Dominik; Srinathan, Sadeesh K; Vandvik, Per Olav; Malaga, German; Alshurafa, Mohamed; Dahm, Philipp; Alonso-Coello, Pablo; Heels-Ansdell, Diane M; Bhatnagar, Neera; Johnston, Bradley C; Wang, Li; Walter, Stephen D; Altman, Douglas G; Guyatt, Gordon H

2009-11-09

Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.

Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials

PubMed Central

Sun, Xin; Briel, Matthias; Busse, Jason W; Akl, Elie A; You, John J; Mejza, Filip; Bala, Malgorzata; Diaz-Granados, Natalia; Bassler, Dirk; Mertz, Dominik; Srinathan, Sadeesh K; Vandvik, Per Olav; Malaga, German; Alshurafa, Mohamed; Dahm, Philipp; Alonso-Coello, Pablo; Heels-Ansdell, Diane M; Bhatnagar, Neera; Johnston, Bradley C; Wang, Li; Walter, Stephen D; Altman, Douglas G; Guyatt, Gordon H

2009-01-01

Background Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. Methods We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. Discussion A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials. PMID:19900273

The REFLECT statement: reporting guidelines for randomized controlled trials in livestock and food safety: explanation and elaboration.

PubMed

Sargeant, J M; O'Connor, A M; Gardner, I A; Dickson, J S; Torrence, M E; Dohoo, I R; Lefebvre, S L; Morley, P S; Ramirez, A; Snedeker, K

2010-03-01

Concerns about the completeness and accuracy of reporting of randomized clinical trials (RCTs) and the impact of poor reporting on decision-making have been documented in the medical field over the past several decades. Experience from RCTs in human medicine would suggest that failure to report critical trial features can be associated with biased estimated effect measures, and there is evidence to suggest similar biases occur in RCTs conducted in livestock populations. In response to these concerns, standardized guidelines for reporting RCTs were developed and implemented in human medicine. The Consolidated Standards of Reporting Trials (CONSORT) statement was first published in 1996 with a revised edition published in 2001. The CONSORT statement consists of a 22-item checklist for reporting a RCT and a flow diagram to follow the number of participants at each stage of a trial. An explanation and elaboration document not only defines and discusses the importance of each of the items, but also provides examples of how this information could be supplied in a publication. Differences between human and livestock populations necessitate modifications to the CONSORT statement to maximize its usefulness for RCTs involving livestock. These have been addressed in an extension of the CONSORT statement titled the REFLECT statement: Methods and processes of creating reporting guidelines for randomized control trials for livestock and food safety. The modifications made for livestock trials specifically addressed the common use of group housing and group allocation to intervention in livestock studies, the use of a deliberate challenge model in some trials, and common use of non-clinical outcomes, such as contamination with a foodborne pathogen. In addition, the REFLECT statement for RCTs in livestock populations proposed specific terms or further clarified terms as they pertained to livestock studies.

The REFLECT statement: reporting guidelines for Randomized Controlled Trials in livestock and food safety: explanation and elaboration.

PubMed

Sargeant, J M; O'Connor, A M; Gardner, I A; Dickson, J S; Torrence, M E

2010-03-01

Concerns about the completeness and accuracy of reporting of randomized clinical trials (RCTs) and the impact of poor reporting on decision making have been documented in the medical field over the past several decades. Experience from RCTs in human medicine would suggest that failure to report critical trial features can be associated with biased estimated effect measures, and there is evidence to suggest that similar biases occur in RCTs conducted in livestock populations. In response to these concerns, standardized guidelines for reporting RCTs were developed and implemented in human medicine. The Consolidated Standards of Reporting Trials (CONSORT) statement was first published in 1996, with a revised edition published in 2001. The CONSORT statement consists of a 22-item checklist for reporting a RCT and a flow diagram to follow the number of participants at each stage of a trial. An explanation and elaboration document not only defines and discusses the importance of each of the items, but also provides examples of how this information could be supplied in a publication. Differences between human and livestock populations necessitate modifications to the CONSORT statement to maximize its usefulness for RCTs involving livestock. These have been addressed in an extension of the CONSORT statement titled the REFLECT statement: Methods and processes of creating reporting guidelines for randomized control trials for livestock and food safety. The modifications made for livestock trials specifically addressed the common use of group housing and group allocation to intervention in livestock studies; the use of deliberate challenge models in some trials and the common use of non-clinical outcomes, such as contamination with a foodborne pathogen. In addition, the REFLECT statement for RCTs in livestock populations proposed specific terms or further clarified terms as they pertained to livestock studies.

Prazosin for Prophylaxis of Chronic Post Traumatic Headaches in OEF/OIF/OND Service Members and Veterans with Mild TBI

DTIC Science & Technology

2017-10-01

does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2017 2. REPORT TYPE...comes from a large open-label case series in Iraq and Afghanistan Veterans with mTBI and posttraumatic headaches and data from a placebo- controlled trial...will be accomplished by conducting a randomized placebo- controlled double blind trial of prazosin vs placebo in 160 Iraq/Afghanistan active-duty

Cinnamon Bark, Water Soluble Cinnamon Extract, and Metformin as Initial Treatment for Type 2 Diabetes Mellitus: A Randomized, Controlled Trial

DTIC Science & Technology

2016-12-14

REPORT DOCUMENTATION PAGE Form ApprovedOMB No. 0704-0188 1 . REPORT DATE (DD-MM-YYYY) 2. REPORT TYPE 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 6...estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the...Cinnamon Extract, and Metformin as Initial Treatment for Type 2 Diabetes Mellitus: A Randomized, Controlled Trial. Paul Crawford, MD Clinical Investigation

Developing a core outcome set for chronic rhinosinusitis: a systematic review of outcomes utilised in the current literature.

PubMed

Soni-Jaiswal, Archana; Lakhani, Raj; Hopkins, Claire

2017-07-11

A core outcome set (COS) is an agreed standardised collection of outcomes that should be measured and reported by all trials for a specific clinical area, in this case chronic rhinosinusitis. These are not restrictive and researchers may continue to explore other outcomes alongside these that they feel are relevant to their intervention. The aim of this systematic review was to identify the need for a COS for chronic rhinosinusitis. A sensitive search strategy was used to identify all published Cochrane systematic reviews and randomised control trials of intervention for adult patients with chronic rhinosinusitis. Two independent authors reviewed these to obtain a list of outcomes and outcome measures reported by each clinical trial. Sixty-nine randomised control trials and eight Cochrane systematic reviews were included in this study. They reported 68 individual outcomes and outcome measures, with an average of four to ten outcomes per clinical trial. These outcomes were mapped to 23 subcategories belonging to eight core categories. The key finding of this review was the heterogeneity of outcomes reported and measured by clinical trials of patients with chronic rhinosinusitis, precluding meaningful meta-analysis of data. This review supports the need for development of a COS, to be used in future trials on adult patients with chronic rhinosinusitis.

Strategies for enhancing the implementation of school-based policies or practices targeting risk factors for chronic disease.

PubMed

Wolfenden, Luke; Nathan, Nicole K; Sutherland, Rachel; Yoong, Sze Lin; Hodder, Rebecca K; Wyse, Rebecca J; Delaney, Tessa; Grady, Alice; Fielding, Alison; Tzelepis, Flora; Clinton-McHarg, Tara; Parmenter, Benjamin; Butler, Peter; Wiggers, John; Bauman, Adrian; Milat, Andrew; Booth, Debbie; Williams, Christopher M

2017-11-29

A number of school-based policies or practices have been found to be effective in improving child diet and physical activity, and preventing excessive weight gain, tobacco or harmful alcohol use. Schools, however, frequently fail to implement such evidence-based interventions. The primary aims of the review are to examine the effectiveness of strategies aiming to improve the implementation of school-based policies, programs or practices to address child diet, physical activity, obesity, tobacco or alcohol use.Secondary objectives of the review are to: Examine the effectiveness of implementation strategies on health behaviour (e.g. fruit and vegetable consumption) and anthropometric outcomes (e.g. BMI, weight); describe the impact of such strategies on the knowledge, skills or attitudes of school staff involved in implementing health-promoting policies, programs or practices; describe the cost or cost-effectiveness of such strategies; and describe any unintended adverse effects of strategies on schools, school staff or children. All electronic databases were searched on 16 July 2017 for studies published up to 31 August 2016. We searched the following electronic databases: Cochrane Library including the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; Embase Classic and Embase; PsycINFO; Education Resource Information Center (ERIC); Cumulative Index to Nursing and Allied Health Literature (CINAHL); Dissertations and Theses; and SCOPUS. We screened reference lists of all included trials for citations of other potentially relevant trials. We handsearched all publications between 2011 and 2016 in two specialty journals (Implementation Science and Journal of Translational Behavioral Medicine) and conducted searches of the WHO International Clinical Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch/) as well as the US National Institutes of Health registry (https://clinicaltrials.gov). We consulted with experts in the field to identify other relevant research. 'Implementation' was defined as the use of strategies to adopt and integrate evidence-based health interventions and to change practice patterns within specific settings. We included any trial (randomised or non-randomised) conducted at any scale, with a parallel control group that compared a strategy to implement policies or practices to address diet, physical activity, overweight or obesity, tobacco or alcohol use by school staff to 'no intervention', 'usual' practice or a different implementation strategy. Citation screening, data extraction and assessment of risk of bias was performed by review authors in pairs. Disagreements between review authors were resolved via consensus, or if required, by a third author. Considerable trial heterogeneity precluded meta-analysis. We narratively synthesised trial findings by describing the effect size of the primary outcome measure for policy or practice implementation (or the median of such measures where a single primary outcome was not stated). We included 27 trials, 18 of which were conducted in the USA. Nineteen studies employed randomised controlled trial (RCT) designs. Fifteen trials tested strategies to implement healthy eating policies, practice or programs; six trials tested strategies targeting physical activity policies or practices; and three trials targeted tobacco policies or practices. Three trials targeted a combination of risk factors. None of the included trials sought to increase the implementation of interventions to delay initiation or reduce the consumption of alcohol. All trials examined multi-strategic implementation strategies and no two trials examined the same combinations of implementation strategies. The most common implementation strategies included educational materials, educational outreach and educational meetings. For all outcomes, the overall quality of evidence was very low and the risk of bias was high for the majority of trials for detection and performance bias.Among 13 trials reporting dichotomous implementation outcomes-the proportion of schools or school staff (e.g. classes) implementing a targeted policy or practice-the median unadjusted (improvement) effect sizes ranged from 8.5% to 66.6%. Of seven trials reporting the percentage of a practice, program or policy that had been implemented, the median unadjusted effect (improvement), relative to the control ranged from -8% to 43%. The effect, relative to control, reported in two trials assessing the impact of implementation strategies on the time per week teachers spent delivering targeted policies or practices ranged from 26.6 to 54.9 minutes per week. Among trials reporting other continuous implementation outcomes, findings were mixed. Four trials were conducted of strategies that sought to achieve implementation 'at scale', that is, across samples of at least 50 schools, of which improvements in implementation were reported in three trials.The impact of interventions on student health behaviour or weight status were mixed. Three of the eight trials with physical activity outcomes reported no significant improvements. Two trials reported reductions in tobacco use among intervention relative to control. Seven of nine trials reported no between-group differences on student overweight, obesity or adiposity. Positive improvements in child dietary intake were generally reported among trials reporting these outcomes. Three trials assessed the impact of implementation strategies on the attitudes of school staff and found mixed effects. Two trials specified in the study methods an assessment of potential unintended adverse effects, of which, they reported none. One trial reported implementation support did not significantly increase school revenue or expenses and another, conducted a formal economic evaluation, reporting the intervention to be cost-effective. Trial heterogeneity, and the lack of consistent terminology describing implementation strategies, were important limitations of the review. Given the very low quality of the available evidence, it is uncertain whether the strategies tested improve implementation of the targeted school-based policies or practices, student health behaviours, or the knowledge or attitudes of school staff. It is also uncertain if strategies to improve implementation are cost-effective or if they result in unintended adverse consequences. Further research is required to guide efforts to facilitate the translation of evidence into practice in this setting.

Interventions for treating osteoarthritis of the big toe joint.

PubMed

Zammit, Gerard V; Menz, Hylton B; Munteanu, Shannon E; Landorf, Karl B; Gilheany, Mark F

2010-09-08

Osteoarthritis affecting of the big toe joint of the foot (hallux limitus or rigidus) is a common and painful condition. Although several treatments have been proposed, few have been adequately evaluated. To identify controlled trials evaluating interventions for osteoarthritis of the big toe joint and to determine the optimum intervention(s). Literature searches were conducted across the following electronic databases: CENTRAL; MEDLINE; EMBASE; CINAHL; and PEDro (to 14th January 2010). No language restrictions were applied. Randomised controlled trials, quasi-randomised trials, or controlled clinical trials that assessed treatment outcomes for osteoarthritis of the big toe joint. Participants of any age or gender with osteoarthritis of the big toe joint (defined either radiographically or clinically) were included. Two authors examined the list of titles and abstracts identified by the literature searches. One content area expert and one methodologist independently applied the pre-determined inclusion and exclusion criteria to the full text of identified trials. To minimise error and reduce potential bias, data were extracted independently by two content experts. Only one trial satisfactorily fulfilled the inclusion criteria and was included in this review. This trial evaluated the effectiveness of two physical therapy programs in 20 individuals with osteoarthritis of the big toe joint. Assessment outcomes included pain levels, big toe joint range of motion and plantar flexion strength of the hallux. Mean differences at four weeks follow up were 3.80 points (95% CI 2.74 to 4.86) for self reported pain, 28.30 degrees (95% CI 21.37 to 35.23) for big toe joint range of motion, and 2.80 kg (95% CI 2.13 to 3.47) for muscle strength. Although differences in outcomes between treatment and control groups were reported, the risk of bias was high. The trial failed to employ appropriate randomisation or adequate allocation concealment, used a relatively small sample and incorporated a short follow up (four weeks). No adverse reactions were reported. The reviewed trial presented a high risk of bias, which limited conclusions that could be drawn from the presented data. The inclusion of only one trial indicates the need for more robust randomised controlled trials to determine the efficacy of interventions for this condition.

Variations in reporting of outcomes in randomized trials on diet and physical activity in pregnancy: A systematic review.

PubMed

Rogozińska, Ewelina; Marlin, Nadine; Yang, Fen; Dodd, Jodie M; Guelfi, Kym; Teede, Helena; Surita, Fernanda; Jensen, Dorte M; Geiker, Nina R W; Astrup, Arne; Yeo, SeonAe; Kinnunen, Tarja I; Stafne, Signe N; Cecatti, Jose G; Bogaerts, Annick; Hauner, Hans; Mol, Ben W; Scudeller, Tânia T; Vinter, Christina A; Renault, Kristina M; Devlieger, Roland; Thangaratinam, Shakila; Khan, Khalid S

2017-07-01

Trials on diet and physical activity in pregnancy report on various outcomes. We aimed to assess the variations in outcomes reported and their quality in trials on lifestyle interventions in pregnancy. We searched major databases without language restrictions for randomized controlled trials on diet and physical activity-based interventions in pregnancy up to March 2015. Two independent reviewers undertook study selection and data extraction. We estimated the percentage of papers reporting 'critically important' and 'important' outcomes. We defined the quality of reporting as a proportion using a six-item questionnaire. Regression analysis was used to identify factors affecting this quality. Sixty-six randomized controlled trials were published in 78 papers (66 main, 12 secondary). Gestational diabetes (57.6%, 38/66), preterm birth (48.5%, 32/66) and cesarian section (60.6%, 40/66), were the commonly reported 'critically important' outcomes. Gestational weight gain (84.5%, 56/66) and birth weight (87.9%, 58/66) were reported in most papers, although not considered critically important. The median quality of reporting was 0.60 (interquartile range 0.25, 0.83) for a maximum score of one. Study and journal characteristics did not affect quality. Many studies on lifestyle interventions in pregnancy do not report critically important outcomes, highlighting the need for core outcome set development. © 2017 Japan Society of Obstetrics and Gynecology.

Outcomes from a School-Randomized Controlled Trial of Steps to Respect: A Bullying Prevention Program

ERIC Educational Resources Information Center

Brown, Eric C.; Low, Sabina; Smith, Brian H.; Haggerty, Kevin P.

2011-01-01

This study reports the outcomes of a randomized controlled trial of Steps to Respect: A Bullying Prevention Program conducted in 33 California elementary schools. Schools were matched on school demographic characteristics and assigned randomly to intervention or waitlisted control conditions. Outcome measures were obtained from (a) all school…

Endorsement for improving the quality of reports on randomized controlled trials of traditional medicine journals in Korea: a systematic review.

PubMed

Choi, Jiae; Jun, Ji Hee; Kang, Byoung Kab; Kim, Kun Hyung; Lee, Myeong Soo

2014-11-05

The aim of this study was to assess the endorsement of reporting guidelines in Korean traditional medicine (TM) journals by reviewing their instructions to authors. We examined the instructions to authors in all of the TM journals published in Korea to assess the appropriate use of reporting guidelines for research studies. The randomized controlled trials (RCTs) published after 2010 in journals that endorsed reporting guidelines were obtained. The reporting quality was assessed using the following guidelines: the 38-item Consolidated Standards of Reporting Trials (CONSORT) statement for non-pharmacological trials (NPT); the 17-item Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) statement, instead of the 5-item CONSORT for acupuncture trials; and the 22-item CONSORT extensions for herbal medicine trials. The overall item score was calculated and expressed as a proportion.One journal that endorsed reporting guidelines was identified. Twenty-nine RCTs published in this journal after 2010 met the selection criteria. General editorial policies such as those of the International Committee of Medical Journal Editors (ICMJE) were endorsed by 15 journals. In each of the CONSORT-NPT articles, 21.6 to 56.8% of the items were reported, with an average of 11.3 items (29.7%) being reported. In the 24 RCTs (24/29, 82.8%) appraised using the STRICTA items, an average of 10.6 items (62.5%) were addressed, with a range of 41.2 to 100%. For the herbal intervention reporting, 17 items (77.27%) were reported. In the RCT studies before and after the endorsement of CONSORT and STRICTA guidelines by each journal, all of the STRICTA items had significant improvement, whereas the CONSORT-NPT items improved without statistical significance.The endorsement of reporting guidelines is limited in the TM journals in Korea. Authors should adhere to the reporting guidelines, and editorial departments should refer authors to the various reporting guidelines to improve the quality of their articles.

Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials

PubMed Central

Isomura, T; Suzuki, S; Origasa, H; Hosono, A; Suzuki, M; Sawada, T; Terao, S; Muto, Y; Koga, T

2016-01-01

There remain liver-related safety concerns, regarding potential hepatotoxicity in humans, induced by green tea intake, despite being supposedly beneficial. Although many randomized controlled trials (RCTs) of green tea extracts have been reported in the literature, the systematic reviews published to date were only based on subjective assessment of case reports. To more objectively examine the liver-related safety of green tea intake, we conducted a systematic review of published RCTs. A systematic literature search was conducted using three databases (PubMed, EMBASE and Cochrane Central Register of Controlled Trials) in December 2013 to identify RCTs of green tea extracts. Data on liver-related adverse events, including laboratory test abnormalities, were abstracted from the identified articles. Methodological quality of RCTs was assessed. After excluding duplicates, 561 titles and abstracts and 119 full-text articles were screened, and finally 34 trials were identified. Of these, liver-related adverse events were reported in four trials; these adverse events involved seven subjects (eight events) in the green tea intervention group and one subject (one event) in the control group. The summary odds ratio, estimated using a meta-analysis method for sparse event data, for intervention compared with placebo was 2.1 (95% confidence interval: 0.5–9.8). The few events reported in both groups were elevations of liver enzymes. Most were mild, and no serious liver-related adverse events were reported. Results of this review, although not conclusive, suggest that liver-related adverse events after intake of green tea extracts are expected to be rare. PMID:27188915

Reporting of analyses from randomized controlled trials with multiple arms: a systematic review.

PubMed

Baron, Gabriel; Perrodeau, Elodie; Boutron, Isabelle; Ravaud, Philippe

2013-03-27

Multiple-arm randomized trials can be more complex in their design, data analysis, and result reporting than two-arm trials. We conducted a systematic review to assess the reporting of analyses in reports of randomized controlled trials (RCTs) with multiple arms. The literature in the MEDLINE database was searched for reports of RCTs with multiple arms published in 2009 in the core clinical journals. Two reviewers extracted data using a standardized extraction form. In total, 298 reports were identified. Descriptions of the baseline characteristics and outcomes per group were missing in 45 reports (15.1%) and 48 reports (16.1%), respectively. More than half of the articles (n = 171, 57.4%) reported that a planned global test comparison was used (that is, assessment of the global differences between all groups), but 67 (39.2%) of these 171 articles did not report details of the planned analysis. Of the 116 articles reporting a global comparison test, 12 (10.3%) did not report the analysis as planned. In all, 60% of publications (n = 180) described planned pairwise test comparisons (that is, assessment of the difference between two groups), but 20 of these 180 articles (11.1%) did not report the pairwise test comparisons. Of the 204 articles reporting pairwise test comparisons, the comparisons were not planned for 44 (21.6%) of them. Less than half the reports (n = 137; 46%) provided baseline and outcome data per arm and reported the analysis as planned. Our findings highlight discrepancies between the planning and reporting of analyses in reports of multiple-arm trials.

Quality of reporting of trial abstracts needs to be improved: using the CONSORT for abstracts to assess the four leading Chinese medical journals of traditional Chinese medicine.

PubMed

Wang, Ling; Li, Yulin; Li, Jing; Zhang, Mingming; Xu, Lin; Yuan, Wenming; Wang, Gang; Hopewell, Sally

2010-07-08

Due to language limitations, the abstract of journal article may be the only way for people of non-Chinese speaking countries to know about trials in traditional Chinese medicine (TCM). However, little is known about the reporting quality of these trial abstracts. Our study is to assess the reporting quality of abstracts of randomized controlled trials (RCT) published in four leading Chinese medical journals of TCM, and to identify any differences in reporting between the Chinese and English version of the same abstract publication. Two reviewers hand-searched the Chinese Journal of Integrated Traditional and Western Medicine, the Chinese Journal of Integrative Medicine, the China Journal of Chinese Materia Medica and the Chinese Acupuncture & Moxibustion for all abstracts of RCTs published between 2006 and 2007. Two reviewers independently assessed the reporting quality of the Chinese and English version of all eligible abstracts based on a modified version of the CONSORT for reporting randomised trials in journal and conference abstracts (CONSORT for abstracts). We identified a total of 345 RCTs of TCM with both a Chinese and English abstract. More than half of Chinese abstracts reported details of the trial participants (68%; 234/345), control group intervention (52%; 179/345), the number of participants randomized (73%; 253/345) and benefits when interpreting the trial results (55%; 190/345). Reporting of methodological quality or key features of trial design and trial results were poor; only 2% (7/345) included details of the trial design, 3% (11/345) defined the primary outcome, 5% (17/345) described the methods of random sequence generation, and only 4% (13/345) reported the number of participants analyzed. No abstracts provided details on allocation concealment and trial registration. The percentage agreement in reporting (between the Chinese and English version of the same abstract) ranged from 84% to 100% across individual checklist item. The reporting quality of abstracts of RCTs published in these four TCM journals needs to be improved. Since none of the four journals adopted CONSORT for Abstracts, we hope that the introduction and adoption of CONSORT for Abstracts by TCM journals will lead to an improvement in reporting quality.

Quality of reporting of trial abstracts needs to be improved: using the CONSORT for abstracts to assess the four leading Chinese medical journals of traditional Chinese medicine

PubMed Central

2010-01-01

Background Due to language limitations, the abstract of journal article may be the only way for people of non-Chinese speaking countries to know about trials in traditional Chinese medicine (TCM). However, little is known about the reporting quality of these trial abstracts. Our study is to assess the reporting quality of abstracts of randomized controlled trials (RCT) published in four leading Chinese medical journals of TCM, and to identify any differences in reporting between the Chinese and English version of the same abstract publication. Method Two reviewers hand-searched the Chinese Journal of Integrated Traditional and Western Medicine, the Chinese Journal of Integrative Medicine, the China Journal of Chinese Materia Medica and the Chinese Acupuncture & Moxibustion for all abstracts of RCTs published between 2006 and 2007. Two reviewers independently assessed the reporting quality of the Chinese and English version of all eligible abstracts based on a modified version of the CONSORT for reporting randomised trials in journal and conference abstracts (CONSORT for abstracts). Results We identified a total of 345 RCTs of TCM with both a Chinese and English abstract. More than half of Chinese abstracts reported details of the trial participants (68%; 234/345), control group intervention (52%; 179/345), the number of participants randomized (73%; 253/345) and benefits when interpreting the trial results (55%; 190/345). Reporting of methodological quality or key features of trial design and trial results were poor; only 2% (7/345) included details of the trial design, 3% (11/345) defined the primary outcome, 5% (17/345) described the methods of random sequence generation, and only 4% (13/345) reported the number of participants analyzed. No abstracts provided details on allocation concealment and trial registration. The percentage agreement in reporting (between the Chinese and English version of the same abstract) ranged from 84% to 100% across individual checklist item. Conclusion The reporting quality of abstracts of RCTs published in these four TCM journals needs to be improved. Since none of the four journals adopted CONSORT for Abstracts, we hope that the introduction and adoption of CONSORT for Abstracts by TCM journals will lead to an improvement in reporting quality. PMID:20615225

Industry Bias in Randomized Controlled Trials in General and Abdominal Surgery: An Empirical Study.

PubMed

Probst, Pascal; Knebel, Phillip; Grummich, Kathrin; Tenckhoff, Solveig; Ulrich, Alexis; Büchler, Markus W; Diener, Markus K

2016-07-01

Industry sponsorship has been identified as a source of bias in several fields of medical science. To date, the influence of industry sponsorship in the field of general and abdominal surgery has not been evaluated. A systematic literature search (1985-2014) was performed in the Cochrane Library, MEDLINE, and EMBASE to identify randomized controlled trials in general and abdominal surgery. Information on funding source, outcome, and methodological quality was extracted. Association of industry sponsorship and positive outcome was expressed as odds ratio (OR) with 95% confidence interval (CI). A χ test and a multivariate logistic regression analysis with study characteristics and known sources of bias were performed. A total of 7934 articles were screened and 165 randomized controlled trials were included. No difference in methodological quality was found. Industry-funded trials more often presented statistically significant results for the primary endpoint (OR, 2.44; CI, 1.04-5.71; P = 0.04). Eighty-eight of 115 (76.5%) industry-funded trials and 19 of 50 (38.0%) non-industry-funded trials reported a positive outcome (OR, 5.32; CI, 2.60-10.88; P < 0.001). Industry-funded trials more often reported a positive outcome without statistical justification (OR, 5.79; CI, 2.13-15.68; P < 0.001). In a multivariate analysis, funding source remained significantly associated with reporting of positive outcome (P < 0.001). Industry funding of surgical trials leads to exaggerated positive reporting of outcomes. This study emphasizes the necessity for declaration of funding source. Industry involvement in surgical research has to ensure scientific integrity and independence and has to be based on full transparency.

Differences in reporting of analyses in internal company documents versus published trial reports: comparisons in industry-sponsored trials in off-label uses of gabapentin.

PubMed

Vedula, S Swaroop; Li, Tianjing; Dickersin, Kay

2013-01-01

Details about the type of analysis (e.g., intent to treat [ITT]) and definitions (i.e., criteria for including participants in the analysis) are necessary for interpreting a clinical trial's findings. Our objective was to compare the description of types of analyses and criteria for including participants in the publication (i.e., what was reported) with descriptions in the corresponding internal company documents (i.e., what was planned and what was done). Trials were for off-label uses of gabapentin sponsored by Pfizer and Parke-Davis, and documents were obtained through litigation. For each trial, we compared internal company documents (protocols, statistical analysis plans, and research reports, all unpublished), with publications. One author extracted data and another verified, with a third person verifying discordant items and a sample of the rest. Extracted data included the number of participants randomized and analyzed for efficacy, and types of analyses for efficacy and safety and their definitions (i.e., criteria for including participants in each type of analysis). We identified 21 trials, 11 of which were published randomized controlled trials, and that provided the documents needed for planned comparisons. For three trials, there was disagreement on the number of randomized participants between the research report and publication. Seven types of efficacy analyses were described in the protocols, statistical analysis plans, and publications, including ITT and six others. The protocol or publication described ITT using six different definitions, resulting in frequent disagreements between the two documents (i.e., different numbers of participants were included in the analyses). Descriptions of analyses conducted did not agree between internal company documents and what was publicly reported. Internal company documents provide extensive documentation of methods planned and used, and trial findings, and should be publicly accessible. Reporting standards for randomized controlled trials should recommend transparent descriptions and definitions of analyses performed and which study participants are excluded.

Vector and reservoir control for preventing leishmaniasis.

PubMed

González, Urbà; Pinart, Mariona; Sinclair, David; Firooz, Alireza; Enk, Claes; Vélez, Ivan D; Esterhuizen, Tonya M; Tristan, Mario; Alvar, Jorge

2015-08-05

Leishmaniasis is caused by the Leishmania parasite, and transmitted by infected phlebotomine sandflies. Of the two distinct clinical syndromes, cutaneous leishmaniasis (CL) affects the skin and mucous membranes, and visceral leishmaniasis (VL) affects internal organs. Approaches to prevent transmission include vector control by reducing human contact with infected sandflies, and reservoir control, by reducing the number of infected animals. To assess the effects of vector and reservoir control interventions for cutaneous and for visceral leishmaniasis. We searched the following databases to 13 January 2015: Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS and WHOLIS, Web of Science, and RePORTER. We also searched trials registers for ongoing trials. Randomized controlled trials (RCTs) evaluating the effects of vector and reservoir control interventions in leishmaniasis-endemic regions. Two review authors independently searched for trials and extracted data from included RCTs. We resolved any disagreements by discussion with a third review author. We assessed the quality of the evidence using the GRADE approach. We included 14 RCTs that evaluated a range of interventions across different settings. The study methods were generally poorly described, and consequently all included trials were judged to be at high or unclear risk of selection and reporting bias. Only seven trials reported clinical outcome data which limits our ability to make broad generalizations to different epidemiological settings and cultures. Cutaneous leishmaniasisOne four-arm RCT from Afghanistan compared indoor residual spraying (IRS), insecticide-treated bednets (ITNs), and insecticide-treated bedsheets, with no intervention. Over 15 months follow-up, all three insecticide-based interventions had a lower incidence of CL than the control area (IRS: risk ratio (RR) 0.61, 95% confidence interval (CI) 0.38 to 0.97, 2892 participants, moderate quality evidence; ITNs: RR 0.32, 95% CI 0.18 to 0.56, 2954 participants, low quality evidence; ITS: RR 0.34, 95% CI 0.20 to 0.57, 2784 participants, low quality evidence). No difference was detected between the three interventions (low quality evidence). One additional trial of ITNs from Iran was underpowered to show a difference.Insecticide treated curtains were compared with no intervention in one RCT from Venezuela, where there were no CL episodes in the intervention areas over 12 months follow-up compared to 142 in control areas (RR 0.00, 95% CI 0.00 to 0.49, one trial, 2938 participants, low quality evidence).Personal protection using insecticide treated clothing was evaluated by two RCTs in soldiers, but the trials were underpowered to reliably detect effects on the incidence of CL (RR 0.40, 95% CI 0.13 to 1.20, two trials, 558 participants, low quality evidence). Visceral leishmaniasisIn a single RCT of ITNs versus no intervention from India and Nepal, the incidence of VL was low in both groups and no difference was detected (RR 0.99, 95% CI 0.46 to 2.15, one trial, 19,810 participants, moderate quality evidence).Two trials from Brazil evaluated the effects of culling infected dogs compared to no intervention or IRS. Although they report a reduction in seroconversion over 18 months follow-up, they did not measure or report effects on clinical disease. Using insecticides to reduce phlebotomine sandfly numbers may be effective at reducing the incidence of CL, but there is insufficient evidence from trials to know whether it is better to spray the internal walls of houses or to treat bednets, curtains, bedsheets or clothing.

Diet and dietary supplement intervention trials for the prevention of prostate cancer recurrence: a review of the randomized controlled trial evidence.

PubMed

Van Patten, Cheri L; de Boer, Johan G; Tomlinson Guns, Emma S

2008-12-01

We review the effect of diet and dietary supplement interventions on prostate cancer progression, recurrence and survival. A literature search was conducted in MEDLINE, EMBASE and CINAHL to identify diet and dietary supplement intervention studies in men with prostate cancer using prostate specific antigen or prostate specific antigen doubling time as a surrogate serum biomarker of prostate cancer recurrence and/or survival. Of the 32 studies identified 9 (28%) were randomized controlled trials and the focus of this review. In these studies men had confirmed prostate cancer and elevated or increasing prostate specific antigen. Only 1 trial included men with metastatic disease. When body mass index was reported, men were overweight or obese. A significant decrease in prostate specific antigen was observed in some studies using a low fat vegan diet, soy beverage or lycopene supplement. While not often reported as an end point, a significant increase in prostate specific antigen doubling time was observed in a study on lycopene supplementation. In only 1 randomized controlled trial in men undergoing orchiectomy was a survival end point of fewer deaths with lycopene supplementation reported. A limited number of randomized controlled trials were identified in which diet and dietary supplement interventions appeared to slow disease progression in men with prostate cancer, although results vary. Studies were limited by reliance on the surrogate biomarker prostate specific antigen, sample size and study duration. Well designed trials are warranted to expand knowledge, replicate findings and further assess the impact of diet and dietary supplement interventions on recurrence and treatment associated morbidities.

Comparison of reporting phase III randomized controlled trials of antibiotic treatment for common bacterial infections in ClinicalTrials.gov and matched publications.

PubMed

Shepshelovich, D; Yelin, D; Gafter-Gvili, A; Goldman, S; Avni, T; Yahav, D

2018-02-15

Discrepancies between ClinicalTrials.gov entries and matching publications were previously described in general medicine. We aimed to evaluate the consistency of reporting in trials addressing systemic antibiotic therapy. We searched ClinicalTrials.gov for completed phase III trials comparing antibiotic regimens until May 2017. Matched publications were identified in PubMed. Two independent reviewers extracted data and identified inconsistencies. Reporting was assessed among studies started before and after 1 July 2005, when the International Committee of Medical Journal Editors (ICMJE) required mandatory registration as a prerequisite for considering a trial for publication. Matching publications were identified for 75 (70%) of 107 ClinicalTrials.gov entries. Median time from study completion to publication was 26 months (interquartile range 19-42). Primary outcome definition was inconsistent between ClinicalTrials.gov and publications in seven trials (7/72, 10%) and reporting of the primary outcome timeframe was inconsistent in 14 (14/71, 20%). Secondary outcomes definitions were inconsistent in 36 trials (36/66, 55%). Reporting of inclusion criteria and study timeline were inconsistent in 17% (13/65) and 3% (2/65), respectively. Trials started after July 2005 were significantly less likely to have reporting inconsistencies and were published in higher impact factor journals. We found a lower inconsistency rate of outcome reporting compared with other medical disciplines. Reporting completeness and consistency were significantly better after July 2005. The ICMJE requirement for mandatory registration was associated with significant improvement in reporting quality in infectious diseases trials. Prolonged time lag to publication and missing data from unpublished trials should raise a discussion on current reporting and publishing procedures. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Impact of a Daily SMS Medication Reminder System on Tuberculosis Treatment Outcomes: A Randomized Controlled Trial.

PubMed

Mohammed, Shama; Glennerster, Rachel; Khan, Aamir J

2016-01-01

The rapid uptake of mobile phones in low and middle-income countries over the past decade has provided public health programs unprecedented access to patients. While programs have used text messages to improve medication adherence, there have been no high-powered trials evaluating their impact on tuberculosis treatment outcomes. To measure the impact of Zindagi SMS, a two-way SMS reminder system, on treatment success of people with drug-sensitive tuberculosis. We conducted a two-arm, parallel design, effectiveness randomized controlled trial in Karachi, Pakistan. Individual participants were randomized to either Zindagi SMS or the control group. Zindagi SMS sent daily SMS reminders to participants and asked them to respond through SMS or missed (unbilled) calls after taking their medication. Non-respondents were sent up to three reminders a day. Public and private sector tuberculosis clinics in Karachi, Pakistan. Newly-diagnosed patients with smear or bacteriologically positive pulmonary tuberculosis who were on treatment for less than two weeks; 15 years of age or older; reported having access to a mobile phone; and intended to live in Karachi throughout treatment were eligible to participate. We enrolled 2,207 participants, with 1,110 randomized to Zindagi SMS and 1,097 to the control group. The primary outcome was clinically recorded treatment success based upon intention-to-treat. We found no significant difference between the Zindagi SMS or control groups for treatment success (719 or 83% vs. 903 or 83%, respectively, p = 0·782). There was no significant program effect on self-reported medication adherence reported during unannounced visits during treatment. In this large-scale randomized controlled effectiveness trial of SMS medication reminders for tuberculosis treatment, we found no significant impact. The trial was registered with ClinicalTrials.gov, NCT01690754.

Relaxation techniques for pain management in labour.

PubMed

Smith, Caroline A; Levett, Kate M; Collins, Carmel T; Armour, Mike; Dahlen, Hannah G; Suganuma, Machiko

2018-03-28

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute to the popularity of complementary methods of pain management. This review examined currently available evidence on the use of relaxation therapies for pain management in labour. This is an update of a review first published in 2011. To examine the effects of mind-body relaxation techniques for pain management in labour on maternal and neonatal well-being during and after labour. We searched Cochrane Pregnancy and Childbirth's Trials Register (9 May 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 5 2017), MEDLINE (1966 to 24 May 2017), CINAHL (1980 to 24 May 2017), the Australian New Zealand Clinical Trials Registry (18 May 2017), ClinicalTrials.gov (18 May 2017), the ISRCTN Register (18 May 2017), the WHO International Clinical Trials Registry Platform (ICTRP) (18 May 2017), and reference lists of retrieved studies. Randomised controlled trials (including quasi randomised and cluster trials) comparing relaxation methods with standard care, no treatment, other non-pharmacological forms of pain management in labour or placebo. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We attempted to contact study authors for additional information. We assessed evidence quality with GRADE methodology. This review update includes 19 studies (2519 women), 15 of which (1731 women) contribute data. Interventions examined included relaxation, yoga, music and mindfulness. Approximately half of the studies had a low risk of bias for random sequence generation and attrition bias. The majority of studies had a high risk of bias for performance and detection bias, and unclear risk of bias for, allocation concealment, reporting bias and other bias. We assessed the evidence from these studies as ranging from low to very low quality, and therefore the effects below should be interpreted with caution.RelaxationWe found that relaxation compared to usual care provided lowered the intensity of pain (measured on a scale of 0 to 10 with low scores indicating less pain) during the latent phase of labour (mean difference (MD) -1.25, 95% confidence interval (CI) -1.97 to -0.53, one trial, 40 women). Four trials reported pain intensity in the active phase; there was high heterogeneity between trials and very low-quality evidence suggested that there was no strong evidence that the effects were any different between groups for this outcome (MD -1.08, 95% CI -2.57 to 0.41, four trials, 271 women, random-effects analysis). Very low-quality evidence showed that women receiving relaxation reported greater satisfaction with pain relief during labour (risk ratio (RR) 8.00, 95% CI 1.10 to 58.19, one trial, 40 women), and showed no clear benefit for satisfaction with childbirth experience (assessed using different scales) (standard mean difference (SMD) -0.03, 95% CI -0.37 to 0.31, three trials, 1176 women). For safety outcomes there was very low-quality evidence of no clear reduction in assisted vaginal birth (average RR 0.61, 95% CI 0.20 to 1.84, four trials, 1122 women) or in caesarean section rates (average RR 0.73, 95% CI 0.26 to 2.01, four trials, 1122 women). Sense of control in labour, and breastfeeding were not reported under this comparison.YogaWhen comparing yoga to control interventions there was low-quality evidence that yoga lowered pain intensity (measured on a scale of 0 to 10) with low scores indicating less pain) (MD -6.12, 95% CI -11.77 to -0.47, one trial, 66 women), greater satisfaction with pain relief (MD 7.88, 95% CI 1.51 to 14.25, one trial, 66 women) and greater satisfaction with childbirth experience (MD 6.34, 95% CI 0.26 to 12.42 one trial, 66 women (assessed using the Maternal Comfort Scale with higher score indicating greater comfort). Sense of control in labour, breastfeeding, assisted vaginal birth, and caesarean section were not reported under this comparison.MusicWhen comparing music to control interventions there was evidence of lower pain intensity in the latent phase for women receiving music (measured on a scale of 0 to 10 with low scores indicating less pain) (MD -0.73, 95% CI -1.01 to -0.45, random-effects analysis, two trials, 192 women) and very low-quality evidence of no clear benefit in the active phase (MD -0.51, 95% CI -1.10 to 0.07, three trials, 217 women). Very low-quality evidence suggested no clear benefit in terms of reducing assisted vaginal birth (RR 0.41, 95% CI 0.08 to 2.05, one trial, 156 women) or caesarean section rate (RR 0.78, 95% CI 0.36 to 1.70, two trials, 216 women). Satisfaction with pain relief, sense of control in labour, satisfaction with childbirth experience, and breastfeeding were not reported under this comparison.Audio analgesiaOne trial evaluating audio analgesia versus control only reported one outcome and showed no evidence of benefit in satisfaction with pain relief.MindfulnessOne trial evaluating mindfulness versus usual care found an increase in sense of control for the mindfulness group (using the Childbirth Self-Efficacy Inventory) (MD 31.30, 95% CI 1.61 to 60.99, 26 women). There is no strong evidence that the effects were any different between groups for satisfaction in childbirth, or for caesarean section rate, need for assisted vaginal delivery or need for pharmacological pain relief. No other outcomes were reported in this trial. Relaxation, yoga and music may have a role with reducing pain, and increasing satisfaction with pain relief, although the quality of evidence varies between very low to low. There was insufficient evidence for the role of mindfulness and audio-analgesia. The majority of trials did not report on the safety of the interventions. Further randomised controlled trials of relaxation modalities for pain management in labour are needed. Trials should be adequately powered and include clinically relevant outcomes such as those described in this review.

Weight change in control group participants in behavioural weight loss interventions: a systematic review and meta-regression study

PubMed Central

2012-01-01

Background Unanticipated control group improvements have been observed in intervention trials targeting various health behaviours. This phenomenon has not been studied in the context of behavioural weight loss intervention trials. The purpose of this study is to conduct a systematic review and meta-regression of behavioural weight loss interventions to quantify control group weight change, and relate the size of this effect to specific trial and sample characteristics. Methods Database searches identified reports of intervention trials meeting the inclusion criteria. Data on control group weight change and possible explanatory factors were abstracted and analysed descriptively and quantitatively. Results 85 trials were reviewed and 72 were included in the meta-regression. While there was no change in control group weight, control groups receiving usual care lost 1 kg more than control groups that received no intervention, beyond measurement. Conclusions There are several possible explanations why control group changes occur in intervention trials targeting other behaviours, but not for weight loss. Control group participation may prevent weight gain, although more research is needed to confirm this hypothesis. PMID:22873682

Weight change in control group participants in behavioural weight loss interventions: a systematic review and meta-regression study.

PubMed

Waters, Lauren; George, Alexis S; Chey, Tien; Bauman, Adrian

2012-08-08

Unanticipated control group improvements have been observed in intervention trials targeting various health behaviours. This phenomenon has not been studied in the context of behavioural weight loss intervention trials. The purpose of this study is to conduct a systematic review and meta-regression of behavioural weight loss interventions to quantify control group weight change, and relate the size of this effect to specific trial and sample characteristics. Database searches identified reports of intervention trials meeting the inclusion criteria. Data on control group weight change and possible explanatory factors were abstracted and analysed descriptively and quantitatively. 85 trials were reviewed and 72 were included in the meta-regression. While there was no change in control group weight, control groups receiving usual care lost 1 kg more than control groups that received no intervention, beyond measurement. There are several possible explanations why control group changes occur in intervention trials targeting other behaviours, but not for weight loss. Control group participation may prevent weight gain, although more research is needed to confirm this hypothesis.

Registration status and outcome reporting of trials published in core headache medicine journals.

PubMed

Rayhill, Melissa L; Sharon, Roni; Burch, Rebecca; Loder, Elizabeth

2015-11-17

To evaluate randomized controlled trial (RCT) registration and outcome reporting compliance in core headache medicine journals. We identified RCTs published in core journals (Headache, Cephalalgia, and the Journal of Headache and Pain) from 2005 through 2014. We searched articles for trial registration numbers, which were verified in the corresponding trial registry. We categorized trial funding sources as industry, academic, government, or mixed. We contacted corresponding authors to assess reasons for nonregistration. We evaluated whether primary outcomes in trial registries matched those in corresponding publications. The journals published 225 RCTs over the study period. Fifty-eight of 225 (26%) reported a trial registration number in the article that could be linked to a corresponding registry entry. Trial registration rates increased over the 9 years of the study. Forty-six of 118 (39%) of industry-funded studies were registered compared with 27% of academic and 0% of government-funded studies. Only 5% of RCTs were prospectively registered, reported primary outcomes identical to those in the trial registry, and did not report unacknowledged post hoc outcomes. The most common reason for nonregistration was lack of awareness. Only about a quarter of the articles published in the core headache medicine journals are compliant with trial registration, but compliance has increased over time. Selective reporting of outcomes remains a problem, and very few trials met all 3 reporting standards assessed in this study. Efforts to improve the quality of trial reporting in the headache literature should continue. © 2015 American Academy of Neurology.

The quality of the reported sample size calculations in randomized controlled trials indexed in PubMed.

PubMed

Lee, Paul H; Tse, Andy C Y

2017-05-01

There are limited data on the quality of reporting of information essential for replication of the calculation as well as the accuracy of the sample size calculation. We examine the current quality of reporting of the sample size calculation in randomized controlled trials (RCTs) published in PubMed and to examine the variation in reporting across study design, study characteristics, and journal impact factor. We also reviewed the targeted sample size reported in trial registries. We reviewed and analyzed all RCTs published in December 2014 with journals indexed in PubMed. The 2014 Impact Factors for the journals were used as proxies for their quality. Of the 451 analyzed papers, 58.1% reported an a priori sample size calculation. Nearly all papers provided the level of significance (97.7%) and desired power (96.6%), and most of the papers reported the minimum clinically important effect size (73.3%). The median (inter-quartile range) of the percentage difference of the reported and calculated sample size calculation was 0.0% (IQR -4.6%;3.0%). The accuracy of the reported sample size was better for studies published in journals that endorsed the CONSORT statement and journals with an impact factor. A total of 98 papers had provided targeted sample size on trial registries and about two-third of these papers (n=62) reported sample size calculation, but only 25 (40.3%) had no discrepancy with the reported number in the trial registries. The reporting of the sample size calculation in RCTs published in PubMed-indexed journals and trial registries were poor. The CONSORT statement should be more widely endorsed. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

PubMed

Kwan, I; Bhattacharya, S; McNeil, A; van Rumste, M M E

2008-04-16

Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) treatment has included ultrasonography plus serum estradiol concentration to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS). The need for intensive monitoring during ovarian stimulation in IVF is controversial. It has been suggested that close monitoring is time consuming, expensive and inconvenient for the woman and simplification of IVF therapy by using ultrasound only should be considered. This systematic review assessed the effects of ovarian monitoring by ultrasound only versus ultrasound plus serum estradiol measurement on IVF outcomes and the occurrence of OHSS in women undergoing stimulated cycles in IVF and intra-cytoplasmic sperm injection (ICSI) treatment. To quantify the effect of monitoring controlled ovarian stimulation in IVF and ICSI cycles with ultrasound plus serum estradiol concentration versus ultrasound only in terms of live birth rates, pregnancy rates and the incidence of OHSS. We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL) on the latest issue of The Cochrane Library, MEDLINE (1966 to May 2007), EMBASE (1980 to May 2007), CINAHL (1982 to May 2007), the National Research Register, and web-based trial databases such as Current Controlled Trials. There was no language restriction. Additionally all references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with ultrasound plus serum estradiol concentration versus ultrasound only in women undergoing ovarian hyperstimulation for IVF and ICSI treatment were included. Two review authors independently examined the electronic search results for relevant trials, extracted data and assessed trial quality. They resolved disagreements by discussion with two other authors. Outcomes data were pooled when appropriate and summary statistics presented when limited data did not allow meta-analysis. Our search strategy identified 1119 potentially eligible reports, of which two met our inclusion criteria. These involved 411 women who underwent controlled ovarian stimulation monitoring. Our primary outcome of live birth rate was not reported in either study. One trial reported clinical pregnancy rate per woman (33% versus 31%; RR 1.07, 95% CI 0.77 to 1.49), the second trial reported clinical pregnancy rate per oocyte retrieval (22% versus 25%). There was no significant difference between the ultrasound plus estradiol group and the ultrasound alone group in the mean number of oocytes retrieved (WMD -0.55, 95% CI -1.79 to 0.69) and the incidence of ovarian hyperstimulation (RR 0.73, 95% CI 0.30 to 1.78) for the two studies. There is no evidence from randomised trials to support cycle monitoring by ultrasound plus serum estradiol as more efficacious than cycle monitoring by ultrasound only on outcomes of live birth and pregnancy rates. A large well-designed randomised controlled trial is needed that reports on live birth rates and pregnancy, with economic evaluation of the costs involved and the views of the women undergoing cycle monitoring. A randomised trial with sufficiently large sample size to test the effects of different monitoring protocols on OHSS, a rare outcome, will pose a great challenge. Until such a trial is considered feasible, cycle monitoring by transvaginal ultrasound plus serum estradiol may need to be retained as a precautionary good practice point.

Systematic review: Outcome reporting bias is a problem in high impact factor neurology journals

PubMed Central

Scott, Jared T.; Blubaugh, Mark; Roepke, Brie; Scheckel, Caleb; Vassar, Matt

2017-01-01

Background Selective outcome reporting is a significant methodological concern. Comparisons between the outcomes reported in clinical trial registrations and those later published allow investigators to understand the extent of selection bias among trialists. We examined the possibility of selective outcome reporting in randomized controlled trials (RCTs) published in neurology journals. Methods We searched PubMed for randomized controlled trials from Jan 1, 2010 –Dec 31, 2015 published in the top 3 impact factor neurology journals. These articles were screened according to specific inclusion criteria. Each author individually extracted data from trials following a standardized protocol. A second author verified each extracted element and discrepancies were resolved. Consistency between registered and published outcomes was evaluated and correlations between discrepancies and funding, journal, and temporal trends were examined. Results 180 trials were included for analysis. 10 (6%) primary outcomes were demoted, 38 (21%) primary outcomes were omitted from the publication, and 61 (34%) unregistered primary outcomes were added to the published report. There were 18 (10%) cases of secondary outcomes being upgraded to primary outcomes in the publication, and there were 53 (29%) changes in timing of assessment. Of 82 (46%) major discrepancies with reported p-values, 54 (66.0%) favored publication of statistically significant results. Conclusion Across trials, we found 180 major discrepancies. 66% of major discrepancies with a reported p-value (n = 82) favored statistically significant results. These results suggest a need within neurology to provide more consistent and timely registration of outcomes. PMID:28727834

Systematic review: Outcome reporting bias is a problem in high impact factor neurology journals.

PubMed

Howard, Benjamin; Scott, Jared T; Blubaugh, Mark; Roepke, Brie; Scheckel, Caleb; Vassar, Matt

2017-01-01

Selective outcome reporting is a significant methodological concern. Comparisons between the outcomes reported in clinical trial registrations and those later published allow investigators to understand the extent of selection bias among trialists. We examined the possibility of selective outcome reporting in randomized controlled trials (RCTs) published in neurology journals. We searched PubMed for randomized controlled trials from Jan 1, 2010 -Dec 31, 2015 published in the top 3 impact factor neurology journals. These articles were screened according to specific inclusion criteria. Each author individually extracted data from trials following a standardized protocol. A second author verified each extracted element and discrepancies were resolved. Consistency between registered and published outcomes was evaluated and correlations between discrepancies and funding, journal, and temporal trends were examined. 180 trials were included for analysis. 10 (6%) primary outcomes were demoted, 38 (21%) primary outcomes were omitted from the publication, and 61 (34%) unregistered primary outcomes were added to the published report. There were 18 (10%) cases of secondary outcomes being upgraded to primary outcomes in the publication, and there were 53 (29%) changes in timing of assessment. Of 82 (46%) major discrepancies with reported p-values, 54 (66.0%) favored publication of statistically significant results. Across trials, we found 180 major discrepancies. 66% of major discrepancies with a reported p-value (n = 82) favored statistically significant results. These results suggest a need within neurology to provide more consistent and timely registration of outcomes.

Adaptive adjustment of the randomization ratio using historical control data.

PubMed

Hobbs, Brian P; Carlin, Bradley P; Sargent, Daniel J

2013-01-01

Prospective trial design often occurs in the presence of 'acceptable' historical control data. Typically, these data are only utilized for treatment comparison in a posteriori retrospective analysis to estimate population-averaged effects in a random-effects meta-analysis. We propose and investigate an adaptive trial design in the context of an actual randomized controlled colorectal cancer trial. This trial, originally reported by Goldberg et al., succeeded a similar trial reported by Saltz et al., and used a control therapy identical to that tested (and found beneficial) in the Saltz trial. The proposed trial implements an adaptive randomization procedure for allocating patients aimed at balancing total information (concurrent and historical) among the study arms. This is accomplished by assigning more patients to receive the novel therapy in the absence of strong evidence for heterogeneity among the concurrent and historical controls. Allocation probabilities adapt as a function of the effective historical sample size (EHSS), characterizing relative informativeness defined in the context of a piecewise exponential model for evaluating time to disease progression. Commensurate priors are utilized to assess historical and concurrent heterogeneity at interim analyses and to borrow strength from the historical data in the final analysis. The adaptive trial's frequentist properties are simulated using the actual patient-level historical control data from the Saltz trial and the actual enrollment dates for patients enrolled into the Goldberg trial. Assessing concurrent and historical heterogeneity at interim analyses and balancing total information with the adaptive randomization procedure lead to trials that on average assign more new patients to the novel treatment when the historical controls are unbiased or slightly biased compared to the concurrent controls. Large magnitudes of bias lead to approximately equal allocation of patients among the treatment arms. Using the proposed commensurate prior model to borrow strength from the historical data, after balancing total information with the adaptive randomization procedure, provides admissible estimators of the novel treatment effect with desirable bias-variance trade-offs. Adaptive randomization methods in general are sensitive to population drift and more suitable for trials that initiate with gradual enrollment. Balancing information among study arms in time-to-event analyses is difficult in the presence of informative right-censoring. The proposed design could prove important in trials that follow recent evaluations of a control therapy. Efficient use of the historical controls is especially important in contexts where reliance on preexisting information is unavoidable because the control therapy is exceptionally hazardous, expensive, or the disease is rare.

Efficacy and safety of Suanzaoren decoction for primary insomnia: a systematic review of randomized controlled trials

PubMed Central

2013-01-01

Background Insomnia is a widespread human health problem, but there currently are the limitations of conventional therapies available. Suanzaoren decoction (SZRD) is a well known classic Chinese herbal prescription for insomnia and has been treating people’s insomnia for more than thousand years. The objective of this study was to evaluate the efficacy and safety of SZRD for insomnia. Methods A systematic literature search was performed for 6 databases up to July of 2012 to identify randomized control trials (RCTs) involving SZRD for insomniac patients. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. Results Twelve RCTs with total of 1376 adult participants were identified. The methodological quality of all included trials are no more than 3/8 score. Majority of the RCTs concluded that SZRD was more significantly effective than benzodiazepines for treating insomnia. Despite these positive outcomes, there were many methodological shortcomings in the studies reviewed, including insufficient information about randomization generation and absence of allocation concealment, lack of blinding and no placebo control, absence of intention-to-treat analysis and lack of follow-ups, selective publishing and reporting, and small number of sample sizes. A number of clinical heterogeneity such as diagnosis, intervention, control, and outcome measures were also reviewed. Only 3 trials reported adverse events, whereas the other 9 trials did not provide the safety information. Conclusions Despite the apparent reported positive findings, there is insufficient evidence to support efficacy of SZRD for insomnia due to the poor methodological quality and the small number of trials of the included studies. SZRD seems generally safe, but is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further large sample-size and well-designed RCTs are needed. PMID:23336848

Attitudes towards fever amongst UK paediatric intensive care staff.

PubMed

Brick, Thomas; Agbeko, Rachel S; Davies, Patrick; Davis, Peter J; Deep, Akash; Fortune, Peter-Marc; Inwald, David P; Jones, Amy; Levin, Richard; Morris, Kevin P; Pappachan, John; Ray, Samiran; Tibby, Shane M; Tume, Lyvonne N; Peters, Mark J

2017-03-01

The role played by fever in the outcome of critical illness in children is unclear. This survey of medical and nursing staff in 35 paediatric intensive care units and transport teams in the United Kingdom and Ireland established attitudes towards the management of children with fever. Four hundred sixty-two medical and nursing staff responded to a web-based survey request. Respondents answered eight questions regarding thresholds for temperature control in usual clinical practice, indications for paracetamol use, and readiness to participate in a clinical trial of permissive temperature control. The median reported threshold for treating fever in clinical practice was 38 °C (IQR 38-38.5 °C). Paracetamol was reported to be used as an analgesic and antipyretic but also for non-specific comfort indications. There was a widespread support for a clinical trial of a permissive versus a conservative approach to fever in paediatric intensive care units. Within a trial, 58% of the respondents considered a temperature of 39 °C acceptable without treatment. Staff on paediatric intensive care units in the United Kingdom and Ireland tends to treat temperatures within the febrile range. There was a willingness to conduct a randomized controlled trial of treatment of fever. What is known: • The effect of fever on the outcome in paediatric critical illness is unknown. • Paediatricians have traditionally been reluctant to allow fever in sick children. What is new: • Paediatric intensive care staff report a tendency towards treating fever, with a median reported treatment threshold of 38 °C. • There is widespread support amongst PICU staff in the UK for a randomized controlled trial of temperature in critically ill children. • Within a trial setting, PICU staff attitudes to fever are more permissive than in clinical practice.

Reporting Quality of Randomized, Controlled Trials Evaluating Combined Chemoradiotherapy in Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yu-Pei; Chen, Lei; Li, Wen-Fei

Purpose: To comprehensively assess the reporting quality of randomized, controlled trials (RCTs) in nasopharyngeal carcinoma (NPC), and to identify significant predictors of quality. Methods and Materials: Two investigators searched MEDLINE and EMBASE for RCTs published between January 1988 and December 2015 that assessed the effect of combined chemoradiotherapy for NPC. The overall quality of each report was assessed using a 28-point overall quality score (OQS) based on the 2010 Consolidated Standards of Reporting Trials (CONSORT) statement. To provide baseline data for further evaluation, we also investigated the reporting quality of certain important issues in detail, including key methodologic items (allocationmore » concealment, blinding, intention-to-treat principle), endpoints, follow-up, subgroup analyses, and adverse events. Results: We retrieved 24 relevant RCTs including 6591 patients. Median 2010 OQS was 15.5 (range, 10-24). Half of the items in the 2010 OQS were poorly reported in at least 40% of trials. Multivariable regression models revealed that publication after 2010 and high impact factor were significant predictors of improved 2010 OQS. Additionally, many issues that we consider significant were not reported adequately. Conclusions: Despite publication of the CONSORT statement more than a decade ago, overall reporting quality for RCTs in NPC was unsatisfactory. Additionally, substantial selectivity and heterogeneity exists in reporting of certain crucial issues. This survey provides the first prompt for NPC trial investigators to improve reporting quality according to the CONSORT statement; increased scrutiny and diligence by editors and peer reviewers is also required.« less

Reporting Quality of Social and Psychological Intervention Trials: A Systematic Review of Reporting Guidelines and Trial Publications

PubMed Central

Grant, Sean P.; Mayo-Wilson, Evan; Melendez-Torres, G. J.; Montgomery, Paul

2013-01-01

Background Previous reviews show that reporting guidelines have improved the quality of trial reports in medicine, yet existing guidelines may not be fully suited for social and psychological intervention trials. Objective/Design We conducted a two-part study that reviewed (1) reporting guidelines for and (2) the reporting quality of social and psychological intervention trials. Data Sources (1) To identify reporting guidelines, we systematically searched multiple electronic databases and reporting guideline registries. (2) To identify trials, we hand-searched 40 journals with the 10 highest impact factors in clinical psychology, criminology, education, and social work. Eligibility (1) Reporting guidelines consisted of articles introducing a checklist of reporting standards relevant to social and psychological intervention trials. (2) Trials reported randomised experiments of complex interventions with psychological, social, or health outcomes. Results (1) We identified 19 reporting guidelines that yielded 147 reporting standards relevant to social and psychological interventions. Social and behavioural science guidelines included 89 standards not found in CONSORT guidelines. However, CONSORT guidelines used more recommended techniques for development and dissemination compared to other guidelines. (2) Our review of trials (n = 239) revealed that many standards were poorly reported, such as identification as a randomised trial in titles (20% reported the information) and abstracts (55%); information about blinding (15%), sequence generation (23%), and allocation concealment (17%); and details about actual delivery of experimental (43%) and control interventions (34%), participant uptake (25%), and service environment (28%). Only 11 of 40 journals referenced reporting guidelines in “Instructions to Authors.” Conclusion Existing reporting guidelines have important limitations in content, development, and/or dissemination. Important details are routinely missing from trial publications; most leading journals in social and behavioural sciences do not ask authors to follow reporting standards. Findings demonstrate a need to develop a CONSORT extension with updated standards for social and psychological intervention trials. PMID:23734256

An evaluation of the completeness of safety reporting in reports of complementary and alternative medicine trials

PubMed Central

2011-01-01

Background Adequate reporting of safety in publications of randomized controlled trials (RCTs) is a pre-requisite for accurate and comprehensive profile evaluation of conventional as well as complementary and alternative medicine (CAM) treatments. Clear and concise information on the definition, frequency, and severity of adverse events (AEs) is necessary for assessing the benefit-harm ratio of any intervention. The objectives of this study are to assess the quality of safety reporting in CAM RCTs; to explore the influence of different trial characteristics on the quality of safety reporting. Methods Survey of safety reporting in RCTs published in 2009 across 15 widely used CAM interventions identified from the Cochrane Collaboration's CAM Field specialized register of trials. Primary outcome measures, the adequacy of reporting of AEs; was defined and categorized according to the CONSORT for harms extension; the percentage of words devoted to the reporting of safety in the entire report and in the results section. Results Two-hundred and five trials were included in the review. Of these, 15% (31/205) reported that no harms were observed during the trial period. Of the remaining 174 trials reporting any safety information, only 21% (36/174) had adequate safety reporting. For all trials, the median percentage of words devoted to the reporting of safety in the results section was 2.6. Moreover, 69% (n = 141) of all trials devoted a lesser or equal percentage of words to safety compared to author affiliations. Of the predictor variables used in regression analysis, multicenter trials had more words devoted to safety in the results section than single centre trials (P = 0.045). Conclusions An evaluation of safety reporting in the reports of CAM RCTs across 15 different CAM interventions demonstrated that the reporting of harms was largely inadequate. The quality of reporting safety information in primary reports of CAM randomized trials requires improvement. PMID:21859470

A systematic review of the reporting of Data Monitoring Committees' roles, interim analysis and early termination in pediatric clinical trials

PubMed Central

2009-01-01

Background Decisions about interim analysis and early stopping of clinical trials, as based on recommendations of Data Monitoring Committees (DMCs), have far reaching consequences for the scientific validity and clinical impact of a trial. Our aim was to evaluate the frequency and quality of the reporting on DMC composition and roles, interim analysis and early termination in pediatric trials. Methods We conducted a systematic review of randomized controlled clinical trials published from 2005 to 2007 in a sample of four general and four pediatric journals. We used full-text databases to identify trials which reported on DMCs, interim analysis or early termination, and included children or adolescents. Information was extracted on general trial characteristics, risk of bias, and a set of parameters regarding DMC composition and roles, interim analysis and early termination. Results 110 of the 648 pediatric trials in this sample (17%) reported on DMC or interim analysis or early stopping, and were included; 68 from general and 42 from pediatric journals. The presence of DMCs was reported in 89 of the 110 included trials (81%); 62 papers, including 46 of the 89 that reported on DMCs (52%), also presented information about interim analysis. No paper adequately reported all DMC parameters, and nine (15%) reported all interim analysis details. Of 32 trials which terminated early, 22 (69%) did not report predefined stopping guidelines and 15 (47%) did not provide information on statistical monitoring methods. Conclusions Reporting on DMC composition and roles, on interim analysis results and on early termination of pediatric trials is incomplete and heterogeneous. We propose a minimal set of reporting parameters that will allow the reader to assess the validity of trial results. PMID:20003383

Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support.

PubMed

Free, Caroline; Hoile, Elizabeth; Robertson, Steven; Knight, Rosemary

2010-06-01

Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment. We report three controlled trials of interventions to increase recruitment to the Txt2stop trial. To evaluate: Trial 1. The impact on registrations of a text message regarding an online registration facility; Trial 2. The impact on randomizations of sending pound5 with a covering letter to those eligible to join the trial; Trial 3. The impact on randomizations of text messages containing quotes from existing participants. Single blind controlled trials with allocation concealment. Trial 1: A text message regarding our new online registration facility; Trial 2: A letter with pound5 enclosed; Trial 3: A series of four text messages containing quotes from participants. The control group in each trial received standard Txt2stop procedures. Trial 1: 3.6% (17/470) of the intervention group and 1.1% (5/467) of the control group registered for the trial, risk difference 2.5% (95% CI 0.6-4.5). 0% (0/ 470) of the intervention group and 0.2% (1/467) of the control group registered successfully online, risk difference -0.2 (95% CI -0.6-0.2); Trial 2: 4.5% (11/246) of the intervention group and 0.4% (1/245) of the control group were randomized into the Txt2stop trial, risk difference 4.0% (95% CI 1.4-6.7); Trial 3: 3.5% (14/405) of the intervention group and 0% (0/406) of the control group were randomized into the Txt2stop trial, risk difference 3.5 (95% CI 1.7-5.2). There were no baseline data available for trial 1. Allocation of participant IDs in trials 2 and 3 were systematic. Sending a text message about an online registration facility increased registrations to Txt2stop, but did not increase online registrations. Sending a pound5 reimbursement for participants' time and sending text messages containing quotes from existing participants increased randomizations into the Txt2stop trial. Clinical Trials 2010; 7: 265-273. http://ctj.sagepub.com.

The contribution of attentional lapses to individual differences in visual working memory capacity.

PubMed

Adam, Kirsten C S; Mance, Irida; Fukuda, Keisuke; Vogel, Edward K

2015-08-01

Attentional control and working memory capacity are important cognitive abilities that substantially vary between individuals. Although much is known about how attentional control and working memory capacity relate to each other and to constructs like fluid intelligence, little is known about how trial-by-trial fluctuations in attentional engagement impact trial-by-trial working memory performance. Here, we employ a novel whole-report memory task that allowed us to distinguish between varying levels of attentional engagement in humans performing a working memory task. By characterizing low-performance trials, we can distinguish between models in which working memory performance failures are caused by either (1) complete lapses of attention or (2) variations in attentional control. We found that performance failures increase with set-size and strongly predict working memory capacity. Performance variability was best modeled by an attentional control model of attention, not a lapse model. We examined neural signatures of performance failures by measuring EEG activity while participants performed the whole-report task. The number of items correctly recalled in the memory task was predicted by frontal theta power, with decreased frontal theta power associated with poor performance on the task. In addition, we found that poor performance was not explained by failures of sensory encoding; the P1/N1 response and ocular artifact rates were equivalent for high- and low-performance trials. In all, we propose that attentional lapses alone cannot explain individual differences in working memory performance. Instead, we find that graded fluctuations in attentional control better explain the trial-by-trial differences in working memory that we observe.

The Contribution of Attentional Lapses to Individual Differences in Visual Working Memory Capacity

PubMed Central

Adam, Kirsten C. S.; Mance, Irida; Fukuda, Keisuke; Vogel, Edward K.

2015-01-01

Attentional control and working memory capacity are important cognitive abilities that substantially vary between individuals. Although much is known about how attentional control and working memory capacity relate to each other and to constructs like fluid intelligence, little is known about how trial-by-trial fluctuations in attentional engagement impact trial-by-trial working memory performance. Here, we employ a novel whole-report memory task that allowed us to distinguish between varying levels of attentional engagement in humans performing a working memory task. By characterizing low-performance trials, we can distinguish between models in which working memory performance failures are caused by either (1) complete lapses of attention or (2) variations in attentional control. We found that performance failures increase with set-size and strongly predict working memory capacity. Performance variability was best modeled by an attentional control model of attention, not a lapse model. We examined neural signatures of performance failures by measuring EEG activity while participants performed the whole-report task. The number of items correctly recalled in the memory task was predicted by frontal theta power, with decreased frontal theta power associated with poor performance on the task. In addition, we found that poor performance was not explained by failures of sensory encoding; the P1/N1 response and ocular artifact rates were equivalent for high- and low-performance trials. In all, we propose that attentional lapses alone cannot explain individual differences in working memory performance. Instead, we find that graded fluctuations in attentional control better explain the trial-by-trial differences in working memory that we observe. PMID:25811710

Randomised controlled trials of veterinary homeopathy: characterising the peer-reviewed research literature for systematic review.

PubMed

Mathie, Robert T; Hacke, Daniela; Clausen, Jürgen

2012-10-01

Systematic review of the research evidence in veterinary homeopathy has never previously been carried out. This paper presents the search methods, together with categorised lists of retrieved records, that enable us to identify the literature that is acceptable for future systematic review of randomised controlled trials (RCTs) in veterinary homeopathy. All randomised and controlled trials of homeopathic intervention (prophylaxis and/or treatment of disease, in any species except man) were appraised according to pre-specified criteria. The following databases were systematically searched from their inception up to and including March 2011: AMED; Carstens-Stiftung Homeopathic Veterinary Clinical Research (HomVetCR) database; CINAHL; Cochrane Central Register of Controlled Trials; Embase; Hom-Inform; LILACS; PubMed; Science Citation Index; Scopus. One hundred and fifty records were retrieved; 38 satisfied the acceptance criteria (substantive report of a clinical treatment or prophylaxis trial in veterinary homeopathic medicine randomised and controlled and published in a peer-reviewed journal), and were thus eligible for future planned systematic review. Approximately half of the rejected records were theses. Seven species and 27 different species-specific medical conditions were represented in the 38 papers. Similar numbers of papers reported trials of treatment and prophylaxis (n=21 and n=17 respectively) and were controlled against placebo or other than placebo (n=18, n=20 respectively). Most research focused on non-individualised homeopathy (n=35 papers) compared with individualised homeopathy (n=3). The results provide a complete and clarified view of the RCT literature in veterinary homeopathy. We will systematically review the 38 substantive peer-reviewed journal articles under the main headings: treatment trials; prophylaxis trials. Copyright © 2012 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

A systematic review found that deviations from intention-to-treat are common in randomized trials and systematic reviews.

PubMed

Abraha, Iosief; Cozzolino, Francesco; Orso, Massimiliano; Marchesi, Mauro; Germani, Antonella; Lombardo, Guido; Eusebi, Paolo; De Florio, Rita; Luchetta, Maria Laura; Iorio, Alfonso; Montedori, Alessandro

2017-04-01

To describe the characteristics, and estimate the incidence, of trials included in systematic reviews deviating from the intention-to-treat (ITT) principle. A 5% random sample of reviews were selected (Medline 2006-2010). Trials from reviews were classified based on the ITT: (1) ITT trials (trials reporting standard ITT analyses); (2) modified ITT (mITT) trials (modified ITT; trials deviating from standard ITT); or (3) no ITT trials. Of 222 reviews, 81 (36%) included at least one mITT trial. Reviews with mITT trials were more likely to contain trials that used placebo, that investigated drugs, and that reported favorable results. The incidence of reviews with mITT trial ranged from 29% (17/58) to 48% (23/48). Of the 2,349 trials, 597 (25.4%) were classified as ITT trials, 323 (13.8%) as mITT trials, and 1,429 (60.8%) as no ITT trials. The mITT trials were more likely to have reported exclusions compared to studies classified as ITT trials and to have received funding. The reporting of the type of ITT may differ according to the clinical area and the type of intervention. Deviation from ITT in randomized controlled trials is a widespread phenomenon that significantly affects systematic reviews. Copyright © 2017 Elsevier Inc. All rights reserved.

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology

PubMed Central

Azar, Marleine; Riehm, Kira E.; McKay, Dean; Thombs, Brett D.

2015-01-01

Background Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Methods Eligible RCTs were published in JCCP in 2013–2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Results Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). Conclusions The quality of published outcome analysis definitions and trial registrations in JCCP is suboptimal. Greater attention to proper trial registration and outcome analysis definition in published reports is needed. PMID:26581079

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology.

PubMed

Azar, Marleine; Riehm, Kira E; McKay, Dean; Thombs, Brett D

2015-01-01

Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Eligible RCTs were published in JCCP in 2013-2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). The quality of published outcome analysis definitions and trial registrations in JCCP is suboptimal. Greater attention to proper trial registration and outcome analysis definition in published reports is needed.

Physician acceptance of the IRIS user interface during a clinical trial at the Ottawa Civic Hospital

NASA Astrophysics Data System (ADS)

Coristine, Marjorie; Beeton, Carolyn; Tombaugh, Jo W.; Ahuja, J.; Belanger, Garry; Dillon, Richard F.; Currie, Shawn; Hind, E.

1990-07-01

During a clinical trial, emergency physicians and radiologists at the Ottawa Civic Hospital used IRIS (Integrated Radiological Information System) to process patients' x-rays, requisitions, and reports, and to have consultations, for 319 active cases. This paper discusses IRIS user interface issues raised during the clinical trial. The IRIS workstation consists of three major system components: 1) an image screen for viewing and enhancing images; 2) a control screen for presenting patient information, selecting images, and executing commands; and 3) a hands-free telephone for reporting activities and consultations. The control screen and hands-free telephone user interface allow physicians to navigate through patient files, select images and access reports, enter new reports, and perform remote consultations. Physicians were observed using the system during the trial and responded to questions about the user interface on an extensive debriefing interview after the trial. Overall, radiologists and emergency physicians were satisfied with IRIS control screen functionality and user interface. In a number of areas radiologists and emergency physicians differed in their user interface needs. Some features were found to be acceptable to one group of physicians but required modification to meet the needs of the other physician group. The data from the interviews, along with the comments from radiologists and emergency physicians provided important information for the revision of some features, and for the evolution of new features.

The effect of glutamine therapy on outcomes in critically ill patients: a meta-analysis of randomized controlled trials

PubMed Central

2014-01-01

Introduction Glutamine supplementation is supposed to reduce mortality and nosocomial infections in critically ill patients. However, the recently published reducing deaths due to oxidative stress (REDOX) trials did not provide evidence supporting this. This study investigated the impact of glutamine-supplemented nutrition on the outcomes of critically ill patients using a meta-analysis. Methods We searched for and gathered data from the Cochrane Central Register of Controlled Trials, MEDLINE, Elsevier, Web of Science and ClinicalTrials.gov databases reporting the effects of glutamine supplementation on outcomes in critically ill patients. We produced subgroup analyses of the trials according to specific patient populations, modes of nutrition and glutamine dosages. Results Among 823 related articles, eighteen Randomized Controlled Trials (RCTs) met all inclusion criteria. Mortality events among 3,383 patients were reported in 17 RCTs. Mortality showed no significant difference between glutamine group and control group. In the high dosage subgroup (above 0.5 g/kg/d), the mortality rate in the glutamine group was significantly higher than that of the control group (relative risk (RR) 1.18; 95% confidence interval (CI), 1.02 to 1.38; P = 0.03). In 15 trials, which included a total of 2,862 patients, glutamine supplementation reportedly affected the incidence of nosocomial infections in the critically ill patients observed. The incidence of nosocomial infections in the glutamine group was significantly lower than that of the control group (RR 0.85; 95% CI, 0.74 to 0.97; P = 0.02). In the surgical ICU subgroup, glutamine supplementation statistically reduced the rate of nosocomial infections (RR 0.70; 95% CI, 0.52 to 0.94; P = 0.04). In the parental nutrition subgroup, glutamine supplementation statistically reduced the rate of nosocomial infections (RR 0.83; 95% CI, 0.70 to 0.98; P = 0.03). The length of hospital stay was reported in 14 trials, in which a total of 2,777 patients were enrolled; however, the patient length of stay was not affected by glutamine supplementation. Conclusions Glutamine supplementation conferred no overall mortality and length of hospital stay benefit in critically ill patients. However, this therapy reduced nosocomial infections among critically ill patients, which differed according to patient populations, modes of nutrition and glutamine dosages. PMID:24401636

Quality of reporting in clinical trials of preharvest food safety interventions and associations with treatment effect.

PubMed

Sargeant, Jan M; Saint-Onge, Jacqueline; Valcour, James; Thompson, Adam; Elgie, Robyn; Snedeker, Kate; Marcynuk, Pasha

2009-10-01

Randomized controlled trials (RCTs) are the gold standard for evaluating treatment efficacy. Therefore, it is important that RCTs are conducted with methodological rigor to prevent biased results and report results in a manner that allows the reader to evaluate internal and external validity. Most human health journals now require manuscripts to meet the Consolidated Standards of Reporting Trials (CONSORT) criteria for reporting of RCTs. Our objective was to evaluate preharvest food safety trials using a modification of the CONSORT criteria to assess methodological quality and completeness of reporting, and to investigate associations between reporting and treatment effects. One hundred randomly selected trials were evaluated using a modified CONSORT statement. The majority of the selected trials (84%) used a deliberate disease challenge, with the remainder representing natural pathogen exposure. There were widespread deficiencies in the reporting of many trial features. Randomization, double blinding, and the number of subjects lost to follow-up were reported in only 46%, 0%, and 43% of trials, respectively. The inclusion criteria for study subjects were only described in 16% of trials, and the number of animals housed together was only stated in 52% of the trials. Although 91 trials had more than one outcome, no trials specified the primary outcome of interest. There were significant bivariable associations between the proportion of positive treatment effects and failure to report the number of subjects lost to follow-up, the number of animals housed together in a group, the level of treatment allocation, and possible study limitations. The results suggest that there are substantive deficiencies in reporting of preharvest food safety trials, and that these deficiencies may be associated with biased treatment effects. The creation and adoption of standards for reporting in preharvest food safety trials will help to ensure the inclusion of important trial details in all publications.

Improved quality monitoring of multi-center acupuncture clinical trials in China

PubMed Central

2009-01-01

Background In 2007, the Chinese Science Division of the State Administration of Traditional Chinese Medicine(TCM) convened a special conference to discuss quality control for TCM clinical research. Control and assurance standards were established to guarantee the quality of clinical research. This paper provides practical guidelines for implementing strict and reproducible quality control for acupuncture randomized controlled trials (RCTs). Methods A standard quality control program (QCP) was established to monitor the quality of acupuncture trials. Case report forms were designed; qualified investigators, study personnel and data management personnel were trained. Monitors, who were directly appointed by the project leader, completed the quality control programs. They guaranteed data accuracy and prevented or detected protocol violations. Clinical centers and clinicians were audited, the randomization system of the centers was inspected, and the treatment processes were audited as well. In addition, the case report forms were reviewed for completeness and internal consistency, the eligibility and validity of the patients in the study was verified, and data was monitored for compliance and accuracy. Results and discussion The monitors complete their reports and submit it to quality assurance and the sponsors. Recommendations and suggestions are made for improving performance. By holding regular meetings to discuss improvements in monitoring standards, the monitors can improve quality and efficiency. Conclusions Supplementing and improving the existed guidelines for quality monitoring will ensure that large multi-centre acupuncture clinical trials will be considered as valid and scientifically stringent as pharmaceutical clinical trials. It will also develop academic excellence and further promote the international recognition of acupuncture. PMID:20035630

Randomized controlled trials in dentistry: common pitfalls and how to avoid them.

PubMed

Fleming, Padhraig S; Lynch, Christopher D; Pandis, Nikolaos

2014-08-01

Clinical trials are used to appraise the effectiveness of clinical interventions throughout medicine and dentistry. Randomized controlled trials (RCTs) are established as the optimal primary design and are published with increasing frequency within the biomedical sciences, including dentistry. This review outlines common pitfalls associated with the conduct of randomized controlled trials in dentistry. Common failings in RCT design leading to various types of bias including selection, performance, detection and attrition bias are discussed in this review. Moreover, methods of minimizing and eliminating bias are presented to ensure that maximal benefit is derived from RCTs within dentistry. Well-designed RCTs have both upstream and downstream uses acting as a template for development and populating systematic reviews to permit more precise estimates of treatment efficacy and effectiveness. However, there is increasing awareness of waste in clinical research, whereby resource-intensive studies fail to provide a commensurate level of scientific evidence. Waste may stem either from inappropriate design or from inadequate reporting of RCTs; the importance of robust conduct of RCTs within dentistry is clear. Optimal reporting of randomized controlled trials within dentistry is necessary to ensure that trials are reliable and valid. Common shortcomings leading to important forms or bias are discussed and approaches to minimizing these issues are outlined. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reporting on blinding in trial protocols and corresponding publications was often inadequate but rarely contradictory.

PubMed

Hróbjartsson, Asbjørn; Pildal, Julie; Chan, An-Wen; Haahr, Mette T; Altman, Douglas G; Gøtzsche, Peter C

2009-09-01

To compare the reporting on blinding in protocols and articles describing randomized controlled trials. We studied 73 protocols of trials approved by the scientific/ethical committees for Copenhagen and Frederiksberg, 1994 and 1995, and their corresponding publications. Three out of 73 trials (4%) reported blinding in the protocol that contradicted that in the publication (e.g., "open" vs. "double blind"). The proportion of "double-blind" trials with a clear description of the blinding of participants increased from 11 out of 58 (19%) when based on publications alone to 39 (67%) when adding the information in the protocol. The similar proportions for the blinding of health care providers were 2 (3%) and 22 (38%); and for the blinding of data collectors, they were 8 (14%) and 14 (24%). In 52 of 58 publications (90%), it was unclear whether all patients, health care providers, and data collectors had been blinded. In 4 of the 52 trials (7%), the protocols clarified that all three key trial persons had been blinded. The reporting on blinding in both trial protocols and publications is often inadequate. We suggest developing international guidelines for the reporting of trial protocols and public access to protocols.

A retrospective survey of the quality of reports and their correlates among randomized controlled trials of immunotherapy for Guillain-Barré syndrome.

PubMed

Lu, Liming; Luo, Gaoquan; Xiao, Fang

2013-08-01

This study aims to assess the quality of reports and their correlates in randomized controlled trials (RCTs) of immunotherapy for Guillain-Barré syndrome (GBS). A search was performed in multiple databases of reports published between April 1992 and November 2012. Reporting quality was assessed by items of the Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement. An overall quality score (OQS) and a key methodological index score (MIS) were calculated for each trial. Factors associated with OQS and MIS were then identified. A total of 19 RCTs were included in the full text. The median OQS was 7.0, with a range of 1-10. However, the quality of reporting in items of 'flow chart' and 'ancillary analyses' was poor with a positive rate of less than 40%. The median MIS was 0 with a range of 0-2. Twelve (63.2%) did not report any of the three key methodological items. Specifically, the mean OQS increased by approximately 2.73 for manuscripts published in the New England Journal of Medicine, The Lancet, Pediatrics and Neurology (95% CI: 0.35-5.12; p < 0.05). Multivariate linear regression and the Poisson regression model could not be presented as the number of included trials was too small. The reporting quality in RCTs on immunotherapy for GBS was poor, which indicated that reporting in RCTs of immunotherapy for GBS needed substantial improvement in order to meet the guideline of the CONSORT Statement.

Assessing adherence in the CAPRISA 004 tenofovir gel HIV prevention trial: results of a nested case-control study.

PubMed

MacQueen, Kathleen M; Weaver, Mark A; van Loggerenberg, Francois; Succop, Stacey; Majola, Nelisle; Taylor, Doug; Karim, Quarraisha Abdool; Karim, Salim Abdool

2014-05-01

Adherence undeniably impacts product effectiveness in microbicide trials, but the connection has proven challenging to quantify using routinely collected behavioral data. We explored this relationship using a nested case-control study in the CAPRISA 004 Tenofovir (TFV) gel HIV prevention trial. Detailed 3-month recall data on sex events, condom and gel use were collected from 72 incident cases and 205 uninfected controls. We then assessed how the relationship between self-reported adherence and HIV acquisition differed between the TFV and placebo gel groups, an interaction effect that should exist if effectiveness increases with adherence. The CAPRISA 004 trial determined that randomization to TFV gel was associated with a significant reduction in risk of HIV acquisition. In our nested case-control study, however, we did not observe a meaningful decrease in the relative odds of infection-TFV versus placebo-as self-reported adherence increased. To the contrary, exploratory sub-group analysis of the case-control data identified greater evidence for a protective effect of TFV gel among participants reporting less than 80 % adherence to the protocol-defined regimen (odds ratio (OR) 0.30; 95 % CI 0.11-0.78) than among those reporting ≥ 80 % adherence (Odds Ratio 0.81; 95 % CI 0.34-1.92). The small number of cases may have inhibited our ability to detect the hypothesized interaction between adherence and effectiveness. Nonetheless, our results re-emphasize the challenges faced by investigators when adherence may be miss-measured, miss-reported, or confounded with the risk of HIV.

Gut-directed hypnotherapy for functional abdominal pain or irritable bowel syndrome in children: a systematic review.

PubMed

Rutten, Juliette M T M; Reitsma, Johannes B; Vlieger, Arine M; Benninga, Marc A

2013-04-01

Gut directed hypnotherapy (HT) is shown to be effective in adult functional abdominal pain (FAP) and irritable bowel syndrome (IBS) patients. We performed a systematic review to assess efficacy of HT in paediatric FAP/IBS patients. We searched Medline, Embase, PsychINFO, Cumulative Index to Nursing and Allied Health Literature databases and Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) in children with FAP or IBS, investigating efficacy of HT on the following outcomes: abdominal pain scores, quality of life, costs and school absenteeism. Three RCT comparing HT to a control treatment were included with sample sizes ranging from 22 to 52 children. We refrained from statistical pooling because of low number of studies and many differences in design and outcomes. Two studies examined HT performed by a therapist, one examined HT through self-exercises on audio CD. All trials showed statistically significantly greater improvement in abdominal pain scores among children receiving HT. One trial reported beneficial effects sustained after 1 year of follow-up. One trial reported statistically significant improvement in quality of life in the HT group. Two trials reported significant reductions in school absenteeism after HT. Therapeutic effects of HT seem superior to standard medical care in children with FAP or IBS. It remains difficult to quantify exact benefits. The need for more high quality research is evident.

Transparency of outcome reporting and trial registration of randomized controlled trials in top psychosomatic and behavioral health journals: A systematic review.

PubMed

Milette, Katherine; Roseman, Michelle; Thombs, Brett D

2011-03-01

The most reliable evidence for evaluating healthcare interventions comes from well-designed and conducted randomized controlled trials (RCTs). The extent to which published RCTs reflect the efficacy of interventions, however, depends on the completeness and accuracy of published results. The Consolidated Standards of Reporting Trials statement, initially developed in 1996, provides guidelines intended to improve the transparency of published RCT reports. A policy of the International Committee of Medical Journal Editors, initiated in 2005, requires clinical trials published in member journals to be registered in publicly accessible registries prior to patient enrollment. The objective of this study was to assess the clarity of outcome reporting, proportion of registered trials, and adequacy of outcome registration in RCTs published in top behavioral health journals. Eligible studies were primary or secondary reports of RCTs published in Annals of Behavioral Medicine, Health Psychology, Journal of Psychosomatic Research, and Psychosomatic Medicine from January 2008 to September 2009. Data were extracted for each study on adequacy of outcome reporting and registration. Of 63 articles reviewed, only 25 (39.7%) had adequately declared primary or secondary outcomes, whereas 38 (60.3%) had multiple primary outcomes or did not define outcomes. Only 13 studies (20.6%) were registered. Only 1 study registered sufficiently precise outcome information to compare with published outcomes, and registered and published outcomes were discrepant in that study. Greater attention to outcome reporting and trial registration by researchers, peer reviewers, and journal editors will increase the likelihood that effective behavioral health interventions are readily identified and made available to patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Adaptive adjustment of the randomization ratio using historical control data

PubMed Central

Hobbs, Brian P.; Carlin, Bradley P.; Sargent, Daniel J.

2013-01-01

Background Prospective trial design often occurs in the presence of “acceptable” [1] historical control data. Typically this data is only utilized for treatment comparison in a posteriori retrospective analysis to estimate population-averaged effects in a random-effects meta-analysis. Purpose We propose and investigate an adaptive trial design in the context of an actual randomized controlled colorectal cancer trial. This trial, originally reported by Goldberg et al. [2], succeeded a similar trial reported by Saltz et al. [3], and used a control therapy identical to that tested (and found beneficial) in the Saltz trial. Methods The proposed trial implements an adaptive randomization procedure for allocating patients aimed at balancing total information (concurrent and historical) among the study arms. This is accomplished by assigning more patients to receive the novel therapy in the absence of strong evidence for heterogeneity among the concurrent and historical controls. Allocation probabilities adapt as a function of the effective historical sample size (EHSS) characterizing relative informativeness defined in the context of a piecewise exponential model for evaluating time to disease progression. Commensurate priors [4] are utilized to assess historical and concurrent heterogeneity at interim analyses and to borrow strength from the historical data in the final analysis. The adaptive trial’s frequentist properties are simulated using the actual patient-level historical control data from the Saltz trial and the actual enrollment dates for patients enrolled into the Goldberg trial. Results Assessing concurrent and historical heterogeneity at interim analyses and balancing total information with the adaptive randomization procedure leads to trials that on average assign more new patients to the novel treatment when the historical controls are unbiased or slightly biased compared to the concurrent controls. Large magnitudes of bias lead to approximately equal allocation of patients among the treatment arms. Using the proposed commensurate prior model to borrow strength from the historical data, after balancing total information with the adaptive randomization procedure, provides admissible estimators of the novel treatment effect with desirable bias-variance trade-offs. Limitations Adaptive randomization methods in general are sensitive to population drift and more suitable for trials that initiate with gradual enrollment. Balancing information among study arms in time-to-event analyses is difficult in the presence of informative right-censoring. Conclusions The proposed design could prove important in trials that follow recent evaluations of a control therapy. Efficient use of the historical controls is especially important in contexts where reliance on pre-existing information is unavoidable because the control therapy is exceptionally hazardous, expensive, or the disease is rare. PMID:23690095

Randomized Control Trials on the Dynamic Geometry Approach

ERIC Educational Resources Information Center

Jiang, Zhonghong; White, Alexander; Rosenwasser, Alana

2011-01-01

The project reported here is conducting repeated randomized control trials of an approach to high school geometry that utilizes Dynamic Geometry (DG) software to supplement ordinary instructional practices. It compares effects of that intervention with standard instruction that does not make use of computer drawing/exploration tools. The basic…

Protocol for north of England and Scotland study of tonsillectomy and adeno-tonsillectomy in children (NESSTAC). A pragmatic randomised controlled trial comparing surgical intervention with conventional medical treatment in children with recurrent sore throats

PubMed Central

Bond, John; Wilson, Janet; Eccles, Martin; Vanoli, Alessandra; Steen, Nick; Clarke, Ray; Zarod, Andrew; Lock, Catherine; Brittain, Katie; Speed, Chris; Rousseau, Nikki

2006-01-01

Background Uncertainties surrounding the effectiveness and cost-effectiveness of childhood tonsillectomy for recurrent sore throat led the NHS Health Technology Assessment Programme to commission this research to evaluate the effectiveness and cost-effectiveness of tonsillectomy and adeno-tonsillectomy in comparison with standard non-surgical management in children aged under 16 with recurrent throat infections. The aim is to evaluate if tonsillectomy and adeno-tonsillectomy reduces the number of episodes of sore throats among children to a clinically significant extent. Methods/design A simple prospective pragmatic randomised controlled trial with economic analysis and prospective cohort study of non-trial participants comparing surgical intervention with conventional medical treatment. The treatment arm will receive tonsillectomy and adeno-tonsillectomy while in the control arm non-surgical conventional medical treatment only will be used. The primary outcome measure will be reported number of episodes of sore throat over two years with secondary outcomes measures of reported number of episodes of sore throat, otitis media and upper respiratory tract infection which invoke a GP consultation; reported number of symptom-free days; reported severity of sore throats and surgical and anaesthetic morbidity. The study will take place in five hospitals in the UK. The trial population will be 406 children aged 4–15 on their last birthday with recurrent sore throat referred by primary care to the 5 otolaryngology departments. The duration of the study is seven years (July 2001- July 2008). Discussion As with all pragmatic randomised controlled trials it is impossible to control the external environment in which the research is taking place. Since this trial began a number of factors have arisen which could affect the outcome including; a reduction in the incidence of respiratory tract infections, marked socio-economic differences in consultation rates, the results from the National Prospective Tonsillectomy Audit and the Government's waiting list initiatives. PMID:16899123

Protocol for north of England and Scotland study of tonsillectomy and adeno-tonsillectomy in children (NESSTAC). A pragmatic randomised controlled trial comparing surgical intervention with conventional medical treatment in children with recurrent sore throats.

PubMed

Bond, John; Wilson, Janet; Eccles, Martin; Vanoli, Alessandra; Steen, Nick; Clarke, Ray; Zarod, Andrew; Lock, Catherine; Brittain, Katie; Speed, Chris; Rousseau, Nikki

2006-08-09

Uncertainties surrounding the effectiveness and cost-effectiveness of childhood tonsillectomy for recurrent sore throat led the NHS Health Technology Assessment Programme to commission this research to evaluate the effectiveness and cost-effectiveness of tonsillectomy and adeno-tonsillectomy in comparison with standard non-surgical management in children aged under 16 with recurrent throat infections. The aim is to evaluate if tonsillectomy and adeno-tonsillectomy reduces the number of episodes of sore throats among children to a clinically significant extent. A simple prospective pragmatic randomised controlled trial with economic analysis and prospective cohort study of non-trial participants comparing surgical intervention with conventional medical treatment. The treatment arm will receive tonsillectomy and adeno-tonsillectomy while in the control arm non-surgical conventional medical treatment only will be used. The primary outcome measure will be reported number of episodes of sore throat over two years with secondary outcomes measures of reported number of episodes of sore throat, otitis media and upper respiratory tract infection which invoke a GP consultation; reported number of symptom-free days; reported severity of sore throats and surgical and anaesthetic morbidity. The study will take place in five hospitals in the UK. The trial population will be 406 children aged 4-15 on their last birthday with recurrent sore throat referred by primary care to the 5 otolaryngology departments. The duration of the study is seven years (July 2001-July 2008). As with all pragmatic randomised controlled trials it is impossible to control the external environment in which the research is taking place. Since this trial began a number of factors have arisen which could affect the outcome including; a reduction in the incidence of respiratory tract infections, marked socio-economic differences in consultation rates, the results from the National Prospective Tonsillectomy Audit and the Government's waiting list initiatives.

Decline in placebo-controlled trial results suggests new directions for comparative effectiveness research.

PubMed

Olfson, Mark; Marcus, Steven C

2013-06-01

The Affordable Care Act offers strong support for comparative effectiveness research, which entails comparisons among active treatments, to provide the foundation for evidence-based practice. Traditionally, a key form of research into the effectiveness of therapeutic treatments has been placebo-controlled trials, in which a specified treatment is compared to placebo. These trials feature high-contrast comparisons between treatments. Historical trends in placebo-controlled trials have been evaluated to help guide the comparative effectiveness research agenda. We investigated placebo-controlled trials reported in four leading medical journals between 1966 and 2010. We found that there was a significant decline in average effect size or average difference in efficacy (the ability to produce a desired effect) between the active treatment and placebo. On average, recently studied treatments offered only small benefits in efficacy over placebo. A decline in effect sizes in conventional placebo-controlled trials supports an increased emphasis on other avenues of research, including comparative studies on the safety, tolerability, and cost of treatments with established efficacy.

Outcome selection and role of patient reported outcomes in contemporary cardiovascular trials: systematic review

PubMed Central

Malhotra, Aneil; Banning, Adrian P; Jenkinson, Crispin

2010-01-01

Objectives To systematically assess the type of outcomes selected and the prevalence of patient reported outcomes in contemporary cardiovascular trials and to quantify any misuse or underuse of patient reported outcomes using a specially developed tool that would allow estimation of the relevance of such outcomes to clinical decision making. Design Systematic review. Data sources Medline and Embase. Study selection Randomised controlled trials of the treatment for or prevention of cardiovascular disease published in 10 leading general medical and cardiology journals from January 2005 to December 2008. Results Primary outcomes were patient important (death, morbidity, or patient reported outcomes) in only 93 of 413 trials (23%, SE 2%), whereas another 92 (22%, SE 2%) combined these outcomes with other less important ones into a composite. Sixty five trials (16%; SE 2%) used at least one instrument to measure patient reported outcomes, mostly in trials where such information would have been important or crucial for clinical decision making (52 trials). Patient reported outcomes were judged to be of little incremental value to a large number of, mostly explanatory, cardiovascular trials (152 trials). However, many trials in which patient reported outcomes would have been important or crucial for clinical decision making did not report such outcomes (122 of 174 trials, 70%). These included several trials that primarily aimed to improve symptoms or functional status, trials that tested interventions with a considerable potential for causing harm (mainly bleeding) that were not meaningfully measured, and trials with composite outcomes that were dominated by outcomes of questionable importance to patients. Conclusions Despite a continued rise in the reporting of patient reported outcomes with no evidence for their misuse in more recent cardiovascular trials, they seem to be still underused once their relevance to clinical decision making has been taken into account. This was largely explained by inappropriate use of composite outcomes and inadequate measurement of harms. PMID:21041324

CONSORT for Reporting Randomized Controlled Trials in Journal and Conference Abstracts: Explanation and Elaboration

PubMed Central

Hopewell, Sally; Clarke, Mike; Moher, David; Wager, Elizabeth; Middleton, Philippa; Altman, Douglas G; Schulz, Kenneth F

2008-01-01

Background Clear, transparent, and sufficiently detailed abstracts of conferences and journal articles related to randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract. Here, we extend the CONSORT (Consolidated Standards of Reporting Trials) Statement to develop a minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract. Methods and Findings We generated a list of items from existing quality assessment tools and empirical evidence. A three-round, modified-Delphi process was used to select items. In all, 109 participants were invited to participate in an electronic survey; the response rate was 61%. Survey results were presented at a meeting of the CONSORT Group in Montebello, Canada, January 2007, involving 26 participants, including clinical trialists, statisticians, epidemiologists, and biomedical editors. Checklist items were discussed for eligibility into the final checklist. The checklist was then revised to ensure that it reflected discussions held during and subsequent to the meeting. CONSORT for Abstracts recommends that abstracts relating to RCTs have a structured format. Items should include details of trial objectives; trial design (e.g., method of allocation, blinding/masking); trial participants (i.e., description, numbers randomized, and number analyzed); interventions intended for each randomized group and their impact on primary efficacy outcomes and harms; trial conclusions; trial registration name and number; and source of funding. We recommend the checklist be used in conjunction with this explanatory document, which includes examples of good reporting, rationale, and evidence, when available, for the inclusion of each item. Conclusions CONSORT for Abstracts aims to improve reporting of abstracts of RCTs published in journal articles and conference proceedings. It will help authors of abstracts of these trials provide the detail and clarity needed by readers wishing to assess a trial's validity and the applicability of its results. PMID:18215107

[CONSORT for reporting randomized controlled trials in journal and conference abstracts: explanation and elaboration].

PubMed

Hopewel, Sally; Clarke, Mike; Moher, David; Wager, Elizabeth; Middleton, Philippa; Altman, Douglas G; Schulz, Kenneth F; The, Consort Group

2008-03-01

Clear, transparent, and sufficiently detailed abstracts of conferences and journal articles related to randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract. Here, we extend the CONSORT (Consolidated Standards of Reporting Trials) Statement to develop a minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract. We generated a list of items from existing quality assessment tools and empirical evidence. A three-round, modified-Delphi process was used to select items. In all, 109 participants were invited to participate in an electronic survey; the response rate was 61%. Survey results were presented at a meeting of the CONSORT Group in Montebello, Canada, January 2007, involving 26 participants, including clinical trialists, statisticians, epidemiologists, and biomedical editors. Checklist items were discussed for eligibility into the final checklist. The checklist was then revised to ensure that it reflected discussions held during and subsequent to the meeting. CONSORT for Abstracts recommends that abstracts relating to RCTs have a structured format. Items should include details of trial objectives; trial design (e.g., method of allocation, blinding/masking); trial participants (i.e., description, numbers randomized, and number analyzed); interventions intended for each randomized group and their impact on primary efficacy outcomes and harms; trial conclusions; trial registration name and number; and source of funding. We recommend the checklist be used in conjunction with this explanatory document, which includes examples of good reporting, rationale, and evidence, when available, for the inclusion of each item. CONSORT for Abstracts aims to improve reporting of abstracts of RCTs published in journal articles and conference proceedings. It will help authors of abstracts of these trials provide the detail and clarity needed by readers wishing to assess a trial's validity and the applicability of its results.

WWC Review of the Report "Closing the Achievement Gap through Modification of Neurocognitive and Neuroendocrine Function: Results from a Cluster Randomized Controlled Trial of an Innovative Approach to the Education of Children in Kindergarten." What Works Clearinghouse Single Study Review

ERIC Educational Resources Information Center

What Works Clearinghouse, 2015

2015-01-01

In the 2014 report, "Closing the Achievement Gap Through Modification of Neurocognitive and Neuroendocrine Function: Results from a Cluster Randomized Controlled Trial of an Innovative Approach to the Education of Children in Kindergarten," researchers examined the impacts of "Tools of the Mind" on cognitive and academic…

A Randomized, Placebo-Controlled Trial of D-Cycloserine for the Enhancementof Social Skills Training in Pervasive Developmental Disorders

DTIC Science & Technology

2015-11-01

report (4) Abstracts: Nothing to report b. List presentations made during the last year (international, national, local societies, military meetings...disorders (ASDs). We evaluated the efficacy, tolerability, and last effects of DCS given one hour prior to each of 10 weekly SST sessions for the...treatment of social impairment in 68 children and young adolescents (ages 5-11 years ) with ASDs during a randomized placebo-controlled trial. The

The Quality of Reports of Randomized Controlled Trials Varies between Subdisciplines of Physiotherapy.

PubMed

Moseley, Anne M; Elkins, Mark R; Janer-Duncan, Lee; Hush, Julia M

2014-01-01

The quality of reports of randomized trials of physiotherapy interventions varies by year of publication, language of publication and whether the intervention being assessed is a type of electrotherapy. Whether it also varies by subdiscipline of physiotherapy has not yet been systematically investigated. The purpose of this study was to determine whether the quality of trial reports varies according to the subdiscipline of physiotherapy being evaluated. Reports of physiotherapy trials were identified using the Physiotherapy Evidence Database (PEDro). Quality of the trial report was evaluated using the PEDro scale (total PEDro score and 11 individual PEDro scale items). Multiple linear and logistic regressions were used to predict the quality of trial reports, with subdisciplines, time since publication, language of publication, and evaluation of electrotherapy as independent variables in the model. Total PEDro scores are higher when trial reports are more recent; are published in English; investigate electrotherapy; and are in the subdisciplines of musculoskeletal, neurology, cardiopulmonary, gerontology, continence and women's health, orthopaedics, or paediatrics. Trials in the subdisciplines of ergonomics and occupational health, oncology, and sports are associated with lower total PEDro scores. The musculoskeletal subdiscipline had a positive association with six of the PEDro scale items, more than any other subdiscipline. There is scope to improve the quality of the conduct and reporting of randomized trials across all the physiotherapy subdisciplines. This study provides specific information about how each physiotherapy subdiscipline can improve trial quality.

The Quality of Reports of Randomized Controlled Trials Varies between Subdisciplines of Physiotherapy

PubMed Central

Elkins, Mark R.; Janer-Duncan, Lee; Hush, Julia M.

2014-01-01

ABSTRACT Purpose: The quality of reports of randomized trials of physiotherapy interventions varies by year of publication, language of publication and whether the intervention being assessed is a type of electrotherapy. Whether it also varies by subdiscipline of physiotherapy has not yet been systematically investigated. The purpose of this study was to determine whether the quality of trial reports varies according to the subdiscipline of physiotherapy being evaluated. Methods: Reports of physiotherapy trials were identified using the Physiotherapy Evidence Database (PEDro). Quality of the trial report was evaluated using the PEDro scale (total PEDro score and 11 individual PEDro scale items). Multiple linear and logistic regressions were used to predict the quality of trial reports, with subdisciplines, time since publication, language of publication, and evaluation of electrotherapy as independent variables in the model. Results: Total PEDro scores are higher when trial reports are more recent; are published in English; investigate electrotherapy; and are in the subdisciplines of musculoskeletal, neurology, cardiopulmonary, gerontology, continence and women's health, orthopaedics, or paediatrics. Trials in the subdisciplines of ergonomics and occupational health, oncology, and sports are associated with lower total PEDro scores. The musculoskeletal subdiscipline had a positive association with six of the PEDro scale items, more than any other subdiscipline. Conclusions: There is scope to improve the quality of the conduct and reporting of randomized trials across all the physiotherapy subdisciplines. This study provides specific information about how each physiotherapy subdiscipline can improve trial quality. PMID:24719507

Outcome switching in randomized controlled oncology trials reporting on surrogate endpoints: a cross-sectional analysis.

PubMed

Falk Delgado, Alberto; Falk Delgado, Anna

2017-08-23

Inconsistent reporting of clinical trials is well-known in the literature. Despite this, factors associated with poor practice such as outcome switching in clinical trials are poorly understood. We performed a cross-sectional analysis to evaluate the prevalence of, and the factors associated with outcome switching. PubMed and Embase were searched for pharmaceutical randomized controlled trials (RCTs) in oncology reporting on a surrogate primary outcome published in 2015. Outcome switching was present in 18% (39/216). First-author male sex was significantly more likely associated with outcome switching compared to female sex with an OR of 3.05 (95% CI 1.07-8.64, p = 0.04) after multivariable adjustment. For-profit funded RCTs were less likely associated with outcome switching compared to non-profit funded research with an OR of 0.22 (95% CI 0.07-0.74, p = 0.01). First author male sex was more likely associated with outcome switching compared to female sex in drug oncology RCTs reporting on a primary surrogate endpoint. For-profit funded research was less likely associated with outcome switching compared to research funded by non-profit organizations. Furthermore, 18 percent of drug oncology trials reporting on a surrogate endpoint could have a higher risk of false positive results due to primary outcome switching.

Aggregated data from two double-blind base station provocation studies comparing individuals with idiopathic environmental intolerance with attribution to electromagnetic fields and controls.

PubMed

Eltiti, Stacy; Wallace, Denise; Russo, Riccardo; Fox, Elaine

2015-02-01

Data from two previous studies were aggregated to provide a statistically powerful test of whether exposure to electromagnetic fields (EMFs) produced by telecommunication base stations negatively affects well-being in individuals who report idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) and control participants. A total of 102 IEI-EMF and 237 controls participated in open provocation trials and 88 IEI-EMF and 231 controls went on to complete double-blind trials in which they were exposed to EMFs from a base station emitting either a Global System for Mobile Communication and Universal Mobile Telecommunications System or a Terrestrial Trunked Radio Telecommunications System signal. Both experiments included a comparison sham condition. Visual analog and symptom scales measured subjective well-being. Results showed that IEI-EMF participants reported lower levels of well-being during real compared to sham exposure during open provocation, but not during double-blind trials. Additionally, participants reported lower levels of well-being during high compared to low load trials and this did not interact with radiofrequency-EMF exposure. These findings are consistent with a growing body of literature indicating there is no causal relationship between short-term exposure to EMFs and subjective well-being in members of the public whether or not they report perceived sensitivity to EMFs. © 2015 Wiley Periodicals, Inc.

Contemporary Australian outcomes in childhood and adolescent type 1 diabetes: 10 years post the Diabetes Control and Complications Trial.

PubMed

Ambler, Geoffrey R; Fairchild, Jan; Craig, Maria E; Cameron, Fergus J

2006-01-01

The reporting of the results of the Diabetes Control and Complications Trial in 1993 has led to a major reappraisal of management practices and outcomes in type 1 diabetes in children and adolescents. A considerable body of outcome data has been generated from Australia in this post-Diabetes Control and Complications Trial era relating to incidence, metabolic control, growth, hypoglycaemia, microvascular and macrovascular complications, cognition, behaviour and quality of life. These data are important in planning future management strategies and resource allocation and as a basis for future research.

Acupuncture for Bell's palsy.

PubMed

Chen, Ning; Zhou, Muke; He, Li; Zhou, Dong; Li, N

2010-08-04

Bell's palsy or idiopathic facial palsy is an acute facial paralysis due to inflammation of the facial nerve. A number of studies published in China have suggested acupuncture is beneficial for facial palsy. The objective of this review was to examine the efficacy of acupuncture in hastening recovery and reducing long-term morbidity from Bell's palsy. We updated the searches of the Cochrane Neuromuscular Disease Group Trials Specialized Register (24 May 2010), The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2010), MEDLINE (January 1966 to May 2010), EMBASE (January 1980 to May 2010), AMED (January 1985 to May 2010), LILACS (from January 1982 to May 2010) and the Chinese Biomedical Retrieval System (January 1978 to May 2010) for randomised controlled trials using 'Bell's palsy' and its synonyms, 'idiopathic facial paralysis' or 'facial palsy' as well as search terms including 'acupuncture'. Chinese journals in which we thought we might find randomised controlled trials relevant to our study were handsearched. We reviewed the bibliographies of the randomised trials and contacted the authors and known experts in the field to identify additional published or unpublished data. We included all randomised controlled trials involving acupuncture by needle insertion in the treatment of Bell's palsy irrespective of any language restrictions. Two review authors identified potential articles from the literature search, extracted data and assessed quality of each trial independently. All disagreements were resolved by discussion between the review authors. The literature search and handsearching identified 49 potentially relevant articles. Of these, six RCTs were included involving 537 participants with Bell's palsy. Two more possible trials were identified in the update than the previous version of this systematic review, but both were excluded because they were not real RCTs. Of the six included trials, five used acupuncture while the other one used acupuncture combined with drugs. No trial reported on the outcomes specified for this review. Harmful side effects were not reported in any of the trials. Poor quality caused by flaws in study design or reporting (including uncertain method of randomisation, allocation concealment and blinding) and clinical differences between trials prevented reliable conclusions about the efficacy of acupuncture. The quality of the included trials was inadequate to allow any conclusion about the efficacy of acupuncture. More research with high quality trials is needed.

Do Published Data in Trials Assessing Cancer Drugs Reflect the Real Picture of Efficacy and Safety?

PubMed

Lv, Jia-Wei; Chen, Yu-Pei; Zhou, Guan-Qun; Liu, Xu; Guo, Ying; Mao, Yan-Ping; Ma, Jun; Sun, Ying

2017-11-01

Background: The reporting quality of publications is of vital importance to ensure accurate evidence dissemination. This study aimed to compare the consistency of results reporting between the ClinicalTrials.gov results database and the respective matching publications. Methods: We identified 323 phase III/IV cancer drug trials with a randomized controlled design and searched PubMed for publications in a 50% random sample (n=160). Data were extracted independently from ClinicalTrials.gov and publications. A scoring system was applied to determine characteristics associated with reporting quality. Results: Of 117 reviewed trials with publications, result reporting was significantly more complete in ClinicalTrials.gov for efficacy measurement (92.3% vs 90.6%), serious adverse events (SAEs; 100% vs 43.6%), and other adverse events (OAEs; 100% vs 62.4%). For trials with both posted and published results for design information (n=117), efficacy measurements (n=98), SAEs (n=51), and OAEs (n=73), discrepancies were found in 16 (13.7%), 38 (38.8%), 26 (51.0%), and 54 (74.0%) trials, respectively. Overreporting of treatment effects (7 trials) and alteration of primary end points favoring statistically significant outcomes (11 trials) were the major discrepancies in efficacy reporting; incomplete (66 trials) and underreporting (20 trials) of SAEs were the predominant issues in benefit/risk reporting. Median quality score was 21 (range, 14-28). Trials that had parallel assignment, were phase IV, had primary funding by industry, were completed after 2009, and had earlier results posted possessed better reporting quality. Conclusions: Although most trials showed reasonable completeness and consistency, some discrepancies are prevalent and persistent, jeopardizing evidence-based decision-making. Our findings highlight the need to consult results systematically from both ClinicalTrials.gov and publications. Copyright © 2017 by the National Comprehensive Cancer Network.

Lifestyle Advice Combined with Personalized Estimates of Genetic or Phenotypic Risk of Type 2 Diabetes, and Objectively Measured Physical Activity: A Randomized Controlled Trial

PubMed Central

van Sluijs, Esther M. F.; Marteau, Theresa M.; Sutton, Stephen

2016-01-01

Background Information about genetic and phenotypic risk of type 2 diabetes is now widely available and is being incorporated into disease prevention programs. Whether such information motivates behavior change or has adverse effects is uncertain. We examined the effect of communicating an estimate of genetic or phenotypic risk of type 2 diabetes in a parallel group, open, randomized controlled trial. Methods and Findings We recruited 569 healthy middle-aged adults from the Fenland Study, an ongoing population-based, observational study in the east of England (Cambridgeshire, UK). We used a computer-generated random list to assign participants in blocks of six to receive either standard lifestyle advice alone (control group, n = 190) or in combination with a genetic (n = 189) or a phenotypic (n = 190) risk estimate for type 2 diabetes (intervention groups). After 8 wk, we measured the primary outcome, objectively measured physical activity (kJ/kg/day), and also measured several secondary outcomes (including self-reported diet, self-reported weight, worry, anxiety, and perceived risk). The study was powered to detect a between-group difference of 4.1 kJ/kg/d at follow-up. 557 (98%) participants completed the trial. There were no significant intervention effects on physical activity (difference in adjusted mean change from baseline: genetic risk group versus control group 0.85 kJ/kg/d (95% CI −2.07 to 3.77, p = 0.57); phenotypic risk group versus control group 1.32 (95% CI −1.61 to 4.25, p = 0.38); and genetic risk group versus phenotypic risk group −0.47 (95% CI −3.40 to 2.46, p = 0.75). No significant differences in self-reported diet, self-reported weight, worry, and anxiety were observed between trial groups. Estimates of perceived risk were significantly more accurate among those who received risk information than among those who did not. Key limitations include the recruitment of a sample that may not be representative of the UK population, use of self-reported secondary outcome measures, and a short follow-up period. Conclusions In this study, we did not observe short-term changes in behavior associated with the communication of an estimate of genetic or phenotypic risk of type 2 diabetes. We also did not observe changes in worry or anxiety in the study population. Additional research is needed to investigate the conditions under which risk information might enhance preventive strategies. (Current Controlled Trials ISRCTN09650496; Date applied: April 4, 2011; Date assigned: June 10, 2011). Trial Registration The trial is registered with Current Controlled Trials, ISRCTN09650496. PMID:27898672

Reporting of symptoms in randomized controlled trials of atopic eczema treatments: a systematic review.

PubMed

Gerbens, L A A; Chalmers, J R; Rogers, N K; Nankervis, H; Spuls, P I

2016-10-01

'Symptoms' is a core outcome domain for atopic eczema (AE) trials, agreed by consensus as part of the Harmonising Outcome Measures for Eczema (HOME) initiative. To standardize and validate the core domain symptoms and symptom instruments for AE trials the HOME roadmap is followed. Its first step is to establish if and how symptoms have been measured in published AE treatment trials. Therefore the Global Resource for Eczema Trials database was used to collect all randomized controlled trials (RCTs) of treatments for AE between January 2000 and April 2014. Study selection and data extraction were performed by three reviewers independently. We identified the use of symptoms in 295 of 378 trials (78%). Symptoms as a primary end point were applied by 147 RCTs (50%). Seventeen different symptoms were measured, but mostly itch and sleep loss. Symptoms were assessed by only 37% of trials by a stand-alone symptom measurement. Overall 63% of RCTs used a composite instrument, and 30 different instruments were identified. The Scoring Atopic Dermatitis (SCORAD) index was the most commonly applied, but only 23% of RCTs reported the SCORAD symptom score separately. This systematic review demonstrates that symptoms, most frequently itch and sleep loss, are commonly reported in AE treatment trials, but are measured using many different instruments. Often symptoms are evaluated as part of a composite instrument, and currently it is not possible to extract symptoms-only data from most published studies. Future trials should report symptom scores to permit meta-analysis of the core outcomes. © 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

A randomized, placebo-controlled trial of patient education for acute low back pain (PREVENT Trial): statistical analysis plan.

PubMed

Traeger, Adrian C; Skinner, Ian W; Hübscher, Markus; Lee, Hopin; Moseley, G Lorimer; Nicholas, Michael K; Henschke, Nicholas; Refshauge, Kathryn M; Blyth, Fiona M; Main, Chris J; Hush, Julia M; Pearce, Garry; Lo, Serigne; McAuley, James H

Statistical analysis plans increase the transparency of decisions made in the analysis of clinical trial results. The purpose of this paper is to detail the planned analyses for the PREVENT trial, a randomized, placebo-controlled trial of patient education for acute low back pain. We report the pre-specified principles, methods, and procedures to be adhered to in the main analysis of the PREVENT trial data. The primary outcome analysis will be based on Mixed Models for Repeated Measures (MMRM), which can test treatment effects at specific time points, and the assumptions of this analysis are outlined. We also outline the treatment of secondary outcomes and planned sensitivity analyses. We provide decisions regarding the treatment of missing data, handling of descriptive and process measure data, and blinded review procedures. Making public the pre-specified statistical analysis plan for the PREVENT trial minimizes the potential for bias in the analysis of trial data, and in the interpretation and reporting of trial results. ACTRN12612001180808 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612001180808). Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Enhancing access to reports of randomized trials published world-wide – the contribution of EMBASE records to the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library

PubMed Central

Lefebvre, Carol; Eisinga, Anne; McDonald, Steve; Paul, Nina

2008-01-01

Background Randomized trials are essential in assessing the effects of healthcare interventions and are a key component in systematic reviews of effectiveness. Searching for reports of randomized trials in databases is problematic due to the absence of appropriate indexing terms until the 1990s and inconsistent application of these indexing terms thereafter. Objectives The objectives of this study are to devise a search strategy for identifying reports of randomized trials in EMBASE which are not already indexed as trials in MEDLINE and to make these reports easily accessible by including them in the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, with the permission of Elsevier, the publishers of EMBASE. Methods A highly sensitive search strategy was designed for EMBASE based on free-text and thesaurus terms which occurred frequently in the titles, abstracts, EMTREE terms (or some combination of these) of reports of trials indexed in EMBASE. This search strategy was run against EMBASE from 1980 to 2005 (1974 to 2005 for four of the terms) and records retrieved by the search, which were not already indexed as randomized trials in MEDLINE, were downloaded from EMBASE, printed and read. An analysis of the language of publication was conducted for the reports of trials published in 2005 (the most recent year completed at the time of this study). Results Twenty-two search terms were used (including nine which were later rejected due to poor cumulative precision). More than a third of a million records were downloaded and scanned and approximately 80,000 reports of trials were identified which were not already indexed as randomized trials in MEDLINE. These are now easily identifiable in CENTRAL, in The Cochrane Library. Cumulative sensitivity ranged from 0.1% to 60% and cumulative precision ranged from 8% to 61%. The truncated term 'random$' identified 60% of the total number of reports of trials but only 35% of the more than 130,000 records retrieved by this term were reports of trials. The language analysis for the sample year 2005 indicated that of the 18,427 reports indexed as randomized trials in MEDLINE, 959 (5%) were in languages other than English. The EMBASE search identified an additional 658 reports in languages other than English, of which the highest number were in Chinese (320). Conclusion The results of the search to date have greatly increased access to reports of trials in EMBASE, especially in some languages other than English. The search strategy used was subjectively derived from a small 'gold standard' set of test records and was not validated in an independent test set. We intend to design an objectively-derived validated search strategy using logistic regression based on the frequency of occurrence of terms in the approximately 80,000 reports of randomized trials identified compared with the frequency of these terms across the entire EMBASE database. PMID:18826567

Trial of Propranolol in Children and Youth with ASD and Predictors of Response

DTIC Science & Technology

2017-07-01

youth) predicts treatment response. The design for both aims will be a double-blinded, placebo- controlled trial, 12 weeks in duration, with...the youth) predicts treatment response. The design for both aims will be a double-blinded, placebo- controlled trial, 12 weeks in duration, with...Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704

Neuroreflexotherapy for nonspecific low back pain: a systematic review.

PubMed

Urrútia, Gerard; Burton, Kim; Morral, Antoni; Bonfill, Xavier; Zanoli, Gustavo

2005-03-15

Systematic review. To assess the effectiveness of neuroreflexotherapy (NRT) for low back pain (LBP). Few of the alternatives for the management of LBP have a firm base of evidence for their effectiveness. Recently, a new intervention known as NRT has been developed in Spain and has been reported to have favorable results. Searches were undertaken according to Cochrane Collaboration guidelines, and randomized controlled trials that evaluated NRT as treatment for patients with nonspecific LBP were included. A qualitative synthesis and an assessment of methodological quality were undertaken. Three randomized controlled trials were included, with 125 and 148 subjects in control and intervention groups, respectively. NRT was compared with sham in two trials and standard care in one. Individuals receiving active NRT showed significantly better outcomes for pain, mobility, disability, medication use, consumption of resources, and costs. No major side effects were reported by those receiving active NRT. NRT appears to be a safe and effective intervention for nonspecific LBP. This conclusion is limited to three trials conducted by a small number of experienced clinicians. Further trials in other settings are needed to determine whether these favorable results can be generalized.

Chinese herbal medicine for diabetic peripheral neuropathy.

PubMed

Chen, Wei; Zhang, Yin; Li, Xinxue; Yang, Guoyan; Liu, Jian Ping

2013-10-06

Chinese herbal medicine is frequently used for treating diabetic peripheral neuropathy in China. Many controlled trials have been undertaken to investigate its efficacy.This is an update of a Cochrane review that was first published in the year 2011. To assess the beneficial effects and harms of Chinese herbal medicine for people with diabetic peripheral neuropathy. On 14 May 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register CENTRAL (2012, Issue 4 in The Cochrane Library), MEDLINE (January 1966 to May 2012), EMBASE (January 1980 to May 2012), AMED (January 1985 to May 2012) and in October 2012, the Chinese Biomedical Database (CBM) (1979 to October 2012), Chinese National Knowledge Infrastructure Database (CNKI) (1979 to October 2012), and VIP Chinese Science and Technique Journals Database (1989 to October 2012). We searched for unpublished literature in the Chinese Conference Papers Database, and Chinese Dissertation Database (from inception to October 2012). There were no language or publication restrictions. We included randomised controlled trials of Chinese herbal medicine (with a minimum of four weeks treatment duration) for people with diabetic peripheral neuropathy compared with placebo, no intervention, or conventional interventions. Trials of herbal medicine plus a conventional drug versus the drug alone were also included. Two authors independently extracted data and evaluated trial quality. We contacted study authors for additional information. Forty-nine randomised trials involving 3639 participants were included. All trials were conducted and published in China. Thirty-eight different herbal medicines were tested in these trials, including four single herbs (extracts from a single herb), eight traditional Chinese patent medicines, and 26 self concocted Chinese herbal compound prescriptions. The trials reported on global symptom improvement (including improvement in numbness or pain) and changes in nerve conduction velocity. The positive results described from the 49 studies of low quality are of questionable significance. There was inadequate reporting on adverse events in the included trials. Eighteen trials found no adverse events. Two trials reported adverse events: adverse events occurred in the control group in one trial, and in the other it was unclear in which group the adverse events occurred. 29 trials did not mention whether they monitored adverse events. Conclusions cannot be drawn from this review about the safety of herbal medicines, due to inadequate reporting. Most of the trials were of very low methodological quality and therefore the interpretation of any positive findings for the efficacy of the included Chinese herbal medicines for treating diabetic peripheral neuropathy should be made with caution. Based on this systematic review, there is no evidence to support the objective effectiveness and safety of Chinese herbal medicines for diabetic peripheral neuropathy. No well-designed, randomised, placebo controlled trial with objective outcome measures has been conducted.

What can qualitative research do for randomised controlled trials? A systematic mapping review

PubMed Central

O'Cathain, A; Thomas, K J; Drabble, S J; Rudolph, A; Hewison, J

2013-01-01

Objective To develop an empirically based framework of the aspects of randomised controlled trials addressed by qualitative research. Design Systematic mapping review of qualitative research undertaken with randomised controlled trials and published in peer-reviewed journals. Data sources MEDLINE, PreMEDLINE, EMBASE, the Cochrane Library, Health Technology Assessment, PsycINFO, CINAHL, British Nursing Index, Social Sciences Citation Index and ASSIA. Eligibility criteria Articles reporting qualitative research undertaken with trials published between 2008 and September 2010; health research, reported in English. Results 296 articles met the inclusion criteria. Articles focused on 22 aspects of the trial within five broad categories. Some articles focused on more than one aspect of the trial, totalling 356 examples. The qualitative research focused on the intervention being trialled (71%, 254/356); the design, process and conduct of the trial (15%, 54/356); the outcomes of the trial (1%, 5/356); the measures used in the trial (3%, 10/356); and the target condition for the trial (9%, 33/356). A minority of the qualitative research was undertaken at the pretrial stage (28%, 82/296). The value of the qualitative research to the trial itself was not always made explicit within the articles. The potential value included optimising the intervention and trial conduct, facilitating interpretation of the trial findings, helping trialists to be sensitive to the human beings involved in trials, and saving money by steering researchers towards interventions more likely to be effective in future trials. Conclusions A large amount of qualitative research undertaken with specific trials has been published, addressing a wide range of aspects of trials, with the potential to improve the endeavour of generating evidence of effectiveness of health interventions. Researchers can increase the impact of this work on trials by undertaking more of it at the pretrial stage and being explicit within their articles about the learning for trials and evidence-based practice. PMID:23794542

Differences in Reporting of Analyses in Internal Company Documents Versus Published Trial Reports: Comparisons in Industry-Sponsored Trials in Off-Label Uses of Gabapentin

PubMed Central

Vedula, S. Swaroop; Li, Tianjing; Dickersin, Kay

2013-01-01

Background Details about the type of analysis (e.g., intent to treat [ITT]) and definitions (i.e., criteria for including participants in the analysis) are necessary for interpreting a clinical trial's findings. Our objective was to compare the description of types of analyses and criteria for including participants in the publication (i.e., what was reported) with descriptions in the corresponding internal company documents (i.e., what was planned and what was done). Trials were for off-label uses of gabapentin sponsored by Pfizer and Parke-Davis, and documents were obtained through litigation. Methods and Findings For each trial, we compared internal company documents (protocols, statistical analysis plans, and research reports, all unpublished), with publications. One author extracted data and another verified, with a third person verifying discordant items and a sample of the rest. Extracted data included the number of participants randomized and analyzed for efficacy, and types of analyses for efficacy and safety and their definitions (i.e., criteria for including participants in each type of analysis). We identified 21 trials, 11 of which were published randomized controlled trials, and that provided the documents needed for planned comparisons. For three trials, there was disagreement on the number of randomized participants between the research report and publication. Seven types of efficacy analyses were described in the protocols, statistical analysis plans, and publications, including ITT and six others. The protocol or publication described ITT using six different definitions, resulting in frequent disagreements between the two documents (i.e., different numbers of participants were included in the analyses). Conclusions Descriptions of analyses conducted did not agree between internal company documents and what was publicly reported. Internal company documents provide extensive documentation of methods planned and used, and trial findings, and should be publicly accessible. Reporting standards for randomized controlled trials should recommend transparent descriptions and definitions of analyses performed and which study participants are excluded. Please see later in the article for the Editors' Summary PMID:23382656

Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry.

PubMed

Perlis, Roy H; Perlis, Clifford S; Wu, Yelena; Hwang, Cindy; Joseph, Megan; Nierenberg, Andrew A

2005-10-01

Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied. The extent and implications of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated, to the authors' knowledge. The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry, the Archives of General Psychiatry, the Journal of Clinical Psychopharmacology, and the Journal of Clinical Psychiatry between 2001 and 2003. Among 397 clinical trials identified, 239 (60%) reported receiving funding from a pharmaceutical company or other interested party, and 187 studies (47%) included at least one author with a reported financial conflict of interest. Among the 162 randomized, double-blind, placebo-controlled studies examined, those that reported conflict of interest were 4.9 times more likely to report positive results; this association was significant only among the subset of pharmaceutical industry-funded studies. Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo.

Current Experience in Testing Mitochondrial Nutrients in Disorders Featuring Oxidative Stress and Mitochondrial Dysfunction: Rational Design of Chemoprevention Trials

PubMed Central

Pagano, Giovanni; Aiello Talamanca, Annarita; Castello, Giuseppe; Cordero, Mario D.; d’Ischia, Marco; Gadaleta, Maria Nicola; Pallardó, Federico V.; Petrović, Sandra; Tiano, Luca; Zatterale, Adriana

2014-01-01

An extensive number of pathologies are associated with mitochondrial dysfunction (MDF) and oxidative stress (OS). Thus, mitochondrial cofactors termed “mitochondrial nutrients” (MN), such as α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and l-carnitine (CARN) (or its derivatives) have been tested in a number of clinical trials, and this review is focused on the use of MN-based clinical trials. The papers reporting on MN-based clinical trials were retrieved in MedLine up to July 2014, and evaluated for the following endpoints: (a) treated diseases; (b) dosages, number of enrolled patients and duration of treatment; (c) trial success for each MN or MN combinations as reported by authors. The reports satisfying the above endpoints included total numbers of trials and frequencies of randomized, controlled studies, i.e., 81 trials testing ALA, 107 reports testing CoQ10, and 74 reports testing CARN, while only 7 reports were retrieved testing double MN associations, while no report was found testing a triple MN combination. A total of 28 reports tested MN associations with “classical” antioxidants, such as antioxidant nutrients or drugs. Combinations of MN showed better outcomes than individual MN, suggesting forthcoming clinical studies. The criteria in study design and monitoring MN-based clinical trials are discussed. PMID:25380523

A meta-analysis of randomized controlled trials of azilsartan therapy for blood pressure reduction.

PubMed

Takagi, Hisato; Mizuno, Yusuke; Niwa, Masao; Goto, Shin-Nosuke; Umemoto, Takuya

2014-05-01

Although there have been a number of azilsartan trials, no meta-analysis of the findings has been conducted to date. We performed the first meta-analysis of randomized controlled trials of azilsartan therapy for the reduction of blood pressure (BP) in patients with hypertension. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched from the beginning of the records through March 2013 using web-based search engines (PubMed and OVID). Eligible studies were prospective randomized controlled trials of azilsartan (including azilsartan medoxomil) vs. any control therapy that reported clinic or 24-h mean BP as an outcome. For each study, data for the changes from baseline to final clinic systolic BP (SBP) and diastolic BP (DBP) in both the azilsartan group and the control group were used to generate mean differences and 95% confidence intervals (CIs). Of 27 potentially relevant articles screened initially, 7 reports of randomized trials of azilsartan or azilsartan medoxomil therapy enrolling a total of 6152 patients with hypertension were identified and included. Pooled analysis suggested a significant reduction in BP changes among patients randomized to 40 mg of azilsartan vs. control therapy (clinic SBP: -4.20 mm Hg; 95% CI: -6.05 to -2.35 mm Hg; P<0.00001; clinic DBP: -2.58 mm Hg; 95% CI: -3.69 to -1.48 mm Hg; P<0.00001; 24-h mean SBP: -3.33 mm Hg; 95% CI: -4.74 to -1.93 mm Hg; P<0.00001; 24-h mean DBP: -2.12 mm Hg; 95% CI: -2.74 to -1.49 mm Hg; P<0.00001). In conclusion, azilsartan therapy appears to provide a greater reduction in BP than control therapy in patients with hypertension.

Patient-reported outcomes in randomised controlled trials of colorectal cancer: an analysis determining the availability of robust data to inform clinical decision-making

PubMed Central

Whale, Katie; Fish, Daniel; Fayers, Peter; Cafaro, Valentina; Pusic, Andrea; Blazeby, Jane M.; Efficace, Fabio

2016-01-01

Purpose Randomised controlled trials (RCTs) are the most robust study design measuring outcomes of colorectal cancer (CRC) treatments, but to influence clinical practice trial design and reporting of patient-reported outcomes (PROs) must be of high quality. Objectives of this study were as follows: to examine the quality of PRO reporting in RCTs of CRC treatment; to assess the availability of robust data to inform clinical decision-making; and to investigate whether quality of reporting improved over time. Methods A systematic review from January 2004–February 2012 identified RCTs of CRC treatment describing PROs. Relevant abstracts were screened and manuscripts obtained. Methodological quality was assessed using International Society for Quality of Life Research—patient-reported outcome reporting standards. Changes in reporting quality over time were established by comparison with previous data, and risk of bias was assessed with the Cochrane risk of bias tool. Results Sixty-six RCTs were identified, seven studies (10 %) reported survival benefit favouring the experimental treatment, 35 trials (53 %) identified differences in PROs between treatment groups, and the clinical significance of these differences was discussed in 19 studies (29 %). The most commonly reported treatment type was chemotherapy (n = 45; 68 %). Improvements over time in key methodological issues including the documentation of missing data and the discussion of the clinical significance of PROs were found. Thirteen trials (20 %) had high-quality reporting. Conclusions Whilst improvements in PRO quality reporting over time were found, several recent studies still fail to robustly inform clinical practice. Quality of PRO reporting must continue to improve to maximise the clinical impact of PRO findings. PMID:25910987

Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials.

PubMed

Hou, Li-qiong; Liu, Yun-hui; Zhang, Yi-yi

2015-01-01

Garlic is a common spicy flavouring agent also used for certain therapeutic purposes. Garlic's effects on blood glucose have been the subject of many clinical and animal studies, however, studies reporting hypoglycemic effects of garlic in humans are conflicting. A comprehensive literature search was conducted to identify relevant trials of garlic or garlic extracts on markers of glycemic control [fasting blood glucose (FBG), postprandial glucose (PPG), glycosylated haemoglobin (HbA1c)]. A meta-analysis of the effect of garlic intake on human was done to assess garlic's effectiveness in lowering glucose levels. Two reviewers extracted data from each of the identified studies. Seven eligible randomized controlled trials with 513 subjects were identified. Pooled analyses showed that garlic intake results in a statistically significant lowering in FBG [SMD=-1.67; 95% CI (-2.80, -0.55), p=0.004]. Our pooled analyses did not include PPG control and HbA1c outcomes. Because only 1 study included in the meta-analysis reported PPG variables and only 2 studies reported HbA1c variables. In conclusion, the current meta-analysis showed that the administration of garlic resulted in a significant reduction in FBG concentrations. More trials are needed to investigate the effectiveness of garlic on HbA1c and PPG.

Animal-Assisted Therapy for Post-traumatic Stress Disorder: Lessons from "Case Reports" in Media Stories.

PubMed

Altschuler, Eric L

2018-01-01

Post-traumatic stress disorder (PTSD) can follow war trauma, sexual abuse, other traumas, and even be experienced by commanders for the PTSD of their subordinates. Medications and counseling are sometimes not effective, so new treatments are needed. Some years ago, I suggested that animal-assisted therapy (AAT) (pet therapy) might be beneficial for PTSD. A large randomized controlled trial is underway of canine-assisted therapy for PTSD. Randomized controlled trials are most useful in assessing the efficacy of a medical intervention as these trials control for known and unknown biases. However, due to their very nature and rigorous requirements, knowledge gained from randomized controlled trials may need to be supplemented from other kinds of studies. Here, I note that media reports of AAT for PTSD may effectively function as case reports and suggest further studies: For PTSD, these demonstrate that (1) AAT can be dramatically effective in improving PTSD symptoms; (2) there is the potential for benefit from AAT by multiple different animals besides canines for PTSD; and (3) AAT may have a role in preventing suicide in patients with PTSD. © Association of Military Surgeons of the United States 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Methodological Reporting Quality of Randomized Controlled Trials in 3 Leading Diabetes Journals From 2011 to 2013 Following CONSORT Statement: A System Review.

PubMed

Zhai, Xiao; Wang, Yiran; Mu, Qingchun; Chen, Xiao; Huang, Qin; Wang, Qijin; Li, Ming

2015-07-01

To appraise the current reporting methodological quality of randomized clinical trials (RCTs) in 3 leading diabetes journals.We systematically searched the literature for RCTs in Diabetes Care, Diabetes and Diabetologia from 2011 to 2013.Characteristics were extracted based on Consolidated Standards of Reporting Trials (CONSORT) statement. Generation of allocation, concealment of allocation, intention-to-treat (ITT) analysis and handling of dropouts were defined as primary outcome and "low risk of bias." Sample size calculation, type of intervention, country, number of patients, funding source were also revealed and descriptively reported. Trials were compared among journals, study years, and other characters.A total of 305 RCTs were enrolled in this study. One hundred eight (35.4%) trials reported adequate generation of allocation, 87 (28.5%) trials reported adequate concealment of allocation, 53 (23.8%) trials used ITT analysis, and 130 (58.3%) trials were adequate in handling of dropouts. Only 15 (4.9%) were "low risk of bias" trials. Studies at a large scale (n > 100) or from European presented with more "low risk of bias" trials than those at a small scale (n ≤ 100) or from other regions. No improvements were found in these 3 years.This study shows that methodological reporting quality of RCTs in the major diabetes journals remains suboptimal. It can be further improved to meet and keep up with the standards of the CONSORT statement.

Factors influencing the participation of older people in clinical trials - data analysis from the MAVIS trial.

PubMed

Fearn, P; Avenell, A; McCann, S; Milne, A C; Maclennan, G

2010-01-01

Older people are less likely to be included in clinical trials. Little is known about factors influencing older people's decisions about participating in clinical trials. To examine the views of older people about participating in clinical trials. Postal questionnaire to 801 participants who had completed the MAVIS nutrition trial, aged 65 yrs and older. Closed and open questions sought participants' views about factors important to them when deciding to take part in a trial, features of the MAVIS trial they liked and disliked and changes they would suggest. 540 (59% of MAVIS trial participants) returned the questionnaire. The most important reasons reported for taking part in the trial were helping the research team and medical knowledge, and helping other older people. Participants valued good communication with the trial staff and good organisation. Participants reported concerns about swallowing pills and taking a placebo. Participants reported that future participation in trials could be influenced by poor health status. This questionnaire surveyed older participants who had taken part in a randomised controlled trial. It did not elicit the views of people who had withdrawn or never decided to take part in the trial. Older people report altruistic reasons for taking part in trials. Simple trial designs, which minimise demands on participants and maintain good communications should be preferred. Explaining the need for older people, despite poor health, to participate in trials may help the generalisability of clinical trials.

The Effectiveness of Healthy Start Home Visit Program: Cluster Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Heung, Kitty

2015-01-01

Purpose: The study reported the effectiveness of a home visit program for disadvantaged Chinese parents with preschool children, using cluster randomized controlled trial design. Method: Participants included 191 parents and their children from 24 preschools, with 84 dyads (12 preschools) in the intervention group and 107 dyads (12 preschools) in…

A Randomized Controlled Trial Study of the ABRACADABRA Reading Intervention Program in Grade 1

ERIC Educational Resources Information Center

Savage, Robert S.; Abrami, Philip; Hipps, Geoffrey; Deault, Louise

2009-01-01

This study reports a randomized controlled trial evaluation of a computer-based balanced literacy intervention, ABRACADABRA (http://grover.concordia.ca/abra/version1/abracadabra.html). Children (N = 144) in Grade 1 were exposed either to computer activities for word analysis, text comprehension, and fluency, alongside shared stories (experimental…

A systematic review of natural health product treatment for vitiligo

PubMed Central

Szczurko, Orest; Boon, Heather S

2008-01-01

Background Vitiligo is a hypopigmentation disorder affecting 1 to 4% of the world population. Fifty percent of cases appear before the age of 20 years old, and the disfigurement results in psychiatric morbidity in 16 to 35% of those affected. Methods Our objective was to complete a comprehensive, systematic review of the published scientific literature to identify natural health products (NHP) such as vitamins, herbs and other supplements that may have efficacy in the treatment of vitiligo. We searched eight databases including MEDLINE and EMBASE for vitiligo, leucoderma, and various NHP terms. Prospective controlled clinical human trials were identified and assessed for quality. Results Fifteen clinical trials were identified, and organized into four categories based on the NHP used for treatment. 1) L-phenylalanine monotherapy was assessed in one trial, and as an adjuvant to phototherapy in three trials. All reported beneficial effects. 2) Three clinical trials utilized different traditional Chinese medicine products. Although each traditional Chinese medicine trial reported benefit in the active groups, the quality of the trials was poor. 3) Six trials investigated the use of plants in the treatment of vitiligo, four using plants as photosensitizing agents. The studies provide weak evidence that photosensitizing plants can be effective in conjunction with phototherapy, and moderate evidence that Ginkgo biloba monotherapy can be useful for vitiligo. 4) Two clinical trials investigated the use of vitamins in the therapy of vitiligo. One tested oral cobalamin with folic acid, and found no significant improvement over control. Another trial combined vitamin E with phototherapy and reported significantly better repigmentation over phototherapy only. It was not possible to pool the data from any studies for meta-analytic purposes due to the wide difference in outcome measures and poor quality ofreporting. Conclusion Reports investigating the efficacy of NHPs for vitiligo exist, but are of poor methodological quality and contain significant reporting flaws. L-phenylalanine used with phototherapy, and oral Ginkgo biloba as monotherapy show promise and warrant further investigation. PMID:18498646

Steroids for symptom control in infectious mononucleosis.

PubMed

Rezk, Emtithal; Nofal, Yazan H; Hamzeh, Ammar; Aboujaib, Muhammed F; AlKheder, Mohammad A; Al Hammad, Muhammad F

2015-11-08

Infectious mononucleosis, also known as glandular fever or the kissing disease, is a benign lymphoproliferative disorder. It is a viral infection caused by the Epstein-Barr virus (EBV), a ubiquitous herpes virus that is found in all human societies and cultures. Epidemiological studies show that over 95% of adults worldwide have been infected with EBV. Most cases of symptomatic infectious mononucleosis occur between the ages of 15 and 24 years. It is transmitted through close contact with an EBV shedder, contact with infected saliva or, less commonly, through sexual contact, blood transfusions or by sharing utensils; however, transmission actually occurs less than 10% of the time. Precautions are not needed to prevent transmission because of the high percentage of seropositivity for EBV. Infectious mononucleosis is self-limiting and typically lasts for two to three weeks. Nevertheless, symptoms can last for weeks and occasionally months.Symptoms include fever, lymphadenopathy, pharyngitis, hepatosplenomegaly and fatigue. Symptom relief and rest are commonly recommended treatments. Steroids have been used for their anti-inflammatory effects, but there are no universal criteria for their use. The objectives of the review were to determine the efficacy and safety of steroid therapy versus placebo, usual care or different drug therapies for symptom control in infectious mononucleosis. For this 2015 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (January 1966 to August 2015) and EMBASE (January 1974 to August 2015). We also searched trials registries, however we did not identify any new relevant completed or ongoing trials for inclusion. We combined the MEDLINE search with the Cochrane search strategy for identifying randomised controlled trials (RCTs). We adapted the search terms when searching EMBASE. RCTs comparing the effectiveness of steroids with placebo, usual care, or other interventions for symptom control for people with documented infectious mononucleosis. We used the standard methodological procedures expected by Cochrane. For this 2015 update, we did not identify any new RCTs for inclusion. The previous version of the review included seven trials with a total of 362 participants. Four trials compared the effectiveness of a steroid to placebo for short-term symptom control in glandular fever, one to aspirin, and two trials explored the effects of steroids in conjunction with an antiviral. Heterogeneity between trials prevented a combined analysis.Trials under-reported methodological design features. Three trials did not adequately describe sequence generation for randomisation. Four trials provided adequate details of allocation concealment. All trials were double-blind but four were not specific as to who was blinded. Loss to follow-up was under-reported in four trials, making it difficult to exclude attrition bias. The risk of selective reporting in the included trials was unclear.Across the trials, no benefit was found in 8/10 assessments of health improvement. Two trials found benefit of steroid therapy over placebo in reducing sore throat at 12 hours (eight-day course odds ratio (OR) 21.00, 95% confidence interval (CI) 1.94 to 227.20; one-dose OR 4.20, 95% CI 1.08 to 16.32), but the benefit was not maintained.In combination with an antiviral drug, participants in the steroid group had less pharyngeal discomfort between days two to four (OR 0.31, 95% CI 0.09 to 1.08) compared to placebo. Across the trials the effects on other common symptoms were less clear. Two trials set out to measure safety; they documented no major adverse effects. In two other trials adverse events were reported, including respiratory distress and acute onset of diabetes. However, the association of the events with the steroid is not definite. There is insufficient evidence to the efficacy of steroids for symptom control in infectious mononucleosis. There is a lack of research on the side effects and long-term complications.

Modified Reporting of Positive Urine Cultures to Reduce Inappropriate Treatment of Asymptomatic Bacteriuria Among Nonpregnant, Noncatheterized Inpatients: A Randomized Controlled Trial.

PubMed

Daley, Peter; Garcia, David; Inayatullah, Raheel; Penney, Carla; Boyd, Sarah

2018-05-28

DESIGNWe conducted a randomized, parallel, unblinded, superiority trial of a laboratory reporting intervention designed to reduce antibiotic treatment of asymptomatic bacteriuria (ASB).METHODSResults of positive urine cultures from 110 consecutive inpatients at 2 urban acute-care hospitals were randomized to standard report (control) or modified report (intervention). The standard report included bacterial count, bacterial identification, and antibiotic susceptibility information including drug dosage and cost. The modified report stated: "This POSITIVE urine culture may represent asymptomatic bacteriuria or urinary tract infection. If urinary tract infection is suspected clinically, please call the microbiology laboratory … for identification and susceptibility results." We used the following exclusion criteria: age <18 years, pregnancy, presence of an indwelling urinary catheter, samples from patients already on antibiotics, neutropenia, or admission to an intensive care unit. The primary efficacy outcome was the proportion of appropriate antibiotic therapy prescribed.RESULTSAccording to our intention-to-treat (ITT) analysis, the proportion of appropriate treatment (urinary tract infection treated plus ASB not treated) was higher in the modified arm than in the standard arm: 44 of 55 (80.0%) versus 29 of 55 (52.7%), respectively (absolute difference, -27.3%; RR, 0.42; P = .002; number needed to report for benefit, 3.7).CONCLUSIONSModified reporting resulted in a significant reduction in inappropriate antibiotic treatment without an increase in adverse events. Safety should be further assessed in a large effectiveness trial before implementationTRIAL REGISTRATION. clinicaltrials.gov#NCT02797613Infect Control Hosp Epidemiol 2018;1-6.

Exercise rehabilitation following intensive care unit discharge for recovery from critical illness: executive summary of a Cochrane Collaboration systematic review.

PubMed

Connolly, Bronwen; Salisbury, Lisa; O'Neill, Brenda; Geneen, Louise; Douiri, Abdel; Grocott, Michael P W; Hart, Nicholas; Walsh, Timothy S; Blackwood, Bronagh

2016-12-01

Skeletal muscle wasting and weakness are major complications of critical illness and underlie the profound physical and functional impairments experienced by survivors after discharge from the intensive care unit (ICU). Exercise-based rehabilitation has been shown to be beneficial when delivered during ICU admission. This review aimed to determine the effectiveness of exercise rehabilitation initiated after ICU discharge on primary outcomes of functional exercise capacity and health-related quality of life. We sought randomized controlled trials, quasi-randomized controlled trials, and controlled clinical trials comparing an exercise intervention commenced after ICU discharge vs. any other intervention or a control or 'usual care' programme in adult survivors of critical illness. Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database, and Cumulative Index to Nursing and Allied Health Literature databases were searched up to February 2015. Dual, independent screening of results, data extraction, and quality appraisal were performed. We included six trials involving 483 patients. Overall quality of evidence for both outcomes was very low. All studies evaluated functional exercise capacity, with three reporting positive effects in favour of the intervention. Only two studies evaluated health-related quality of life and neither reported differences between intervention and control groups. Meta-analyses of data were precluded due to variation in study design, types of interventions, and selection and reporting of outcome measurements. We were unable to determine an overall effect on functional exercise capacity or health-related quality of life of interventions initiated after ICU discharge for survivors of critical illness. Findings from ongoing studies are awaited. Future studies need to address methodological aspects of study design and conduct to enhance rigour, quality, and synthesis.

The EC randomised controlled trial of prophylactic ethamsylate for very preterm neonates: early mortality and morbidity. The EC Ethamsylate Trial Group.

PubMed Central

1994-01-01

Immature infants are at increased risk of death and disability, often related to haemorrhagic and ischaemic brain damage. Two controlled trials have suggested that a policy of prophylactic ethamsylate may reduce this damage. The aim of the trial reported here was to assess the effects of such a policy in respect of death, disability, and the use of health service resources up to 2 years of age. Short term findings are reported here. Three hundred and thirty four immature (< or = 32 weeks' gestation) infants were recruited into the trial within four hours of birth from four centres in France and six in Greece. Almost all 165 infants allocated to the ethamsylate group received the drug, compared with one of the 169 infants in the control group. By about 3 months of age the trial groups were similar in terms of death (20% in the two groups), any diagnosis of periventricular or intraventricular haemorrhage (35% in the ethamsylate v 37% in the control group), or major cerebral abnormality assessed by ultrasound (13% v 12%). The trial provides little evidence to support the use of ethamsylate for routine prophylaxis. The confidence intervals are wide, however, and so these results alone cannot rule out a clinically useful benefit or a harmful effect. A follow up study of the surviving children at the age of 2 years is in progress. PMID:8198414

Evaluating the design and reporting of pragmatic trials in osteoarthritis research.

PubMed

Ali, Shabana Amanda; Kloseck, Marita; Lee, Karen; Walsh, Kathleen Ellen; MacDermid, Joy C; Fitzsimmons, Deborah

2018-01-01

Among the challenges in health research is translating interventions from controlled experimental settings to clinical and community settings where chronic disease is managed daily. Pragmatic trials offer a method for testing interventions in real-world settings but are seldom used in OA research. The aim of this study was to evaluate the literature on pragmatic trials in OA research up to August 2016 in order to identify strengths and weaknesses in the design and reporting of these trials. We used established guidelines to assess the degree to which 61 OA studies complied with pragmatic trial design and reporting. We assessed design according to the pragmatic-explanatory continuum indicator summary and reporting according to the pragmatic trials extension of the CONsolidated Standards of Reporting Trials guidelines. None of the pragmatic trials met all 11 criteria evaluated and most of the trials met between 5 and 8 of the criteria. Criteria most often unmet pertained to practitioner expertise (by requiring specialists) and criteria most often met pertained to primary outcome analysis (by using intention-to-treat analysis). Our results suggest a lack of highly pragmatic trials in OA research. We identify this as a point of opportunity to improve research translation, since optimizing the design and reporting of pragmatic trials can facilitate implementation of evidence-based interventions for OA care. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Antiepileptic drugs as prophylaxis for postcraniotomy seizures.

PubMed

Greenhalgh, Janette; Weston, Jennifer; Dundar, Yenal; Nevitt, Sarah J; Marson, Anthony G

2018-05-23

This is an updated version of the Cochrane Review previously published in Issue 3, 2015.The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be between 15% to 20%; however, the risk of experiencing a seizure appears to vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery. The use of antiepileptic drugs (AEDs) administered pre- or postoperatively to prevent seizures following cranial surgery has been investigated in a number of randomised controlled trials (RCTs). To determine the efficacy and safety of AEDs when used prophylactically in people undergoing craniotomy and to examine which AEDs are most effective. For the latest update we searched the following databases on 26 June 2017: Cochrane Epilepsy Group Specialized Register, the CENTRAL, MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We did not apply any language restrictions. We included RCTs of people with no history of epilepsy who were undergoing craniotomy for either therapeutic or diagnostic reasons. We included trials with adequate randomisation methods and concealment; these could either be blinded or unblinded parallel trials. We did not stipulate a minimum treatment period, and we included trials using active drugs or placebo as a control group. Three review authors (JW, JG, YD) independently selected trials for inclusion and performed data extraction and risk of bias assessments. We resolved any disagreements through discussion. Outcomes investigated included the number of participants experiencing seizures (early (occurring within first week following craniotomy), and late (occurring after first week following craniotomy)), the number of deaths and the number of people experiencing disability and adverse effects. Due to the heterogeneous nature of the trials, we did not combine data from the included trials in a meta-analysis; we presented the findings of the review in narrative format. Visual comparisons of outcomes are presented in forest plots. We included 10 RCTs (N = 1815), which were published between 1983 and 2015. Three trials compared a single AED (phenytoin) with placebo or no treatment. One three-armed trial compared two AEDs (phenytoin, carbamazepine) with no treatment. A second three-armed trial compared phenytoin, phenobarbital with no treatment. Of these five trials comparing AEDs with placebo or no treatment, two trials reported a statistically significant advantage for AED treatment compared to controls for early seizure occurrence; all other comparisons showed no clear or statistically significant differences between AEDs and control treatment. None of the trials that were head-to-head comparisons of AEDs (phenytoin versus sodium valproate, phenytoin versus phenobarbital, levetiracetam versus phenytoin, zonisamide versus phenobarbital) reported any statistically significant differences between treatments for either early or late seizure occurrence.Incidences of death were reported in only five trials. One trial reported statistically significantly fewer deaths in the carbamazepine and no-treatment groups compared with the phenytoin group after 24 months of treatment, but not after six months of treatment. Incidences of adverse effects of treatment were poorly reported; however, three trials did show that significantly more adverse events occurred on phenytoin compared to valproate, placebo, or no treatment. No trials reported any results relating to functional outcomes such as disability.We considered the evidence to be of low quality for all reported outcomes due to methodological issues and variability of comparisons made in the trials. There is limited, low-quality evidence to suggest that AED treatment administered prophylactically is either effective or not effective in the prevention of postcraniotomy (early or late) seizures. The current evidence base is limited due to the different methodologies employed in the trials and inconsistencies in the reporting of outcomes including deaths and adverse events. Further evidence from good-quality, contemporary trials is required in order to assess the clinical effectiveness of prophylactic AED treatment compared to placebo or no treatment, or other AEDs in preventing postcraniotomy seizures in this select group of patients.

The natural history of subjective tinnitus in adults: A systematic review and meta-analysis of no-intervention periods in controlled trials.

PubMed

Phillips, John S; McFerran, Don J; Hall, Deborah A; Hoare, Derek J

2018-01-01

Tinnitus is a prevalent condition, but little has been published regarding the natural history of the condition. One technique for evaluating the long-term progression of the disease is to examine what happens to participants in the no-intervention control arm of a clinical trial. The aim of this study was to examine no-intervention or waiting-list data reported in trials, in which participants on the active arm received any form of tinnitus intervention. CINAHL, PsychINFO, EMBASE, ASSIA, PubMed, Web of Science, Science Direct, EBSCO Host, and Cochrane. Inclusion criteria followed the PICOS principles: Participants, adults with tinnitus; Intervention, none; Control, any intervention for alleviating tinnitus; Outcomes, a measure assessing tinnitus symptoms using a multi-item patient-reported tinnitus questionnaire. Secondary outcome measures included multi-item patient-reported questionnaires of mood and health-related quality of life and measures that quantified change in tinnitus loudness; Study design, randomized controlled trials or observational studies utilizing a no-intervention or waiting-list control group. Data were extracted and standardized mean difference was calculated for each study to enable meta-analysis. The evidence strongly favored a statistically significant decrease in the impact of tinnitus over time, though there was significant heterogeneity and clinical significance cannot be interpreted. Outcome data regarding secondary measures did not demonstrate any clinically significant change. Participants allocated to the no-intervention or waiting-list control arm of clinical trials for a tinnitus intervention show a small but significant improvement in self-reported measures of tinnitus with time; the clinical significance of this finding is unknown. There is, however, considerable variation across individuals. These findings support previous work and can cautiously be used when counseling patients. Laryngoscope, 128:217-227, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Autogenic training for stress and anxiety: a systematic review.

PubMed

Ernst, E; Kanji, N

2000-06-01

The aim of this systematic review was to evaluate all controlled trials of autogenic training (AT) as a means of reducing stress and anxiety levels in human subjects. A search for all published and unpublished controlled trials was carried out in the four major databases, specifically CISCOM, Medline, PsychLit and CINAHL. Eight such trials were located, all of which are included here. The majority of trials were methodologically flawed. A range of outcome measures were used, with Spielberger's State-Trait Anxiety Inventory being the most popular. Deviations from the accepted technique of AT were conspicuous and trials using the classical AT were in the minority. Seven trials reported positive effects of AT in reducing stress. One study showed no such benefit. Since one trial had used AT in combination with another technique, visual imagery, no conclusion can be drawn about the effect of AT in this case. No firm conclusions could be drawn from this systematic review. AT, properly applied, remains to be tested in controlled trials that are appropriately planned and executed.

Using the 'Social Marketing Mix Framework' to explore recruitment barriers and facilitators in palliative care randomised controlled trials? A narrative synthesis review.

PubMed

Dunleavy, Lesley; Walshe, Catherine; Oriani, Anna; Preston, Nancy

2018-05-01

Effective recruitment to randomised controlled trials is critically important for a robust, trustworthy evidence base in palliative care. Many trials fail to achieve recruitment targets, but the reasons for this are poorly understood. Understanding barriers and facilitators is a critical step in designing optimal recruitment strategies. To identify, explore and synthesise knowledge about recruitment barriers and facilitators in palliative care trials using the '6 Ps' of the 'Social Marketing Mix Framework'. A systematic review with narrative synthesis. Medline, CINAHL, PsycINFO and Embase databases (from January 1990 to early October 2016) were searched. Papers included the following: interventional and qualitative studies addressing recruitment, palliative care randomised controlled trial papers or reports containing narrative observations about the barriers, facilitators or strategies to increase recruitment. A total of 48 papers met the inclusion criteria. Uninterested participants (Product), burden of illness (Price) and 'identifying eligible participants' were barriers. Careful messaging and the use of scripts/role play (Promotion) were recommended. The need for intensive resources and gatekeeping by professionals were barriers while having research staff on-site and lead clinician support (Working with Partners) was advocated. Most evidence is based on researchers' own reports of experiences of recruiting to trials rather than independent evaluation. The 'Social Marketing Mix Framework' can help guide researchers when planning and implementing their recruitment strategy but suggested strategies need to be tested within embedded clinical trials. The findings of this review are applicable to all palliative care research and not just randomised controlled trials.

Does regular exercise including pelvic floor muscle training prevent urinary and anal incontinence during pregnancy? A randomised controlled trial.

PubMed

Stafne, S N; Salvesen, K Å; Romundstad, P R; Torjusen, I H; Mørkved, S

2012-09-01

To assess whether pregnant women following a general exercise course, including pelvic floor muscle training (PFMT), were less likely to report urinary and anal incontinence in late pregnancy than a group of women receiving standard care. A two-armed, two-centred randomised controlled trial. Trondheim University Hospital (St. Olavs Hospital) and Stavanger University Hospital, in Norway. A total of 855 women were included in this trial. The intervention was a 12-week exercise programme, including PFMT, conducted between 20 and 36 weeks of gestation. One weekly group session was led by physiotherapists, and home exercises were encouraged at least twice a week. Controls received regular antenatal care. Self-reported urinary and anal incontinence after the intervention period (at 32-36 weeks of gestation). Fewer women in the intervention group reported any weekly urinary incontinence (11 versus 19%, P = 0.004). Fewer women in the intervention group reported faecal incontinence (3 versus 5%), but this difference was not statistically significant (P = 0.18). The present trial indicates that pregnant women should exercise, and in particular do PFMT, to prevent and treat urinary incontinence in late pregnancy. Thorough instruction is important, and specific pelvic floor muscle exercises should be included in exercise classes for pregnant women. The preventive effect of PFMT on anal incontinence should be explored in future trials. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults.

PubMed

Hall, Deborah A; Haider, Haula; Szczepek, Agnieszka J; Lau, Pia; Rabau, Sarah; Jones-Diette, Julie; Londero, Alain; Edvall, Niklas K; Cederroth, Christopher R; Mielczarek, Marzena; Fuller, Thomas; Batuecas-Caletrio, Angel; Brueggemen, Petra; Thompson, Dean M; Norena, Arnaud; Cima, Rilana F F; Mehta, Rajnikant L; Mazurek, Birgit

2016-06-01

There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.

Comparison of serious adverse events posted at ClinicalTrials.gov and published in corresponding journal articles.

PubMed

Tang, Eve; Ravaud, Philippe; Riveros, Carolina; Perrodeau, Elodie; Dechartres, Agnes

2015-08-14

The reporting of serious adverse events (SAEs) in clinical trials is crucial to assess the balance between benefits and risks. For trials with serious adverse events posted at ClinicalTrials.gov, we assessed the consistency between SAEs posted at ClinicalTrials.gov and those published in corresponding journal articles. All records from ClinicalTrials.gov up to February 2014 were automatically exported in XML format. Among these, we identified all phase III or IV randomized controlled trials with at least one SAE posted. For a random sample of 300 of these trials, we searched for corresponding publications using MEDLINE via PubMed and extracted safety results from the articles. Among the sample of 300 trials with SAEs posted at ClinicalTrials.gov, 78 (26%) did not have a corresponding publication, and 20 (7%) had a publication that did not match the ClinicalTrials.gov record. For the 202 remaining trials, 26 published articles (13%) did not mention SAEs, 4 (2%) reported no SAEs, and 33 (16%) did not report the total number of SAEs per treatment group. Among the remaining 139 trials, for 44 (32%), the number of SAEs per group published did not match those posted at ClinicalTrials.gov. For 31 trials, the number of SAEs was greater at ClinicalTrials.gov than in the published article, with a difference ≥30 % for at least one group for 21. Only 33 trials (11%) had a publication reporting matching numbers of SAE and describing the type of SAE. Many trials with SAEs posted at ClinicalTrials.gov are not yet published, omit the reporting of these SAEs in corresponding publications, or report a discrepant number of SAEs as compared with ClinicalTrials.gov. These results underline the need to consult ClinicalTrials.gov for more information on serious harms.

Treatment as usual (TAU) as a control condition in trials of cognitive behavioural-based psychotherapy for self-harm: Impact of content and quality on outcomes in a systematic review.

PubMed

Witt, Katrina; de Moraes, Daniela Pache; Salisbury, Tatiana Taylor; Arensman, Ella; Gunnell, David; Hazell, Philip; Townsend, Ellen; van Heeringen, Kees; Hawton, Keith

2018-08-01

Randomized controlled trials (RCTs) are the mainstay of evaluations of the efficacy of psychosocial interventions. In a recent Cochrane systematic review we analysed the efficacy of cognitive behavioural-based psychotherapies compared to treatment as usual (TAU) in adults who self-harm. In this study we examine the content and reporting quality of TAU in these trials and their relationship to outcomes. Five electronic databases (CCDANCTR-Studies and References, CENTRAL, MEDLINE, EMBASE, and PsycINFO) were searched for RCTs, indexed between 1 January 1998 and 30 April 2015, of cognitive-behavioural interventions compared to TAU for adults following a recent (within six months) episode of self-harm. Comparisons were made between outcomes for trials which included different categories of TAU, which were grouped as: multidisciplinary treatment, psychotherapy only, pharmacotherapy only, treatment by primary care physician, minimal contact, or unclear. 18 trials involving 2433 participants were included. The content and reporting quality of TAU varied considerably between trials. The apparent effectiveness of cognitive behavioural psychotherapy varied according to TAU reporting quality and content. Specifically, effects in favour of cognitive-behavioural psychotherapy were strongest in trials in which TAU content was not clearly described (Odds Ratio: 0.29, 95% Confidence Interval 0.15-0.62; three trials) compared to those in which TAU comprised multidisciplinary treatment (Odds Ratio: 0.79, 95% CI 0.63 to 0.97; 12 trials). The included trials had high risk of bias with respect to participant and clinical personnel blinding, and unclear risk of bias for selective outcome reporting. TAU content and quality represents an important source of heterogeneity between trials of psychotherapeutic interventions for prevention of self-harm. Before clinical trials begin, researchers should plan to carefully describe both aspects of TAU to improve the overall quality of investigations. Copyright © 2018 Elsevier B.V. All rights reserved.

A quantitative and qualitative evaluation of reports of clinical trials published in six Brazilian dental journals indexed in the Scientific Electronic Library Online (SciELO)

PubMed Central

de SOUZA, Raphael Freitas; CHAVES, Carolina de Andrade Lima; CHAVES, Carolina de Andrade Lima; CHAVES, Carolina de Andrade Lima; NASSER, Mona; FEDOROWICZ, Zbys

2010-01-01

Open access publishing is becoming increasingly popular within the biomedical sciences. SciELO, the Scientific Electronic Library Online, is a digital library covering a selected collection of Brazilian scientific journals many of which provide open access to full-text articles. This library includes a number of dental journals some of which may include reports of clinical trials in English, Portuguese and/or Spanish. Thus, SciELO could play an important role as a source of evidence for dental healthcare interventions especially if it yields a sizeable number of high quality reports. Objective The aim of this study was to identify reports of clinical trials by handsearching of dental journals that are accessible through SciELO, and to assess the overall quality of these reports. Material and methods Electronic versions of six Brazilian dental Journals indexed in SciELO were handsearched at www.scielo.br in September 2008. Reports of clinical trials were identified and classified as controlled clinical trials (CCTs - prospective, experimental studies comparing 2 or more healthcare interventions in human beings) or randomized controlled trials (RCTs - a random allocation method is clearly reported), according to Cochrane eligibility criteria. Criteria to assess methodological quality included: method of randomization, concealment of treatment allocation, blinded outcome assessment, handling of withdrawals and losses and whether an intention-totreat analysis had been carried out. Results The search retrieved 33 CCTs and 43 RCTs. A majority of the reports provided no description of either the method of randomization (75.3%) or concealment of the allocation sequence (84.2%). Participants and outcome assessors were reported as blinded in only 31.2% of the reports. Withdrawals and losses were only clearly described in 6.5% of the reports and none mentioned an intention-totreat analysis or any similar procedure. Conclusions The results of this study indicate that a substantial number of reports of trials and systematic reviews are available in the dental journals listed in SciELO, and that these could provide valuable evidence for clinical decision making. However, it is clear that the quality of a number of these reports is of some concern and that improvement in the conduct and reporting of these trials could be achieved if authors adhered to internationally accepted guidelines, e.g. the CONSORT statement. PMID:20485919

A quantitative and qualitative evaluation of reports of clinical trials published in six Brazilian dental journals indexed in the Scientific Electronic Library Online (SciELO).

PubMed

de Souza, Raphael Freitas; Chaves, Carolina de Andrade Lima; Nasser, Mona; Fedorowicz, Zbys

2010-01-01

Open access publishing is becoming increasingly popular within the biomedical sciences. SciELO, the Scientific Electronic Library Online, is a digital library covering a selected collection of Brazilian scientific journals many of which provide open access to full-text articles.This library includes a number of dental journals some of which may include reports of clinical trials in English, Portuguese and/or Spanish. Thus, SciELO could play an important role as a source of evidence for dental healthcare interventions especially if it yields a sizeable number of high quality reports. The aim of this study was to identify reports of clinical trials by handsearching of dental journals that are accessible through SciELO, and to assess the overall quality of these reports. Electronic versions of six Brazilian dental Journals indexed in SciELO were handsearched at www.scielo.br in September 2008. Reports of clinical trials were identified and classified as controlled clinical trials (CCTs - prospective, experimental studies comparing 2 or more healthcare interventions in human beings) or randomized controlled trials (RCTs - a random allocation method is clearly reported), according to Cochrane eligibility criteria. CRITERIA TO ASSESS METHODOLOGICAL QUALITY INCLUDED: method of randomization, concealment of treatment allocation, blinded outcome assessment, handling of withdrawals and losses and whether an intention-to-treat analysis had been carried out. The search retrieved 33 CCTs and 43 RCTs. A majority of the reports provided no description of either the method of randomization (75.3%) or concealment of the allocation sequence (84.2%). Participants and outcome assessors were reported as blinded in only 31.2% of the reports. Withdrawals and losses were only clearly described in 6.5% of the reports and none mentioned an intention-to-treat analysis or any similar procedure. The results of this study indicate that a substantial number of reports of trials and systematic reviews are available in the dental journals listed in SciELO, and that these could provide valuable evidence for clinical decision making. However, it is clear that the quality of a number of these reports is of some concern and that improvement in the conduct and reporting of these trials could be achieved if authors adhered to internationally accepted guidelines, e.g. the CONSORT statement.

Role of exercise training in polycystic ovary syndrome: a systematic review and meta-analysis.

PubMed

Benham, J L; Yamamoto, J M; Friedenreich, C M; Rabi, D M; Sigal, R J

2018-06-12

Preliminary evidence suggests exercise in polycystic ovary syndrome (PCOS) may improve reproductive and cardiometabolic parameters. Our primary aim was to determine the impact of exercise training on reproductive health in women with PCOS. Our secondary aim was to determine the effect of exercise training on cardiometabolic indices. A systematic review of published literature was conducted using MEDLINE and EMBASE based on a pre-published protocol (PROSPERO CRD42017065324). The search was not limited by year. Randomized controlled trials, non-randomized controlled trials and uncontrolled trials that evaluated an exercise intervention in women with PCOS and reported reproductive outcomes were included. Reproductive outcomes were analysed semi-quantitatively and a meta-analysis was conducted for reported cardiometabolic outcomes. Of 517 screened abstracts, 14 studies involving 617 women with PCOS were included: seven randomized controlled trials, one non-randomized controlled trial and six uncontrolled trials. There were insufficient published data to describe the effect of exercise interventions on ovulation quantitatively, but semi-quantitative analysis suggested that exercise interventions may improve menstrual regularity, pregnancy and ovulation rates. Our meta-analysis found that exercise improved lipid profiles and decreased waist circumference, systolic blood pressure and fasting insulin. The impact of exercise interventions on reproductive function remains unclear. However, our meta-analysis suggests that exercise interventions may improve cardiometabolic profiles in women with PCOS. © 2018 World Obesity Federation.

The use of recombinant luteinizing hormone in patients undergoing assisted reproductive techniques with advanced reproductive age: a systematic review and meta-analysis.

PubMed

Hill, Micah J; Levens, Eric D; Levy, Gary; Ryan, Mary E; Csokmay, John M; DeCherney, Alan H; Whitcomb, Brian W

2012-05-01

To evaluate the effect of recombinant LH in assisted reproduction technology (ART) cycles in patients of advanced reproductive age. A systematic review and meta-analysis. Published randomized controlled clinical trials comparing recombinant LH plus recombinant FSH versus recombinant FSH only in patients of advanced reproductive age. Patients 35 years and older undergoing assisted reproduction. Recombinant LH plus recombinant FSH controlled ovarian hyperstimulation (COH) versus recombinant FSH stimulation only in assisted reproduction cycles. Implantation and clinical pregnancy. Seven trials were identified that met inclusion criteria and comprised 902 assisted reproduction technology cycles. No differences in serum E(2) on the day of hCG administration were reported in any trials. Two trials reported lower oocyte yield and one trial reported lower metaphase II oocyte yield in the recombinant LH-supplemented group. One trial reported higher fertilization rates in the recombinant LH-supplemented group. In a fixed effect model, implantation was higher in the recombinant LH-supplemented group (odds ratio 1.36, 95% confidence interval 1.05-1.78). Similarly, clinical pregnancy was increased in the recombinant LH-supplemented group (odds ratio 1.37, 95% confidence interval 1.03-1.83). The addition of recombinant LH to ART cycles may improve implantation and clinical pregnancy in patients of advanced reproductive age. Copyright © 2012 American Society for Reproductive Medicine. All rights reserved.

Ketamine for Depression: Where Do We Go from Here?

PubMed Central

aan het Rot, Marije; Zarate, Carlos A.; Charney, Dennis S.; Mathew, Sanjay J.

2012-01-01

Since publication of the first randomized controlled trial describing rapid antidepressant effects of ketamine, several reports have confirmed the potential utility of this dissociative anesthetic medication for treatment of major depressive episodes, including those associated with bipolar disorder and resistant to other medications and electroconvulsive therapy. These reports have generated several questions with respect to who might respond to ketamine, how, and for how long. To start answering these questions. We used PubMed.gov and ClinicalTrials.gov to perform a systematic review of all available published data on the antidepressant effects of ketamine and of all recently completed, ongoing, and planned studies. To date, 163 patients, primarily with treatment-resistant depression, have participated in case studies, open-label investigations, or controlled trials. All controlled trials have used a within-subject, crossover design with an inactive placebo as the control. Ketamine administration has usually involved an anaesthesiologist infusing a single, subanesthetic, intravenous dose, and required hospitalization for at least 24 hours postinfusion. Response rates in the open-label investigations and controlled trials have ranged from 25% to 85% at 24 hours postinfusion and from 14% to 70% at 72 hours postinfusion. Although adverse effects have generally been mild, some patients have experienced brief changes in blood pressure, heart rate, or respiratory rate. Risk–benefit analyses support further research of ketamine for individuals with severe mood disorders. However, given the paucity of randomized controlled trials, lack of an active placebo, limited data on long-term outcomes, and potential risks, ketamine administration is not recommended outside of the hospital setting. PMID:22705040

Polysaccharide K and Coriolus versicolor extracts for lung cancer: a systematic review.

PubMed

Fritz, Heidi; Kennedy, Deborah A; Ishii, Mami; Fergusson, Dean; Fernandes, Rochelle; Cooley, Kieran; Seely, Dugald

2015-05-01

Polysaccharide K, also known as PSK or Krestin, is derived from the Coriolus versicolor mushroom and is widely used in Japan as an adjuvant immunotherapy for a variety of cancer including lung cancer. Despite reported benefits, there has been no English language synthesis of PSK for lung cancer. To address this knowledge gap, we conducted a systematic review of PSK for the treatment of lung cancer. We searched PubMed, EMBASE, CINAHL, the Cochrane Library, AltHealth Watch, and the Library of Science and Technology from inception to August 2014 for clinical and preclinical evidence pertaining to the safety and efficacy of PSK or other Coriolus versicolor extracts for lung cancer. Thirty-one reports of 28 studies were included for full review and analysis. Six studies were randomized controlled trials, 5 were nonrandomized controlled trials, and 17 were preclinical studies. Nine of the reports were Japanese language publications. Fifteen of 17 preclinical studies supported anticancer effects for PSK through immunomodulation and potentiation of immune surveillance, as well as through direct tumor inhibiting actions in vivo that resulted in reduced tumor growth and antimetastatic effects. Nonrandomized controlled trials showed improvement of various survival measures including median survival and 1-, 2-, and 5-year survival. Randomized controlled trials showed benefits on a range of endpoints, including immune parameters and hematological function, performance status and body weight, tumor-related symptoms such as fatigue and anorexia, as well as survival. Although there were conflicting results for impact on some of the tumor-related symptoms and median survival, overall most randomized controlled trials supported a positive impact for PSK on these endpoints. PSK was safely administered following and in conjunction with standard radiation and chemotherapy. PSK may improve immune function, reduce tumor-associated symptoms, and extend survival in lung cancer patients. Larger, more rigorous randomized controlled trials for PSK in lung cancer patients are warranted. © The Author(s) 2015.

Randomized controlled trials of simulation-based interventions in Emergency Medicine: a methodological review.

PubMed

Chauvin, Anthony; Truchot, Jennifer; Bafeta, Aida; Pateron, Dominique; Plaisance, Patrick; Yordanov, Youri

2018-04-01

The number of trials assessing Simulation-Based Medical Education (SBME) interventions has rapidly expanded. Many studies show that potential flaws in design, conduct and reporting of randomized controlled trials (RCTs) can bias their results. We conducted a methodological review of RCTs assessing a SBME in Emergency Medicine (EM) and examined their methodological characteristics. We searched MEDLINE via PubMed for RCT that assessed a simulation intervention in EM, published in 6 general and internal medicine and in the top 10 EM journals. The Cochrane Collaboration risk of Bias tool was used to assess risk of bias, intervention reporting was evaluated based on the "template for intervention description and replication" checklist, and methodological quality was evaluated by the Medical Education Research Study Quality Instrument. Reports selection and data extraction was done by 2 independents researchers. From 1394 RCTs screened, 68 trials assessed a SBME intervention. They represent one quarter of our sample. Cardiopulmonary resuscitation (CPR) is the most frequent topic (81%). Random sequence generation and allocation concealment were performed correctly in 66 and 49% of trials. Blinding of participants and assessors was performed correctly in 19 and 68%. Risk of attrition bias was low in three-quarters of the studies (n = 51). Risk of selective reporting bias was unclear in nearly all studies. The mean MERQSI score was of 13.4/18.4% of the reports provided a description allowing the intervention replication. Trials assessing simulation represent one quarter of RCTs in EM. Their quality remains unclear, and reproducing the interventions appears challenging due to reporting issues.

Are outcomes reported in surgical randomized trials patient-important? A systematic review and meta-analysis

PubMed Central

Adie, Sam; Harris, Ian A.; Naylor, Justine M.; Mittal, Rajat

2017-01-01

Background The dangers of using surrogate outcomes are well documented. They may have little or no association with their patient-important correlates, leading to the approval and use of interventions that lack efficacy. We sought to assess whether primary outcomes in surgical randomized controlled trials (RCTs) are more likely to be patient-important outcomes than surrogate or laboratory-based outcomes. Methods We reviewed RCTs assessing an operative intervention published in 2008 and 2009 and indexed in MEDLINE, EMBASE or the Cochrane Central Register of Controlled Trials. After a pilot of the selection criteria, 1 reviewer selected trials and another reviewer checked the selection. We extracted information on outcome characteristics (patient-important, surrogate, or laboratory-based outcome) and whether they were primary or secondary outcomes. We calculated odds ratios (OR) and pooled in random-effects meta-analysis to obtain an overall estimate of the association between patient importance and primary outcome specification. Results In 350 included RCTs, a total of 8258 outcomes were reported (median 18 per trial. The mean proportion (per trial) of patient-important outcomes was 60%, and 66% of trials specified a patient-important primary outcome. The most commonly reported patient-important primary outcomes were morbid events (41%), intervention outcomes (11%), function (11%) and pain (9%). Surrogate and laboratory-based primary outcomes were reported in 33% and 8% of trials, respectively. Patient-important outcomes were not associated with primary outcome status (OR 0.82, 95% confidence interval 0.63–1.1, I2 = 21%). Conclusion A substantial proportion of surgical RCTs specify primary outcomes that are not patient-important. Authors, journals and trial funders should insist that patient-important outcomes are the focus of study. PMID:28234219

Zonisamide and renal calculi in patients with epilepsy: how big an issue?

PubMed

Wroe, Stephen

2007-08-01

To determine the prevalence of renal calculi in patients treated with zonisamide during randomized, controlled and open-label clinical trials, and from post-marketing surveillance data. Reports of renal calculi from four placebo-controlled double-blind trials of zonisamide, their long-term open-label treatment extension phases, and the US/European zonisamide clinical trial programme were reviewed. One double-blind study and its extension included routine ultrasound screening to identify asymptomatic calculi. Post-marketing surveillance data were also investigated, as was concomitant treatment with topiramate. No symptomatic renal calculi were reported during four randomized double-blind, placebo-controlled trials involving 848 subjects (including 498 zonisamide recipients) treated for up to 3 months. In long-term extension studies with treatment for up to 24 months, symptomatic renal calculi were reported in 9/626 (1.4%) patients. Pooled safety data from all US/European clinical trials identified 15/1296 (1.2%) patients with symptomatic renal calculi during treatment for up to 8.7 years. Post-marketing surveillance revealed nine cases from 59 667 patient-years of exposure in the USA, and 14 from 709 294 patient-years of exposure in Japan; only one case occurred during concomitant topiramate and zonisamide treatment. No imbalance in electrolyte levels was found from 35 patients receiving such co-treatment in clinical trials. The available data suggest that the risk of developing renal calculi during zonisamide treatment is low. Data are insufficient to determine whether concomitant treatment with topiramate increases the risk of renal stones.

Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies.

PubMed

Li, Xue; Meng, Xiangrui; Timofeeva, Maria; Tzoulaki, Ioanna; Tsilidis, Konstantinos K; Ioannidis, John PA; Campbell, Harry; Theodoratou, Evropi

2017-06-07

Objective  To map the diverse health outcomes associated with serum uric acid (SUA) levels. Design  Umbrella review. Data sources  Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references. Eligibility criteria  Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes. Results  57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10 -6 , 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies. Conclusion  Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The efficacy of anticonvulsants on orofacial pain: a systematic review.

PubMed

Martin, Wilhelmus J J M; Forouzanfar, Tymour

2011-05-01

Controversy exists about the effectiveness of anticonvulsants for the management of orofacial pain disorders. To ascertain appropriate therapies, a systematic review was conducted of existing randomized controlled trials. Trials were identified from PubMed, Cochrane, and Ovid Medline databases from 1962 through March 2010, from references in retrieved reports, and from references in review articles. Eight useful trials were identified for this review. Six studies were randomized placebo-controlled trials and 2 studies were randomized active-controlled. Two independent investigators reviewed these articles by using a 15-item checklist. Four studies were classified as "high quality." However, heterogeneity of the trials and the small sample sizes precluded the drawing of firm conclusions about the efficacy of the interventions studied on orofacial pain patients. There is limited to moderate evidence supporting the efficacy of commonly used anticonvulsants for treatment of patients with orofacial pain disorders. More randomized controlled trials are needed on the efficacy of anticonvulsants. Copyright © 2011 Mosby, Inc. All rights reserved.

Reporting Quality Assessment of Randomized Controlled Trials Published in Nephrology Urology Monthly Journal.

PubMed

Mehrazmay, Alireza; Karambakhsh, Alireza; Salesi, Mahmood

2015-07-01

Randomized controlled trials (RCTs) are important tools for evidence-based health care decisions. It is, therefore, important that they be conducted and reported with the highest possible standards. The aim of this study was to evaluate the reporting quality of the RCTs published in nephrology urology monthly journal and to examine whether there was a change over time in the reporting quality. The quality of each report was assessed using the Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement checklist and a 5-point quality assessment instrument, i.e. the Jadad scale. Eighteen (14 Iranian and 4 non-Iranian) RCTs were published from 2012 to 2014 on topics including renal stone (16.6%), hemodialysis and transplantation (38.8%), and prostate conditions (11.1%). Interventions comprised surgery, drugs, and teaching method in 7 (38 %), 10 (55%), and 1 (5%) of them, respectively. According to the CONSORT checklist, the weakest reported items were registration number, identification as a randomized trial in the title, and settings and locations where the data were collected. The mean Jadad score of the reports was 2.72 ± 1.36 (54% of their maximum possible total score). According to the Jadad and CONSORT scales, there was an increase in the quality of reporting from 2012 to 2014. This assessment shows low reporting quality scores in reports. Training courses for researchers, using standard reporting tools (e.g. CONSORT 2010 Statement checklist), and consultation with methodologists can improve the quality of published RCTs.

Assessment of reporting quality of conference abstracts in sports injury prevention according to CONSORT and STROBE criteria and their subsequent publication rate as full papers.

PubMed

Yoon, Uzung; Knobloch, Karsten

2012-04-11

The preliminary results of a study are usually presented as an abstract in conference meetings. The reporting quality of those abstracts and the relationship between their study designs and full paper publication rate is unknown. We hypothesized that randomized controlled trials are more likely to be published as full papers than observational studies. 154 oral abstracts presented at the World Congress of Sports Injury Prevention 2005 Oslo and the corresponding full paper publication were identified and analysed. The main outcome measures were frequency of publication, time to publication, impact factor, CONSORT (for Consolidated Standards of Reporting Trials) score, STROBE (for Strengthening the Reporting of Observational Studies in Epidemiology) score, and minor and major inconsistencies between the abstract and the full paper publication. Overall, 76 of the 154 (49%) presented abstracts were published as full papers in a peer-reviewed journal with an impact factor of 1.946 ± 0.812. No significant difference existed between the impact factor for randomized controlled trials (2.122 ± 1.015) and observational studies (1.913 ± 0.765, p = 0.469). The full papers for the randomized controlled trials were published after an average (SD) of 17 months (± 13 months); for observational studies, the average (SD) was 12 months (± 14 months) (p = 0.323). A trend was observed in this study that a higher percentage of randomized controlled trial abstracts were published as full papers (71% vs. 47%, p = 0.078) than observational trials. The reporting quality of abstracts, published as full papers, significantly increased compared to conference abstracts both in randomized control studies ( 5.7 ± 0.7 to 7.2 ± 1.3; p = 0.018, CI -2.7 to -0.32) and in observational studies (STROBE: 8.2 ± 1.3 to 8.6 ± 1.4; p = 0.007, CI -0.63 to -0.10). All of the published abstracts had at least one minor inconsistency (title, authors, research center, outcome presentation, conclusion), while 65% had at least major inconsistencies (study objective, hypothesis, study design, primary outcome measures, sample size, statistical analysis, results, SD/CI). Comparing the results of conference and full paper; results changed in 90% vs. 68% (randomized, controlled studies versus observational studies); data were added (full paper reported more result data) in 60% vs. 30%, and deleted (full paper reported fewer result data) in 40% vs. 30%. No significant differences with respect to type of study (randomized controlled versus observational), impact factor, and time to publication existed for the likelihood that a World Congress of Sports Injury conference abstract could be published as a full paper.

Evaluation of the COPING parent online universal programme: study protocol for a pilot randomised controlled trial

PubMed Central

Owen, Dawn Adele; Griffith, Nia; Hutchings, Judy

2017-01-01

Trial sponsor Bangor University, Brigantia Building, College Road, Bangor, LL57 2AS, UK Introduction The COPING parent online universal programme is a web-based parenting intervention for parents of children aged 3-8 years with an interest in positive parenting. The programme focuses on strengthening parent-child relationships and encouraging positive child behaviour. This trial will evaluate whether the intervention is effective in increasing the use of positive parenting strategies outlined in the programme using parent report and blind observation measures. Methods and analysis This is a pilot randomised controlled trial with intervention and wait-list control conditions. The intervention is a 10-week online parenting programme to promote positive parent-child relations by teaching core social learning theory principles that encourage positive child behaviour, primarily through the use of praise and rewards. Health visitors and school nurses will circulate a recruitment poster to parents of children aged 3–8 years on their current caseloads. Recruitment posters will also be distributed via local primary schools and nurseries. Parents recruited to the trial will be randomised on a 2:1 ratio to intervention or wait-list control conditions (stratified according to child gender and age). The primary outcome measure is positive parenting as measured by a behavioural observation of parent-child interactions using the Dyadic Parent-Child Interaction Coding System. Secondary outcomes include parent report of child behaviour, and self-reported parental sense of competence, parenting behaviour and parental mental health. Data will be collected at baseline and 3 months later (postintervention) for all participants and 6 months postbaseline for the intervention group only. Analysis of covariance will be the main statistical method used. Ethics and dissemination The trial has received ethical approval from the NHS Betsi Cadwaladr University Health Board Ethics Committee (REC) and the School of Psychology, Bangor University REC (15/WA/0463). Publication of all outcomes will be in peer-reviewed journals and conference presentations. Trial registration number Current Controlled Trials ISRCTN89370147 (5 May 2016). PMID:28446523

Vector and reservoir control for preventing leishmaniasis

PubMed Central

González, Urbà; Pinart, Mariona; Sinclair, David; Firooz, Alireza; Enk, Claes; Vélez, Ivan D; Esterhuizen, Tonya M; Tristan, Mario; Alvar, Jorge

2015-01-01

Background Leishmaniasis is caused by the Leishmania parasite, and transmitted by infected phlebotomine sandflies. Of the two distinct clinical syndromes, cutaneous leishmaniasis (CL) affects the skin and mucous membranes, and visceral leishmaniasis (VL) affects internal organs. Approaches to prevent transmission include vector control by reducing human contact with infected sandflies, and reservoir control, by reducing the number of infected animals. Objectives To assess the effects of vector and reservoir control interventions for cutaneous and for visceral leishmaniasis. Search methods We searched the following databases to 13 January 2015: Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS and WHOLIS, Web of Science, and RePORTER. We also searched trials registers for ongoing trials. Selection criteria Randomized controlled trials (RCTs) evaluating the effects of vector and reservoir control interventions in leishmaniasis-endemic regions. Data collection and analysis Two review authors independently searched for trials and extracted data from included RCTs. We resolved any disagreements by discussion with a third review author. We assessed the quality of the evidence using the GRADE approach. Main results We included 14 RCTs that evaluated a range of interventions across different settings. The study methods were generally poorly described, and consequently all included trials were judged to be at high or unclear risk of selection and reporting bias. Only seven trials reported clinical outcome data which limits our ability to make broad generalizations to different epidemiological settings and cultures. Cutaneous leishmaniasis One four-arm RCT from Afghanistan compared indoor residual spraying (IRS), insecticide-treated bednets (ITNs), and insecticide-treated bedsheets, with no intervention. Over 15 months follow-up, all three insecticide-based interventions had a lower incidence of CL than the control area (IRS: risk ratio (RR) 0.61, 95% confidence interval (CI) 0.38 to 0.97, 2892 participants, moderate quality evidence; ITNs: RR 0.32, 95% CI 0.18 to 0.56, 2954 participants, low quality evidence; ITS: RR 0.34, 95% CI 0.20 to 0.57, 2784 participants, low quality evidence). No difference was detected between the three interventions (low quality evidence). One additional trial of ITNs from Iran was underpowered to show a difference. Insecticide treated curtains were compared with no intervention in one RCT from Venezuela, where there were no CL episodes in the intervention areas over 12 months follow-up compared to 142 in control areas (RR 0.00, 95% CI 0.00 to 0.49, one trial, 2938 participants, low quality evidence). Personal protection using insecticide treated clothing was evaluated by two RCTs in soldiers, but the trials were underpowered to reliably detect effects on the incidence of CL (RR 0.40, 95% CI 0.13 to 1.20, two trials, 558 participants, low quality evidence). Visceral leishmaniasis In a single RCT of ITNs versus no intervention from India and Nepal, the incidence of VL was low in both groups and no difference was detected (RR 0.99, 95% CI 0.46 to 2.15, one trial, 19,810 participants, moderate quality evidence). Two trials from Brazil evaluated the effects of culling infected dogs compared to no intervention or IRS. Although they report a reduction in seroconversion over 18 months follow-up, they did not measure or report effects on clinical disease. Authors' conclusions Using insecticides to reduce phlebotomine sandfly numbers may be effective at reducing the incidence of CL, but there is insufficient evidence from trials to know whether it is better to spray the internal walls of houses or to treat bednets, curtains, bedsheets or clothing. PLAIN LANGUAGE SUMMARY Vector and reservoir control for preventing leishmaniasis This review summarises trials evaluating different measures to prevent leishmaniasis. After searching for relevant trials up to January 2015, we included 14 randomized controlled trials. What is vector and reservoir control and how might they prevent leishmaniasis? Leishmaniasis is a group of infectious diseases caused by Leishmania parasites, which are transmitted between humans and animals by the bite of infected phlebotomine sandflies. There are two main clinical diseases: cutaneous leishmaniasis (CL), where parasites infect the skin, and visceral leishmaniasis (VL), where they infect the internal organs. Leishmaniasis could be prevented by reducing human contact with infected phlebotomine sandflies (the vector), or by reducing the number of infected animals (the reservoir). What the research says? Cutaneous leishmaniasis Using insecticides to reduce the number of sandflies may be effective at reducing the number of new cases of cutaneous leishmaniasis (low quality evidence). However, there is not enough evidence to know whether it is better to use insecticides to spray the internal walls of houses, or use insecticide treated bednets, bedsheets, or curtains. Personal protection using insecticide treated clothing was also evaluated in two small trials in soldiers, but the trials were too small to know whether this was effective (low quality evidence). Visceral leishmaniasis Insecticide treated nets may not be effective at preventing visceral leishmaniasis but this has only been tested in a single trial from India and Nepal (low quality evidence). Although culling dogs is sometimes discussed as a potential way to reduce visceral leishmaniasis, this has not been tested in trials measuring clinical disease. PMID:26246011

Intraperitoneal local anaesthetic instillation versus no intraperitoneal local anaesthetic instillation for laparoscopic cholecystectomy.

PubMed

Gurusamy, Kurinchi Selvan; Nagendran, Myura; Guerrini, Gian Piero; Toon, Clare D; Zinnuroglu, Murat; Davidson, Brian R

2014-03-13

While laparoscopic cholecystectomy is generally considered less painful than open surgery, pain is one of the important reasons for delayed discharge after day surgery and overnight stay laparoscopic cholecystectomy. The safety and effectiveness of intraperitoneal local anaesthetic instillation in people undergoing laparoscopic cholecystectomy is unknown. To assess the benefits and harms of intraperitoneal instillation of local anaesthetic agents in people undergoing laparoscopic cholecystectomy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded to March 2013 to identify randomised clinical trials of relevance to this review. We considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing local anaesthetic intraperitoneal instillation versus placebo, no intervention, or inactive control during laparoscopic cholecystectomy for the review with regards to benefits while we considered quasi-randomised studies and non-randomised studies for treatment-related harms. Two review authors collected the data independently. We analysed the data with both fixed-effect and random-effects models using Review Manager 5 analysis. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). We included 58 trials, of which 48 trials with 2849 participants randomised to intraperitoneal local anaesthetic instillation (1558 participants) versus control (1291 participants) contributed data to one or more of the outcomes. All the trials except one trial with 30 participants were at high risk of bias. Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Various intraperitoneal local anaesthetic agents were used but bupivacaine in the liquid form was the most common local anaesthetic used. There were considerable differences in the methods of local anaesthetic instillation including the location (subdiaphragmatic, gallbladder bed, or both locations) and timing (before or after the removal of gallbladder) between the trials. There was no mortality in either group in the eight trials that reported mortality (0/236 (0%) in local anaesthetic instillation versus 0/210 (0%) in control group; very low quality evidence). One participant experienced the outcome of serious morbidity (eight trials; 446 participants; 1/236 (0.4%) in local anaesthetic instillation group versus 0/210 (0%) in the control group; RR 3.00; 95% CI 0.13 to 67.06; very low quality evidence). Although the remaining trials did not report the overall morbidity, three trials (190 participants) reported that there were no intra-operative complications. Twenty trials reported that there were no serious adverse events in any of the 715 participants who received local anaesthetic instillation. None of the trials reported participant quality of life, return to normal activity, or return to work.The effect of local anaesthetic instillation on the proportion of participants discharged as day surgery between the two groups was imprecise and compatible with benefit and no difference of intervention (three trials; 242 participants; 89/160 (adjusted proportion 61.0%) in local anaesthetic instillation group versus 40/82 (48.8%) in control group; RR 1.25; 95% CI 0.99 to 1.58; very low quality evidence). The MD in length of hospital stay was 0.04 days (95% CI -0.23 to 0.32; five trials; 335 participants; low quality evidence). The pain scores as measured by the visual analogue scale (VAS) were significantly lower in the local anaesthetic instillation group than the control group at four to eight hours (32 trials; 2020 participants; MD -0.99 cm; 95% CI -1.10 to -0.88 on a VAS scale of 0 to 10 cm; very low quality evidence) and at nine to 24 hours (29 trials; 1787 participants; MD -0.53 cm; 95% CI -0.62 to -0.44; very low quality evidence). Various subgroup analyses and meta-regressions to investigate the influence of the different local anaesthetic agents, different methods of local anaesthetic instillation, and different controls on the effectiveness of local anaesthetic intraperitoneal instillation were inconsistent. Serious adverse events were rare in studies evaluating local anaesthetic intraperitoneal instillation (very low quality evidence). There is very low quality evidence that it reduces pain in low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. However, the clinical importance of this reduction in pain is unknown and likely to be small. Further randomised clinical trials of low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment.

Systematic review of blinding assessment in randomized controlled trials in schizophrenia and affective disorders 2000-2010.

PubMed

Baethge, Christopher; Assall, Oliver P; Baldessarini, Ross J

2013-01-01

Blinding is an integral part of many randomized controlled trials (RCTs). However, both blinding and blinding assessment seem to be rarely documented in trial reports. Systematic review of articles on RCTs in schizophrenia and affective disorders research during 2000-2010. Among 2,467 publications, 61 (2.5%; 95% confidence interval: 1.9-3.1%) reported assessing participant, rater, or clinician blinding: 5/672 reports on schizophrenia (0.7%; 0.3-1.6%) and 33/1,079 (3.1%; 2.1-4.2%) on affective disorders, without significant trends across the decade. Rarely was blinding assessed at the beginning, in most studies assessment was at the end. Proportion of patients' and raters' correct guesses of study arm averaged 54.4 and 62.0% per study, with slightly more correct guesses in treatment arms than in placebo arms. Three fourths of responders correctly guessed that they received the active agent. Blinding assessment was more frequently reported in papers on psychotherapy and brain stimulation than on drug trials (5.1%, 1.7-11.9%, vs. 8.3%, 4.3-14.4%, vs. 2.1%, 1.5-2.8%). Lack of assessment of blinding was associated with: (a) positive findings, (b) full industrial sponsorship, and (c) diagnosis of schizophrenia. There was a moderate association of treatment success and blinding status of both trial participants (r = 0.51, p = 0.002) and raters (r = 0.55, p = 0.067). Many RCT reports did not meet CONSORT standards regarding documentation of persons blinded (60%) or of efforts to match interventions (50%). Recent treatment trials in major psychiatric disorders rarely reported on or evaluated blinding. We recommend routine documentation of blinding strategies in reports. Copyright © 2013 S. Karger AG, Basel.

Intraoperative Cryoanalgesia for Reducing Post-Tonsillectomy Pain: A Systemic Review.

PubMed

Raggio, Blake S; Barton, Blair M; Grant, Maria C; McCoul, Edward D

2018-06-01

Summarize the effectiveness of intraoperative cryoanalgesia in the management of postoperative pain among patients undergoing palatine tonsillectomy. A systematic review of PubMED, MEDLINE, EMBASE, Google Scholar, and Cochrane trial registries was performed through January 2017 using the PRISMA standards. We included English-language randomized controlled trials evaluating patients of all age groups with benign pathology who underwent tonsillectomy with cryoanalgesia versus without. Three limited quality randomized controlled trials involving 153 participants (age range, 1-60 years) were included. Cryoanalgesia was performed with a cryotherapy probe (-56°C) in 1 trial and ice-water cooling (4°C to 10°C) in 2. In the 3 trials reviewed, patients who received cryoanalgesia reported 21.38%, 28.33%, and 31.53% less average relative postoperative pain than controls on the visual analog scale. Review of secondary outcomes suggested no significant difference in time to resume normal diet (2 studies) or postoperative bleeding (2 studies) between the 2 groups. Cryoanalgesia allowed patients to return to work 4 days earlier than controls in 1 study. Two studies reported a trend toward less postoperative analgesia use among the treatment group; however, no statistical conclusions could be drawn. The available evidence suggests that patients undergoing tonsillectomy with cryoanalgesia experience less average postoperative pain without additional complications.

How standard is standard care? Exploring control group outcomes in behaviour change interventions for young people with type 1 diabetes.

PubMed

Ayling, K; Brierley, S; Johnson, B; Heller, S; Eiser, C

2015-01-01

Poor descriptions of standard care may compromise interpretation of results in randomised controlled trials (RCTs) of health interventions. We investigated quality of standard care in RCTs of behaviour change interventions for young people with type 1 diabetes and consider implications for evaluating trial outcomes. We conducted systematic searches for articles published between 1999 and 2012. We extracted standard care descriptions and contacted trial authors to complete a checklist of standard care activities. The relationship between standard care quality and outcomes was examined via subgroup meta-analyses and meta-regression. Standard care descriptions, standard care quality, and relationships between standard care quality with medical and psychological outcomes. We identified 20 RCTs described across 26 articles. Published descriptions of standard care were limited to service-level features. Author responses indicated standard care provision extended beyond published accounts. Subgroup analyses suggested control groups receiving higher standard care quality showed larger improvements in both medical and psychological outcomes, although standard care quality did not predict outcomes significantly. The quality of care delivered to control group participants can influence outcomes of RCTs. Inadequate reporting exacerbates this issue by masking variations between trials. We argue for increased clarity in reporting standard care in future trials.

Intention to treat (ITT) analysis as reported in orthodontic randomized controlled trials-evaluations of methodology and recommendations for the accurate use of ITT analysis and handling dropouts.

PubMed

Bondemark, Lars; Abdulraheem, Salem

2017-10-21

To systematically evaluate in five orthodontic journals how many randomized controlled trials (RCTs) use intention to treat (ITT) analysis and to assess the methodological quality of the ITT analysis, and finally, to demonstrate in an academic way how outcomes can be affected when not implementing the ITT analysis. A search of the database, Medline, was performed via PubMed for publication type 'randomized controlled trial' published for each journal between 1 January 2013 and 30 April 2017. The five orthodontic journals assessed were the American Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontics, European Journal of Orthodontics, Journal of Orthodontics, and Orthodontics and Craniofacial Research. Two independent reviewers assessed each RCT to determine whether the trial reported an ITT or not or if a per-protocol analysis was accomplished. The initial search generated 137 possible trials. After applying the inclusion and exclusion criteria, 90 RCTs were included and assessed. Seventeen out of 90 RCTs (18.9%) either reported an ITT analysis in the text and/or supported the ITT by flow diagrams or tables. However, six RCTs applied and reported the ITT analysis correctly, while the majority performed a per-protocol analysis instead. Nearly all the trials that applied the ITT analysis incorrectly analysed the results using a per-protocol analysis, and thus, overestimating the results and/or having a reduced sample size which then could produce a diminished statistical power. © The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

Reporting of sample size calculations in analgesic clinical trials: ACTTION systematic review.

PubMed

McKeown, Andrew; Gewandter, Jennifer S; McDermott, Michael P; Pawlowski, Joseph R; Poli, Joseph J; Rothstein, Daniel; Farrar, John T; Gilron, Ian; Katz, Nathaniel P; Lin, Allison H; Rappaport, Bob A; Rowbotham, Michael C; Turk, Dennis C; Dworkin, Robert H; Smith, Shannon M

2015-03-01

Sample size calculations determine the number of participants required to have sufficiently high power to detect a given treatment effect. In this review, we examined the reporting quality of sample size calculations in 172 publications of double-blind randomized controlled trials of noninvasive pharmacologic or interventional (ie, invasive) pain treatments published in European Journal of Pain, Journal of Pain, and Pain from January 2006 through June 2013. Sixty-five percent of publications reported a sample size calculation but only 38% provided all elements required to replicate the calculated sample size. In publications reporting at least 1 element, 54% provided a justification for the treatment effect used to calculate sample size, and 24% of studies with continuous outcome variables justified the variability estimate. Publications of clinical pain condition trials reported a sample size calculation more frequently than experimental pain model trials (77% vs 33%, P < .001) but did not differ in the frequency of reporting all required elements. No significant differences in reporting of any or all elements were detected between publications of trials with industry and nonindustry sponsorship. Twenty-eight percent included a discrepancy between the reported number of planned and randomized participants. This study suggests that sample size calculation reporting in analgesic trial publications is usually incomplete. Investigators should provide detailed accounts of sample size calculations in publications of clinical trials of pain treatments, which is necessary for reporting transparency and communication of pre-trial design decisions. In this systematic review of analgesic clinical trials, sample size calculations and the required elements (eg, treatment effect to be detected; power level) were incompletely reported. A lack of transparency regarding sample size calculations may raise questions about the appropriateness of the calculated sample size. Copyright © 2015 American Pain Society. All rights reserved.

Working with men to prevent intimate partner violence in a conflict-affected setting: a pilot cluster randomized controlled trial in rural Côte d’Ivoire

PubMed Central

2014-01-01

Background Evidence from armed conflict settings points to high levels of intimate partner violence (IPV) against women. Current knowledge on how to prevent IPV is limited—especially within war-affected settings. To inform prevention programming on gender-based violence in settings affected by conflict, we evaluated the impact of adding a targeted men’s intervention to a community-based prevention programme in Côte d’Ivoire. Methods We conducted a two-armed, non-blinded cluster randomized trial in Côte d’Ivoire among 12 pair-matched communities spanning government-controlled, UN buffer, and rebel–controlled zones. The intervention communities received a 16-week IPV prevention intervention using a men’s discussion group format. All communities received community-based prevention programmes. Baseline data were collected from couples in September 2010 (pre-intervention) and follow-up in March 2012 (one year post-intervention). The primary trial outcome was women’s reported experiences of physical and/or sexual IPV in the last 12 months. We also assessed men’s reported intention to use physical IPV, attitudes towards sexual IPV, use of hostility and conflict management skills, and participation in gendered household tasks. An adjusted cluster-level intention to treat analysis was used to compare outcomes between intervention and control communities at follow-up. Results At follow-up, reported levels of physical and/or sexual IPV in the intervention arm had decreased compared to the control arm (ARR 0.52, 95% CI 0.18-1.51, not significant). Men participating in the intervention reported decreased intentions to use physical IPV (ARR 0.83, 95% CI 0.66-1.06) and improved attitudes toward sexual IPV (ARR 1.21, 95% CI 0.77-1.91). Significant differences were found between men in the intervention and control arms’ reported ability to control their hostility and manage conflict (ARR 1.3, 95% CI 1.06-1.58), and participation in gendered household tasks (ARR 2.47, 95% CI 1.24-4.90). Conclusions This trial points to the value of adding interventions working with men alongside community activities to reduce levels of IPV in conflict-affected settings. The intervention significantly influenced men’s reported behaviours related to hostility and conflict management and gender equitable behaviours. The decreased mean level of IPV and the differences between intervention and control arms, while not statistically significant, suggest that IPV in conflict-affected areas can be reduced through concerted efforts to include men directly in violence prevention programming. A larger-scale trial is needed to replicate these findings and further understand the mechanisms of change. Trial registration clinicaltrials.gov NCT01803932 PMID:24716478

Tackling risky alcohol consumption in sport: a cluster randomised controlled trial of an alcohol management intervention with community football clubs

PubMed Central

Kingsland, Melanie; Wolfenden, Luke; Tindall, Jennifer; Rowland, Bosco C; Lecathelinais, Christophe; Gillham, Karen E; Dodds, Pennie; Sidey, Maree N; Rogerson, John C; McElduff, Patrick; Crundall, Ian; Wiggers, John H

2015-01-01

Background An increased prevalence of risky alcohol consumption and alcohol-related harm has been reported for members of sporting groups and at sporting venues compared with non-sporting populations. While sports clubs and venues represent opportune settings to implement strategies to reduce such risks, no controlled trials have been reported. The purpose of the study was to examine the effectiveness of an alcohol management intervention in reducing risky alcohol consumption and the risk of alcohol-related harm among community football club members. Method A cluster randomised controlled trial of an alcohol management intervention was undertaken with non-elite, community football clubs and their members in New South Wales, Australia. Risky alcohol consumption (5+ drinks) at the club and risk of alcohol-related harm using the Alcohol Use Disorders Identification Test (AUDIT) were measured at baseline and postintervention. Results Eighty-eight clubs participated in the trial (n=43, Intervention; n=45, Control) and separate cross-sectional samples of club members completed the baseline (N=1411) and postintervention (N=1143) surveys. Postintervention, a significantly lower proportion of intervention club members reported: risky alcohol consumption at the club (Intervention: 19%; Control: 24%; OR: 0.63 (95% CI 0.40 to 1.00); p=0.05); risk of alcohol-related harm (Intervention: 38%; Control: 45%; OR: 0.58 (95% CI 0.38 to 0.87); p<0.01); alcohol consumption risk (Intervention: 47%; Control: 55%; OR: 0.60 (95% CI 0.41 to 0.87); p<0.01) and possible alcohol dependence (Intervention: 1%; Control: 4%; OR: 0.20 (95% CI 0.06 to 0.65); p<0.01). Conclusions With large numbers of people worldwide playing, watching and sports officiating, enhancing club-based alcohol management interventions could make a substantial contribution to reducing the burden of alcohol misuse in communities. Trial registration number ACTRN12609000224224. PMID:26038252

A single-blinded, randomized, parallel group superiority trial investigating the effects of footwear and custom foot orthoses versus footwear alone in individuals with patellofemoral joint osteoarthritis: a phase II pilot trial protocol.

PubMed

Wyndow, Narelle; Crossley, Kay M; Vicenzino, Bill; Tucker, Kylie; Collins, Natalie J

2017-01-01

Patellofemoral joint osteoarthritis is a common condition, yet information regarding conservative management is lacking. Foot orthoses are an effective intervention for improving pain and function in younger individuals with patellofemoral pain and may be effective in those with patellofemoral osteoarthritis. This pilot study will seek to establish the feasibility of a phase III randomised controlled trial to investigate whether foot orthoses worn in prescribed motion controlled footwear are superior to prescribed motion control footwear alone in the management of patellofemoral osteoarthritis. This phase II pilot clinical trial is designed as a randomized, single-blind, parallel group, two arm, superiority trial. The trial will recruit 44 participants from Queensland and Tasmania, Australia. Volunteers aged 40 years and over must have clinical symptoms and radiographic evidence of patellofemoral osteoarthritis to be eligible for inclusion. Those eligible will be randomized to receive either foot orthoses and prescribed motion control shoes, or prescribed motion control shoes alone, to be worn for a period of 4 months. The feasibility of a phase III clinical trial will be evaluated by assessing factors such as recruitment rate, number of eligible participants, participant compliance with the study protocol, adverse events, and drop-out rate. A secondary aim of the study will be to determine completion rates and calculate effect sizes for patient reported outcome measures such as knee-related symptoms, function, quality of life, kinesiophobia, self-efficacy, general and mental health, and physical activity at 2 and 4 months. Primary outcomes will be reported descriptively while effect sizes and 95% confidence intervals will be calculated for the secondary outcome measures. Data will be analysed using an intention-to-treat principle. The results of this pilot trial will help determine the feasibility of a phase III clinical trial investigating whether foot orthoses plus motion control footwear are superior to motion control footwear alone in individuals with patellofemoral osteoarthritis. A Phase III clinical trial will help guide footwear and foot orthoses recommendations in the clinical management of this disorder. Retrospectively registered with the Australian New Zealand Clinical Trials Registry: ACTRN12615000002583. Date registered: 07/01/15.

Internet-based interventions for the secondary prevention of coronary heart disease.

PubMed

Devi, Reena; Singh, Sally J; Powell, John; Fulton, Emily A; Igbinedion, Ewemade; Rees, Karen

2015-12-22

The Internet could provide a means of delivering secondary prevention programmes to people with coronary heart disease (CHD). To determine the effectiveness of Internet-based interventions targeting lifestyle changes and medicines management for the secondary prevention of CHD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, in December 2014. We also searched six other databases in October 2014, and three trials registers in January 2015 together with reference checking and handsearching to identify additional studies. Randomised controlled trials (RCTs) evaluating Internet-delivered secondary prevention interventions aimed at people with CHD. Two review authors independently assessed risk of bias and extracted data according to the Cochrane Handbook for Systematic Reviews of Interventions. We assessed evidence quality using the GRADE approach and presented this in a 'Summary of findings' table. Eighteen trials met our inclusion criteria. Eleven studies are complete (1392 participants), and seven are ongoing. Of the completed studies, seven interventions are broad, targeting the lifestyle management of CHD, and four focused on physical activity promotion. The comparison group in trials was usual care (n = 6), minimal intervention (n = 3), or traditional cardiac rehabilitation (n = 2).We found no effects of Internet-based interventions for all-cause mortality (odds ratio (OR) 0.27, 95% confidence interval (CI) 0.04 to 1.63; participants = 895; studies = 6; low-quality evidence). There was only one case of cardiovascular mortality in a control group (participants = 895; studies = 6). No incidences of non-fatal re-infarction were reported across any of the studies. We found no effects for revascularisation (OR 0.69, 95% CI 0.37 to 1.27; participants = 895; studies = 6; low-quality evidence).We found no effects for total cholesterol (mean difference (MD) 0.00, 95% CI -0.27 to 0.28; participants = 439; studies = 4; low-quality evidence), high-density lipoprotein (HDL) cholesterol (MD 0.01, 95% CI -0.06 to 0.07; participants = 437; studies = 4; low-quality evidence), or triglycerides (MD 0.01, 95% CI -0.17 to 0.19; participants = 439; studies = 4; low-quality evidence). We did not pool the data for low-density lipoprotein (LDL) cholesterol due to considerable heterogeneity. Two out of six trials measuring LDL cholesterol detected favourable intervention effects, and four trials reported no effects. Seven studies measured systolic and diastolic blood pressure; we did not pool the data due to substantial heterogeneity. For systolic blood pressure, two studies showed a reduction with the intervention, but the remaining studies showed no effect. For diastolic blood pressure, two studies showed a reduction with the intervention, one study showed an increase with the intervention, and the remaining four studies showed no effect.Five trials measured health-related quality of life (HRQOL). We could draw no conclusions from one study due to incomplete reporting; one trial reported no effect; two studies reported a short- and medium-term effect respectively; and one study reported both short- and medium-term effects.Five trials assessed dietary outcomes: two reported favourable effects, and three reported no effects. Eight studies assessed physical activity: five of these trials reported no physical activity effects, and three reported effectiveness. Trials are yet to measure the impact of these interventions on compliance with medication.Two studies measured healthcare utilisation: one reported no effects, and the other reported increased usage of healthcare services compared to a control group in the intervention group at nine months' follow-up. Two trials collected cost data: both reported that Internet-delivered interventions are likely to be cost-effective.In terms of the risk of bias, the majority of studies reported appropriate randomisation and appropriate concealment of randomisation processes. A lack of blinding resulted in a risk of performance bias in seven studies, and a risk of detection bias in five trials. Two trials were at risk of attrition bias, and five were at risk for reporting bias. In general, evidence was of low quality due to lack of blinding, loss to follow-up, and uncertainty around the effect size. Few studies measured clinical events, and of those that did, a very small number of events were reported, and therefore no firm conclusions can be made. Similarly, there was no clear evidence of effect for cardiovascular risk factors, although again the number of studies reporting these was small. There was some evidence for beneficial effects on HRQOL, dietary outcomes, and physical activity, although firm conclusions cannot yet be made. The effects on healthcare utilisation and cost-effectiveness are also inconclusive, and trials are yet to measure the impact of Internet interventions on compliance with medication. The comparison groups differed across trials, and there were insufficient studies with usable data for subgroup analyses. We intend to study the intensity of comparison groups in future updates of this review when more evidence is available. The completion of the ongoing trials will add to the evidence base.

Effect of a Universal Anxiety Prevention Programme (FRIENDS) on Children's Academic Performance: Results from a Randomised Controlled Trial

ERIC Educational Resources Information Center

Skryabina, Elena; Taylor, Gordon; Stallard, Paul

2016-01-01

Background: Evaluations of school-based anxiety prevention programmes have reported improvements in psychological functioning although little is known about their effect upon educational outcomes. Methods: One thousand three hundred and sixty-two children from 40 primary schools in England took part in the randomised controlled trial, Preventing…

Effectiveness of Multidimensional Family Therapy with Higher Severity Substance-Abusing Adolescents: Report from Two Randomized Controlled Trials

ERIC Educational Resources Information Center

Henderson, Craig E.; Dakof, Gayle A.; Greenbaum, Paul E.; Liddle, Howard A.

2010-01-01

Objective: We used growth mixture modeling to examine heterogeneity in treatment response in a secondary analysis of 2 randomized controlled trials testing multidimensional family therapy (MDFT), an established evidence-based therapy for adolescent drug abuse and delinquency. Method: The first study compared 2 evidence-based adolescent substance…

Reducing Developmental Risk for Emotional/Behavioral Problems: A Randomized Controlled Trial Examining the Tools for Getting Along Curriculum

ERIC Educational Resources Information Center

Daunic, Ann P.; Smith, Stephen W.; Garvan, Cynthia W.; Barber, Brian R.; Becker, Mallory K.; Peters, Christine D.; Taylor, Gregory G.; Van Loan, Christopher L.; Li, Wei; Naranjo, Arlene H.

2012-01-01

Researchers have demonstrated that cognitive-behavioral intervention strategies--such as social problem solving--provided in school settings can help ameliorate the developmental risk for emotional and behavioral difficulties. In this study, we report the results of a randomized controlled trial of Tools for Getting Along (TFGA), a social…

Multisite Randomized Controlled Trial Examining Intelligent Tutoring of Structure Strategy for Fifth-Grade Readers

ERIC Educational Resources Information Center

Wijekumar, Kausalai; Meyer, Bonnie J. F.; Lei, Pui-Wa; Lin, Yu-Chu; Johnson, Lori A.; Spielvogel, James A.; Shurmatz, Kathryn M.; Ray, Melissa; Cook, Michael

2014-01-01

This article reports on a large scale randomized controlled trial to study the efficacy of a web-based intelligent tutoring system for the structure strategy designed to improve content area reading comprehension. The research was conducted with 128 fifth-grade classrooms within 12 school districts in rural and suburban settings. Classrooms within…

A Randomized Controlled Trial of a Standardized Behavior Management Intervention for Students with Externalizing Behavior

ERIC Educational Resources Information Center

Forster, Martin; Sundell, Knut; Morris, Richard J.; Karlberg, Martin; Melin, Lennart

2012-01-01

This study reports the results from a Swedish randomized controlled trial of a standardized behavior management intervention. The intervention targeted students with externalizing behavior in a regular education setting. First- and second-grade students (N = 100) from 38 schools were randomly assigned to either the intervention or an active…

Quality of reporting randomized controlled trials (RCTs) in diabetes in Iran; a systematic review.

PubMed

Gohari, Faeze; Baradaran, Hamid Reza; Tabatabaee, Morteza; Anijidani, Shabnam; Mohammadpour Touserkani, Fatemeh; Atlasi, Rasha; Razmgir, Maryam

2015-01-01

To determine the quality of randomized controlled clinical trial (RCT) reports in diabetes research in Iran. Systematized review. We included RCTs conducted on diabetes mellitus in Iran. Animal studies, educational interventions, and non-randomized trials were excluded. We excluded duplicated publications reporting the same groups of participants and intervention. Two independent reviewers identify all eligible articles specifically designed data extraction form. We searched through international databases; Scopus, ProQuest, EBSCO, Science Direct, Web of Science, Cochrane Library, PubMed; and national databases (In Persian language) such as Magiran, Scientific Information Database (SID) and IranMedex from January 1995 to January of 2013 Two investigators assessed the quality of reporting by CONSORT 2010 (Consolidated Standards of Reporting Trials) checklist statemen.t,. Discrepancies were resolved by third reviewer consulting. One hundred and eight five (185) studies were included and appraised. Half of them (55.7 %) were published in Iranian journals. Most (89.7 %) were parallel RCTs, and being performed on type2 diabetic patients (77.8 %). Less than half of the CONSORT items (43.2 %) were reported in studies, totally. The reporting of randomization and blinding were poor. A few studies 15.1 % mentioned the method of random sequence generation and strategy of allocation concealment. And only 34.8 % of trials report how blinding was applied. The findings of this study show that the quality of RCTs conducted in Iran in diabetes research seems suboptimal and the reporting is also incomplete however an increasing trend of improvement can be seen over time. Therefore, it is suggested Iranian researchers pay much more attention to design and methodological quality in conducting and reporting of diabetes RCTs.

The effect of journal impact factor, reporting conflicts, and reporting funding sources, on standardized effect sizes in back pain trials: a systematic review and meta-regression.

PubMed

Froud, Robert; Bjørkli, Tom; Bright, Philip; Rajendran, Dévan; Buchbinder, Rachelle; Underwood, Martin; Evans, David; Eldridge, Sandra

2015-11-30

Low back pain is a common and costly health complaint for which there are several moderately effective treatments. In some fields there is evidence that funder and financial conflicts are associated with trial outcomes. It is not clear whether effect sizes in back pain trials relate to journal impact factor, reporting conflicts of interest, or reporting funding. We performed a systematic review of English-language papers reporting randomised controlled trials of treatments for non-specific low back pain, published between 2006-2012. We modelled the relationship using 5-year journal impact factor, and categories of reported of conflicts of interest, and categories of reported funding (reported none and reported some, compared to not reporting these) using meta-regression, adjusting for sample size, and publication year. We also considered whether impact factor could be predicted by the direction of outcome, or trial sample size. We could abstract data to calculate effect size in 99 of 146 trials that met our inclusion criteria. Effect size is not associated with impact factor, reporting of funding source, or reporting of conflicts of interest. However, explicitly reporting 'no trial funding' is strongly associated with larger absolute values of effect size (adjusted β=1.02 (95 % CI 0.44 to 1.59), P=0.001). Impact factor increases by 0.008 (0.004 to 0.012) per unit increase in trial sample size (P<0.001), but does not differ by reported direction of the LBP trial outcome (P=0.270). The absence of associations between effect size and impact factor, reporting sources of funding, and conflicts of interest reflects positively on research and publisher conduct in the field. Strong evidence of a large association between absolute magnitude of effect size and explicit reporting of 'no funding' suggests authors of unfunded trials are likely to report larger effect sizes, notwithstanding direction. This could relate in part to quality, resources, and/or how pragmatic a trial is.

Reporting of adverse drug reactions in randomised controlled trials – a systematic survey

PubMed Central

Loke, Yoon Kong; Derry, Sheena

2001-01-01

Background Decisions on treatment are guided, not only by the potential for benefit, but also by the nature and severity of adverse drug reactions. However, some researchers have found numerous deficiencies in trial reports of adverse effects. We sought to confirm these findings by evaluating trials of drug therapy published in seven eminent medical journals in 1997. Methods Literature review to determine whether the definition, recording and reporting of adverse drug reactions in clinical trials were in accordance with published recommendations on structured reporting. Results Of the 185 trials reviewed, 25 (14%) made no mention of adverse drug reactions. Data in a further 60 (32%) could not be fully evaluated, either because numbers were not given for each treatment arm (31 trials), or because a generic statement was made without full details (29 trials). When adverse drug reactions such as clinical events or patient symptoms were mentioned in the reports, details on how they had been recorded were given in only 14/95 (15%) and 18/104 (17%) trials respectively. Of the 86 trials that mentioned severity of adverse drug reactions, only 42 (49%) stated how severity had been defined. The median amount of space used for safety data in the Results and Discussion sections was 5.8%. Conclusions Trial reports often failed to provide details on how adverse drug reactions were defined or recorded. The absence of such methodological information makes comparative evaluation of adverse reaction rates potentially unreliable. Authors and journals should adopt recommendations on the structured reporting of adverse effects. PMID:11591227

Fluoride gel effective at reducing caries in children.

PubMed

Richards, Derek

2015-12-01

Data Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline , Embase, CINAHL, LILACS, ProQuest Dissertations and Theses, the Web of Science Conference Proceedings, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Randomised or quasi-randomised controlled trials comparing topically applied fluoride gel with placebo or no treatment in children up to 16 years were considered. Studies had to be at least one year in duration with a frequency of application of at least once a year with blind outcome assessment. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces in both permanent and primary teeth (D(M)FS and d(e/m)fs). At least two reviewers extracted data and assessed risk of bias. The primary measure of effect was the prevented fraction (PF). Where data could be pooled random-effects meta-analyses were conducted. Potential sources of heterogeneity were examined in random-effects meta-regression analyses. Twenty-eight trials involving 9140 children and adolescents were included. Most of the studies (20) were at high risk of bias, with eight at unclear risk of bias. Twenty-five trials (8479 participants) provided data for meta-analysis on permanent teeth, with a D(M)FS pooled prevented fraction (PF) estimate of 28% (95% CI; 19-36%; P < 0.0001; with substantial heterogeneity (P < 0.0001; I(2) = 82%); moderate quality evidence). Subgroup and metaregression analyses suggested no significant association between estimates of D(M)FS prevented fractions and the prespecified trial characteristics. However, the effect of fluoride gel varied according to the type of control group used, with D(M)FS PF on average being 17% (95% CI 3% to 31%; P = 0.018) higher in non-placebo-controlled trials (the reduction in caries was 38% (95% CI 24% to 52%; P < 0.0001, 2808 participants) for the ten trials with no treatment as control group, and 21% (95% CI 15% to 28%; P < 0.0001, 5671 participants) for the 15 placebo-controlled trials.A funnel plot of the 25 trials in the D(M)FS PF meta-analysis indicated a relationship between prevented fraction and study precision, with an apparent lack of small studies with statistically significant large effects.For primary teeth the d(e/m)fs pooled prevented fraction estimate for the three trials (1254 participants) = 20% (95%CI; 1% - 38%; P = 0.04; with no heterogeneity (P = 0.54; I(2) = 0%); low quality evidence).There was limited reporting of adverse events. Only two trials reported information on acute toxicity signs and symptoms during the application of the gel (risk difference 0.01, 95% CI -0.01 to 0.02; P = 0.36; with no heterogeneity (P = 36; I(2) = 0%); 490 participants; very low quality evidence). None of the trials reported information on tooth staining, mucosal irritation or allergic reaction. The conclusions of this updated review remain the same as those when it was first published. There is moderate quality evidence of a large caries-inhibiting effect of fluoride gel in the permanent dentition. Information concerning the caries-preventive effect of fluoride gel on the primary dentition, which also shows a large effect, is based on low quality evidence from only three placebo-controlled trials. There is little information on adverse effects or on acceptability of treatment. Future trials should include assessment of potential adverse effects.

Acupuncture or acupressure for induction of labour.

PubMed

Smith, Caroline A; Armour, Mike; Dahlen, Hannah G

2017-10-17

This is one of a series of reviews of methods of cervical ripening and labour induction. The use of complementary therapies is increasing. Women may look to complementary therapies during pregnancy and childbirth to be used alongside conventional medical practice. Acupuncture involves the insertion of very fine needles into specific points of the body. Acupressure is using the thumbs or fingers to apply pressure to specific points. The limited observational studies to date suggest acupuncture for induction of labour has no known adverse effects to the fetus, and may be effective. However, the evidence regarding the clinical effectiveness of this technique is limited. To determine, from the best available evidence, the effectiveness and safety of acupuncture and acupressure for third trimester cervical ripening or induction of labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2016), PubMed (1966 to 25 November 2016), ProQuest Dissertations & Theses (25 November 2016), CINAHL (25 November 2016), Embase (25 November 2016), the WHO International Clinical Trials Registry Portal (ICTRP) (3 October 2016), and bibliographies of relevant papers. Randomised controlled trials comparing acupuncture or acupressure, used for third trimester cervical ripening or labour induction, with placebo/no treatment or other methods on a predefined list of labour induction methods. Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. The quality of the evidence was assessed using GRADE. This updated review includes 22 trials, reporting on 3456 women. The trials using manual or electro-acupuncture were compared with usual care (eight trials, 760 women), sweeping of membranes (one trial, 207 women), or sham controls (seven trials, 729 women). Trials using acupressure were compared with usual care (two trials, 151 women) or sham controls (two trials, 239 women). Many studies had a moderate risk of bias.Overall, few trials reported on primary outcomes. No trial reported vaginal delivery not achieved within 24 hours and uterine hyperstimulation with fetal heart rate (FHR) changes. Serious maternal and neonatal death or morbidity were only reported under acupuncture versus sham control. Acupuncture versus sham control There was no clear difference in caesarean sections between groups (average risk ratio (RR) 0.80, 95% confidence interval (CI) 0.56 to 1.15, eight trials, 789 women; high-quality evidence). There were no reports of maternal death or perinatal death in the one trial that reported this outcome. There was evidence of a benefit from acupuncture in improving cervical readiness for labour (mean difference (MD) 0.40, 95% CI 0.11 to 0.69, one trial, 125 women), as measured by cervical maturity within 24 hours using Bishop's score. There was no evidence of a difference between groups for oxytocin augmentation, epidural analgesia, instrumental vaginal birth, meconium-stained liquor, Apgar score < 7 at five minutes, neonatal intensive care admission, maternal infection, postpartum bleeding greater than 500 mL, time from the trial to time of birth, use of induction methods, length of labour, and spontaneous vaginal birth. Acupuncture versus usual care There was no clear difference in caesarean sections between groups (average RR 0.77, 95% CI 0.51 to 1.17, eight trials, 760 women; low-quality evidence). There was an increase in cervical maturation for the acupuncture (electro) group compared with control (MD 1.30, 95% CI 0.11 to 2.49, one trial, 67 women) and a shorter length of labour (minutes) in the usual care group compared to electro-acupuncture (MD 124.00, 95% CI 37.39 to 210.61, one trial, 67 women).There appeared be a differential effect according to type of acupuncture based on subgroup analysis. Electro-acupuncture appeared to have more of an effect than manual acupuncture for the outcomes caesarean section (CS), and instrumental vaginal and spontaneous vaginal birth. It decreased the rate of CS (average RR 0.54, 95% CI 0.37 to 0.80, 3 trials, 327 women), increased the rate of instrumental vaginal birth (average RR 2.30, 95%CI 1.15 to 4.60, two trials, 271 women), and increased the rate of spontaneous vaginal birth (average RR 2.06, 95% CI 1.20 to 3.56, one trial, 72 women). However, subgroup analyses are observational in nature and so results should be interpreted with caution.There were no clear differences between groups for other outcomes: oxytocin augmentation, use of epidural analgesia, Apgar score < 7 at 5 minutes, neonatal intensive care admission, maternal infection, perineal tear, fetal infection, maternal satisfaction, use of other induction methods, and postpartum bleeding greater than 500 mL. Acupuncture versus sweeping if fetal membranes One trial of acupuncture versus sweeping of fetal membranes showed no clear differences between groups in caesarean sections (RR 0.64, 95% CI 0.34 to 1.22, one trial, 207 women, moderate-quality evidence), need for augmentation, epidural analgesia, instrumental vaginal birth, Apgar score < 7 at 5 minutes, neonatal intensive care admission, and postpartum bleeding greater than 500 mL. Acupressure versus sham control There was no evidence of benefit from acupressure in reducing caesarean sections compared to control (RR, 0.94, 95% CI 0.68 to 1.30, two trials, 239 women, moderate-quality evidence). There was no evidence of a clear benefit in reduced oxytocin augmentation, instrumental vaginal birth, meconium-stained liquor, time from trial intervention to birth of the baby, and spontaneous vaginal birth. Acupressure versus usual care There was no evidence of benefit from acupressure in reducing caesarean sections compared to usual care (RR 1.02, 95% CI 0.68 to 1.53, two trials, 151 women, moderate-quality evidence). There was no evidence of a clear benefit in reduced epidural analgesia, Apgar score < 7 at 5 minutes, admission to neonatal intensive care, time from trial intervention to birth of the baby, use of other induction methods, and spontaneous vaginal birth. Overall, there was no clear benefit from acupuncture or acupressure in reducing caesarean section rate. The quality of the evidence varied between low to high. Few trials reported on neonatal morbidity or maternal mortality outcomes. Acupuncture showed some benefit in improving cervical maturity, however, more well-designed trials are needed. Future trials could include clinically relevant safety outcomes.

Lifestyle Advice Combined with Personalized Estimates of Genetic or Phenotypic Risk of Type 2 Diabetes, and Objectively Measured Physical Activity: A Randomized Controlled Trial.

PubMed

Godino, Job G; van Sluijs, Esther M F; Marteau, Theresa M; Sutton, Stephen; Sharp, Stephen J; Griffin, Simon J

2016-11-01

Information about genetic and phenotypic risk of type 2 diabetes is now widely available and is being incorporated into disease prevention programs. Whether such information motivates behavior change or has adverse effects is uncertain. We examined the effect of communicating an estimate of genetic or phenotypic risk of type 2 diabetes in a parallel group, open, randomized controlled trial. We recruited 569 healthy middle-aged adults from the Fenland Study, an ongoing population-based, observational study in the east of England (Cambridgeshire, UK). We used a computer-generated random list to assign participants in blocks of six to receive either standard lifestyle advice alone (control group, n = 190) or in combination with a genetic (n = 189) or a phenotypic (n = 190) risk estimate for type 2 diabetes (intervention groups). After 8 wk, we measured the primary outcome, objectively measured physical activity (kJ/kg/day), and also measured several secondary outcomes (including self-reported diet, self-reported weight, worry, anxiety, and perceived risk). The study was powered to detect a between-group difference of 4.1 kJ/kg/d at follow-up. 557 (98%) participants completed the trial. There were no significant intervention effects on physical activity (difference in adjusted mean change from baseline: genetic risk group versus control group 0.85 kJ/kg/d (95% CI -2.07 to 3.77, p = 0.57); phenotypic risk group versus control group 1.32 (95% CI -1.61 to 4.25, p = 0.38); and genetic risk group versus phenotypic risk group -0.47 (95% CI -3.40 to 2.46, p = 0.75). No significant differences in self-reported diet, self-reported weight, worry, and anxiety were observed between trial groups. Estimates of perceived risk were significantly more accurate among those who received risk information than among those who did not. Key limitations include the recruitment of a sample that may not be representative of the UK population, use of self-reported secondary outcome measures, and a short follow-up period. In this study, we did not observe short-term changes in behavior associated with the communication of an estimate of genetic or phenotypic risk of type 2 diabetes. We also did not observe changes in worry or anxiety in the study population. Additional research is needed to investigate the conditions under which risk information might enhance preventive strategies. (Current Controlled Trials ISRCTN09650496; Date applied: April 4, 2011; Date assigned: June 10, 2011). The trial is registered with Current Controlled Trials, ISRCTN09650496.

Reporting characteristics and risk of bias in randomised controlled trials of acupuncture analgesia published in PubMed-listed journals.

PubMed

Li, Xiuxia; Wang, Rong; Shi, Xiue; Chen, Zehao; Pan, Yuanqing; Li, Xusheng; Yang, Kehu

2017-08-01

Acupuncture analgesia has been evaluated by a number of randomised controlled trials (RCTs); however, a systematic summary of reporting quality of RCTs in this specific field is lacking. To examine the reporting characteristics and risk of bias of RCTs of acupuncture analgesia indexed in the PubMed database. A PubMed search of RCTs of acupuncture analgesia was conducted through November 2015. The Cochrane Collaboration Risk of Bias Tool was used to assess the risk of bias of each trial. 206 articles were identified across 59 journals (impact factor 0.4-20), of which 56% of articles and 86% of journals were Science Citation Index (SCI)-indexed. Nearly half of the articles were published in China. The next most represented countries of origin were the UK (22%) and USA (21%). Of the included trials, postoperative pain was the most prevalent phenotype, and manual acupuncture was the most frequently applied type of stimulation (46%). A total of 12% of articles reported on analgesic mechanisms. The most frequently used acupuncture points were LI4, ST36, PC6, SP6 and Shenmen . The overwhelming majority of trials were considered to be at high risk of bias (84%). Furthermore, 79% of trials enrolled <50 participants per treatment arm. RCTs of acupuncture analgesia indexed in PubMed journals generally exhibited poor reporting of methodological and treatment details. Future studies should provide more information regarding clinical trial registration, blinding of participants (including sham procedures where applicable) and outcome assessors, as well as the training and qualification of acupuncturists. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Comparison of noninferiority margins reported in protocols and publications showed incomplete and inconsistent reporting.

PubMed

Dekkers, Olaf M; Cevallos, Myriam; Bührer, Jonas; Poncet, Antoine; Ackermann Rau, Sabine; Perneger, Thomas V; Egger, Matthias

2015-05-01

To compare noninferiority margins defined in study protocols and trial registry records with margins reported in subsequent publications. Comparison of protocols of noninferiority trials submitted 2001 to 2005 to ethics committees in Switzerland and The Netherlands with corresponding publications and registry records. We searched MEDLINE via PubMed, the Cochrane Controlled Trials Register (Cochrane Library issue 01/2012), and Google Scholar in September 2013 to identify published reports, and the International Clinical Trials Registry Platform of the World Health Organization in March 2013 to identify registry records. Two readers recorded the noninferiority margin and other data using a standardized data-abstraction form. The margin was identical in study protocol and publication in 43 (80%) of 54 pairs of study protocols and articles. In the remaining pairs, reporting was inconsistent (five pairs, 9%), or the noninferiority margin was either not reported in the publication (five pairs, 9%) or not defined in the study protocol (one pair). The confidence interval or the exact P-value required to judge whether the result was compatible with noninferior, inferior, or superior efficacy was reported in 43 (80%) publications. Complete and consistent reporting of both noninferiority margin and confidence interval (or exact P-value) was present in 39 (72%) protocol-publication pairs. Twenty-nine trials (54%) were registered in trial registries, but only one registry record included the noninferiority margin. The reporting of noninferiority margins was incomplete and inconsistent with study protocols in a substantial proportion of published trials, and margins were rarely reported in trial registries. Copyright © 2015 Elsevier Inc. All rights reserved.

Effectiveness of Exercise Interventions to Improve Postural Control in Older Adults: A Systematic Review and Meta-Analyses of Centre of Pressure Measurements.

PubMed

Low, Daniel C; Walsh, Gregory S; Arkesteijn, Marco

2017-01-01

Previous reviews have shown balance in older adults to be improved with exercise. However, it is currently unclear whether postural control, indicated by centre of pressure (COP) measurement, can be improved in older adults and thus whether postural control could be a mechanism to improve balance. The purpose of this systematic review was to assess the effectiveness of force platform COP variables to identify changes in postural control following exercise interventions in older adults. In addition, a secondary purpose was to determine whether the exercise types (balance, resistance or multi-component exercise interventions) are equally effective to improve postural control. Randomised controlled trials were identified using searches of databases and reference lists (PROSPERO registration number CRD42014010617). Trials performing exercise interventions, reporting force platform COP measurements, in participants with a mean age of ≥60 years were included. Risk of bias assessments were performed following the Cochrane guidelines. Data were pooled in meta-analyses, and standardised mean differences (SMDs) with 95 % confidence intervals (CIs) were calculated. Twenty-three trials met the inclusion criteria for the systematic review. Twenty-two trials could be defined as either utilising a balance, resistance or multi-component exercise intervention. These 22 trials were used in the meta-analyses. All trials reported measurements of double leg stance; eight trials reported additional stance conditions. The meta-analyses of double leg stance showed that balance exercise interventions significantly decreased total sway path length/velocity [SMD -1.13, 95 % CI -1.75 to -0.51 (eyes open); SMD -0.79, 95 % CI -1.33 to -0.26 (eyes closed)] and anterior-posterior sway path length/velocity [SMD -1.02, 95 % CI -2.01 to -0.02 (eyes open); SMD -0.82, 95 % CI -1.46 to -0.17 (eyes closed)] in both eyes open and eyes closed conditions. Balance exercise interventions also decreased sway area in eyes closed conditions (SMD -0.57, 95 % CI -1.01 to -0.13) and medio-lateral sway path length/velocity in eyes open conditions (SMD -0.8, 95 % CI -1.48 to -0.12). In contrast, neither resistance nor multi-component exercise interventions affected any of the included COP measurements. Postural control is improved by balance exercise interventions. In contrast, strength or multi-component exercise interventions did not influence postural control measurements in older adults. In addition, a lack of standardisation in collection protocol and COP variables calculated across trials was identified.

A Quantitative Assessment of the Reporting Quality of Herbal Medicine Research: The Road to Improvement.

PubMed

Naumann, Ken

2018-02-01

To quantify different aspects of the quality of reporting of herbal medicine clinical trials, to determine how that quality is affecting the conclusions of meta-analyses, and to target areas for improvement in future herbal medicine research reporting. The Electronic databases PubMed, Academic Search Premier, ScienceDirect, and Alt HealthWatch were searched for meta-analyses of herbal medicines in refereed journals and Cochrane Reviews in the years 2000-2004 and 2010-2014. The search was limited to meta-analyses of randomized controlled trials involving humans and published in English. Judgments and descriptions within the meta-analyses were used to report on risks of bias in the included clinical trials and the meta-analyses themselves. Out of 3264 citations, 9 journal-published meta-analyses were selected from 2000 to 2004, 116 from 2010 to 2014, and 44 Cochrane Reviews from 2010 to 2014. Across both time frames and categories of publication, <42% of the trials included in the meta-analyses described adequate randomization; <19% described concealment methods; <26% described double blinding; <29% described outcome assessment blinding, ≤53% discussed incomplete data, and <36% were nonselective in their reporting. Less than 54% of trials reported on adverse events and 64% of meta-analyses did not include a single trial with a low risk of bias. Taxonomic verification and chemical characterization of test products were infrequent in trials. Only 40% of meta-analyses considered publication bias and, of those that did, 90% found evidence for it. Cochrane Reviews were more likely than other sources to make negative conclusions of efficacy or to defer conclusions because of the absence of high quality trials. Meta-analyses of herbal medicines include a significant number of clinical trials that do not meet the recommended standards for clinical trial reporting. This quantitative assessment identified significant publication bias and other bias risks that may be due to inadequate trial design or incomplete reporting of outcomes. Suggested improvements to herbal medicine clinical trial reporting are discussed.

Efficacy of early controlled motion of the ankle compared with no motion after non-operative treatment of an acute Achilles tendon rupture: study protocol for a randomized controlled trial.

PubMed

Barfod, Kristoffer Weisskirchner; Hansen, Maria Swennergren; Holmich, Per; Troelsen, Anders; Kristensen, Morten Tange

2016-11-29

Early controlled ankle motion is widely used in the non-operative treatment of acute Achilles tendon rupture, though its safety and efficacy have never been investigated in a randomized setup. The objectives of this study are to investigate if early controlled motion of the ankle affects functional and patient-reported outcomes. The study is performed as a blinded, randomized, controlled trial with patients allocated in a 1:1 ratio to one of two parallel groups. Patients aged from 18 to 70 years are eligible for inclusion. The intervention group performs early controlled motion of the ankle in weeks 3-8 after rupture. The control group is immobilized. In total, 130 patients will be included from one big orthopedic center over a period of 2½ years. The primary outcome is the patient-reported Achilles tendon Total Rupture Score evaluated at 12 months post-injury. Secondary outcome measures are the heel-rise work test, Achilles tendon elongation, and the rate of re-rupture. The primary analysis will be conducted as intention-to-treat analyses. This trial is the first to investigate the safety and efficacy of early controlled motion in the treatment of acute Achilles tendon rupture in a randomized setup. The study uses the patient-reported outcome measure, the Achilles tendon Total Rupture Score, as the primary endpoint, as it is believed to be the best surrogate measure for the tendon's actual capability to function in everyday life. ClinicalTrials.gov: NCT02015364 . Registered on 13 December 2013.

Standards for reporting randomized controlled trials in medical informatics: a systematic review of CONSORT adherence in RCTs on clinical decision support

PubMed Central

Berntsen, G; Lassen, K; Bellika, J G; Wootton, R; Lindsetmo, R O

2011-01-01

Introduction The Consolidated Standards for Reporting Trials (CONSORT) were published to standardize reporting and improve the quality of clinical trials. The objective of this study is to assess CONSORT adherence in randomized clinical trials (RCT) of disease specific clinical decision support (CDS). Methods A systematic search was conducted of the Medline, EMBASE, and Cochrane databases. RCTs on CDS were assessed against CONSORT guidelines and the Jadad score. Result 32 of 3784 papers identified in the primary search were included in the final review. 181 702 patients and 7315 physicians participated in the selected trials. Most trials were performed in primary care (22), including 897 general practitioner offices. RCTs assessing CDS for asthma (4), diabetes (4), and hyperlipidemia (3) were the most common. Thirteen CDS systems (40%) were implemented in electronic medical records, and 14 (43%) provided automatic alerts. CONSORT and Jadad scores were generally low; the mean CONSORT score was 30.75 (95% CI 27.0 to 34.5), median score 32, range 21–38. Fourteen trials (43%) did not clearly define the study objective, and 11 studies (34%) did not include a sample size calculation. Outcome measures were adequately identified and defined in 23 (71%) trials; adverse events or side effects were not reported in 20 trials (62%). Thirteen trials (40%) were of superior quality according to the Jadad score (≥3 points). Six trials (18%) reported on long-term implementation of CDS. Conclusion The overall quality of reporting RCTs was low. There is a need to develop standards for reporting RCTs in medical informatics. PMID:21803926

Industry funding and the reporting quality of large long-term weight loss trials

PubMed Central

Thomas, Olivia; Thabane, Lehana; Douketis, James; Chu, Rong; Westfall, Andrew O.; Allison, David B.

2009-01-01

Background Quality of reporting (QR) in industry-funded research is a concern of the scientific community. Greater scrutiny of industry-sponsored research reporting has been suggested, although differences in QR by sponsorship type have not been evaluated in weight loss interventions. Objective To evaluate the association of funding source and QR of long-term obesity randomized clinical trials. Methods We analyzed papers that reported long-term weight loss trials. Articles were obtained through searches of MEDLINE, HealthStar, and the Cochrane Controlled Trials Register between the years 1966–2003. QR scores were determined for each study based upon expanded criteria from the Consolidated Standards for Reporting Trials (CONSORT) checklist for a maximum score of 44 points. Studies were coded by category of industry support (0=no industry support, 1= industry support, 2= in kind contribution from industry and 3=duality of interest reported). Individual CONSORT reporting criteria were tabulated by funding type. An independent samples t-test compared differences in QR scores by funding source and the Wilcox-Mann-Whitney test and generalized estimating equations (GEE) were used for sensitivity analyses. Results Of the 63 RCTs evaluated, 67% were industry-supported trials. Industry funding was associated with higher QR score in long-term weight loss trials compared to non-industry funded studies (Mean QR (SD): Industry = 27.9 (4.1), Non-Industry =23.4 (4.1); p < 0.0005). The Wilcox-Mann-Whitney test confirmed this result (p<0.0005). Controlling for the year of publication and whether paper was published before the CONSORT statement was released in a GEE regression analysis, the direction and magnitude of effect was similar and statistically significant (p=0.035). Of the individual criteria that prior research has associated with biases, industry funding was associated with greater reporting of intent-to-treat analysis (p=0.0158), but was not different from non-industry studies in reporting of treatment allocation and blinding. Conclusion Our findings suggest that efforts to improve reporting quality be directed at all obesity RCTs irrespective of funding source. PMID:18711388

Industry funding and the reporting quality of large long-term weight loss trials.

PubMed

Thomas, O; Thabane, L; Douketis, J; Chu, R; Westfall, A O; Allison, D B

2008-10-01

Quality of reporting (QR) in industry-funded research is a concern of the scientific community. Greater scrutiny of industry-sponsored research reporting has been suggested, although differences in QR by sponsorship type have not been evaluated in weight loss interventions. To evaluate the association of funding source and QR of long-term obesity randomized clinical trials (RCT). We analysed papers that reported long-term weight loss trials. Articles were obtained through searches of Medline, HealthStar, and the Cochrane Controlled Trials Register between the years 1966 and 2003. QR scores were determined for each study based upon expanded criteria from the Consolidated Standards for Reporting Trials (CONSORT) checklist for a maximum score of 44 points. Studies were coded by category of industry support (0=no industry support, 1=industry support, 2=in kind contribution from industry and 3=duality of interest reported). Individual CONSORT reporting criteria were tabulated by funding type. An independent samples t-test compared the differences in QR scores by funding source and the Wilcox-Mann-Whitney test and generalised estimating equations (GEE) were used for sensitivity analyses. Of the 63 RCTs evaluated, 67% were industry-supported trials. Industry funding was associated with higher QR score in long-term weight loss trials compared with nonindustry-funded studies (mean QR (s.d.): industry=27.9 (4.1), nonindustry=23.4 (4.1); P<0.0005). The Wilcox-Mann-Whitney test confirmed this result (P<0.0005). Controlling for the year of publication and whether the paper was published before the CONSORT statement was released in the GEE regression analysis, the direction and magnitude of effect were similar and statistically significant (P=0.035). Of the individual criteria that prior research has associated with biases, industry funding was associated with greater reporting of intent-to-treat analysis (P=0.0158), but was not different from nonindustry studies in reporting of treatment allocation and blinding. Our findings suggest that the efforts to improve reporting quality be directed to all obesity RCTs, irrespective of funding source.

Advice for acute low back pain: a comparison of what research supports and what guidelines recommend.

PubMed

Stevens, Matthew L; Lin, Chung-Wei C; de Carvalho, Flavia A; Phan, Kevin; Koes, Bart; Maher, Chris G

2017-10-01

Advice is widely considered an effective treatment for acute low back pain (LBP); however, details on what and how to deliver this intervention is less clear. We assessed and compared clinical trials that test advice for acute LBP with practice guidelines for their completeness of reporting and concordance on the content, method of delivery, and treatment regimen of advice interventions. Systematic review. Advice randomized controlled trials were identified through a systematic search. Guidelines were taken from recent overviews of guidelines for LBP. Completeness of reporting was assessed using the Template for Intervention Description and Replication checklist. Thematic analysis was used to characterize advice interventions into topics across the aspects of content, method of delivery, and regimen. Concordance between clinical trials and guidelines was assessed by comparing the number of trials that found a statistically significant treatment effect for an intervention that included a specific advice topic with the number of guidelines recommending that topic. The median (interquartile range) completeness of reporting for clinical trials and guidelines was 8 (7-9) and 3 (2-4) out of nine items on the Template for Intervention Description and Replication checklist, respectively. Guideline recommendations were discordant with clinical trials for 50% of the advice topics identified. Completeness of reporting was less than ideal for randomized controlled trials and extremely poor for guidelines. The recommendations made in guidelines of advice for acute LBP were often not concordant with the results of clinical trials. Taken together, these findings mean that the potential clinical value of advice interventions for patients with acute LBP is probably not being realized. Copyright © 2017 Elsevier Inc. All rights reserved.

Effectiveness and Patient Acceptability of Stellate Ganglion Block (SGB) for Treatment of Posttraumatic Stress Disorder (PTSD) Symptoms among Active Duty Military Members

DTIC Science & Technology

2017-03-01

ORGANIZATION: Research Triangle Institute Research Triangle Park, NC 27709-0155 REPORT DATE: March 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S...ganglion block, Posttraumatic Stress Disorder, randomized controlled trial, qualitative research 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...Posttraumatic Stress Disorder, randomized controlled trial,  qualitative   research     3.  Accomplishments    The major goals of this project for year two

Clinical efficacy of composite versus ceramic inlays and onlays: a systematic review.

PubMed

Fron Chabouis, Hélène; Smail Faugeron, Violaine; Attal, Jean-Pierre

2013-12-01

Large tooth substance losses are frequent in posterior teeth because of primary caries or aging restorations. Inlays and onlays are often the minimal invasive solution in such cases, but the efficacy of the composite and ceramic materials used is unknown. We performed a systematic review of randomized controlled trials comparing the efficacy of composite and ceramic inlays or onlays. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched without any restriction on date or language, as were references of eligible studies and ClinicalTrials.gov. Eligible studies were randomized trials comparing the clinical efficacy of composite to ceramic inlays or onlays in adults with any clinical outcome for at least 6 months. From 172 records identified, we examined reports of 2 randomized controlled trials involving 138 inlays (no onlays evaluated) in 80 patients and exhibiting a high-risk of bias. Outcomes were clinical scores and major failures. The 3-year overall failure risk ratio was 2 [0.38-10.55] in favor of ceramic inlays although not statistically significant. The reported clinical scores (United States Public Health Services and Californian Dental Association) showed considerable heterogeneity between trials and could not be combined. We have very limited evidence that ceramics perform better than composite material for inlays in the short term. However, this result may not be valid in the long term, and other trials are needed. Trials should follow Fédération dentaire internationale recommendations and enhance their methodology. Trials comparing composite and ceramic onlays are needed. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

When is a randomised controlled trial health equity relevant? Development and validation of a conceptual framework

PubMed Central

Jull, J; Whitehead, M; Petticrew, M; Kristjansson, E; Gough, D; Petkovic, J; Volmink, J; Weijer, C; Taljaard, M; Edwards, S; Mbuagbaw, L; Cookson, R; McGowan, J; Lyddiatt, A; Boyer, Y; Cuervo, L G; Armstrong, R; White, H; Yoganathan, M; Pantoja, T; Shea, B; Pottie, K; Norheim, O; Baird, S; Robberstad, B; Sommerfelt, H; Asada, Y; Wells, G; Tugwell, P; Welch, V

2017-01-01

Background Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials. Methods An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials. Results A randomised trial can usefully be classified as ‘health equity relevant’ if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as ‘health equity relevant’ may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies. Conclusion The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity. PMID:28951402

Can psychotherapists function as their own controls? Meta-analysis of the crossed therapist design in comparative psychotherapy trials.

PubMed

Falkenström, Fredrik; Markowitz, John C; Jonker, Hanske; Philips, Björn; Holmqvist, Rolf

2013-05-01

Clinical trials sometimes have the same therapists deliver more than 1 psychotherapy, ostensibly to control for therapist effects. This "crossed therapist" design makes controlling for therapist allegiance imperative, as therapists may prefer one treatment they deliver to the other(s). Research has established a strong relationship between principal investigators' allegiances and treatment outcome. Study therapists' allegiances probably also influence outcome, yet this moderating factor on outcome has never been studied. English language abstracts in PsycINFO and MEDLINE from January 1985 to December 2011 were searched for keywords psychotherapy and randomized trial. The search yielded 990 abstracts that were searched manually. Trials using the same therapists in more than 1 condition were included. Thirty-nine studies fulfilled inclusion criteria. Meta-regression analyses assessed the influence of researchers' allegiance on treatment outcome, testing the hypothesis that studies poorly controlling for therapist allegiance would show stronger influence of researcher allegiance on outcome. A single-item measure assessed researchers' reported attempts to control for therapist allegiance. Only 1 of 39 studies (3%) measured therapist treatment allegiance. Another 5 (13%) mentioned controlling for, without formally assessing, therapist allegiance. Most publications (67%) did not even mention therapist allegiance. In studies not controlling for therapist allegiance, researcher allegiance strongly influenced outcome, whereas studies reporting control for therapist allegiance showed no differential researcher allegiance. Researchers with cognitive-behavioral therapy allegiance described controlling for therapist allegiance less frequently than other researchers. The crossed therapist design is subject to bias due to differential psychotherapist allegiance. Worrisome results suggest that researchers strongly allied to a treatment may ignore therapist allegiance, potentially skewing outcomes. All clinical trials, and especially crossed therapist designs, should measure psychotherapist allegiance to evaluate this possible bias. © Copyright 2013 Physicians Postgraduate Press, Inc.

The Effect of Biologic and Targeted Synthetic Drugs on Work- and Productivity-related Outcomes for Patients with Psoriatic Arthritis: A Systematic Review.

PubMed

Iragorri, Nicolas; Hofmeister, Mark; Spackman, Eldon; Hazlewood, Glen S

2018-05-01

To systematically review the effects of biologic therapies for psoriatic arthritis [secukinumab, ustekinumab, adalimumab, etanercept, certolizumab pegol (CZP), apremilast, golimumab (GOL), or infliximab (IFX)] on work productivity. A systematic review of Medline, EMBASE, CENTRAL, and ClinicalTrials.gov was conducted to identify randomized controlled trials reporting on work productivity outcomes at the end of the placebo-controlled double-blind period. There were 7959 records identified. Full text of 377 records was further assessed for eligibility, of which 5 trials were included. All included trials were assessed with the Cochrane Risk of Bias Tool, and 4 out of 5 were judged to be of low risk of bias in most domains. Improvements in self-assessed work productivity were observed in 5 trials (IFX, GOL, CZP, ustekinumab, and apremilast), ranging from a mean difference of -0.9 to -1.8 on a 1-10 scale of self-assessed work productivity (negative change represents improvement), although statistical significance of the results was not reported for CZP and apremilast. Treatment with CZP resulted in a statistically significant reduction in absenteeism (200 mg) and presenteeism (200 and 400 mg). IFX and GOL reported a nonsignificant reduction of absenteeism. The Work Productivity Survey, the Work Limitations Questionnaire, and visual analog scales were used to measure work productivity. Treatment with IFX, GOL, CZP, ustekinumab, and apremilast resulted in improvements in self-reported work productivity. A pooled analysis was not possible because of the clinical heterogeneity of the trials and variability in outcome reporting.

Exercise-based cardiac rehabilitation for coronary heart disease.

PubMed

Anderson, Lindsey; Thompson, David R; Oldridge, Neil; Zwisler, Ann-Dorthe; Rees, Karen; Martin, Nicole; Taylor, Rod S

2016-01-05

Coronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people live with CHD and may need support to manage their symptoms and prognosis. Exercise-based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane systematic review previously published in 2011. To assess the effectiveness and cost-effectiveness of exercise-based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with usual care on mortality, morbidity and HRQL in patients with CHD.To explore the potential study level predictors of the effectiveness of exercise-based CR in patients with CHD. We updated searches from the previous Cochrane review, by searching Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 6, 2014) from December 2009 to July 2014. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and Science Citation Index Expanded (December 2009 to July 2014). We included randomised controlled trials (RCTs) of exercise-based interventions with at least six months' follow-up, compared with a no exercise control. The study population comprised men and women of all ages who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or who have angina pectoris, or coronary artery disease. We included RCTs that reported at least one of the following outcomes: mortality, MI, revascularisations, hospitalisations, health-related quality of life (HRQL), or costs. Two review authors independently screened all identified references for inclusion based on the above inclusion and exclusion criteria. One author extracted data from the included trials and assessed their risk of bias; a second review author checked data. We stratified meta-analysis by the duration of follow up of trials, i.e. short-term: 6 to 12 months, medium-term: 13 to 36 months, and long-term: > 3 years. This review included 63 trials which randomised 14,486 people with CHD. This latest update identified 16 new trials (3872 participants). The population included predominantly post-MI and post-revascularisation patients and the mean age of patients within the trials ranged from 47.5 to 71.0 years. Women accounted for fewer than 15% of the patients recruited. Overall trial reporting was poor, although there was evidence of an improvement in quality of reporting in more recent trials.As we found no significant difference in the impact of exercise-based CR on clinical outcomes across follow-up, we focused on reporting findings pooled across all trials at their longest follow-up (median 12 months). Exercise-based CR reduced cardiovascular mortality compared with no exercise control (27 trials; risk ratio (RR) 0.74, 95% CI 0.64 to 0.86). There was no reduction in total mortality with CR (47 trials, RR 0.96, 95% CI 0.88 to 1.04). The overall risk of hospital admissions was reduced with CR (15 trials; RR 0.82, 95% CI 0.70 to 0.96) but there was no significant impact on the risk of MI (36 trials; RR 0.90, 95% CI 0.79 to 1.04), CABG (29 trials; RR 0.96, 95% CI 0.80 to 1.16) or PCI (18 trials; RR 0.85, 95% CI 0.70 to 1.04).There was little evidence of statistical heterogeneity across trials for all event outcomes, and there was evidence of small study bias for MI and hospitalisation, but no other outcome. Predictors of clinical outcomes were examined across the longest follow-up of studies using univariate meta-regression. Results show that benefits in outcomes were independent of participants' CHD case mix (proportion of patients with MI), type of CR (exercise only vs comprehensive rehabilitation) dose of exercise, length of follow-up, trial publication date, setting (centre vs home-based), study location (continent), sample size or risk of bias.Given the heterogeneity in outcome measures and reporting methods, meta-analysis was not undertaken for HRQL. In five out of 20 trials reporting HRQL using validated measures, there was evidence of significant improvement in most or all of the sub-scales with exercise-based CR compared to control at follow-up. Four trial-based economic evaluation studies indicated exercise-based CR to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years.The quality of the evidence for outcomes reported in the review was rated using the GRADE method. The quality of the evidence varied widely by outcome and ranged from low to moderate. This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise-based CR reduces the risk of cardiovascular mortality but not total mortality. We saw a significant reduction in the risk of hospitalisation with CR but not in the risk of MI or revascularisation. We identified further evidence supporting improved HRQL with exercise-based CR. More recent trials were more likely to be well reported and include older and female patients. However, the population studied in this review still consists predominantly of lower risk individuals following MI or revascularisation. Further well conducted RCTs are needed to assess the impact of exercise-based CR in higher risk CHD groups and also those presenting with stable angina. These trials should include validated HRQL outcome measures, explicitly report clinical event outcomes including mortality and hospital admissions, and assess costs and cost-effectiveness.

Diet, physical activity or both for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus.

PubMed

Hemmingsen, Bianca; Gimenez-Perez, Gabriel; Mauricio, Didac; Roqué I Figuls, Marta; Metzendorf, Maria-Inti; Richter, Bernd

2017-12-04

The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether diet, physical activity or both can prevent or delay T2DM and its associated complications in at-risk people is unknown. To assess the effects of diet, physical activity or both on the prevention or delay of T2DM and its associated complications in people at increased risk of developing T2DM. This is an update of the Cochrane Review published in 2008. We searched the CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, ICTRP Search Portal and reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was January 2017. We continuously used a MEDLINE email alert service to identify newly published studies using the same search strategy as described for MEDLINE up to September 2017. We included randomised controlled trials (RCTs) with a duration of two years or more. We used standard Cochrane methodology for data collection and analysis. We assessed the overall quality of the evidence using GRADE. We included 12 RCTs randomising 5238 people. One trial contributed 41% of all participants. The duration of the interventions varied from two to six years. We judged none of the included trials at low risk of bias for all 'Risk of bias' domains.Eleven trials compared diet plus physical activity with standard or no treatment. Nine RCTs included participants with impaired glucose tolerance (IGT), one RCT included participants with IGT, impaired fasting blood glucose (IFG) or both, and one RCT included people with fasting glucose levels between 5.3 to 6.9 mmol/L. A total of 12 deaths occurred in 2049 participants in the diet plus physical activity groups compared with 10 in 2050 participants in the comparator groups (RR 1.12, 95% CI 0.50 to 2.50; 95% prediction interval 0.44 to 2.88; 4099 participants, 10 trials; very low-quality evidence). The definition of T2DM incidence varied among the included trials. Altogether 315 of 2122 diet plus physical activity participants (14.8%) developed T2DM compared with 614 of 2389 comparator participants (25.7%) (RR 0.57, 95% CI 0.50 to 0.64; 95% prediction interval 0.50 to 0.65; 4511 participants, 11 trials; moderate-quality evidence). Two trials reported serious adverse events. In one trial no adverse events occurred. In the other trial one of 51 diet plus physical activity participants compared with none of 51 comparator participants experienced a serious adverse event (low-quality evidence). Cardiovascular mortality was rarely reported (four of 1626 diet plus physical activity participants and four of 1637 comparator participants (the RR ranged between 0.94 and 3.16; 3263 participants, 7 trials; very low-quality evidence). Only one trial reported that no non-fatal myocardial infarction or non-fatal stroke had occurred (low-quality evidence). Two trials reported that none of the participants had experienced hypoglycaemia. One trial investigated health-related quality of life in 2144 participants and noted that a minimal important difference between intervention groups was not reached (very low-quality evidence). Three trials evaluated costs of the interventions in 2755 participants. The largest trial of these reported an analysis of costs from the health system perspective and society perspective reflecting USD 31,500 and USD 51,600 per quality-adjusted life year (QALY) with diet plus physical activity, respectively (low-quality evidence). There were no data on blindness or end-stage renal disease.One trial compared a diet-only intervention with a physical-activity intervention or standard treatment. The participants had IGT. Three of 130 participants in the diet group compared with none of the 141 participants in the physical activity group died (very low-quality evidence). None of the participants died because of cardiovascular disease (very low-quality evidence). Altogether 57 of 130 diet participants (43.8%) compared with 58 of 141 physical activity participants (41.1%) group developed T2DM (very low-quality evidence). No adverse events were recorded (very low-quality evidence). There were no data on non-fatal myocardial infarction, non-fatal stroke, blindness, end-stage renal disease, health-related quality of life or socioeconomic effects.Two trials compared physical activity with standard treatment in 397 participants. One trial included participants with IGT, the other trial included participants with IGT, IFG or both. One trial reported that none of the 141 physical activity participants compared with three of 133 control participants died. The other trial reported that three of 84 physical activity participants and one of 39 control participants died (very low-quality evidence). In one trial T2DM developed in 58 of 141 physical activity participants (41.1%) compared with 90 of 133 control participants (67.7%). In the other trial 10 of 84 physical activity participants (11.9%) compared with seven of 39 control participants (18%) developed T2DM (very low-quality evidence). Serious adverse events were rarely reported (one trial noted no events, one trial described events in three of 66 physical activity participants compared with one of 39 control participants - very low-quality evidence). Only one trial reported on cardiovascular mortality (none of 274 participants died - very low-quality evidence). Non-fatal myocardial infarction or stroke were rarely observed in the one trial randomising 123 participants (very low-quality evidence). One trial reported that none of the participants in the trial experienced hypoglycaemia. One trial investigating health-related quality of life in 123 participants showed no substantial differences between intervention groups (very low-quality evidence). There were no data on blindness or socioeconomic effects. There is no firm evidence that diet alone or physical activity alone compared to standard treatment influences the risk of T2DM and especially its associated complications in people at increased risk of developing T2DM. However, diet plus physical activity reduces or delays the incidence of T2DM in people with IGT. Data are lacking for the effect of diet plus physical activity for people with intermediate hyperglycaemia defined by other glycaemic variables. Most RCTs did not investigate patient-important outcomes.

A pilot effectiveness study of the Enhancing Parenting Skills (EPaS) 2014 programme for parents of children with behaviour problems: study protocol for a randomised controlled trial.

PubMed

Williams, Margiad Elen; Hutchings, Judy

2015-05-20

The Enhancing Parenting Skills (EPaS) 2014 programme is a home-based, health visitor-delivered parenting support programme for parents of children with identified behaviour problems. This trial aims to evaluate the effectiveness of the EPaS 2014 programme compared to a waiting-list treatment as usual control group. This is a pragmatic, multicentre randomised controlled trial. Sixty health visitors will each be asked to identify two families that have a child scoring above the clinical cut-off for behaviour problems using the Eyberg Child Behaviour Inventory (ECBI). Families recruited to the trial will be randomised in a 1:1 ratio into an intervention or waiting-list control group. Randomisation will occur within health visitor to ensure that each health visitor has one intervention family and one control family. The primary outcome is change in child behaviour problems as measured by the parent-reported ECBI. Secondary outcomes include other measures of child behaviour, parent behaviour, and parental depression as measured by parent-reports and an independent observation of parent and child behaviour. Follow-up measures will be collected 6-months after the collection of baseline measures. This is the first rigorous evaluation of the EPaS 2014 programme. The trial will provide important information on the effectiveness of a one-to-one home-based intervention, delivered by health visitors, for pre-school children with behaviour problems. It will also examine potential mediating (improved parent behaviour and/or improved parental depression) and moderating (single parent, teenage parent, poverty, low education level) factors. Current Controlled Trials ISRCTN06867279 (18 June 2014).

Ear Acupuncture for Acute Sore Throat: A Randomized Controlled Trial

DTIC Science & Technology

2014-09-26

SEP 2014 2. REPORT TYPE Final 3. DATES COVERED 4. TITLE AND SUBTITLE Ear acupuncture for acute sore throat. A randomized controlled trial...Auncular Acupuncture is a low risk option for acute pain control •Battlefield acupuncture (BFA) IS a specific auncular acupuncture technique •BFA IS...Strengths: Prospect1ve RCT •Weaknesses Small sample stze. no sham acupuncture performed, patients not blinded to treatment •Th1s study represents an

Can Psychotherapists Function as Their Own Controls? Meta-Analysis of the “Crossed Therapist” Design in Comparative Psychotherapy Trials

PubMed Central

Falkenström, Fredrik; Markowitz, John C.; Jonker, Hanske; Philips, Björn; Holmqvist, Rolf

2013-01-01

Objective Clinical trials sometimes have the same therapists deliver more than one psychotherapy, ostensibly to control for therapist effects. This “crossed therapists” design makes controlling for therapist allegiance imperative, as therapists may prefer one treatment they deliver to the other(s). Research has established a strong relationship between principal investigators’ allegiances and treatment outcome. Study therapists’ allegiances probably also influence outcome, yet this moderating factor on outcome has never been studied. Data Sources English language abstracts in Psychinfo and MedLine from January 1985 to December 2011 were searched for keywords “psychotherapy” and “randomized trial.” Study Selection The search yielded 990 abstracts that were searched manually. Trials using the same therapists in more than one condition were included. Data extraction Thirty-nine studies fulfilled inclusion criteria. Meta-regression analyses assessed the influence of researchers’ allegiance on treatment outcome, testing the hypothesis that studies poorly controlling for therapist allegiance would show stronger influence of researcher allegiance on outcome. A single-item measure assessed researchers’ reported attempts to control for therapist allegiance. Results Only one (3%) of 39 studies measured therapist treatment allegiance. Another five (13%) mentioned controlling for, without formally assessing, therapist allegiance. Most publications (64%) did not even mention therapist allegiance. In studies not controlling for therapist allegiance, researcher allegiance strongly influenced outcome, whereas studies reporting control for therapist allegiance showed no differential researcher allegiance. Cognitive-behavioral trials less frequently described controlling for therapist allegiance. Conclusions The “crossed therapist” design is subject to bias due to differential psychotherapist allegiance. Worrisome results suggest that researchers strongly allied to a treatment may ignore therapist allegiance, potentially skewing outcomes. All clinical trials, and especially “crossed therapist” designs, should measure psychotherapist allegiance to evaluate this possible bias. One of the sacrosanct assumptions of a client is that their therapist believes in the treatment being delivered. -- Wampold, 2001 (1, p159) PMID:23146326

Randomized controlled trial in rural Ethiopia to assess a portable water treatment device.

PubMed

Boisson, Sophie; Schmidt, Wolf-Peter; Berhanu, Tsegahiwot; Gezahegn, Henock; Clasen, Thomas

2009-08-01

We conducted a randomized controlled trial to assess the Lifestraw Personal pipe-style water treatment device among a rural population in Ethiopia. A total of 313 households (including 1516 persons) were randomly assigned either to an intervention group in which each householder received a Lifestraw Personal or a control. Households were visited fortnightly over a five-month intervention period and asked to report any episode of diarrhea during the previous week. A random sample of 160 devices was tested each month to assess the presence of thermotolerant coliforms (TTC) and residual iodine in treated water and to measure flow rate under simulated use. Members of the intervention group had 25% fewer weeks with diarrhea than those of the control group (longitudinal prevalence ratio = 0.75; 95% CI 0.60; 0.95). All 718 filtered water samples were free of TTC, were free of detectable iodine disinfectant, and showed a constant flow rate over time. After the five-month intervention period, 34% of participants reported use of device in the preceding week and 13% reported consistent use. While the device was associated with a 25% reduction in longitudinal prevalence of diarrhea, low levels of use suggest that much of this effect is likely to be attributable to reporting bias that is common in open trials with nonobjective outcomes.

Use of placebo controls in the evaluation of surgery: systematic review

PubMed Central

Judge, Andrew; Hopewell, Sally; Collins, Gary S; Dean, Benjamin J F; Rombach, Ines; Brindley, David; Savulescu, Julian; Beard, David J; Carr, Andrew J

2014-01-01

Objective To investigate whether placebo controls should be used in the evaluation of surgical interventions. Design Systematic review. Data sources We searched Medline, Embase, and the Cochrane Controlled Trials Register from their inception to November 2013. Study selection Randomised clinical trials comparing any surgical intervention with placebo. Surgery was defined as any procedure that both changes the anatomy and requires a skin incision or use of endoscopic techniques. Data extraction Three reviewers (KW, BJFD, IR) independently identified the relevant trials and extracted data on study details, outcomes, and harms from included studies. Results In 39 out of 53 (74%) trials there was improvement in the placebo arm and in 27 (51%) trials the effect of placebo did not differ from that of surgery. In 26 (49%) trials, surgery was superior to placebo but the magnitude of the effect of the surgical intervention over that of the placebo was generally small. Serious adverse events were reported in the placebo arm in 18 trials (34%) and in the surgical arm in 22 trials (41.5%); in four trials authors did not specify in which arm the events occurred. However, in many studies adverse events were unrelated to the intervention or associated with the severity of the condition. The existing placebo controlled trials investigated only less invasive procedures that did not involve laparotomy, thoracotomy, craniotomy, or extensive tissue dissection. Conclusions Placebo controlled trial is a powerful, feasible way of showing the efficacy of surgical procedures. The risks of adverse effects associated with the placebo are small. In half of the studies, the results provide evidence against continued use of the investigated surgical procedures. Without well designed placebo controlled trials of surgery, ineffective treatment may continue unchallenged. PMID:24850821

Patient reported outcomes (PROs) in clinical trials: is 'in-trial' guidance lacking? a systematic review.

PubMed

Kyte, Derek G; Draper, Heather; Ives, Jonathan; Liles, Clive; Gheorghe, Adrian; Calvert, Melanie

2013-01-01

Patient reported outcomes (PROs) are increasingly assessed in clinical trials, and guidelines are available to inform the design and reporting of such trials. However, researchers involved in PRO data collection report that specific guidance on 'in-trial' activity (recruitment, data collection and data inputting) and the management of 'concerning' PRO data (i.e., data which raises concern for the well-being of the trial participant) appears to be lacking. The purpose of this review was to determine the extent and nature of published guidelines addressing these areas. Systematic review of 1,362 articles identified 18 eligible papers containing 'in-trial' guidelines. Two independent authors undertook a qualitative content analysis of the selected papers. Guidelines presented in each of the articles were coded according to an a priori defined coding frame, which demonstrated reliability (pooled Kappa 0.86-0.97), and validity (<2% residual category coding). The majority of guidelines present were concerned with 'pre-trial' activities (72%), for example, outcome measure selection and study design issues, or 'post-trial' activities (16%) such as data analysis, reporting and interpretation. 'In-trial' guidelines represented 9.2% of all guidance across the papers reviewed, with content primarily focused on compliance, quality control, proxy assessment and reporting of data collection. There were no guidelines surrounding the management of concerning PRO data. The findings highlight there are minimal in-trial guidelines in publication regarding PRO data collection and management in clinical trials. No guidance appears to exist for researchers involved with the handling of concerning PRO data. Guidelines are needed, which support researchers to manage all PRO data appropriately and which facilitate unbiased data collection.

A Randomized, Wait-List Controlled Effectiveness Trial Assessing School-Wide Positive Behavior Support in Elementary Schools

ERIC Educational Resources Information Center

Horner, Robert H.; Sugai, George; Smolkowski, Keith; Eber, Lucille; Nakasato, Jean; Todd, Anne W.; Esperanza, Jody

2009-01-01

We report a randomized, wait-list controlled trial assessing the effects of school-wide positive behavior support (SWPBS). An effectiveness analysis was conducted with elementary schools in Hawaii and Illinois where training and technical assistance in SWPBS was provided by regular state personnel over a 3-year period. Results document that the…

Brief Report: Pilot Randomized Controlled Trial of Reciprocal Imitation Training for Teaching Elicited and Spontaneous Imitation to Children with Autism

ERIC Educational Resources Information Center

Ingersoll, Brooke

2010-01-01

Children with autism exhibit significant deficits in imitation skills. Reciprocal Imitation Training (RIT), a naturalistic imitation intervention, was developed to teach young children with autism to imitate during play. This study used a randomized controlled trial to evaluate the efficacy of RIT on elicited and spontaneous imitation skills in 21…

What to Do when Data Are Missing in Group Randomized Controlled Trials. NCEE 2009-0049

ERIC Educational Resources Information Center

Puma, Michael J.; Olsen, Robert B.; Bell, Stephen H.; Price, Cristofer

2009-01-01

This NCEE Technical Methods report examines how to address the problem of missing data in the analysis of data in Randomized Controlled Trials (RCTs) of educational interventions, with a particular focus on the common educational situation in which groups of students such as entire classrooms or schools are randomized. Missing outcome data are a…

WWC Review of the Report "Evaluation of the College Possible Program: Results from a Randomized Controlled Trial." What Works Clearinghouse Single Study Review

ERIC Educational Resources Information Center

What Works Clearinghouse, 2014

2014-01-01

The 2013 study, "Evaluation of the College Possible Program: Results From a Randomized Controlled Trial", investigated the effect of the "College Possible" program, which is designed to serve low-income high school students by providing SAT/ACT test preparation, financial aid consulting, and college admissions guidance in an…

The Results of a Randomized Control Trial Evaluation of the SPARK Literacy Program

ERIC Educational Resources Information Center

Jones, Curtis J.; Christian, Michael; Rice, Andrew

2016-01-01

The purpose of this report is to present the results of a two-year randomized control trial evaluation of the SPARK literacy program. SPARK is an early grade literacy program developed by Boys & Girls Clubs of Greater Milwaukee. In 2010, SPARK was awarded an Investing in Innovation (i3) Department of Education grant to further develop the…

The Impact of Achieve3000 on Elementary Literacy Outcomes: Evidence from a Two-Year Randomized Control Trial

ERIC Educational Resources Information Center

Hill, Darryl V.; Lenard, Matthew A.; Page, Lindsay Coleman

2016-01-01

School districts are increasingly adopting technology-based resources in an attempt to improve student achievement. This paper reports the two-year results from randomized control trial of Achieve3000 in the Wake County Public School System (WCPSS) in Raleigh, North Carolina. Achieve3000 is an early literacy program that differentiates non-fiction…

Outcomes of a Telehealth Intervention for Homebound Older Adults with Heart or Chronic Respiratory Failure: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Gellis, Zvi D.; Kenaley, Bonnie; McGinty, Jean; Bardelli, Ellen; Davitt, Joan; Ten Have, Thomas

2012-01-01

Purpose: Telehealth care is emerging as a viable intervention model to treat complex chronic conditions, such as heart failure (HF) and chronic obstructive pulmonary disease (COPD), and to engage older adults in self-care disease management. Design and Methods: We report on a randomized controlled trial examining the impact of a multifaceted…

Impact of a Social-Emotional and Character Development Program on School-Level Indicators of Academic Achievement, Absenteeism, and Disciplinary Outcomes: A Matched-Pair, Cluster-Randomized, Controlled Trial

ERIC Educational Resources Information Center

Snyder, Frank; Flay, Brian; Vuchinich, Samuel; Acock, Alan; Washburn, Isaac; Beets, Michael; Li, Kin-Kit

2010-01-01

This article reports the effects of a comprehensive elementary school-based social-emotional and character education program on school-level achievement, absenteeism, and disciplinary outcomes utilizing a matched-pair, cluster-randomized, controlled design. The "Positive Action" Hawai'i trial included 20 racially/ethnically diverse…

Publishing interim results of randomised clinical trials in peer-reviewed journals.

PubMed

Counsell, Nicholas; Biri, Despina; Fraczek, Joanna; Hackshaw, Allan

2017-02-01

Interim analyses of randomised controlled trials are sometimes published before the final results are available. In several cases, the treatment effects were noticeably different after patient recruitment and follow-up completed. We therefore conducted a literature review of peer-reviewed journals to compare the reported treatment effects between interim and final publications and to examine the magnitude of the difference. We performed an electronic search of MEDLINE from 1990 to 2014 (keywords: 'clinical trial' OR 'clinical study' AND 'random*' AND 'interim' OR 'preliminary'), and we manually identified the corresponding final publication. Where the electronic search produced a final report in which the abstract cited interim results, we found the interim publication. We also manually searched every randomised controlled trial in eight journals, covering a range of impact factors and general medical and specialist publications (1996-2014). All paired articles were checked to ensure that the same comparison between interventions was available in both. In all, 63 studies are included in our review, and the same quantitative comparison was available in 58 of these. The final treatment effects were smaller than the interim ones in 39 (67%) trials and the same size or larger in 19 (33%). There was a marked reduction, defined as a ≥20% decrease in the size of the treatment effect from interim to final analysis, in 11 (19%) trials compared to a marked increase in 3 (5%), p = 0.057. The magnitude of percentage change was larger in trials where commercial support was reported, and increased as the proportion of final events at the interim report decreased in trials where commercial support was reported (interaction p = 0.023). There was no evidence of a difference between trials that stopped recruitment at the interim analysis where this was reported as being pre-specified versus those that were not pre-specified (interaction p = 0.87). Published interim trial results were more likely to be associated with larger treatment effects than those based on the final report. Publishing interim results should be discouraged, in order to have reliable estimates of treatment effects for clinical decision-making, regulatory authority reviews and health economic analyses. Our work should be expanded to include conference publications and manual searches of additional journal publications.

Fibrin Sealants in Dura Sealing: A Systematic Literature Review

PubMed Central

2016-01-01

Background Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. Methods A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. Results A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. Conclusions A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety. PMID:27119993

Fibrin Sealants in Dura Sealing: A Systematic Literature Review.

PubMed

Esposito, Felice; Angileri, Filippo Flavio; Kruse, Peter; Cavallo, Luigi Maria; Solari, Domenico; Esposito, Vincenzo; Tomasello, Francesco; Cappabianca, Paolo

2016-01-01

Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety.

Informing efficient randomised controlled trials: exploration of challenges in developing progression criteria for internal pilot studies.

PubMed

Avery, Kerry N L; Williamson, Paula R; Gamble, Carrol; O'Connell Francischetto, Elaine; Metcalfe, Chris; Davidson, Peter; Williams, Hywel; Blazeby, Jane M

2017-02-17

Designing studies with an internal pilot phase may optimise the use of pilot work to inform more efficient randomised controlled trials (RCTs). Careful selection of preagreed decision or 'progression' criteria at the juncture between the internal pilot and main trial phases provides a valuable opportunity to evaluate the likely success of the main trial and optimise its design or, if necessary, to make the decision not to proceed with the main trial. Guidance on the appropriate selection and application of progression criteria is, however, lacking. This paper outlines the key issues to consider in the optimal development and review of operational progression criteria for RCTs with an internal pilot phase. A structured literature review and exploration of stakeholders' opinions at a Medical Research Council (MRC) Hubs for Trials Methodology Research workshop. Key stakeholders included triallists, methodologists, statisticians and funders. There is considerable variation in the use of progression criteria for RCTs with an internal pilot phase, although 3 common issues predominate: trial recruitment, protocol adherence and outcome data. Detailed and systematic reporting around the decision-making process for stopping, amending or proceeding to a main trial is uncommon, which may hamper understanding in the research community about the appropriate and optimal use of RCTs with an internal pilot phase. 10 top tips for the development, use and reporting of progression criteria for internal pilot studies are presented. Systematic and transparent reporting of the design, results and evaluation of internal pilot trials in the literature should be encouraged in order to facilitate understanding in the research community and to inform future trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Informing efficient randomised controlled trials: exploration of challenges in developing progression criteria for internal pilot studies

PubMed Central

Williamson, Paula R; Gamble, Carrol; O'Connell Francischetto, Elaine; Metcalfe, Chris; Davidson, Peter; Williams, Hywel; Blazeby, Jane M

2017-01-01

Objectives Designing studies with an internal pilot phase may optimise the use of pilot work to inform more efficient randomised controlled trials (RCTs). Careful selection of preagreed decision or ‘progression’ criteria at the juncture between the internal pilot and main trial phases provides a valuable opportunity to evaluate the likely success of the main trial and optimise its design or, if necessary, to make the decision not to proceed with the main trial. Guidance on the appropriate selection and application of progression criteria is, however, lacking. This paper outlines the key issues to consider in the optimal development and review of operational progression criteria for RCTs with an internal pilot phase. Design A structured literature review and exploration of stakeholders' opinions at a Medical Research Council (MRC) Hubs for Trials Methodology Research workshop. Key stakeholders included triallists, methodologists, statisticians and funders. Results There is considerable variation in the use of progression criteria for RCTs with an internal pilot phase, although 3 common issues predominate: trial recruitment, protocol adherence and outcome data. Detailed and systematic reporting around the decision-making process for stopping, amending or proceeding to a main trial is uncommon, which may hamper understanding in the research community about the appropriate and optimal use of RCTs with an internal pilot phase. 10 top tips for the development, use and reporting of progression criteria for internal pilot studies are presented. Conclusions Systematic and transparent reporting of the design, results and evaluation of internal pilot trials in the literature should be encouraged in order to facilitate understanding in the research community and to inform future trials. PMID:28213598

Control charts for monitoring accumulating adverse event count frequencies from single and multiple blinded trials.

PubMed

Gould, A Lawrence

2016-12-30

Conventional practice monitors accumulating information about drug safety in terms of the numbers of adverse events reported from trials in a drug development program. Estimates of between-treatment adverse event risk differences can be obtained readily from unblinded trials with adjustment for differences among trials using conventional statistical methods. Recent regulatory guidelines require monitoring the cumulative frequency of adverse event reports to identify possible between-treatment adverse event risk differences without unblinding ongoing trials. Conventional statistical methods for assessing between-treatment adverse event risks cannot be applied when the trials are blinded. However, CUSUM charts can be used to monitor the accumulation of adverse event occurrences. CUSUM charts for monitoring adverse event occurrence in a Bayesian paradigm are based on assumptions about the process generating the adverse event counts in a trial as expressed by informative prior distributions. This article describes the construction of control charts for monitoring adverse event occurrence based on statistical models for the processes, characterizes their statistical properties, and describes how to construct useful prior distributions. Application of the approach to two adverse events of interest in a real trial gave nearly identical results for binomial and Poisson observed event count likelihoods. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Twenty-year perspective of randomized controlled trials for surgery of chronic nonspecific low back pain: citation bias and tangential knowledge.

PubMed

Andrade, Nicholas S; Flynn, John P; Bartanusz, Viktor

2013-11-01

After decades of clinical research, the role of surgery for chronic nonspecific low back pain (CNLBP) remains equivocal. Despite significant intellectual, human, and economic investments into randomized controlled trials (RCTs) in the past two decades, the role of surgery in the treatment for CNLBP has not been clarified. To delineate the historical research agenda of surgical RCTs for CNLBP performed between 1993 and 2012 investigating whether conclusions from earlier published trials influenced the choice of research questions of subsequent RCTs on elucidating the role of surgery in the management of CNLBP. Literature review. We searched the literature for all RCTs involving surgery for CNLBP. We reviewed relevant studies to identify the study question, comparator arms, and sample size. Randomized controlled trials were classified as "indication" trials if they evaluated the effectiveness of surgical therapy versus nonoperative care or as "technical" if they compared different surgical techniques, adjuncts, or procedures. We used citation analysis to determine the impact of trials on subsequent research in the field. Altogether 33 technical RCTs (3,790 patients) and 6 indication RCTs (981 patients) have been performed. Since 2007, despite the unclear benefits of surgery reported by the first four indication trials published in 2001 to 2006, technical trials have continued to predominate (16 vs. 2). Of the technical trials, types of instrumentation (13 trials, 1,332 patients), bone graft materials and substitutes (11 trials, 833 patients), and disc arthroplasty versus fusion (5 trials, 1,337 patients) were the most common comparisons made. Surgeon authors have predominantly cited one of the indication trials that reported more favorable results for surgery, despite a lack of superior methodology or sample size. Trials evaluating bone morphogenic protein, instrumentation, and disc arthroplasty were all cited more frequently than the largest trial of surgical versus nonsurgical therapy. The research agenda of RCTs for surgery of CNLBP has not changed substantially in the last 20 years. Technical trials evaluating nuances of surgical techniques significantly predominate. Despite the publication of four RCTs reporting equivocal benefits of surgery for CNLBP between 2001 and 2006, there was no change in the research agenda of subsequent RCTs, and technical trials continued to outnumber indication trials. Rather than clarifying what, if any, indications for surgery exist, investigators in the field continue to analyze variations in surgical technique, which will probably have relatively little impact on patient outcomes. As a result, clinicians unfortunately have little evidence to advise patients regarding surgical intervention for CNLBP. Copyright © 2013 Elsevier Inc. All rights reserved.

Use of qualitative methods alongside randomised controlled trials of complex healthcare interventions: methodological study

PubMed Central

Glenton, Claire; Oxman, Andrew D

2009-01-01

Objective To examine the use of qualitative approaches alongside randomised trials of complex healthcare interventions. Design Review of randomised controlled trials of interventions to change professional practice or the organisation of care. Data sources Systematic sample of 100 trials published in English from the register of the Cochrane Effective Practice and Organisation of Care Review Group. Methods Published and unpublished qualitative studies linked to the randomised controlled trials were identified through database searches and contact with authors. Data were extracted from each study by two reviewers using a standard form. We extracted data describing the randomised controlled trials and qualitative studies, the quality of these studies, and how, if at all, the qualitative and quantitative findings were combined. A narrative synthesis of the findings was done. Results 30 of the 100 trials had associated qualitative work and 19 of these were published studies. 14 qualitative studies were done before the trial, nine during the trial, and four after the trial. 13 studies reported an explicit theoretical basis and 11 specified their methodological approach. Approaches to sampling and data analysis were poorly described. For most cases (n=20) we found no indication of integration of qualitative and quantitative findings at the level of either analysis or interpretation. The quality of the qualitative studies was highly variable. Conclusions Qualitative studies alongside randomised controlled trials remain uncommon, even where relatively complex interventions are being evaluated. Most of the qualitative studies were carried out before or during the trials with few studies used to explain trial results. The findings of the qualitative studies seemed to be poorly integrated with those of the trials and often had major methodological shortcomings. PMID:19744976

Comparison between publicly accessible publications, registries, and protocols of phase III trials indicated persistence of selective outcome reporting.

PubMed

Zhang, Sheng; Liang, Fei; Li, Wenfeng

2017-11-01

The decision to make protocols of phase III randomized controlled trials (RCTs) publicly accessible by leading journals was a landmark event in clinical trial reporting. Here, we compared primary outcomes defined in protocols with those in publications describing the trials and in trial registration. We identified phase III RCTs published between January 1, 2012, and June 30, 2015, in The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The BMJ with available protocols. Consistency in primary outcomes between protocols and registries (articles) was evaluated. We identified 299 phase III RCTs with available protocols in this analysis. Out of them, 25 trials (8.4%) had some discrepancy for primary outcomes between publications and protocols. Types of discrepancies included protocol-defined primary outcome reported as nonprimary outcome in publication (11 trials, 3.7%), protocol-defined primary outcome omitted in publication (10 trials, 3.3%), new primary outcome introduced in publication (8 trials, 2.7%), protocol-defined nonprimary outcome reported as primary outcome in publication (4 trials, 1.3%), and different timing of assessment of primary outcome (4 trials, 1.3%). Out of trials with discrepancies in primary outcome, 15 trials (60.0%) had discrepancies that favored statistically significant results. Registration could be seen as a valid surrogate of protocol in 237 of 299 trials (79.3%) with regard to primary outcome. Despite unrestricted public access to protocols, selective outcome reporting persists in a small fraction of phase III RCTs. Only studies from four leading journals were included, which may cause selection bias and limit the generalizability of this finding. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuroreflexotherapy for non-specific low-back pain.

PubMed

Urrútia, G; Burton, A K; Morral, A; Bonfill, X; Zanoli, G

2004-01-01

Among the wide range of therapeutic alternatives proposed for the management of low-back pain (LBP), a less widely used technique from Spain, called neuroreflexotherapy (NRT) has claimed to show very favourable results, mainly in patients with chronic low-back pain. The aim of this review was to systematically assess the effectiveness of NRT for the treatment of non-specific LBP in adult patients, aged 16 to 65 years. A secondary objective was to compare NRT with other conventional interventions. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE to October 1, 2002. Only randomised controlled trials (RCTs) of NRT for the treatment of patients with a clinical diagnosis of non-specific LBP were included. Two reviewers independently selected trials and extracted data using pre-designed forms. Because the outcome variables were not assessed in a homogenous way, it was not possible to pool the results to obtain an estimate of global effect, as initially planned. Three RCT were included, with a total of 125 subjects randomised to the control groups and 148 subjects receiving active NRT. Neuroreflexotherapy was the same in all three trials, while the control groups received sham-NRT in two trials and standard care in one. Two trials studied patients with chronic LBP, the third studied patients with a mix of chronic and sub-acute LBP. Clinical outcomes were measured in the short-term (15 to 60 days) in all three trials; in one trial, resource utilization was measured after one year. Individuals who received active NRT showed statistically significantly better outcomes than the control groups for measures of pain, degree of mobility, disability, medication use, consumption of resources and costs. No significant differences were observed for quality of life measures. Side effects were more frequently reported in the control groups during short-term follow-up, with no major side effects reported by those receiving active NRT. NRT appears to be a safe and effective intervention for the treatment of chronic non-specific LBP. The efficacy is less clear for sub-acute LBP. However, these results are limited to three trials conducted by a small number of specifically trained and experienced clinicians, in a limited geographical location. No data are available on the ease and time-frame needed to achieve that level of expertise. RCTs by other practitioners, in other locations, that replicate the effects reported in this review are needed before recommending a broader practice.

External cephalic version for breech presentation before term.

PubMed

Hutton, E K; Hofmeyr, G J

2006-01-25

External cephalic version (ECV) of the breech fetus at term (after 37 weeks) has been shown to be effective in reducing the number of breech presentations and caesarean sections, but the rates of success are relatively low. This review examines studies initiating ECV prior to term (before 37 weeks' gestation). To assess the effectiveness of a policy of beginning ECV before term (before 37 weeks' gestation) for breech presentation on fetal presentation at birth, method of delivery, and the rate of preterm birth, perinatal morbidity, stillbirth or neonatal mortality. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2005), MEDLINE (1965 to April 2005), EMBASE (1988 to April 2005), and Controlled Clinical Trials randomised controlled trials registry (April 2005). Randomised trials of ECV beginning before term (before 37 weeks' gestation) compared with a control group in women with breech presentation before term. Two review authors independently assessed eligibility and trial quality and extracted data. Three studies are included. One study reported on ECV that was undertaken and completed before 37 weeks' gestation compared to no ECV. No difference was found in the rate of non-cephalic presentation at birth. One study reported on a policy of ECV that was initiated before term (33 weeks) and up until 40 weeks' gestation and which could be repeated up until delivery compared to no ECV. This study showed a decrease in the rate of non-cephalic presentation at birth (relative risk 0.59, 95% confidence interval 0.45 to 0.77). One study reported on ECV started at between 34 to 35 weeks' gestation compared to beginning at 37 to 38 weeks' gestation. Although findings were not statistically significant, a 9.5% decrease in the rate of non-cephalic presentation at birth and a 7% decrease in the caesarean section rate were reported when ECV was started early. Compared with no ECV attempt, ECV commenced before term reduces non-cephalic births. Compared with ECV at term, beginning ECV at between 34 to 35 weeks may have some benefit in terms of decreasing the rate of non-cephalic presentation, and caesarean section. Further trials are needed to confirm this finding and to rule out increased rates of preterm birth, or other adverse perinatal outcomes. A large pragmatic trial is ongoing (www.utoronto.ca/miru/eecv2).

Evaluating information prescriptions in two clinical environments*

PubMed Central

Oliver, Kathleen Burr; Lehmann, Harold P; Wolff, Antonio C; Davidson, Laurie W; Donohue, Pamela K; Gilmore, Maureen M; Craven, Catherine K.

2011-01-01

Objective: The research sought to evaluate whether providing personalized information services by libraries can improve satisfaction with information services for specific types of patients. Methods: Adult breast cancer (BrCa) clinic patients and mothers of inpatient neonatal intensive care unit (NICU) patients were randomized to receive routine information services (control) or an IRx intervention. Results: The BrCa trial randomized 211 patients and the NICU trial, 88 mothers. The BrCa trial showed no statistically significant differences in satisfaction ratings between the treatment and control groups. The IRx group in the NICU trial reported higher satisfaction than the control group regarding information received about diagnosis, treatments, respiratory tradeoffs, and medication tradeoffs. BrCa patients posed questions to librarians more frequently than did NICU mothers, and a higher percentage reported using the website. Questions asked of the librarians by BrCa patients were predominantly clinical and focused on the areas of treatment and side effects. Conclusions: Study results provide some evidence to support further efforts to both implement information prescription projects in selected settings and to conduct additional research on the costs and benefits of services. PMID:21753916

Peripheral iridotomy for pigmentary glaucoma

PubMed Central

Michelessi, Manuele; Lindsley, Kristina

2016-01-01

Background Glaucoma is a chronic optic neuropathy characterized by retinal ganglion cell death resulting in damage to the optic nerve head and the retinal nerve fiber layer. Pigment dispersion syndrome is characterized by a structural disturbance in the iris pigment epithelium (the densely pigmented posterior surface of the iris) that leads to dispersion of the pigment and its deposition on various structures within the eye. Pigmentary glaucoma is a specific form of open-angle glaucoma found in patients with pigment dispersion syndrome. Topcial medical therapy is usually the first-line treatment; however, peripheral laser iridotomy has been proposed as an alternate treatment. Peripheral laser iridotomy involves creating an opening in the iris tissue to allow drainage of fluid from the posterior chamber to the anterior chamber and vice versa. Equalizing the pressure within the eye may help to alleviate the friction that leads to pigment dispersion and prevent visual field deterioration. However, the effectiveness of peripheral laser iridotomy in reducing the development or progression of pigmentary glaucoma is unknown. Objectives The objective of this review was to assess the effects of peripheral laser iridotomy compared with other interventions, including medication, trabeculoplasty, and trabeculectomy, or no treatment, for pigment dispersion syndrome and pigmentary glaucoma. Search methods We searched a number of electronic databases including CENTRAL, MEDLINE and EMBASE and clinical trials websites such as (mRCT) and ClinicalTrials.gov. We last searched the electronic databases on 2 November 2015. Selection criteria We included randomized controlled trials (RCTs) that had compared peripheral laser iridotomy versus no treatment or other treatments for pigment dispersion syndrome and pigmentary glaucoma. Data collection and analysis We used standard methodological procedures for systematic reviews. Two review authors independently screened articles for eligibility, extracted data, and assessed included trials for risk of bias. We did not perform a meta-analysis because of variability in reporting and follow-up intervals for primary and secondary outcomes of interest. Main results We included five RCTs (260 eyes of 195 participants) comparing yttrium-aluminum-garnet (YAG) laser iridotomy versus no laser iridotomy. Three trials included participants with pigmentary glaucoma at baseline, and two trials enrolled participants with pigment dispersion syndrome. Only two trials reported the country of enrollment: one - Italy, the other - United Kingdom. Overall, we assessed trials as having high or unclear risk of bias owing to incomplete or missing data and selective outcome reporting. Data on visual fields were available for one of three trials that included participants with pigmentary glaucoma at baseline. At an average follow-up of 28 months, the risk of progression of visual field damage was uncertain when comparing laser iridotomy with no iridotomy (risk ratio (RR) 1.00, 95% confidence interval (95% CI) 0.16 to 6.25; 32 eyes; very low-quality evidence). The two trials that enrolled participants with pigment dispersion syndrome at baseline reported the proportion of participants with onset of glaucomatous visual field changes during the study period. At three-year follow-up, one trial reported that the risk ratio for conversion to glaucoma was 2.72 (95% CI 0.76 to 9.68; 42 eyes; very low-quality evidence). At 10-year follow-up, the other trial reported that no eye showed visual field progression. One trial reported the mean change in intraocular pressure (IOP) in eyes with pigmentary glaucoma: At an average of nine months of follow-up, the mean difference in IOP between groups was 2.69 mmHg less in the laser iridotomy group than in the control group (95% CI −6.05 to 0.67; 14 eyes; very low-quality evidence). This trial also reported the mean change in anterior chamber depth at an average of nine months of follow-up and reported no meaningful differences between groups (mean difference 0.04 mm, 95% CI −0.07 to 0.15; 14 eyes; very low-quality evidence). No other trial reported mean change in anterior chamber depth. Two trials reported greater flattening of iris configuration in the laser iridotomy group than in the control group among eyes with pigmentary glaucoma; however, investigators provided insufficient data for analysis. No trial reported data related to mean visual acuity, aqueous melanin granules, costs, or quality of life outcomes. Two trials assessed the need for additional treatment for control of IOP. One trial that enrolled participants with pigmentary glaucoma reported that more eyes in the laser iridotomy group required additional treatment between six and 23 months of follow-up than eyes in the control group (RR 1.73, 95% CI 1.08 to 2.75; 46 eyes); however, the other trial enrolled participants with pigment dispersion syndrome and indicated that the difference between groups at three-year follow-up was uncertain (RR 0.91, 95% CI 0.38 to 2.17; 105 eyes). We graded the certainty of evidence for this outcome as very low. Two trials reported that no serious adverse events were observed in either group among eyes with pigment dispersion syndrome. Mild adverse events included postoperative inflammation; two participants required cataract surgery (at 18 and 34 months after baseline), and two participants required a repeat iridotomy. Authors' conclusions We found insufficient evidence of high quality on the effectiveness of peripheral iridotomy for pigmentary glaucoma or pigment dispersion syndrome. Although adverse events associated with peripheral iridotomy may be minimal, the long-term effects on visual function and other patient-important outcomes have not been established. Future research on this topic should focus on outcomes that are important to patients and the optimal timing of treatment in the disease process (eg, pigment dispersion syndrome with normal IOP, pigment dispersion syndrome with established ocular hypertension, pigmentary glaucoma). PMID:26871761

Scoliosis and dental occlusion: a review of the literature

PubMed Central

2011-01-01

Background Idiopathic scoliosis is a deformity without clear etiology. It is unclear wether there is an association between malocclusion and scoliosis. Several types of occlusion were described in subjects with scoliosis, mostly case-reports. Objectives The aim of this review was to evaluate the type of occluslins more prevalent in subjects with scoliosis Search strategy All randomised and controlled clinical trials identified from the Cochrane Oral Health Group Trials Register, a MEDLINE search using the Mesh term scoliosis, malocclusion, and relevant free text words, and the bibliographies of papers and review articles which reported the outcome of orthodontic treatment in subjects with scoliosis that were published as abstracts or papers between 1970 and 2010. Selection criteria All randomised and controlled clinical trials published as full papers or abstracts which reported quantitative data on the outcomes malocclusion in subjects with scoliosis. Data collection and analysis Data were extracted without blinding to the authors, age of patients or type of occlusion. Main results Using the search strategy eleven observational longitudinal studies were identified. No randomized clinical trials were recorded. Twenty-three cross-sectional studies were recorderd, and the others studies were reviews, editorials, case-reports, or opinions. The clinical trials were often not controlled and were about the cephalometric evaluation after treatment with the modified Milwuakee brace, followed by the orthodontic treatment of the class II relationship with a functional appliance. Clinical trials also included the study of the associations between scoliosis and unilateral crossbite, in children with asymmetry of the upper cervical spine. This association was also investigated in rats, pigs and rabbits in clinical trials. The other associations between scoliosis and occlusion seems to be based only on cross-sectional studies, case-reports, opinions. Authors' conclusions Based on selected studies, this review concludes that there is plausible evidence for an increased prevalence of unilateral Angle Class II malocclusions associated with scoliosis, and an increased risk of lateral crossbite, midline deviation in children affected by scoliosis. Also, documentation of associations between reduced range of lateral movements and scoliosis seem convincing. Data are also mentioned about the association between plagiocephaly and scoliosis. PMID:21801357

Women's experiences as members of attention control and experimental intervention groups in a randomized controlled trial.

PubMed

Beal, Claudia C; Stuifbergen, Alexa; Volker, Deborah; Becker, Heather

2009-12-01

Attention control groups are often used in research testing the efficacy of psychosocial and behavioural interventions in order to control for placebo effects. The authors conducted a descriptive qualitative study to investigate how participants viewed their experiences in attention control and experimental intervention groups following a randomized controlled trial for women with fibromyalgia syndrome. Moderately structured interviews were conducted with 18 women (12 from the experimental intervention group and 6 from the attention control group). Members of the control group reported some benefits but few behavioural changes as a result of participating in the RCT, and some participants expressed disappointment at not receiving the intervention. Perceptions of changes in attitudes towards fibromyalgia syndrome and behaviours reported by the intervention group appear to be consistent with the theory underlying the intervention. Possible placebo effects identified in both groups include negative and positive social interactions with other participants.

Reporting and Methodological Quality of Randomised Controlled Trials in Vascular and Endovascular Surgery.

PubMed

Hajibandeh, S; Hajibandeh, S; Antoniou, G A; Green, P A; Maden, M; Torella, F

2015-11-01

Randomised controlled trials (RCTs) are subject to bias if they lack methodological quality. Moreover, optimal and transparent reporting of RCT findings aids their critical appraisal and interpretation. The aim of this study was to ascertain whether the methodological and reporting quality of RCTs in vascular and endovascular surgery is improving. The most recent 75 and oldest 75 RCTs published in leading journals over a 10-year period (2003-2012) were identified. The reporting quality and methodological quality data of the old and new RCTs were extracted and compared. The former was analysed using the Consolidated Standards of Reporting Trials (CONSORT) statement, the latter with the Scottish Intercollegiate Guidelines Network (SIGN) checklist. Reporting quality measured by CONSORT was better in the new studies than in the old studies (0.68 [95% CI, 0.66-0.7] vs. 0.60 [95% CI, 0.58-0.62], p < .001); however, both new and old studies had similar methodological quality measured by SIGN (0.9 [IQR 0.1] vs. .09 [IQR: 0.2], p = .787). Unlike clinical items, the methodological items of the CONSORT statement were not well reported in old and new RCTs. More trials in the new group were endovascular related (33.33% vs. 17.33%, p = .038) and industry sponsored (28% vs. 6.67%, p = .001). Despite some progress, there remains room for improvement in the reporting quality of RCTs in vascular and endovascular surgery. The methodological quality of recent RCTs is similar to that of trials performed >10 years ago. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Placebo effects in trials evaluating 12 selected minimally invasive interventions: a systematic review and meta-analysis

PubMed Central

Holtedahl, Robin; Brox, Jens Ivar; Tjomsland, Ole

2015-01-01

Objectives To analyse the impact of placebo effects on outcome in trials of selected minimally invasive procedures and to assess reported adverse events in both trial arms. Design A systematic review and meta-analysis. Data sources and study selection We searched MEDLINE and Cochrane library to identify systematic reviews of musculoskeletal, neurological and cardiac conditions published between January 2009 and January 2014 comparing selected minimally invasive with placebo (sham) procedures. We searched MEDLINE for additional randomised controlled trials published between January 2000 and January 2014. Data synthesis Effect sizes (ES) in the active and placebo arms in the trials’ primary and pooled secondary end points were calculated. Linear regression was used to analyse the association between end points in the active and sham groups. Reported adverse events in both trial arms were registered. Results We included 21 trials involving 2519 adult participants. For primary end points, there was a large clinical effect (ES≥0.8) after active treatment in 12 trials and after sham procedures in 11 trials. For secondary end points, 7 and 5 trials showed a large clinical effect. Three trials showed a moderate difference in ES between active treatment and sham on primary end points (ES ≥0.5) but no trials reported a large difference. No trials showed large or moderate differences in ES on pooled secondary end points. Regression analysis of end points in active treatment and sham arms estimated an R2 of 0.78 for primary and 0.84 for secondary end points. Adverse events after sham were in most cases minor and of short duration. Conclusions The generally small differences in ES between active treatment and sham suggest that non-specific mechanisms, including placebo, are major predictors of the observed effects. Adverse events related to sham procedures were mainly minor and short-lived. Ethical arguments frequently raised against sham-controlled trials were generally not substantiated. PMID:25636794

Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies.

PubMed

Li, Ling; Li, Sheyu; Deng, Ke; Liu, Jiali; Vandvik, Per Olav; Zhao, Pujing; Zhang, Longhao; Shen, Jiantong; Bala, Malgorzata M; Sohani, Zahra N; Wong, Evelyn; Busse, Jason W; Ebrahim, Shanil; Malaga, German; Rios, Lorena P; Wang, Yingqiang; Chen, Qunfei; Guyatt, Gordon H; Sun, Xin

2016-02-17

To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes. Systematic review and meta-analysis of randomised and observational studies. Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts. Randomised controlled trials, non-randomised controlled trials, cohort studies, and case-control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure. Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach. Eligible studies included 43 trials (n=68,775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1,777,358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15,701 v 33/12,591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18,554 v 552/18,474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use. The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Quality of reporting in abstracts of randomized controlled trials published in leading journals of periodontology and implant dentistry: a survey.

PubMed

Faggion, Clovis Mariano; Giannakopoulos, Nikolaos Nikitas

2012-10-01

Most readers, reviewers, and editors rely on abstracts to decide whether to assess the full text of an article. A research abstract should, therefore, be as informative as possible. The standard of reporting in abstracts of randomized controlled trials (RCTs) in periodontology and implant dentistry has not yet been assessed. The objectives of this review are: 1) to assess the quality of reporting in abstracts of RCTs in periodontology and implant dentistry, and 2) to investigate changes in the quality of reporting by comparing samples from different periods. The authors searched the PubMed electronic database, independently and in duplicate, for abstracts of RCTs published in seven leading journals of periodontology and implant dentistry from 2005 to 2007 and from 2009 to 2011. The quality of reporting in selected abstracts with reference to the CONSORT (Consolidated Standards of Reporting Trials) for Abstracts checklist published in January 2008 was assessed independently and in duplicate. Cohen κ statistic was used to determine the extent of agreement of the reviewers. Pearson χ(2) test and/or Fisher exact test were used to assess differences in reporting in the two samples. Level of significance was set at P <0.05. Three hundred ninety-two abstracts are included in this review. Three items (intervention, objective, and conclusions) were almost fully reported in both samples. In contrast, other items (randomization, trial registration, and funding) were never reported. There were significant changes in reporting for only two items, trial design and title (items better reported in the pre- and post-CONSORT samples, respectively). Most topics, however, were similarly poorly reported in both samples of abstracts. The quality of reporting in abstracts of RCTs in periodontology and implant dentistry can be improved. Authors should follow the CONSORT for Abstracts guidelines, and journal editors should promote clear rules to improve authors' adherence to these guidelines.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

PubMed

Solomon, Sharon D; Lindsley, Kristina; Vedula, Satyanarayana S; Krzystolik, Magdalena G; Hawkins, Barbara S

2014-08-29

Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to neovascular AMD accounts for most AMD-related severe vision loss. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, aim to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, improve vision. To investigate: (1) the ocular and systemic effects of, and quality of life associated with, intravitreally injected anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) for the treatment of neovascular AMD compared with no anti-VEGF treatment; and (2) the relative effects of one anti-VEGF agent compared with another when administered in comparable dosages and regimens. We searched Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2014), EMBASE (January 1980 to March 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 March 2014. We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or a control treatment (e.g., sham treatment or photodynamic therapy). All trials followed participants for at least one year. Two review authors independently screened records, extracted data, and assessed risks of bias. We contacted trial authors for additional data. We analyzed outcomes as risk ratios (RRs) or mean differences (MDs). We used the standard methodological procedures expected by The Cochrane Collaboration. We included 12 RCTs including a total of 5496 participants with neovascular AMD (the number of participants per trial ranged from 28 to 1208). One trial compared pegaptanib, three trials ranibizumab, and two trials bevacizumab versus controls; six trials compared bevacizumab with ranibizumab. Four trials were conducted by pharmaceutical companies; none of the eight studies which evaluated bevacizumab were funded by pharmaceutical companies. The trials were conducted at various centers across five continents (North and South America, Europe, Asia and Australia). The overall quality of the evidence was very good, with most trials having an overall low risk of bias.When compared with control treatments, participants who received any of the three anti-VEGF agents were more likely to have gained 15 letters or more of visual acuity, lost fewer than 15 letters of visual acuity, and had vision 20/200 or better after one year of follow up. Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same regimens were compared in the same RCTs, despite the substantially lower cost for bevacizumab compared with ranibizumab. No trial directly compared pegaptanib with other anti-VEGF agents; however, when compared with controls, ranibizumab or bevacizumab yielded larger improvements in visual acuity outcomes than pegaptanib.Participants treated with anti-VEGFs showed improvements in morphologic outcomes (e.g., size of CNV or central retinal thickness) compared with participants not treated with anti-VEGF agents. There was less reduction in central retinal thickness among bevacizumab-treated participants than among ranibizumab-treated participants after one year (MD -13.97 μm; 95% confidence interval (CI) -26.52 to -1.41); however, this difference is within the range of measurement error and we did not interpret it as being clinically meaningful.Ocular inflammation and increased intraocular pressure after intravitreal injection were the most frequently reported serious ocular adverse events. Endophthalmitis was reported in fewer than 1% of anti-VEGF treated participants; no cases were reported in control groups. The occurrence of serious systemic adverse events was comparable across anti-VEGF-treated groups and control groups; however, the numbers of events and trial participants may have been insufficient to detect a meaningful difference between groups. Data for visual function, quality of life, and economic outcomes were sparsely measured and reported. The results of this review indicate the effectiveness of anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) in terms of maintaining visual acuity; ranibizumab and bevacizumab were also shown to improve visual acuity. The information available on the adverse effects of each medication do not suggest a higher incidence of potentially vision-threatening complications with intravitreal injection compared with control interventions; however, clinical trial sample sizes may not have been sufficient to detect rare safety outcomes. Research evaluating variable dosing regimens with anti-VEGF agents, effects of long-term use, combination therapies (e.g., anti-VEGF treatment plus photodynamic therapy), and other methods of delivering the agents should be incorporated into future Cochrane reviews.

Punctal occlusion for dry eye syndrome.

PubMed

Ervin, Ann-Margret; Law, Andrew; Pucker, Andrew D

2017-06-26

Dry eye syndrome is a disorder of the tear film that is associated with symptoms of ocular discomfort. Punctal occlusion is a mechanical treatment that blocks the tear drainage system in order to aid in the preservation of natural tears on the ocular surface. To assess the effects of punctal plugs versus no punctal plugs, different types of punctal plugs, and other interventions for managing dry eye. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), MEDLINE Ovid (1946 to 8 December 2016), Embase.com (1947 to 8 December 2016), PubMed (1948 to 8 December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 8 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com; last searched 18 November 2012 - this resource is now archived), ClinicalTrials.gov (www.clinicaltrials.gov; searched 8 December 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en; searched 8 December 2016). We did not use any date or language restrictions in the electronic searches for trials. We also searched the Science Citation Index-Expanded database and reference lists of included studies. The evidence was last updated on 8 December 2016 SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials of collagen or silicone punctal plugs in symptomatic participants diagnosed with aqueous tear deficiency or dry eye syndrome. Two review authors independently assessed trial quality and extracted data. We contacted study investigators for additional information when needed. We included 18 trials (711 participants, 1249 eyes) from Austria, Canada, China, Greece, Japan, Mexico, Netherlands, Turkey, the UK, and the USA in this review. We also identified one ongoing trial. Overall we judged these trials to be at unclear risk of bias because they were poorly reported. We assessed the evidence for eight comparisons.Five trials compared punctal plugs with no punctal plugs (control). Three of these trials employed a sham treatment and two trials observed the control group. Two trials did not report outcome data relevant to this review. There was very low-certainty evidence on symptomatic improvement. The three trials that reported this outcome used different scales to measure symptoms. In all three trials, there was little or no improvement in symptom scores with punctal plugs compared with no punctal plugs. Low-certainty evidence from one trial suggested less ocular surface staining in the punctal plug group compared with the no punctal plug group however this difference was small and possibly clinically unimportant (mean difference (MD) in fluorescein staining score -1.50 points, 95% CI -1.88 to -1.12; eyes = 61). Similarly there was a small difference in tear film stability with people in the punctal plug group having more stability (MD 1.93 seconds more, 95% CI 0.67 to 3.20; eyes = 28, low-certainty evidence). The number of artificial tear applications was lower in the punctal plug group compared with the no punctal plugs group in one trial (MD -2.70 applications, 95% CI -3.11 to -2.29; eyes = 61, low-certainty evidence). One trial with low-certainty evidence reported little or no difference between the groups in Schirmer scores, but did not report any quantitative data on aqueous tear production. Very low-certainty evidence on adverse events suggested that events occurred reasonably frequently in the punctal plug group and included epiphora, itching, tenderness and swelling of lids with mucous discharge, and plug displacement.One trial compared punctal plugs with cyclosporine (20 eyes) and one trial compared punctal plugs with oral pilocarpine (55 eyes). The evidence was judged to be very low-certainty due to a combination of risk of bias and imprecision.Five trials compared punctal plugs with artificial tears. In one of the trials punctal plugs was combined with artificial tears and compared with artificial tears alone. There was very low-certainty evidence on symptomatic improvement. Low-certainty evidence of little or no improvement in ocular surface staining comparing punctal plugs with artificial tears (MD right eye 0.10 points higher, 0.56 lower to 0.76 higher, MD left eye 0.60 points higher, 0.10 to 1.10 higher) and low-certainty evidence of little or no difference in aqueous tear production (MD 0.00 mm/5 min, 0.33 lower to 0.33 higher)Three trials compared punctal plugs in the upper versus the lower puncta, and none of them reported the review outcomes at long-term follow-up. One trial with very low-certainty evidence reported no observed complications, but it was unclear which complications were collected.One trial compared acrylic punctal plugs with silicone punctal plugs and the trial reported outcomes at approximately 11 weeks of follow-up (36 eyes). The evidence was judged to be very low-certainty due to a combination of risk of bias and imprecision.One trial compared intracanalicular punctal plugs with silicone punctal plugs at three months follow-up (57 eyes). The evidence was judged to be very low-certainty due to a combination of risk of bias and imprecision.Finally, two trials with very low-certainty evidence compared collagen punctal plugs versus silicone punctal plugs (98 eyes). The evidence was judged to be very low-certainty due to a combination of risk of bias and imprecision. Although the investigators of the individual trials concluded that punctal plugs are an effective means for treating dry eye signs and symptoms, the evidence in this systematic review suggests that improvements in symptoms and commonly tested dry eye signs are inconclusive. Despite the inclusion of 11 additional trials, the findings of this updated review are consistent with the previous review published in 2010. The type of punctal plug investigated, the type and severity of dry eye being treated, and heterogeneity in trial methodology confounds our ability to make decisive statements regarding the effectiveness of punctal plug use. Although punctal plugs are believed to be relatively safe, their use is commonly associated with epiphora and, less commonly, with inflammatory conditions such as dacryocystitis.

Punctal occlusion for dry eye syndrome

PubMed Central

Ervin, Ann-Margret; Law, Andrew; Pucker, Andrew D

2017-01-01

Background Dry eye syndrome is a disorder of the tear film that is associated with symptoms of ocular discomfort. Punctal occlusion is a mechanical treatment that blocks the tear drainage system in order to aid in the preservation of natural tears on the ocular surface. Objectives To assess the effects of punctal plugs versus no punctal plugs, different types of punctal plugs, and other interventions for managing dry eye. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), MEDLINE Ovid (1946 to 8 December 2016), Embase.com (1947 to 8 December 2016), PubMed (1948 to 8 December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 8 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com; last searched 18 November 2012 - this resource is now archived), ClinicalTrials.gov (www.clinicaltrials.gov; searched 8 December 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en; searched 8 December 2016). We did not use any date or language restrictions in the electronic searches for trials. We also searched the Science Citation Index-Expanded database and reference lists of included studies. The evidence was last updated on 8 December 2016 Selection criteria We included randomized and quasi-randomized controlled trials of collagen or silicone punctal plugs in symptomatic participants diagnosed with aqueous tear deficiency or dry eye syndrome. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We contacted study investigators for additional information when needed. Main results We included 18 trials (711 participants, 1249 eyes) from Austria, Canada, China, Greece, Japan, Mexico, Netherlands, Turkey, the UK, and the USA in this review. We also identified one ongoing trial. Overall we judged these trials to be at unclear risk of bias because they were poorly reported. We assessed the evidence for eight comparisons. Five trials compared punctal plugs with no punctal plugs (control). Three of these trials employed a sham treatment and two trials observed the control group. Two trials did not report outcome data relevant to this review. There was very low-certainty evidence on symptomatic improvement. The three trials that reported this outcome used different scales to measure symptoms. In all three trials, there was little or no improvement in symptom scores with punctal plugs compared with no punctal plugs. Low-certainty evidence from one trial suggested less ocular surface staining in the punctal plug group compared with the no punctal plug group however this difference was small and possibly clinically unimportant (mean difference (MD) in fluorescein staining score -1.50 points, 95% CI -1.88 to -1.12; eyes = 61). Similarly there was a small difference in tear film stability with people in the punctal plug group having more stability (MD 1.93 seconds more, 95% CI 0.67 to 3.20; eyes = 28, low-certainty evidence). The number of artificial tear applications was lower in the punctal plug group compared with the no punctal plugs group in one trial (MD -2.70 applications, 95% CI -3.11 to -2.29; eyes = 61, low-certainty evidence). One trial with low-certainty evidence reported little or no difference between the groups in Schirmer scores, but did not report any quantitative data on aqueous tear production. Very low-certainty evidence on adverse events suggested that events occurred reasonably frequently in the punctal plug group and included epiphora, itching, tenderness and swelling of lids with mucous discharge, and plug displacement. One trial compared punctal plugs with cyclosporine (20 eyes) and one trial compared punctal plugs with oral pilocarpine (55 eyes). The evidence was judged to be very low-certainty due to a combination of risk of bias and imprecision. Five trials compared punctal plugs with artificial tears. In one of the trials punctal plugs was combined with artificial tears and compared with artificial tears alone. There was very low-certainty evidence on symptomatic improvement. Low-certainty evidence of little or no improvement in ocular surface staining comparing punctal plugs with artificial tears (MD right eye 0.10 points higher, 0.56 lower to 0.76 higher, MD left eye 0.60 points higher, 0.10 to 1.10 higher) and low-certainty evidence of little or no difference in aqueous tear production (MD 0.00 mm/5 min, 0.33 lower to 0.33 higher) Three trials compared punctal plugs in the upper versus the lower puncta, and none of them reported the review outcomes at long-term follow-up. One trial with very low-certainty evidence reported no observed complications, but it was unclear which complications were collected. One trial compared acrylic punctal plugs with silicone punctal plugs and the trial reported outcomes at approximately 11 weeks of follow-up (36 eyes). The evidence was judged to be very low-certainty due to a combination of risk of bias and imprecision. One trial compared intracanalicular punctal plugs with silicone punctal plugs at three months follow-up (57 eyes). The evidence was judged to be very low-certainty due to a combination of risk of bias and imprecision. Finally, two trials with very low-certainty evidence compared collagen punctal plugs versus silicone punctal plugs (98 eyes). The evidence was judged to be very low-certainty due to a combination of risk of bias and imprecision. Authors' conclusions Although the investigators of the individual trials concluded that punctal plugs are an effective means for treating dry eye signs and symptoms, the evidence in this systematic review suggests that improvements in symptoms and commonly tested dry eye signs are inconclusive. Despite the inclusion of 11 additional trials, the findings of this updated review are consistent with the previous review published in 2010. The type of punctal plug investigated, the type and severity of dry eye being treated, and heterogeneity in trial methodology confounds our ability to make decisive statements regarding the effectiveness of punctal plug use. Although punctal plugs are believed to be relatively safe, their use is commonly associated with epiphora and, less commonly, with inflammatory conditions such as dacryocystitis. PMID:28649802

Gaze-Contingent Music Reward Therapy for Social Anxiety Disorder: A Randomized Controlled Trial.

PubMed

Lazarov, Amit; Pine, Daniel S; Bar-Haim, Yair

2017-07-01

Patients with social anxiety disorder exhibit increased attentional dwelling on social threats, providing a viable target for therapeutics. This randomized controlled trial examined the efficacy of a novel gaze-contingent music reward therapy for social anxiety disorder designed to reduce attention dwelling on threats. Forty patients with social anxiety disorder were randomly assigned to eight sessions of either gaze-contingent music reward therapy, designed to divert patients' gaze toward neutral stimuli rather than threat stimuli, or to a control condition. Clinician and self-report measures of social anxiety were acquired pretreatment, posttreatment, and at 3-month follow-up. Dwell time on socially threatening faces was assessed during the training sessions and at pre- and posttreatment. Gaze-contingent music reward therapy yielded greater reductions of symptoms of social anxiety disorder than the control condition on both clinician-rated and self-reported measures. Therapeutic effects were maintained at follow-up. Gaze-contingent music reward therapy, but not the control condition, also reduced dwell time on threat, which partially mediated clinical effects. Finally, gaze-contingent music reward therapy, but not the control condition, also altered dwell time on socially threatening faces not used in training, reflecting near-transfer training generalization. This is the first randomized controlled trial to examine a gaze-contingent intervention in social anxiety disorder. The results demonstrate target engagement and clinical effects. This study sets the stage for larger randomized controlled trials and testing in other emotional disorders.

Interventions for dissociated vertical deviation

PubMed Central

Hatt, Sarah R; Wang, Xue; Holmes, Jonathan M

2015-01-01

Background The term “strabismus” describes misalignment of the eyes. One or both eyes may deviate inward, outward, upward, or downward. Dissociated vertical deviation (DVD) is a well-recognized type of upward drifting of one or both eyes, which can occur in children or adults. DVD often develops in the context of infantile- or childhood-onset horizontal strabismus, either esotropia (inward-turning) or exotropia (outward-turning). For some individuals, DVD remains controlled and can only be detected during clinical testing. For others, DVD becomes spontaneously “manifest” and the eye drifts up of its own accord. Spontaneously manifest DVD can be difficult to control and often causes psychosocial concerns. Traditionally, DVD has been thought to be asymptomatic, although some individuals have double vision. More recently it has been suggested that individuals with DVD may also suffer from eyestrain. Treatment for DVD may be sought either due to psychosocial concerns or because of these symptoms. The standard treatment for DVD is a surgical procedure; non-surgical treatments are offered less commonly. Although there are many studies evaluating different management options for the correction of DVD, a lack of clarity remains regarding which treatments are most effective. Objectives The objective of this review was to determine the effectiveness and safety of various surgical and non-surgical interventions in randomized controlled trials of participants with DVD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 8), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2015), EMBASE (January 1980 to August 2015), PubMed (1948 to August 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to August 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 3 February 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 August 2015. Selection criteria We included randomized controlled trials (RCTs) of surgical and non-surgical interventions for the correction of DVD. Data collection and analysis We used standard procedures expected by Cochrane. Two review authors independently completed eligibility screening, data abstraction, ‘Risk of bias’ assessment, and grading of the evidence. Main results We found four RCTs eligible for inclusion in this review (248 eyes of 151 participants between the ages of 6 months to 22 years). All trials were assessed as having unclear risk of bias overall due to insufficient reporting of study methods. One trial was conducted in Canada and compared anteriorization of the inferior oblique muscle with resection versus anteriorization of the inferior oblique muscle alone; one in the USA compared superior rectus recession with posterior fixation suture versus superior rectus recession alone; and two in the Czech Republic compared anteriorization of the inferior oblique muscle versus myectomy of the inferior oblique muscle. Only one trial reported data that allowed analysis of the primary outcome for this review, the proportion of participants with treatment success. The difference between inferior oblique anteriorization plus resection versus inferior oblique anteriorization alone was uncertain when measured at least four months postoperatively (risk ratio 1.13, 95% confidence interval 0.60 to 2.11, 30 participants, very low-quality evidence). Three trials measured the magnitude of hyperdeviation, but did not provide sufficient data for analysis. All four trials reported a relatively low rate of adverse events; hypotropia, limited elevation, and need for repeat surgery were reported as adverse events associated with some of the surgical interventions. No trials reported any other secondary outcome specified for our review. Authors' conclusions The four trials included in this review assessed the effectiveness of five different surgical procedures for the treatment of DVD. Nevertheless, insufficient reporting of study methods and data led to methodological concerns that undermine the conclusions of all studies. There is a pressing need for carefully executed RCTs of treatment for DVD in order to improve the evidence for the optimal management of this condition. PMID:26587695

Interventions for dissociated vertical deviation.

PubMed

Hatt, Sarah R; Wang, Xue; Holmes, Jonathan M

2015-11-20

The term "strabismus" describes misalignment of the eyes. One or both eyes may deviate inward, outward, upward, or downward. Dissociated vertical deviation (DVD) is a well-recognized type of upward drifting of one or both eyes, which can occur in children or adults. DVD often develops in the context of infantile- or childhood-onset horizontal strabismus, either esotropia (inward-turning) or exotropia (outward-turning). For some individuals, DVD remains controlled and can only be detected during clinical testing. For others, DVD becomes spontaneously "manifest" and the eye drifts up of its own accord. Spontaneously manifest DVD can be difficult to control and often causes psychosocial concerns. Traditionally, DVD has been thought to be asymptomatic, although some individuals have double vision. More recently it has been suggested that individuals with DVD may also suffer from eyestrain. Treatment for DVD may be sought either due to psychosocial concerns or because of these symptoms. The standard treatment for DVD is a surgical procedure; non-surgical treatments are offered less commonly. Although there are many studies evaluating different management options for the correction of DVD, a lack of clarity remains regarding which treatments are most effective. The objective of this review was to determine the effectiveness and safety of various surgical and non-surgical interventions in randomized controlled trials of participants with DVD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 8), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2015), EMBASE (January 1980 to August 2015), PubMed (1948 to August 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to August 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 3 February 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 August 2015. We included randomized controlled trials (RCTs) of surgical and non-surgical interventions for the correction of DVD. We used standard procedures expected by Cochrane. Two review authors independently completed eligibility screening, data abstraction, 'Risk of bias' assessment, and grading of the evidence. We found four RCTs eligible for inclusion in this review (248 eyes of 151 participants between the ages of 6 months to 22 years). All trials were assessed as having unclear risk of bias overall due to insufficient reporting of study methods. One trial was conducted in Canada and compared anteriorization of the inferior oblique muscle with resection versus anteriorization of the inferior oblique muscle alone; one in the USA compared superior rectus recession with posterior fixation suture versus superior rectus recession alone; and two in the Czech Republic compared anteriorization of the inferior oblique muscle versus myectomy of the inferior oblique muscle.Only one trial reported data that allowed analysis of the primary outcome for this review, the proportion of participants with treatment success. The difference between inferior oblique anteriorization plus resection versus inferior oblique anteriorization alone was uncertain when measured at least four months postoperatively (risk ratio 1.13, 95% confidence interval 0.60 to 2.11, 30 participants, very low-quality evidence). Three trials measured the magnitude of hyperdeviation, but did not provide sufficient data for analysis. All four trials reported a relatively low rate of adverse events; hypotropia, limited elevation, and need for repeat surgery were reported as adverse events associated with some of the surgical interventions. No trials reported any other secondary outcome specified for our review. The four trials included in this review assessed the effectiveness of five different surgical procedures for the treatment of DVD. Nevertheless, insufficient reporting of study methods and data led to methodological concerns that undermine the conclusions of all studies. There is a pressing need for carefully executed RCTs of treatment for DVD in order to improve the evidence for the optimal management of this condition.

A Systematic Review of Herbal Medicine for Chemotherapy Induced Peripheral Neuropathy

PubMed Central

Noh, Hyeonseok

2018-01-01

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in cancer patients. The aim of this review was to assess the effectiveness of herbal medicine in preventing and treating CIPN. Methods Randomised controlled trials were included in this review. Extracting and assessing the data independently, two authors searched 13 databases. Results Twenty-eight trials involving 2174 patients met the inclusion criteria. Although there were some exceptions, the methodological quality was typically low. Seventeen trials reported the incidence rate of CIPN assessed by various tools and 14 showed a significant difference regarding the decrease of the incidence rate between the two groups. For clinical improvement, 12 trials reported it using various tools and 10 showed a significant difference between two groups. Two cases of adverse events occurred in one trial; the other nine trials reported no adverse events. Conclusions We found that herbal medicines in combination with and/or without other therapies potentially have preventive or therapeutic effects on CIPN. However, conclusions cannot be drawn because of the generally low quality of the methodology, the clinical heterogeneity, and the small sample size for each single herbal medicine. Trials that are more rigorous and report sufficient methodological data are needed. PMID:29636782

Surrogate endpoints for overall survival in metastatic melanoma: a meta-analysis of randomised controlled trials

PubMed Central

Flaherty, Keith T; Hennig, Michael; Lee, Sandra J; Ascierto, Paolo A; Dummer, Reinhard; Eggermont, Alexander M M; Hauschild, Axel; Kefford, Richard; Kirkwood, John M; Long, Georgina V; Lorigan, Paul; Mackensen, Andreas; McArthur, Grant; O'Day, Steven; Patel, Poulam M; Robert, Caroline; Schadendorf, Dirk

2015-01-01

Summary Background Recent phase 3 trials have shown an overall survival benefit in metastatic melanoma. We aimed to assess whether progression-free survival (PFS) could be regarded as a reliable surrogate for overall survival through a meta-analysis of randomised trials. Methods We systematically reviewed randomised trials comparing treatment regimens in metastatic melanoma that included dacarbazine as the control arm, and which reported both PFS and overall survival with a standard hazard ratio (HR). We correlated HRs for overall survival and PFS, weighted by sample size or by precision of the HR estimate, assuming fixed and random effects. We did sensitivity analyses according to presence of crossover, trial size, and dacarbazine dose. Findings After screening 1649 reports and meeting abstracts published before Sept 8, 2013, we identified 12 eligible randomised trials that enrolled 4416 patients with metastatic melanoma. Irrespective of weighting strategy, we noted a strong correlation between the treatment effects for PFS and overall survival, which seemed independent of treatment type. Pearson correlation coefficients were 0.71 (95% CI 0.29–0.90) with a random-effects assumption, 0.85 (0.59–0.95) with a fixed-effects assumption, and 0.89 (0.68–0.97) with sample-size weighting. For nine trials without crossover, the correlation coefficient was 0.96 (0.81–0.99), which decreased to 0.93 (0.74–0.98) when two additional trials with less than 50% crossover were included. Inclusion of mature follow-up data after at least 50% crossover (in vemurafenib and dabrafenib phase 3 trials) weakened the PFS to overall survival correlation (0.55, 0.03–0.84). Inclusion of trials with no or little crossover with the random-effects assumption yielded a conservative statement of the PFS to overall survival correlation of 0.85 (0.51–0.96). Interpretation PFS can be regarded as a robust surrogate for overall survival in dacarbazine-controlled randomised trials of metastatic melanoma; we postulate that this association will hold as treatment standards evolve and are adopted as the control arm in future trials. Funding None. PMID:24485879

Treating neurocysticercosis medically: a systematic review of randomized, controlled trials.

PubMed

Salinas, R; Counsell, C; Prasad, K; Gelband, H; Garner, P

1999-11-01

To summarize the evidence from randomized controlled trials on the effects of cysticidal therapy used for treating human cysticercosis. Published and unpublished studies in any language identified through MEDLINE (1966 - June 1999) specialized databases, abstracts, proceedings and contact with experts were analysed. Those which compared, using randomized or quasi-randomized methods, any cysticidal drug with placebo or symptomatic therapy were entered in the study. Data were extracted independently by two reviewers and trial quality assessed. Meta-analysis using fixed effects models calculated provided there was no significant heterogeneity, expressed as relative risk. Four trials met the inclusion criteria, treating intraparenchymatous neurocysticercosis with either albendazole or praziquantel compared to placebo or no treatment. In the two trials reporting clinical outcomes, treatment was not associated with a reduction in the risk of seizures, although numbers were small (RR 0.95, 95% CI 0.59-1.51). Four trials reported radiological outcomes, and cysticidal treatment was associated with a lower risk of cyst persistence of scans taken within six months of start of treatment (RR 0.83, 95% CI 0.70-0.99). Subsidiary analysis assuming different outcomes in patients lost to follow-up did not alter the findings of the main analysis. There is insufficient evidence to determine whether cysticidal therapy is of any clinical benefit to patients with neurocysticercosis. The review does not exclude the possibility that more patients remain seizure-free when treated with cysticidal drugs. Further testing through placebo-controlled trials is required.

Patient-Centred Innovations for Persons with Multimorbidity: funded evaluation protocol.

PubMed

Stewart, Moira; Fortin, Martin

2017-05-09

The high prevalence of multimorbidity necessitates rethinking of the health care system. The overarching goal of the Patient-Centred Innovations for Persons with Multimorbidity program is to build on existing structures and find and evaluate patient-centred innovations relevant to multimorbidity. We describe the protocol for a proposed multijurisdictional (Quebec and Ontario) concurrent triangulation mixed-methods study. In both provinces, a qualitative descriptive study will be used to explore innovations in patient-centred multimorbidity care. Two randomized controlled trials, 1 in either province, will evaluate the innovations in a wait-list-controlled design using patient-reported outcomes. An additional control group, matched on age, sex, enrolment/index date (± 3 mo) and propensity score, will be created with the use of health administrative data. Patients will be 18-80 years of age and will have 3 or more chronic conditions. The innovations will have elements of relevance to multimorbidity care, patient-centred partnerships and integration of care. The primary outcome measures will be 2 patient-reported outcomes: patient education and self-efficacy. Secondary outcomes will include patient-reported health status, quality of life, psychological distress and health behaviours, and costs of care. This protocol describes a mixed-method study in 2 jurisdictions. The studies will answer the questions of what innovations work and how they work for patients, health care professionals and policy-makers. Trial registration: ClinicalTrials.gov, no NCT02789800 (Quebec Trial), NCT02742597 (Ontario Trial). Copyright 2017, Joule Inc. or its licensors.

Role of massage therapy on reduction of neonatal hyperbilirubinemia in term and preterm neonates: a review of clinical trials.

PubMed

Garg, Bhawan Deep; Kabra, Nandkishor S; Balasubramanian, Haribalakrishna

2017-09-13

Neonatal hyperbilirubinemia (NNH) is one of the leading causes of admissions in nursery throughout the world. It affects approximately 2.4-15% of neonates during the first 2 weeks of life. To evaluate the role of massage therapy for reduction of NNH in both term and preterm neonates. The literature search was done for various randomized control trials (RCTs) by searching the Cochrane Library, PubMed, and EMBASE. This review included total of 10 RCTs (two in preterm neonates and eight in term neonates) that fulfilled inclusion criteria. In most of the trials, Field massage was given. Six out of eight trials reported reduction in bilirubin levels in term neonates. However, only one trial (out of two) reported significant reduction in bilirubin levels in preterm neonates. Both trials in preterm neonates and most of the trials in term neonates (five trials) reported increased stool frequencies. Role of massage therapy in the management of NNH is supported by the current evidence. However, due to limitations of the trials, current evidences are not sufficient to use massage therapy for the management of NNH in routine practice.

[Constraints on publication rights in industry-initiated clinical trials--secondary publication].

PubMed

Gøtzsche, Peter C; Hróbjartsson, Asbjørn; Johansen, Helle Krogh; Haahr, Mette T; Altman, Douglas G; Chan, An-Wen

2006-06-19

In 22 of 44 industry-initiated clinical trial protocols from 1994-95, it was noted that the sponsor either owned the data or needed to approve the manuscript; another 18 protocols had other constraints. Furthermore, in 16 trials, the sponsor had access to accumulating data, and in an additional 16 trials the sponsor could stop the trial at any time, for any reason. These facts were not noted in any of the trial reports. We found similar constraints on publication rights in 44 protocols from 2004. This tight sponsor control over industry-initiated trials should be changed.

The Effect of Endothelin Receptor Antagonists in Patients with Eisenmenger Syndrome: A Systematic Review.

PubMed

Elshafay, Abdelrahman; Truong, Duy Hieu; AboElnas, Mohamed M; Idrees, Hossam; Metwali, Hatem G; Vuong, Nguyen Lam; Saad, Omar Ahmed; Hirayama, Kenji; Huy, Nguyen Tien

2018-04-01

The efficacy of endothelin receptor antagonists (ERAs) in the management of Eisenmenger syndrome (ES) remains controversial. The aim of this study is to systemically review the safety and effects of ERAs in improving the quality of life and basic cardiac functions of these patients. Twelve databases were searched, including PubMed, Web of Science, Scopus, Virtual Health Library, World Health Organization (WHO) Global Health Library, Google Scholar, POPLINE, Systems for Information of Grey Literature in Europe, New York Academy of Medicine, ClinicalTrials.gov, metaRegister of Controlled Trials and the WHO International Clinical Trials Registry Platform, through August 2016. We included randomized clinical trials addressing the effect of ERAs on cardiac functions in patients with ES. The quality of studies was assessed using the Cochrane Collaboration tool. We included two trials represented by four papers, of which three papers reported the efficacy of bosentan against placebo and one paper reported the results of a combination of bosentan and sildenafil versus placebo and bosentan. One trial showed a significant effect of bosentan treatment over placebo on indexed pulmonary vascular resistance and mean pulmonary artery pressure, but a non-significant increase in 6-min walk distance and a non-significant effect on systemic pulse oximetry. The other trial reported the safe but non-significant effect of combination therapy of bosentan and sildenafil compared with bosentan and placebo. This study demonstrated safety and improved hemodynamic effects of bosentan in ES, with a controversial effect on exercise capacity. Further randomized controlled trials with longer follow-up duration are needed to confirm these results.

14th International Congress on Antiphospholipid Antibodies: task force report on antiphospholipid syndrome treatment trends.

PubMed

Erkan, Doruk; Aguiar, Cassyanne L; Andrade, Danieli; Cohen, Hannah; Cuadrado, Maria J; Danowski, Adriana; Levy, Roger A; Ortel, Thomas L; Rahman, Anisur; Salmon, Jane E; Tektonidou, Maria G; Willis, Rohan; Lockshin, Michael D

2014-06-01

Antiphospholipid Syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity occurring in patients with persistent antiphospholipid antibodies (aPL). The primary objective of the APS Treatment Trends Task Force, created as part of the 14th International Congress on aPL, was to systematically review the potential future treatment strategies for aPL-positive patients. The task force chose as future clinical research directions: a) determining the necessity for controlled clinical trials in venous thromboembolism with the new oral direct thrombin or anti-factor Xa inhibitors pending the results of the ongoing rivaroxaban in APS (RAPS) trial, and designing controlled clinical trials in other forms of thrombotic APS; b) systematically analyzing the literature as well as aPL/APS registries, and creating specific registries for non-warfarin/heparin anticoagulants; c) increasing recruitment for an ongoing primary thrombosis prevention trial, and designing secondary thrombosis and pregnancy morbidity prevention trials with hydroxychloroquine; d) determining surrogate markers to select patients for statin trials; e) designing controlled studies with rituximab and other anti-B-cell agents; f) designing mechanistic and clinical studies with eculizumab and other complement inhibitors; and g) chemically modifying peptide therapy to improve the half-life and minimize immunogenicity. The report also includes recommendations for clinicians who consider using these agents in difficult-to-manage aPL-positive patients. Copyright © 2014 Elsevier B.V. All rights reserved.

A systematic review of evidence for the effectiveness of practitioner-based complementary and alternative therapies in the management of rheumatic diseases: osteoarthritis.

PubMed

Macfarlane, Gary J; Paudyal, Priya; Doherty, Michael; Ernst, Edzard; Lewith, George; MacPherson, Hugh; Sim, Julius; Jones, Gareth T

2012-12-01

To critically review the evidence on the efficacy and effectiveness of practitioner-based complementary therapies for patients with osteoarthritis. We excluded t'ai chi and acupuncture, which have been the subject of recent reviews. Randomized controlled trials, published in English up to May 2011, were identified using systematic searches of bibliographic databases and searching of reference lists. Information was extracted on outcomes, statistical significance in comparison with alternative treatments and reported side effects. The methodological quality of the identified studies was determined using the Jadad scoring system. Outcomes considered were pain and patient global assessment. In all, 16 eligible trials were identified covering 12 therapies. Overall, there was no good evidence of the effectiveness of any of the therapies in relation to pain or global health improvement/quality of life because most therapies only had a single randomized controlled trial. Where positive results were reported, they were often comparing an active intervention with no intervention. Therapies with multiple trials either provided null (biofeedback) or inconsistent results (magnet therapy), or the trials available scored poorly for quality (chiropractic). There were few adverse events reported in the trials. There is not sufficient evidence to recommend any of the practitioner-based complementary therapies considered here for the management of OA, but neither is there sufficient evidence to conclude that they are not effective or efficacious.

Adverse event reporting in cancer clinical trial publications.

PubMed

Sivendran, Shanthi; Latif, Asma; McBride, Russell B; Stensland, Kristian D; Wisnivesky, Juan; Haines, Lindsay; Oh, William K; Galsky, Matthew D

2014-01-10

Reporting adverse events is a critical element of a clinical trial publication. In 2003, the Consolidated Standards of Reporting Trials (CONSORT) group generated recommendations regarding the appropriate reporting of adverse events. The degree to which these recommendations are followed in oncology publications has not been comprehensively evaluated. A review of citations from PubMed, Medline, and Embase published between Jan 1, 2009 and December 31, 2011, identified eligible randomized, controlled phase III trials in metastatic solid malignancies. Publications were assessed for 14 adverse event-reporting elements derived from the CONSORT harms extension statement; a completeness score (range, 0 to 14) was calculated by adding the number of elements reported. Linear regression analysis identified which publication characteristics associated with reporting completeness. A total of 175 publications, with data for 96,125 patients, were included in the analysis. The median completeness score was eight (range, three to 12). Most publications (96%) reported only adverse events occurring above a threshold rate or severity, 37% did not specify the criteria used to select which adverse events were reported, and 88% grouped together adverse events of varying severity. Regression analysis revealed that trials without a stated funding source and with an earlier year of publication had significantly lower completeness scores. Reporting of adverse events in oncology publications of randomized trials is suboptimal and characterized by substantial selectivity and heterogeneity. The development of oncology-specific standards for adverse event reporting should be established to ensure consistency and provide critical information required for medical decision-making.

Meta-analysis: protein and energy supplementation in older people.

PubMed

Milne, Anne C; Avenell, Alison; Potter, Jan

2006-01-03

Protein and energy undernutrition is common in older people, and further deterioration may occur during illness. To assess whether oral protein and energy supplementation improves clinical and nutritional outcomes for older people in the hospital, in an institution, or in the community. Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, HealthStar, CINAHL, BIOSIS, and CAB abstracts. The authors included English- and non-English-language studies and hand-searched journals, contacted manufacturers, and sought information from trialists. The date of the most recent search of CENTRAL and MEDLINE is June 2005. Randomized and quasi-randomized controlled trials of oral protein and energy supplementation compared with placebo or control treatment in older people. Two reviewers independently assessed trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus. Fifty-five trials were included (n = 9187 randomly assigned participants). For patients in short-term care hospitals who were given oral supplements, evidence suggested fewer complications (Peto odds ratio, 0.72 [95% CI, 0.53 to 0.97]) and reduced mortality (Peto odds ratio, 0.66 [CI, 0.49 to 0.90]) for those undernourished at baseline. Few studies reported evidence that suggested any change in mortality, morbidity, or function for those given supplements at home. Ten trials reported gastrointestinal disturbances, such as nausea, vomiting, and diarrhea, with oral supplements. The quality of most studies, as reported, was poor, particularly for concealment of allocation and blinding of outcome assessors. Many studies were too small or the follow-up time was too short to detect a statistically significant change in clinical outcome. The clinical results are dominated by 1 very large recent trial in patients with stroke. Although this was a high-quality trial, few participants were undernourished at baseline. Oral nutritional supplements can improve nutritional status and seem to reduce mortality and complications for undernourished elderly patients in the hospital. Current evidence does not support routine supplementation for older people at home or for well-nourished older patients in any setting.

Educational Benefits of Using Game Consoles in a Primary Classroom: A Randomised Controlled Trial

ERIC Educational Resources Information Center

Miller, David J.; Robertson, Derek P.

2011-01-01

It is known that computer games are motivating for children, but there is limited direct evidence of their effects on classroom learning. The studies that are available tend to be limited in terms of output data reported, or small in scale, or both. The aim of this randomised controlled trial was to upscale a recent study by Miller and Robertson…

Whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults.

PubMed

Costello, Joseph T; Baker, Philip R A; Minett, Geoffrey M; Bieuzen, Francois; Stewart, Ian B; Bleakley, Chris

2015-09-18

Recovery strategies are often used with the intention of preventing or minimising muscle soreness after exercise. Whole-body cryotherapy, which involves a single or repeated exposure(s) to extremely cold dry air (below -100 °C) in a specialised chamber or cabin for two to four minutes per exposure, is currently being advocated as an effective intervention to reduce muscle soreness after exercise. To assess the effects (benefits and harms) of whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, the British Nursing Index and the Physiotherapy Evidence Database. We also searched the reference lists of articles, trial registers and conference proceedings, handsearched journals and contacted experts.The searches were run in August 2015. We aimed to include randomised and quasi-randomised trials that compared the use of whole-body cryotherapy (WBC) versus a passive or control intervention (rest, no treatment or placebo treatment) or active interventions including cold or contrast water immersion, active recovery and infrared therapy for preventing or treating muscle soreness after exercise in adults. We also aimed to include randomised trials that compared different durations or dosages of WBC. Our prespecified primary outcomes were muscle soreness, subjective recovery (e.g. tiredness, well-being) and adverse effects. Two review authors independently screened search results, selected studies, assessed risk of bias and extracted and cross-checked data. Where appropriate, we pooled results of comparable trials. The random-effects model was used for pooling where there was substantial heterogeneity. We assessed the quality of the evidence using GRADE. Four laboratory-based randomised controlled trials were included. These reported results for 64 physically active predominantly young adults (mean age 23 years). All but four participants were male. Two trials were parallel group trials (44 participants) and two were cross-over trials (20 participants). The trials were heterogeneous, including the type, temperature, duration and frequency of WBC, and the type of preceding exercise. None of the trials reported active surveillance of predefined adverse events. All four trials had design features that carried a high risk of bias, potentially limiting the reliability of their findings. The evidence for all outcomes was classified as 'very low' quality based on the GRADE criteria.Two comparisons were tested: WBC versus control (rest or no WBC), tested in four studies; and WBC versus far-infrared therapy, also tested in one study. No studies compared WBC with other active interventions, such as cold water immersion, or different types and applications of WBC.All four trials compared WBC with rest or no WBC. There was very low quality evidence for lower self-reported muscle soreness (pain at rest) scores after WBC at 1 hour (standardised mean difference (SMD) -0.77, 95% confidence interval (CI) -1.42 to -0.12; 20 participants, 2 cross-over trials); 24 hours (SMD -0.57, 95% CI -1.48 to 0.33) and 48 hours (SMD -0.58, 95% CI -1.37 to 0.21), both with 38 participants, 2 cross-over studies, 1 parallel group study; and 72 hours (SMD -0.65, 95% CI -2.54 to 1.24; 29 participants, 1 cross-over study, 1 parallel group study). Of note is that the 95% CIs also included either no between-group differences or a benefit in favour of the control group. One small cross-over trial (9 participants) found no difference in tiredness but better well-being after WBC at 24 hours post exercise. There was no report of adverse events.One small cross-over trial involving nine well-trained runners provided very low quality evidence of lower levels of muscle soreness after WBC, when compared with infrared therapy, at 1 hour follow-up, but not at 24 or 48 hours. The same trial found no difference in well-being but less tiredness after WBC at 24 hours post exercise. There was no report of adverse events. There is insufficient evidence to determine whether whole-body cryotherapy (WBC) reduces self-reported muscle soreness, or improves subjective recovery, after exercise compared with passive rest or no WBC in physically active young adult males. There is no evidence on the use of this intervention in females or elite athletes. The lack of evidence on adverse events is important given that the exposure to extreme temperature presents a potential hazard. Further high-quality, well-reported research in this area is required and must provide detailed reporting of adverse events.

A Randomized Controlled Trial of an Electronic Informed Consent Process

PubMed Central

Rothwell, Erin; Wong, Bob; Rose, Nancy C.; Anderson, Rebecca; Fedor, Beth; Stark, Louisa A.; Botkin, Jeffrey R.

2018-01-01

A pilot study assessed an electronic informed consent model within a randomized controlled trial (RCT). Participants who were recruited for the parent RCT project were randomly selected and randomized to either an electronic consent group (n = 32) or a simplified paper-based consent group (n = 30). Results from the electronic consent group reported significantly higher understanding of the purpose of the study, alternatives to participation, and who to contact if they had questions or concerns about the study. However, participants in the paper-based control group reported higher mean scores on some survey items. This research suggests that an electronic informed consent presentation may improve participant understanding for some aspects of a research study. PMID:25747685

Reporting of methods was better in the Clinical Trials Registry-India than in Indian journal publications.

PubMed

Tharyan, Prathap; George, Aneesh Thomas; Kirubakaran, Richard; Barnabas, Jabez Paul

2013-01-01

We sought to evaluate if editorial policies and the reporting quality of randomized controlled trials (RCTs) had improved since our 2004-05 survey of 151 RCTs in 65 Indian journals, and to compare reporting quality of protocols in the Clinical Trials Registry-India (CTRI). An observational study of endorsement of Consolidated Standards for the Reporting of Trials (CONSORT) and International Committee of Medical Journal Editors (ICMJE) requirements in the instructions to authors in Indian journals, and compliance with selected requirements in all RCTs published during 2007-08 vs. our previous survey and between all RCT protocols in the CTRI on August 31, 2010 and published RCTs from both surveys. Journal policies endorsing the CONSORT statement (22/67, 33%) and ICMJE requirements (35/67, 52%) remained suboptimal, and only 4 of 13 CONSORT items were reported in more than 50% of the 145 RCTs assessed. Reporting of ethical issues had improved significantly, and that of methods addressing internal validity had not improved. Adequate methods were reported significantly more frequently in 768 protocols in the CTRI, than in the 296 published trials. The CTRI template facilitates the reporting of valid methods in registered trial protocols. The suboptimal compliance with CONSORT and ICMJE requirements in RCTs published in Indian journals reduces credibility in the reliability of their results. Copyright © 2013 Elsevier Inc. All rights reserved.

The Relaxation Exercise and Social Support Trial (RESST): a community-based randomized controlled trial to alleviate medically unexplained vaginal discharge symptoms.

PubMed

Kobeissi, Loulou; Mahfoud, Ziyad; Khoury, Brigitte; El Kak, Fayssal; Ghantous, Zeina; Khawaja, Marwan; Nakkash, Rima; Ramia, Sami; Zurayk, Huda; Araya, Ricardo; Peters, Tim J

2012-11-09

Symptoms such as medically unexplained vaginal discharge (MUVD) are common and bothersome, leading to potentially unnecessary use of resources. A community-based individually randomized controlled trial to assess the effectiveness of a relatively simple, culturally appropriate multi-component intervention on reducing reported MUVD, among women suffering from low-moderate levels of common mental distress. The setting was a socio-economically deprived, informal settlement in the southern suburbs of Beirut, Lebanon. The intervention comprised up to 12 group sessions implemented over a six-week period, each divided into a psychosocial and a relaxation exercise component. The primary outcome was self-reported MUVD, which was defined as a complaint of vaginal discharge upon ruling out reproductive tract infections (RTIs), through lab analysis. Anxiety and/or depression symptoms were the secondary outcomes for this trial. These were assessed using an Arabic validated version of the Hopkins Symptoms Checklist-25 (HSCL-25). Assessments were done at baseline and six months using face-to face interviews, pelvic examinations and laboratory tests. Women were randomized into either intervention or control group. Blinding on the intervention status was not possible for both logistic and ethical reasons, especially as knowledge of involvement in the intervention was integral to its delivery. Intent to treat analysis was used. Of 75 women randomized to the intervention, 48% reported MUVD at 6 months compared with 63% of 73 in the control group (difference of -15%, 95% confidence interval (CI) -31%, 0%, p=0.067). Adjustments for baseline imbalances and any factors relating to consent had no appreciable effect on these results. The risk of MUVD was reduced in absolute terms by 2.4% for each intervention session attended (95% CI -4.9%, 0.0%, p=0.049). While there was also marginal evidence of a beneficial effect on anxiety, there was no evidence of mediation of the effect on MUVD through measures of common mental disorders. This study confirms that MUVD is an important public health problem. While the benefits of this intervention may appear modest, the intervention offers an opportunity for women to enhance their problem-solving skills as well as use physical relaxation techniques that can help them deal with stressful in their lives. Further research is needed in a variety of contexts, for different populations and preferably involving larger randomized trials of such an intervention. * Title of trial: The Relaxation Exercise and Social Support Trial ISRCTN assigned: ISRCTN98441241 Date of assignation: 10/09/2010 Link: http://www.controlled-trials.com/ISRCTN98441241* Also registered at the Wellcome Trust register:http://www.controlled-trials.com/mrct/trial/469943/98441241.

Lee Silverman Voice Treatment versus standard speech and language therapy versus control in Parkinson's disease: a pilot randomised controlled trial (PD COMM pilot).

PubMed

Sackley, Catherine M; Smith, Christina H; Rick, Caroline E; Brady, Marian C; Ives, Natalie; Patel, Smitaa; Woolley, Rebecca; Dowling, Francis; Patel, Ramilla; Roberts, Helen; Jowett, Sue; Wheatley, Keith; Kelly, Debbie; Sands, Gina; Clarke, Carl E

2018-01-01

Speech-related problems are common in Parkinson's disease (PD), but there is little evidence for the effectiveness of standard speech and language therapy (SLT) or Lee Silverman Voice Treatment (LSVT LOUD®). The PD COMM pilot was a three-arm, assessor-blinded, randomised controlled trial (RCT) of LSVT LOUD®, SLT and no intervention (1:1:1 ratio) to assess the feasibility and to inform the design of a full-scale RCT. Non-demented patients with idiopathic PD and speech problems and no SLT for speech problems in the past 2 years were eligible. LSVT LOUD® is a standardised regime (16 sessions over 4 weeks). SLT comprised individualised content per local practice (typically weekly sessions for 6-8 weeks). Outcomes included recruitment and retention, treatment adherence, and data completeness. Outcome data collected at baseline, 3, 6, and 12 months included patient-reported voice and quality of life measures, resource use, and assessor-rated speech recordings. Eighty-nine patients were randomised with 90% in the therapy groups and 100% in the control group completing the trial. The response rate for Voice Handicap Index (VHI) in each arm was ≥ 90% at all time-points. VHI was highly correlated with the other speech-related outcome measures. There was a trend to improvement in VHI with LSVT LOUD® (difference at 3 months compared with control: - 12.5 points; 95% CI - 26.2, 1.2) and SLT (difference at 3 months compared with control: - 9.8 points; 95% CI - 23.2, 3.7) which needs to be confirmed in an adequately powered trial. Randomisation to a three-arm trial of speech therapy including a no intervention control is feasible and acceptable. Compliance with both interventions was good. VHI and other patient-reported outcomes were relevant measures and provided data to inform the sample size for a substantive trial. International Standard Randomised Controlled Trial Number Register: ISRCTN75223808. registered 22 March 2012.

Momordica charantia for type 2 diabetes mellitus.

PubMed

Ooi, Cheow Peng; Yassin, Zaitun; Hamid, Tengku-Aizan

2012-08-15

Momordica charantia (bitter gourd) is not only a nutritious vegetable but it is also used in traditional medical practices to treat type 2 diabetes mellitus. Experimental studies with animals and humans suggested that the vegetable has a possible role in glycaemic control. To assess the effects of mormodica charantia for type 2 diabetes mellitus. Several electronic databases were searched, among these were The Cochrane Library (Issue 1, 2012), MEDLINE, EMBASE, CINAHL, SIGLE and LILACS (all up to February 2012), combined with handsearches. No language restriction was used. We included randomised controlled trials (RCTs) that compared momordica charantia with placebo or a control intervention, with or without pharmacological or non-pharmacological interventions. Two authors independently extracted data. Risk of bias of the trials was evaluated using the parameters of randomisation, allocation concealment, blinding, completeness of outcome data, selective reporting and other potential sources of bias. A meta-analysis was not performed given the quality of data and the variability of preparations of momordica charantia used in the interventions (no similar preparation was tested twice). Four randomised controlled trials with up to three months duration and investigating 479 participants met the inclusion criteria. Risk of bias of these trials (only two studies were published as a full peer-reviewed publication) was generally high. Two RCTs compared the effects of preparations from different parts of the momordica charantia plant with placebo on glycaemic control in type 2 diabetes mellitus. There was no statistically significant difference in the glycaemic control with momordica charantia preparations compared to placebo. When momordica charantia was compared to metformin or glibenclamide, there was also no significant change in reliable parameters of glycaemic control. No serious adverse effects were reported in any trial. No trial investigated death from any cause, morbidity, health-related quality of life or costs. There is insufficient evidence on the effects of momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice.

Reporting of Randomized Trials in Common Cancers in the Lay Media.

PubMed

Ribnikar, Domen; Goldvaser, Hadar; Ocana, Alberto; Templeton, Arnoud J; Seruga, Bostjan; Amir, Eitan

2018-01-01

Limited data exist about the role of the lay media in the dissemination of results of randomized controlled trials (RCTs) in common cancers. Completed phase III RCTs evaluating new drugs in common cancers between January 2005 and October 2016 were identified from ClinicalTrials.gov. Lay media reporting was identified by searching LexisNexis Academic. Scientific reporting was defined as presentation at an academic conference or publication in full. Associations between reporting in the lay media before scientific reporting and study design and sponsorship were evaluated using logistic regression. Of 180 RCTs identified, 52% were reported in the lay media and in 27%, lay media reporting occurred before scientific reporting with an increasing trend over time (p = 0.009). Reporting in the lay media before scientific reporting was associated with positive results (OR: 2.10, p = 0.04), targeted therapy compared to chemotherapy (OR: 4.75, p = 0.006), immunotherapy compared to chemotherapy (OR: 7.60, p = 0.02), and prostate cancer compared to breast cancer (OR: 3.25, p = 0.02). Over a quarter of all RCTs in common cancers are reported in the lay media before they are reported scientifically with an increasing proportion over time. Positive trials, studies in prostate cancer, and trials of immunotherapy are associated with early reporting in the lay media. © 2017 S. Karger AG, Basel.

Parent-only interventions for childhood overweight or obesity in children aged 5 to 11 years.

PubMed

Loveman, Emma; Al-Khudairy, Lena; Johnson, Rebecca E; Robertson, Wendy; Colquitt, Jill L; Mead, Emma L; Ells, Louisa J; Metzendorf, Maria-Inti; Rees, Karen

2015-12-21

Child and adolescent overweight and obesity have increased globally, and are associated with short- and long-term health consequences. To assess the efficacy of diet, physical activity and behavioural interventions delivered to parents only for the treatment of overweight and obesity in children aged 5 to 11 years. We performed a systematic literature search of databases including the Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS as well trial registers. We checked references of identified trials and systematic reviews. We applied no language restrictions. The date of the last search was March 2015 for all databases. We selected randomised controlled trials (RCTs) of diet, physical activity and behavioural interventions delivered to parents only for treating overweight or obesity in children aged 5 to 11 years. Two review authors independently assessed trials for risk of bias and evaluated overall study quality using the GRADE instrument. Where necessary, we contacted authors for additional information. We included 20 RCTs, including 3057 participants. The number of participants ranged per trial between 15 and 645. Follow-up ranged between 24 weeks and two years. Eighteen trials were parallel RCTs and two were cluster RCTs. Twelve RCTs had two comparisons and eight RCTs had three comparisons. The interventions varied widely; the duration, content, delivery and follow-up of the interventions were heterogeneous. The comparators also differed. This review categorised the comparisons into four groups: parent-only versus parent-child, parent-only versus waiting list controls, parent-only versus minimal contact interventions and parent-only versus other parent-only interventions.Trial quality was generally low with a large proportion of trials rated as high risk of bias on individual risk of bias criteria.In trials comparing a parent-only intervention with a parent-child intervention, the body mass index (BMI) z score change showed a mean difference (MD) at the longest follow-up period (10 to 24 months) of -0.04 (95% confidence interval (CI) -0.15 to 0.08); P = 0.56; 267 participants; 3 trials; low quality evidence. In trials comparing a parent-only intervention with a waiting list control, the BMI z score change in favour of the parent-only intervention at the longest follow-up period (10-12 months) had an MD of -0.10 (95% CI -0.19 to -0.01); P = 0.04; 136 participants; 2 trials; low quality evidence. BMI z score change of parent-only interventions when compared with minimal contact control interventions at the longest follow-up period (9 to 12 months) showed an MD of 0.01 (95% CI -0.07 to 0.09); P = 0.81; 165 participants; 1 trial; low quality evidence. There were few similarities between interventions and comparators across the included trials in the parent-only intervention versus other parent-only interventions and we did not pool these data. Generally, these trials did not show substantial differences between their respective parent-only groups on BMI outcomes.Other outcomes such as behavioural measures, parent-child relationships and health-related quality of life were reported inconsistently. Adverse effects of the interventions were generally not reported, two trials stated that there were no serious adverse effects. No trials reported on all-cause mortality, morbidity or socioeconomic effects.All results need to be interpreted cautiously because of their low quality, the heterogeneous interventions and comparators, and the high rates of non-completion. Parent-only interventions may be an effective treatment option for overweight or obese children aged 5 to 11 years when compared with waiting list controls. Parent-only interventions had similar effects compared with parent-child interventions and compared with those with minimal contact controls. However, the evidence is at present limited; some of the trials had a high risk of bias with loss to follow-up being a particular issue and there was a lack of evidence for several important outcomes. The systematic review has identified 10 ongoing trials that have a parent-only arm, which will contribute to future updates. These trials will improve the robustness of the analyses by type of comparator, and may permit subgroup analysis by intervention component and the setting. Trial reports should provide adequate details about the interventions to be replicated by others. There is a need to conduct and report cost-effectiveness analyses in future trials in order to establish whether parent-only interventions are more cost-effective than parent-child interventions.

Sample size and number of outcome measures of veterinary randomised controlled trials of pharmaceutical interventions funded by different sources, a cross-sectional study.

PubMed

Wareham, K J; Hyde, R M; Grindlay, D; Brennan, M L; Dean, R S

2017-10-04

Randomised controlled trials (RCTs) are a key component of the veterinary evidence base. Sample sizes and defined outcome measures are crucial components of RCTs. To describe the sample size and number of outcome measures of veterinary RCTs either funded by the pharmaceutical industry or not, published in 2011. A structured search of PubMed identified RCTs examining the efficacy of pharmaceutical interventions. Number of outcome measures, number of animals enrolled per trial, whether a primary outcome was identified, and the presence of a sample size calculation were extracted from the RCTs. The source of funding was identified for each trial and groups compared on the above parameters. Literature searches returned 972 papers; 86 papers comprising 126 individual trials were analysed. The median number of outcomes per trial was 5.0; there were no significant differences across funding groups (p = 0.133). The median number of animals enrolled per trial was 30.0; this was similar across funding groups (p = 0.302). A primary outcome was identified in 40.5% of trials and was significantly more likely to be stated in trials funded by a pharmaceutical company. A very low percentage of trials reported a sample size calculation (14.3%). Failure to report primary outcomes, justify sample sizes and the reporting of multiple outcome measures was a common feature in all of the clinical trials examined in this study. It is possible some of these factors may be affected by the source of funding of the studies, but the influence of funding needs to be explored with a larger number of trials. Some veterinary RCTs provide a weak evidence base and targeted strategies are required to improve the quality of veterinary RCTs to ensure there is reliable evidence on which to base clinical decisions.

Piracetam for acute ischaemic stroke.

PubMed

Ricci, Stefano; Celani, Maria Grazia; Cantisani, Teresa Anna; Righetti, Enrico

2012-09-12

Piracetam has neuroprotective and antithrombotic effects that may help to reduce death and disability in people with acute stroke. This is an update of a Cochrane Review first published in 1999, and previously updated in 2006 and 2009. To assess the effects of piracetam in acute, presumed ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched 15 May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1966 to May 2011), EMBASE (1980 to May 2011), and ISI Science Citation Index (1981 to May 2011). We also contacted the manufacturer of piracetam to identify further published and unpublished studies. Randomised trials comparing piracetam with control, with at least mortality reported and entry to the trial within three days of stroke onset. Two review authors extracted data and assessed trial quality and this was checked by the other two review authors. We contacted study authors for missing information. We included three trials involving 1002 patients, with one trial contributing 93% of the data. Participants' ages ranged from 40 to 85 years, and both sexes were equally represented. Piracetam was associated with a statistically non-significant increase in death at one month (approximately 31% increase, 95% confidence interval 81% increase to 5% reduction). This trend was no longer apparent in the large trial after correction for imbalance in stroke severity. Limited data showed no difference between the treatment and control groups for functional outcome, dependence or proportion of patients dead or dependent. Adverse effects were not reported. There is some suggestion (but no statistically significant result) of an unfavourable effect of piracetam on early death, but this may have been caused by baseline differences in stroke severity in the trials. There is not enough evidence to assess the effect of piracetam on dependence.

When is a randomised controlled trial health equity relevant? Development and validation of a conceptual framework.

PubMed

Jull, J; Whitehead, M; Petticrew, M; Kristjansson, E; Gough, D; Petkovic, J; Volmink, J; Weijer, C; Taljaard, M; Edwards, S; Mbuagbaw, L; Cookson, R; McGowan, J; Lyddiatt, A; Boyer, Y; Cuervo, L G; Armstrong, R; White, H; Yoganathan, M; Pantoja, T; Shea, B; Pottie, K; Norheim, O; Baird, S; Robberstad, B; Sommerfelt, H; Asada, Y; Wells, G; Tugwell, P; Welch, V

2017-09-25

Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials. An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials. A randomised trial can usefully be classified as 'health equity relevant' if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as 'health equity relevant' may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies. The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparison of Percentage of Syllables Stuttered With Parent-Reported Severity Ratings as a Primary Outcome Measure in Clinical Trials of Early Stuttering Treatment.

PubMed

Onslow, Mark; Jones, Mark; O'Brian, Sue; Packman, Ann; Menzies, Ross; Lowe, Robyn; Arnott, Simone; Bridgman, Kate; de Sonneville, Caroline; Franken, Marie-Christine

2018-04-17

This report investigates whether parent-reported stuttering severity ratings (SRs) provide similar estimates of effect size as percentage of syllables stuttered (%SS) for randomized trials of early stuttering treatment with preschool children. Data sets from 3 randomized controlled trials of an early stuttering intervention were selected for analyses. Analyses included median changes and 95% confidence intervals per treatment group, Bland-Altman plots, analysis of covariance, and Spearman rho correlations. Both SRs and %SS showed large effect sizes from pretreatment to follow-up, although correlations between the 2 measures were moderate at best. Absolute agreement between the 2 measures improved as percentage reduction of stuttering frequency and severity increased, probably due to innate measurement limitations for participants with low baseline severity. Analysis of covariance for the 3 trials showed consistent results. There is no statistical reason to favor %SS over parent-reported stuttering SRs as primary outcomes for clinical trials of early stuttering treatment. However, there are logistical reasons to favor parent-reported stuttering SRs. We conclude that parent-reported rating of the child's typical stuttering severity for the week or month prior to each assessment is a justifiable alternative to %SS as a primary outcome measure in clinical trials of early stuttering treatment.

Massage, reflexology and other manual methods for pain management in labour.

PubMed

Smith, Caroline A; Levett, Kate M; Collins, Carmel T; Dahlen, Hannah G; Ee, Carolyn C; Suganuma, Machiko

2018-03-28

Many women would like to avoid pharmacological or invasive methods of pain management in labour, and this may contribute towards the popularity of complementary methods of pain management. This review examined the evidence currently available on manual methods, including massage and reflexology, for pain management in labour. This review is an update of the review first published in 2012. To assess the effect, safety and acceptability of massage, reflexology and other manual methods to manage pain in labour. For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (30 June 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 6), MEDLINE (1966 to 30 June 2017, CINAHL (1980 to 30 June 2017), the Australian New Zealand Clinical Trials Registry (4 August 2017), Chinese Clinical Trial Registry (4 August 2017), ClinicalTrials.gov, (4 August 2017), the National Center for Complementary and Integrative Health (4 August 2017), the WHO International Clinical Trials Registry Platform (ICTRP) (4 August 2017) and reference lists of retrieved trials. We included randomised controlled trials comparing manual methods with standard care, other non-pharmacological forms of pain management in labour, no treatment or placebo. We searched for trials of the following modalities: massage, warm packs, thermal manual methods, reflexology, chiropractic, osteopathy, musculo-skeletal manipulation, deep tissue massage, neuro-muscular therapy, shiatsu, tuina, trigger point therapy, myotherapy and zero balancing. We excluded trials for pain management relating to hypnosis, aromatherapy, acupuncture and acupressure; these are included in other Cochrane reviews. Two review authors independently assessed trial quality, extracted data and checked data for accuracy. We contacted trial authors for additional information. We assessed the quality of the evidence using the GRADE approach. We included a total of 14 trials; 10 of these (1055 women) contributed data to meta-analysis. Four trials, involving 274 women, met our inclusion criteria but did not contribute data to the review. Over half the trials had a low risk of bias for random sequence generation and attrition bias. The majority of trials had a high risk of performance bias and detection bias, and an unclear risk of reporting bias. We found no trials examining the effectiveness of reflexology.MassageWe found low-quality evidence that massage provided a greater reduction in pain intensity (measured using self-reported pain scales) than usual care during the first stage of labour (standardised mean difference (SMD) -0.81, 95% confidence interval (CI) -1.06 to -0.56, six trials, 362 women). Two trials reported on pain intensity during the second and third stages of labour, and there was evidence of a reduction in pain scores in favour of massage (SMD -0.98, 95% CI -2.23 to 0.26, 124 women; and SMD -1.03, 95% CI -2.17 to 0.11, 122 women). There was very low-quality evidence showing no clear benefit of massage over usual care for the length of labour (in minutes) (mean difference (MD) 20.64, 95% CI -58.24 to 99.52, six trials, 514 women), and pharmacological pain relief (average risk ratio (RR) 0.81, 95% CI 0.37 to 1.74, four trials, 105 women). There was very low-quality evidence showing no clear benefit of massage for assisted vaginal birth (average RR 0.71, 95% CI 0.44 to 1.13, four trials, 368 women) and caesarean section (RR 0.75, 95% CI 0.51 to 1.09, six trials, 514 women). One trial reported less anxiety during the first stage of labour for women receiving massage (MD -16.27, 95% CI -27.03 to -5.51, 60 women). One trial found an increased sense of control from massage (MD 14.05, 95% CI 3.77 to 24.33, 124 women, low-quality evidence). Two trials examining satisfaction with the childbirth experience reported data on different scales; both found more satisfaction with massage, although the evidence was low quality in one study and very low in the other.Warm packsWe found very low-quality evidence for reduced pain (Visual Analogue Scale/VAS) in the first stage of labour (SMD -0.59, 95% CI -1.18 to -0.00, three trials, 191 women), and the second stage of labour (SMD -1.49, 95% CI -2.85 to -0.13, two trials, 128 women). Very low-quality evidence showed reduced length of labour (minutes) in the warm-pack group (MD -66.15, 95% CI -91.83 to -40.47; two trials; 128 women).Thermal manual methodsOne trial evaluated thermal manual methods versus usual care and found very low-quality evidence of reduced pain intensity during the first phase of labour for women receiving thermal methods (MD -1.44, 95% CI -2.24 to -0.65, one trial, 96 women). There was a reduction in the length of labour (minutes) (MD -78.24, 95% CI -118.75 to -37.73, one trial, 96 women, very low-quality evidence). There was no clear difference for assisted vaginal birth (very low-quality evidence). Results were similar for cold packs versus usual care, and intermittent hot and cold packs versus usual care, for pain intensity, length of labour and assisted vaginal birth.Music One trial that compared manual methods with music found very low-quality evidence of reduced pain intensity during labour in the massage group (RR 0.40, 95% CI 0.18 to 0.89, 101 women). There was no evidence of benefit for reduced use of pharmacological pain relief (RR 0.41, 95% CI 0.16 to 1.08, very low-quality evidence).Of the seven outcomes we assessed using GRADE, only pain intensity was reported in all comparisons. Satisfaction with the childbirth experience, sense of control, and caesarean section were rarely reported in any of the comparisons. Massage, warm pack and thermal manual methods may have a role in reducing pain, reducing length of labour and improving women's sense of control and emotional experience of labour, although the quality of evidence varies from low to very low and few trials reported on the key GRADE outcomes. Few trials reported on safety as an outcome. There is a need for further research to address these outcomes and to examine the effectiveness and efficacy of these manual methods for pain management.

Intervention description is not enough: evidence from an in-depth multiple case study on the untold role and impact of context in randomised controlled trials of seven complex interventions

PubMed Central

2012-01-01

Background A number of single case reports have suggested that the context within which intervention studies take place may challenge the assumptions that underpin randomised controlled trials (RCTs). However, the diverse ways in which context may challenge the central tenets of the RCT, and the degree to which this information is known to researchers or subsequently reported, has received much less attention. In this paper, we explore these issues by focusing on seven RCTs of interventions varying in type and degree of complexity, and across diverse contexts. Methods This in-depth multiple case study using interviews, focus groups and documentary analysis was conducted in two phases. In phase one, a RCT of a nurse-led intervention provided a single exploratory case and informed the design, sampling and data collection within the main study. Phase two consisted of a multiple explanatory case study covering a spectrum of trials of different types of complex intervention. A total of eighty-four data sources across the seven trials were accessed. Results We present consistent empirical evidence across all trials to indicate that four key elements of context (personal, organisational, trial and problem context) are crucial to understanding how a complex intervention works and to enable both assessments of internal validity and likely generalisability to other settings. The ways in which context challenged trial operation was often complex, idiosyncratic, and subtle; often falling outside of current trial reporting formats. However, information on such issues appeared to be available via first hand ‘insider accounts’ of each trial suggesting that improved reporting on the role of context is possible. Conclusions Sufficient detail about context needs to be understood and reported in RCTs of complex interventions, in order for the transferability of complex interventions to be assessed. Improved reporting formats that require and encourage the clarification of both general and project-specific threats to the likely internal and external validity need to be developed. In addition, a cultural change is required in which the open and honest reporting of such issues is seen as an indicator of study strength and researcher integrity, rather than a symbol of a poor quality study or investigator ability. PMID:22742939

Podiatry intervention versus usual care to prevent falls in care homes: pilot randomised controlled trial (the PIRFECT study).

PubMed

Wylie, Gavin; Menz, Hylton B; McFarlane, Sarah; Ogston, Simon; Sullivan, Frank; Williams, Brian; Young, Zoe; Morris, Jacqui

2017-07-12

Common foot problems are independent risk factors for falls in older people. There is evidence that podiatry can prevent falls in community-dwelling populations. The feasibility of implementing a podiatry intervention and trial in the care home population is unknown. To inform a potential future definitive trial, we performed a pilot randomised controlled trial to assess: (i) the feasibility of a trial of a podiatry intervention to reduce care home falls, and (ii) the potential direction and magnitude of the effect of the intervention in terms of number of falls in care home residents. Informed by Medical Research Council guidance on developing and evaluating complex interventions, we conducted a single blind, pilot randomised controlled trial in six care homes in the East of Scotland. Participants were randomised to either: (i) a three month podiatry intervention comprising core podiatry care, foot and ankle exercises, orthoses and footwear provision or (ii) usual care. Falls-related outcomes (number of falls, time to first fall) and feasibility-related outcomes (recruitment, retention, adherence, data collection rates) were collected. Secondary outcomes included: generic health status, balance, mobility, falls efficacy, and ankle joint strength. 474 care home residents were screened. 43 (9.1%) participants were recruited: 23 to the intervention, 20 to control. Nine (21%) participants were lost to follow-up due to declining health or death. It was feasible to deliver the trial elements in the care home setting. 35% of participants completed the exercise programme. 48% reported using the orthoses 'all or most of the time'. Completion rates of the outcome measures were between 93% and 100%. No adverse events were reported. At the nine month follow-up period, the intervention group per-person fall rate was 0.77 falls vs. 0.83 falls in the control group. A podiatry intervention to reduce falls can be delivered to care home residents within a pilot randomised controlled trial of the intervention. Although not powered to determine effectiveness, these preliminary data provide justification for a larger trial, incorporating a full process evaluation, to determine whether this intervention can significantly reduce falls in this high-risk population. ClinicalTrials.gov identifier: NCT02178527 ; Date of registration: 17 June 2014.

Integrative treatment for low back pain: An exploratory systematic review and meta-analysis of randomized controlled trials.

PubMed

Hu, Xiao-Yang; Chen, Ni-Ni; Chai, Qian-Yun; Yang, Guo-Yan; Trevelyan, Esmé; Lorenc, Ava; Liu, Jian-Ping; Robinson, Nicola

2015-10-26

Low back pain (LBP) is a common musculoskeletal condition often treated using integrative medicine (IM). Most reviews have focused on a single complementary and alternative medicine (CAM) therapy for LBP rather than evaluating wider integrative approaches. This exploratory systematic review aimed to identify randomized controlled trials (RCTs) and provide evidence on the effectiveness, cost effectiveness and adverse effects of integrative treatment for LBP. A literature search was conducted in 12 English and Chinese databases. RCTs evaluating an integrative treatment for musculoskeletal related LBP were included. Reporting, methodological quality and relevant clinical characteristics were assessed and appraised. Metaanalyses were performed for outcomes where trials were sufficiently homogenous. Fifty-six RCTs were identified evaluating integrative treatment for LBP. Although reporting and methodological qualities were poor, meta-analysis showed a favourable effect for integrative treatment over conventional and CAM treatment for back pain and function at 3 months or less follow-up. Two trials investigated costs, reporting £ 5332 per quality adjusted life years with 6 Alexander technique lessons plus exercise at 12 months follow-up; and an increased total costs of $244 when giving an additional up to 15 sessions of CAM package of care at 12 weeks. Sixteen trials mentioned safety; no severe adverse effects were reported. Integrative treatment that combines CAM with conventional therapies appeared to have beneficial effects on pain and function. However, evidence is limited due to heterogeneity, the relatively small numbers available for subgroup analyses and the low methodological quality of the included trials. Identification of studies of true IM was not possible due to lack of reporting of the intervention details (registration No. CRD42013003916).

On the Feasibility of Conducting Randomised Trials in Education: Case Study of a Sex Education Intervention

ERIC Educational Resources Information Center

Moore, Laurence; Graham, Anna; Diamond, Ian

2003-01-01

This article reports on the conduct and results of a randomised controlled trial to test the effectiveness of a teacher-led intervention to improve teenagers' knowledge of emergency contraception. The trial was successfully conducted in 24 mixed-sex state secondary schools in Avon, South-west England. The intervention was popular with both…

Contextual control over selective attention: evidence from a two-target method.

PubMed

MacLellan, Ellen; Shore, David I; Milliken, Bruce

2015-07-01

Selective attention is generally studied with conflict tasks, using response time as the dependent measure. Here, we study the impact of selective attention to a first target, T1, presented simultaneously with a distractor, on the accuracy of subsequent encoding of a second target item, T2. This procedure produces an "attentional blink" (AB) effect much like that reported in other studies, and allowed us to study the influence of context on cognitive control with a novel method. In particular, we examined whether preparation to attend selectively to T1 had an impact on the selective encoding of T1 that would translate to report of T2. Preparation to attend selectively was manipulated by varying whether difficult selective attention T1 trials were presented in the context of other difficult selective attention T1 trials. The results revealed strong context effects of this nature, with smaller AB effects when difficult selective attention T1 trials were embedded in a context with many, rather than few, other difficult selective attention T1 trials. Further, the results suggest that both the trial-to-trial local context and the block-wide global context modulate performance in this task.

Does adding ketamine to morphine patient-controlled analgesia safely improve post-thoracotomy pain?

PubMed

Mathews, Timothy J; Churchhouse, Antonia M D; Housden, Tessa; Dunning, Joel

2012-02-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'is the addition of ketamine to morphine patient-controlled analgesia (PCA) following thoracic surgery superior to morphine alone'. Altogether 201 papers were found using the reported search, of which nine represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. This consisted of one systematic review of PCA morphine with ketamine (PCA-MK) trials, one meta-analysis of PCA-MK trials, four randomized controlled trials of PCA-MK, one meta-analysis of trials using a variety of peri-operative ketamine regimes and two cohort studies of PCA-MK. Main outcomes measured included pain score rated on visual analogue scale, morphine consumption and incidence of psychotomimetic side effects/hallucination. Two papers reported the measurements of respiratory function. This evidence shows that adding ketamine to morphine PCA is safe, with a reported incidence of hallucination requiring intervention of 2.9%, and a meta-analysis finding an incidence of all central nervous system side effects of 18% compared with 15% with morphine alone, P = 0.31, RR 1.27 with 95% CI (0.8-2.01). All randomized controlled trials of its use following thoracic surgery found no hallucination or psychological side effect. All five studies in thoracic surgery (n = 243) found reduced morphine requirements with PCA-MK. Pain scores were significantly lower in PCA-MK patients in thoracic surgery papers, with one paper additionally reporting increased patient satisfaction. However, no significant improvement was found in a meta-analysis of five papers studying PCA-MK in a variety of surgical settings. Both papers reporting respiratory outcomes found improved oxygen saturations and PaCO(2) levels in PCA-MK patients following thoracic surgery. We conclude that adding low-dose ketamine to morphine PCA is safe and post-thoracotomy may provide better pain control than PCA with morphine alone (PCA-MO), with reduced morphine consumption and possible improvement in respiratory function. These studies thus support the routine use of PCA-MK instead of PCA-MO to improve post-thoracotomy pain control.

Clinical trials of homoeopathy.

PubMed Central

Kleijnen, J; Knipschild, P; ter Riet, G

1991-01-01

OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800

Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases.

PubMed

Tsao, May N; Xu, Wei; Wong, Rebecca Ks; Lloyd, Nancy; Laperriere, Normand; Sahgal, Arjun; Rakovitch, Eileen; Chow, Edward

2018-01-25

This is an update to the review published in the Cochrane Library (2012, Issue 4).It is estimated that 20% to 40% of people with cancer will develop brain metastases during the course of their illness. The burden of brain metastases impacts quality and length of survival. To assess the effectiveness and adverse effects of whole brain radiotherapy (WBRT) given alone or in combination with other therapies to adults with newly diagnosed multiple brain metastases. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase to May 2017 and the National Cancer Institute Physicians Data Query for ongoing trials. We included phase III randomised controlled trials (RCTs) comparing WBRT versus other treatments for adults with newly diagnosed multiple brain metastases. Two review authors independently assessed trial quality and abstracted information in accordance with Cochrane methods. We added 10 RCTs to this updated review. The review now includes 54 published trials (45 fully published reports, four abstracts, and five subsets of data from previously published RCTs) involving 11,898 participants.Lower biological WBRT doses versus controlThe hazard ratio (HR) for overall survival (OS) with lower biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 1.21 (95% confidence interval (CI) 1.04 to 1.40; P = 0.01; moderate-certainty evidence) in favour of control. The HR for neurological function improvement (NFI) was 1.74 (95% CI 1.06 to 2.84; P = 0.03; moderate-certainty evidence) in favour of control fractionation.Higher biological WBRT doses versus controlThe HR for OS with higher biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 0.97 (95% CI 0.83 to 1.12; P = 0.65; moderate-certainty evidence). The HR for NFI was 1.14 (95% CI 0.92 to 1.42; P = 0.23; moderate-certainty evidence).WBRT and radiosensitisersThe addition of radiosensitisers to WBRT did not confer additional benefit for OS (HR 1.05, 95% CI 0.99 to 1.12; P = 0.12; moderate-certainty evidence) or for brain tumour response rates (odds ratio (OR) 0.84, 95% CI 0.63 to 1.11; P = 0.22; high-certainty evidence).Radiosurgery and WBRT versus WBRT aloneThe HR for OS with use of WBRT and radiosurgery boost as compared with WBRT alone for selected participants was 0.61 (95% CI 0.27 to 1.39; P = 0.24; moderate-certainty evidence). For overall brain control at one year, the HR was 0.39 (95% CI 0.25 to 0.60; P < 0.0001; high-certainty evidence) favouring the WBRT and radiosurgery boost group.Radiosurgery alone versus radiosurgery and WBRTThe HR for local brain control was 2.73 (95% CI 1.87 to 3.99; P < 0.00001; high-certainty evidence)favouring the addition of WBRT to radiosurgery. The HR for distant brain control was 2.34 (95% CI 1.73 to 3.18; P < 0.00001; high-certainty evidence) favouring WBRT and radiosurgery. The HR for OS was 1.00 (95% CI 0.80 to 1.25; P = 0.99; moderate-certainty evidence). Two trials reported worse neurocognitive outcomes and one trial reported worse quality of life outcomes when WBRT was added to radiosurgery.We could not pool data from trials related to chemotherapy, optimal supportive care (OSC), molecular targeted agents, neurocognitive protective agents, and hippocampal sparing WBRT. However, one trial reported no differences in quality-adjusted life-years for selected participants with brain metastases from non-small-cell lung cancer randomised to OSC and WBRT versus OSC alone. None of the trials with altered higher biological WBRT dose-fractionation schemes reported benefit for OS, NFI, or symptom control compared with standard care. However, OS and NFI were worse for lower biological WBRT dose-fractionation schemes than for standard dose schedules.The addition of WBRT to radiosurgery improved local and distant brain control in selected people with brain metastases, but data show worse neurocognitive outcomes and no differences in OS.Selected people with multiple brain metastases from non-small-cell lung cancer may show no difference in OS when OSC is given and WBRT is omitted.Use of radiosensitisers, chemotherapy, or molecular targeted agents in conjunction with WBRT remains experimental.Further trials are needed to evaluate the use of neurocognitive protective agents and hippocampal sparing with WBRT. As well, future trials should examine homogeneous participants with brain metastases with focus on prognostic features and molecular markers.

Blood and Marrow Transplant Clinical Trials Network Report on the Development of Novel Endpoints and Selection of Promising Approaches for Graft-versus-Host Disease Prevention Trials.

PubMed

Pasquini, Marcelo C; Logan, Brent; Jones, Richard J; Alousi, Amin M; Appelbaum, Frederick R; Bolaños-Meade, Javier; Flowers, Mary E D; Giralt, Sergio; Horowitz, Mary M; Jacobsohn, David; Koreth, John; Levine, John E; Luznik, Leo; Maziarz, Richard; Mendizabal, Adam; Pavletic, Steven; Perales, Miguel-Angel; Porter, David; Reshef, Ran; Weisdorf, Daniel; Antin, Joseph H

2018-06-01

Graft-versus-host disease (GVHD) is a common complication after hematopoietic cell transplantation (HCT) and associated with significant morbidity and mortality. Preventing GVHD without chronic therapy or increasing relapse is a desired goal. Here we report a benchmark analysis to evaluate the performance of 6 GVHD prevention strategies tested at single institutions compared with a large multicenter outcomes database as a control. Each intervention was compared with the control for the incidence of acute and chronic GVHD and overall survival and against novel composite endpoints: acute and chronic GVHD, relapse-free survival (GRFS), and chronic GVHD, relapse-free survival (CRFS). Modeling GRFS and CRFS using the benchmark analysis further informed the design of 2 clinical trials testing GVHD prophylaxis interventions. This study demonstrates the potential benefit of using an outcomes database to select promising interventions for multicenter clinical trials and proposes novel composite endpoints for use in GVHD prevention trials. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Negative pressure wound therapy for partial-thickness burns.

PubMed

Dumville, Jo C; Munson, Christopher; Christie, Janice

2014-12-15

A burn wound is a complex and evolving injury, with both local and systemic consequences. Burn treatments include a variety of dressings, as well as newer strategies, such as negative pressure wound therapy (NPWT), which, by means of a suction force that drains excess fluids from the burn, tries to promote the wound healing process and minimise progression of the burn wound. To assess the effectiveness of NPWT for people with partial-thickness burns. We searched the Cochrane Wounds Group Specialised Register (searched 04 September 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8). All randomised controlled trials (RCTs) and controlled clinical trials (CCTs) that evaluated the safety and effectiveness of NPWT for partial-thickness burns. Two review authors used standardised forms, and extracted the data independently. We assessed each trial for risk of bias, and resolved differences by discussion. One RCT, that was an interim report, satisfied the inclusion criteria. We undertook a narrative synthesis of results, as the absence of data and poor reporting precluded us from carrying out any formal statistical analysis. The trial was at high risk of bias. There was not enough evidence available to permit any conclusions to be drawn regarding the use of NPWT for treatment of partial-thickness burn wounds.

An assessment of quality characteristics of randomised control trials published in dental journals.

PubMed

Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2010-09-01

The purpose of this study was to investigate the quality of reporting of randomised clinical trials (RCTs) published in dental specialty journals. The journals possessing the highest impact factor (2008 data) in the six major dental specialties were included in the study. The contents of the 24 most recent issues of each journal were hand-searched and research articles identified as randomised controlled trials (RCTs) were selected. Quality evaluation was performed using the modified Consolidated Standards of Reporting Trials (CONSORT) statement checklist. The data were analysed using descriptive statistics followed by univariate and multivariate examination of statistical associations (alpha=0.05). Ninety-five RCTs were identified with generally suboptimal scores on quality reporting on key CONSORT areas. Significant differences were found among journals with the Journal of Clinical Periodontology achieving the highest score, followed by the American Journal of Orthodontics and Dentofacial Orthopedics. There was a positive association between quality score and number of authors, involvement of statistician/epidemiologist, and multicentre trials. The quality scores of RCTs in major dental journals are considered suboptimal in key CONSORT areas. This receives critical importance considering that improved quality of RCTs is a fundamental prerequisite for improved dental care. Copyright 2010 Elsevier Ltd. All rights reserved.

Prevalence and reporting of recruitment, randomisation and treatment errors in clinical trials: A systematic review.

PubMed

Yelland, Lisa N; Kahan, Brennan C; Dent, Elsa; Lee, Katherine J; Voysey, Merryn; Forbes, Andrew B; Cook, Jonathan A

2018-06-01

Background/aims In clinical trials, it is not unusual for errors to occur during the process of recruiting, randomising and providing treatment to participants. For example, an ineligible participant may inadvertently be randomised, a participant may be randomised in the incorrect stratum, a participant may be randomised multiple times when only a single randomisation is permitted or the incorrect treatment may inadvertently be issued to a participant at randomisation. Such errors have the potential to introduce bias into treatment effect estimates and affect the validity of the trial, yet there is little motivation for researchers to report these errors and it is unclear how often they occur. The aim of this study is to assess the prevalence of recruitment, randomisation and treatment errors and review current approaches for reporting these errors in trials published in leading medical journals. Methods We conducted a systematic review of individually randomised, phase III, randomised controlled trials published in New England Journal of Medicine, Lancet, Journal of the American Medical Association, Annals of Internal Medicine and British Medical Journal from January to March 2015. The number and type of recruitment, randomisation and treatment errors that were reported and how they were handled were recorded. The corresponding authors were contacted for a random sample of trials included in the review and asked to provide details on unreported errors that occurred during their trial. Results We identified 241 potentially eligible articles, of which 82 met the inclusion criteria and were included in the review. These trials involved a median of 24 centres and 650 participants, and 87% involved two treatment arms. Recruitment, randomisation or treatment errors were reported in 32 in 82 trials (39%) that had a median of eight errors. The most commonly reported error was ineligible participants inadvertently being randomised. No mention of recruitment, randomisation or treatment errors was found in the remaining 50 of 82 trials (61%). Based on responses from 9 of the 15 corresponding authors who were contacted regarding recruitment, randomisation and treatment errors, between 1% and 100% of the errors that occurred in their trials were reported in the trial publications. Conclusion Recruitment, randomisation and treatment errors are common in individually randomised, phase III trials published in leading medical journals, but reporting practices are inadequate and reporting standards are needed. We recommend researchers report all such errors that occurred during the trial and describe how they were handled in trial publications to improve transparency in reporting of clinical trials.

A Phase II Trial on the Effect of Low-Dose versus High-Dose Vitamin D Supplementation on Bone Mass in Adults with Neurofibromatosis 1 (NF1)

DTIC Science & Technology

2013-10-01

MD, PhD CONTRACTING ORGANIZATION: University of Utah REPORT DATE : October 2013 TYPE OF REPORT: Annual PREPARED FOR: U.S...of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE ...October 2013 2. REPORT TYPE Annual 3. DATES COVERED 15 September 2012-14 September 2013 4. TITLE AND SUBTITLE A Phase II Trial on the Effect of

Effects of an intervention aimed at reducing the intake of sugar-sweetened beverages in primary school children: a controlled trial

PubMed Central

2014-01-01

Background Since sugar-sweetened beverages (SSB) may contribute to the development of overweight in children, effective interventions to reduce their consumption are needed. Here we evaluated the effect of a combined school- and community-based intervention aimed at reducing children’s SSB consumption by promoting the intake of water. Favourable intervention effects on children’s SSB consumption were hypothesized. Methods In 2011-2012, a controlled trial was conducted among four primary schools, comprising 1288 children aged 6-12 years who lived in multi-ethnic, socially deprived neighbourhoods in Rotterdam, the Netherlands. Intervention schools adopted the ‘water campaign’, an intervention developed using social marketing. Control schools continued with their regular health promotion programme. Primary outcome was children’s SSB consumption, measured using parent and child questionnaires and through observations at school, both at baseline and after one year of intervention. Results Significant positive intervention effects were found for average SSB consumption (B -0.19 litres, 95% CI -0.28;-0.10; parent report), average SSB servings (B -0.54 servings, 95% CI -0.82;-0.26; parent report) and bringing SSB to school (OR 0.51, 95% CI 0.36;0.72; observation report). Conclusions This study supports the effectiveness of the water campaign intervention in reducing children’s SSB consumption. Further studies are needed to replicate our findings. Trial registration Current Controlled Trials: NTR3400 PMID:25060113

Bayesian survival analysis in clinical trials: What methods are used in practice?

PubMed

Brard, Caroline; Le Teuff, Gwénaël; Le Deley, Marie-Cécile; Hampson, Lisa V

2017-02-01

Background Bayesian statistics are an appealing alternative to the traditional frequentist approach to designing, analysing, and reporting of clinical trials, especially in rare diseases. Time-to-event endpoints are widely used in many medical fields. There are additional complexities to designing Bayesian survival trials which arise from the need to specify a model for the survival distribution. The objective of this article was to critically review the use and reporting of Bayesian methods in survival trials. Methods A systematic review of clinical trials using Bayesian survival analyses was performed through PubMed and Web of Science databases. This was complemented by a full text search of the online repositories of pre-selected journals. Cost-effectiveness, dose-finding studies, meta-analyses, and methodological papers using clinical trials were excluded. Results In total, 28 articles met the inclusion criteria, 25 were original reports of clinical trials and 3 were re-analyses of a clinical trial. Most trials were in oncology (n = 25), were randomised controlled (n = 21) phase III trials (n = 13), and half considered a rare disease (n = 13). Bayesian approaches were used for monitoring in 14 trials and for the final analysis only in 14 trials. In the latter case, Bayesian survival analyses were used for the primary analysis in four cases, for the secondary analysis in seven cases, and for the trial re-analysis in three cases. Overall, 12 articles reported fitting Bayesian regression models (semi-parametric, n = 3; parametric, n = 9). Prior distributions were often incompletely reported: 20 articles did not define the prior distribution used for the parameter of interest. Over half of the trials used only non-informative priors for monitoring and the final analysis (n = 12) when it was specified. Indeed, no articles fitting Bayesian regression models placed informative priors on the parameter of interest. The prior for the treatment effect was based on historical data in only four trials. Decision rules were pre-defined in eight cases when trials used Bayesian monitoring, and in only one case when trials adopted a Bayesian approach to the final analysis. Conclusion Few trials implemented a Bayesian survival analysis and few incorporated external data into priors. There is scope to improve the quality of reporting of Bayesian methods in survival trials. Extension of the Consolidated Standards of Reporting Trials statement for reporting Bayesian clinical trials is recommended.

Feasibility and Efficacy of a Parent-Focused, Text Message–Delivered Intervention to Reduce Sedentary Behavior in 2- to 4-Year-Old Children (Mini Movers): Pilot Randomized Controlled Trial

PubMed Central

Salmon, Jo; Hinkley, Trina; Hnatiuk, Jill A; Hesketh, Kylie D

2018-01-01

Background Despite public health guidelines to limit sedentary behavior, many young children spend large amounts of time sedentary (eg, screen and sitting time) during waking hours. Objective The objective of this study was to test the feasibility and efficacy of a parent-focused, predominantly text message–delivered intervention to support parents to reduce the amount of time their children spend in sedentary behavior. Methods Mini Movers was a pilot randomized controlled trial delivered to parents of 2- to 4-year-old children in Melbourne, Australia. Participants were recruited through playgroups, social media, and snowball sampling. Eligibility criteria were having an ambulatory child (2-4 years), English literacy, and smartphone ownership. Participants were randomized to intervention or wait-list control on a 1:1 ratio after baseline data collection. The 6-week intervention was predominantly delivered via text messages, using a Web-based bulk text message platform managed by the interventionist. Intervention strategies focused on increasing parental knowledge, building self-efficacy, setting goals, and providing reinforcement, and were underpinned by the Coventry, Aberdeen & London-Refined taxonomy of behavior change techniques and social cognitive theory. The primary outcome was intervention feasibility, measured by recruitment, retention, intervention delivery, and fidelity; process evaluation questionnaires; and qualitative interviews with a subsample of participants. Secondary outcomes were children’s screen and restraint time (parent report), sitting time (parent report, activPAL), and potential mediators (parent report). Linear regression models were used to determine intervention effects on secondary outcomes, controlling for the child’s sex and age and clustering by playgroup; effect sizes (Cohen's d) were calculated. Results A total of 57 participants (30 intervention; 27 wait-list control) were recruited, and retention was high (93%). Process evaluation results showed that the intervention was highly acceptable to parents. The majority of intervention components were reported to be useful and relevant. Compared with children in the control group, children in the intervention group had significantly less screen time postintervention (adjusted difference [95% CI]=−35.0 [−64.1 to −5.9] min/day; Cohen's d=0.82). All other measures of sedentary behavior were in the expected direction, with small to moderate effect sizes. Conclusions Mini Movers was shown to be a feasible, acceptable, and efficacious pilot intervention for parents of young children, warranting a larger-scale randomized control trial. Trial Registration Australian New Zealand Clinical Trials registry: ACTRN12616000628448; https://www.anzctr.org.au/ Trial/Registration/TrialReview.aspx?ACTRN=12616000628448p (Archived by WebCite at http://www.webcitation.org/ 6wZcA3cYM) PMID:29426816

Published methodological quality of randomized controlled trials does not reflect the actual quality assessed in protocols

PubMed Central

Mhaskar, Rahul; Djulbegovic, Benjamin; Magazin, Anja; Soares, Heloisa P.; Kumar, Ambuj

2011-01-01

Objectives To assess whether reported methodological quality of randomized controlled trials (RCTs) reflect the actual methodological quality, and to evaluate the association of effect size (ES) and sample size with methodological quality. Study design Systematic review Setting Retrospective analysis of all consecutive phase III RCTs published by 8 National Cancer Institute Cooperative Groups until year 2006. Data were extracted from protocols (actual quality) and publications (reported quality) for each study. Results 429 RCTs met the inclusion criteria. Overall reporting of methodological quality was poor and did not reflect the actual high methodological quality of RCTs. The results showed no association between sample size and actual methodological quality of a trial. Poor reporting of allocation concealment and blinding exaggerated the ES by 6% (ratio of hazard ratio [RHR]: 0.94, 95%CI: 0.88, 0.99) and 24% (RHR: 1.24, 95%CI: 1.05, 1.43), respectively. However, actual quality assessment showed no association between ES and methodological quality. Conclusion The largest study to-date shows poor quality of reporting does not reflect the actual high methodological quality. Assessment of the impact of quality on the ES based on reported quality can produce misleading results. PMID:22424985

Predictors of exercise capacity following exercise-based rehabilitation in patients with coronary heart disease and heart failure: A meta-regression analysis.

PubMed

Uddin, Jamal; Zwisler, Ann-Dorthe; Lewinter, Christian; Moniruzzaman, Mohammad; Lund, Ken; Tang, Lars H; Taylor, Rod S

2016-05-01

The aim of this study was to undertake a comprehensive assessment of the patient, intervention and trial-level factors that may predict exercise capacity following exercise-based rehabilitation in patients with coronary heart disease and heart failure. Meta-analysis and meta-regression analysis. Randomized controlled trials of exercise-based rehabilitation were identified from three published systematic reviews. Exercise capacity was pooled across trials using random effects meta-analysis, and meta-regression used to examine the association between exercise capacity and a range of patient (e.g. age), intervention (e.g. exercise frequency) and trial (e.g. risk of bias) factors. 55 trials (61 exercise-control comparisons, 7553 patients) were included. Following exercise-based rehabilitation compared to control, overall exercise capacity was on average 0.95 (95% CI: 0.76-1.41) standard deviation units higher, and in trials reporting maximum oxygen uptake (VO2max) was 3.3 ml/kg.min(-1) (95% CI: 2.6-4.0) higher. There was evidence of a high level of statistical heterogeneity across trials (I(2) statistic > 50%). In multivariable meta-regression analysis, only exercise intervention intensity was found to be significantly associated with VO2max (P = 0.04); those trials with the highest average exercise intensity had the largest mean post-rehabilitation VO2max compared to control. We found considerable heterogeneity across randomized controlled trials in the magnitude of improvement in exercise capacity following exercise-based rehabilitation compared to control among patients with coronary heart disease or heart failure. Whilst higher exercise intensities were associated with a greater level of post-rehabilitation exercise capacity, there was no strong evidence to support other intervention, patient or trial factors to be predictive. © The European Society of Cardiology 2015.

Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov

PubMed Central

Bothwell, Laura E; Avorn, Jerry; Khan, Nazleen F; Kesselheim, Aaron S

2018-01-01

Objectives This review investigates characteristics of implemented adaptive design clinical trials and provides examples of regulatory experience with such trials. Design Review of adaptive design clinical trials in EMBASE, PubMed, Cochrane Registry of Controlled Clinical Trials, Web of Science and ClinicalTrials.gov. Phase I and seamless Phase I/II trials were excluded. Variables extracted from trials included basic study characteristics, adaptive design features, size and use of independent data monitoring committees (DMCs) and blinded interim analyses. We also examined use of the adaptive trials in new drug submissions to the Food and Drug Administration (FDA) and European Medicines Agency (EMA) and recorded regulators’ experiences with adaptive designs. Results 142 studies met inclusion criteria. There has been a recent growth in publicly reported use of adaptive designs among researchers around the world. The most frequently appearing types of adaptations were seamless Phase II/III (57%), group sequential (21%), biomarker adaptive (20%), and adaptive dose-finding designs (16%). About one-third (32%) of trials reported an independent DMC, while 6% reported blinded interim analysis. We found that 9% of adaptive trials were used for FDA product approval consideration, and 12% were used for EMA product approval consideration. International regulators had mixed experiences with adaptive trials. Many product applications with adaptive trials had extensive correspondence between drug sponsors and regulators regarding the adaptive designs, in some cases with regulators requiring revisions or alterations to research designs. Conclusions Wider use of adaptive designs will necessitate new drug application sponsors to engage with regulatory scientists during planning and conduct of the trials. Investigators need to more consistently report protections intended to preserve confidentiality and minimise potential operational bias during interim analysis. PMID:29440155

The effect of intensive glucose control on all-cause and cardiovascular mortality, myocardial infarction and stroke in persons with type 2 diabetes mellitus: a systematic review and meta-analysis.

PubMed

Marso, Steven P; Kennedy, Kevin F; House, John A; McGuire, Darren K

2010-04-01

We performed a meta-analysis of studies evaluating the effect of intensive glucose control on major adverse cardiovascular events in patients with type 2 diabetes from 1990 to 2009. A search of the published literature and the Cochran Central Register for Controlled Trials was performed using pre-specified inclusion criteria consisting of randomised controlled trials evaluating intensive glycaemic control and reporting the individual endpoints of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke. Incident rate ratios for these endpoints were calculated using standard meta-analytic techniques of pooled data from eligible trials. Six reports from four randomised trials including 27,544 patients met the pre-specified inclusion criteria. Mean follow-up was 5.4 years; haemoglobin A(1C) at study end was 6.6% vs. 7.4% in patients randomised to intensive compared with conventional glucose control. Intensive glucose control did not affect the incident rate ratio for all-cause mortality (1.01, 95% confidence interval 0.86-1.18, p=0.54) or stroke (1.02, 95% confidence interval 0.88-1.20, p=0.62). However, there was a statistically significant 14% reduction in non-fatal myocardial infarction in patients randomised to intensive glucose control (0.86, 95% confidence interval 0.77-0.97, p=0.015). Although intensification of glucose control did not affect mortality or non-fatal stroke, the risk for non-fatal myocardial infarction was significantly reduced in patients with type 2 diabetes.

Financial ties of principal investigators and randomized controlled trial outcomes: cross sectional study.

PubMed

Ahn, Rosa; Woodbridge, Alexandra; Abraham, Ann; Saba, Susan; Korenstein, Deborah; Madden, Erin; Boscardin, W John; Keyhani, Salomeh

2017-01-17

 To examine the association between the presence of individual principal investigators' financial ties to the manufacturer of the study drug and the trial's outcomes after accounting for source of research funding.  Cross sectional study of randomized controlled trials (RCTs).  Studies published in "core clinical" journals, as identified by Medline, between 1 January 2013 and 31 December 2013.  Random sample of RCTs focused on drug efficacy.  Association between financial ties of principal investigators and study outcome.  A total of 190 papers describing 195 studies met inclusion criteria. Financial ties between principal investigators and the pharmaceutical industry were present in 132 (67.7%) studies. Of 397 principal investigators, 231 (58%) had financial ties and 166 (42%) did not. Of all principal investigators, 156 (39%) reported advisor/consultancy payments, 81 (20%) reported speakers' fees, 81 (20%) reported unspecified financial ties, 52 (13%) reported honorariums, 52 (13%) reported employee relationships, 52 (13%) reported travel fees, 41 (10%) reported stock ownership, and 20 (5%) reported having a patent related to the study drug. The prevalence of financial ties of principal investigators was 76% (103/136) among positive studies and 49% (29/59) among negative studies. In unadjusted analyses, the presence of a financial tie was associated with a positive study outcome (odds ratio 3.23, 95% confidence interval 1.7 to 6.1). In the primary multivariate analysis, a financial tie was significantly associated with positive RCT outcome after adjustment for the study funding source (odds ratio 3.57 (1.7 to 7.7). The secondary analysis controlled for additional RCT characteristics such as study phase, sample size, country of first authors, specialty, trial registration, study design, type of analysis, comparator, and outcome measure. These characteristics did not appreciably affect the relation between financial ties and study outcomes (odds ratio 3.37, 1.4 to 7.9).  Financial ties of principal investigators were independently associated with positive clinical trial results. These findings may be suggestive of bias in the evidence base. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Behavioural, educational and respiratory outcomes of antenatal betamethasone for term caesarean section (ASTECS trial)

PubMed Central

Stutchfield, Peter Roy; Whitaker, Rhiannon; Gliddon, Angela E; Hobson, Lucie; Kotecha, Sailesh; Doull, Iolo J M

2013-01-01

Objectives To determine whether antenatal betamethasone prior to elective term caesarean section (CS) affects long term behavioural, cognitive or developmental outcome, and whether the risk of asthma or atopic disease is reduced. Design A questionnaire based follow-up of a multicentre randomised controlled trial (Antenatal Steroids for Term Elective Caesarean Section, BMJ 2005). Setting Four UK study centres from the original trial. Participants 862 participants from the four largest recruiting centres, 92% of the original study. 824 (96%) were traced and 799 (93%) were successfully contacted. Fifty-one percent (407/799) completed and returned the questionnaire. The children were aged 8–15 years (median 12.2 years, 52% girls). 386 gave consent to contact schools with 352 (91%) reports received. Main outcome measures Questionnaires including a strengths and difficulties questionnaire, International Study of Asthma and Allergies in Childhood, general health and school performance. Results There were no significant differences between children whose mothers received betamethasone and controls for the mean total strengths and difficulties questionnaire scores and subscores for hyperactivity, emotional symptoms, prosocial behaviour, conduct or peer problems. 25 (12%) children whose mothers received betamethasone had reported learning difficulties compared with 27 (14%) control children. The proportion of children who achieved standard assessment tests KS2 exams level 4 or above for mathematics, English or science was similar as were the rates of ever reported wheeze (30% vs 30%), asthma (24% vs 21%), eczema (34% vs 37%) and hay fever (25% vs 27%). Conclusions Antenatal betamethasone did not result in any adverse outcomes or reduction in asthma or atopy. It should be considered for elective CS at 37–38 weeks of gestation. Trial registration: Original trial was preregistration, the trial publication is BMJ. 2005 Sep 24;331(7518):662. PMID:23424017

A Cluster Randomized-Controlled Trial of a Classroom-Based Drama Workshop Program to Improve Mental Health Outcomes among Immigrant and Refugee Youth in Special Classes

PubMed Central

Rousseau, Cécile; Beauregard, Caroline; Daignault, Katherine; Petrakos, Harriet; Thombs, Brett D.; Steele, Russell; Vasiliadis, Helen-Maria; Hechtman, Lily

2014-01-01

Objectives The aim of this cluster randomized trial was to evaluate the effectiveness of a school-based theatre intervention program for immigrant and refugee youth in special classes for improving mental health and academic outcomes. The primary hypothesis was that students in the theatre intervention group would report a greater reduction in impairment from symptoms compared to students in the control and tutoring groups. Methods Special classrooms in five multiethnic high schools were randomly assigned to theater intervention (n = 10), tutoring (n = 10) or control status (n = 9), for a total of 477 participants. Students and teachers were non-blinded to group assignment. The primary outcome was impairment from emotional and behavioural symptoms assessed by the Impact Supplement of the Strengths and Difficulties Questionnaire (SDQ) completed by the adolescents. The secondary outcomes were the SDQ global scores (teacher and youth reports), impairment assessed by teachers and school performance. The effect of the interventions was assessed through linear mixed effect models which incorporate the correlation between students in the same class, due to the nature of the randomization of the interventions by classroom. Results The theatre intervention was not associated with a greater reduction in self-reported impairment and symptoms in youth placed in special class because of learning, emotional and behavioural difficulties than a tutoring intervention or a non-active control group. The estimates of the different models show a non-significant decrease in both self-reported and impairment scores in the theatre intervention group for the overall group, but the impairment score decreased significantly for first generation adolescents while it increased for second generation adolescents. Conclusion The difference between the population of immigrant and refugee youth newcomers studied previously and the sample of this trial may explain some of the differences in the observed impact of the theatre intervention. Trial Registration ClinicalTrials.gov NCT01426451 PMID:25127251

A randomised controlled trial to assess the effectiveness of a nurse-led palliative care intervention for HIV positive patients on antiretroviral therapy: recruitment, refusal, randomisation and missing data.

PubMed

Lowther, Keira; Higginson, Irene J; Simms, Victoria; Gikaara, Nancy; Ahmed, Aabid; Ali, Zipporah; Afuande, Gaudencia; Kariuki, Hellen; Sherr, Lorraine; Jenkins, Rachel; Selman, Lucy; Harding, Richard

2014-09-03

Despite the life threatening nature of an HIV diagnosis and the multidimensional problems experienced by this patient population during antiretroviral therapy, the effectiveness of a palliative care approach for HIV positive patients on ART is as yet unknown. A randomised controlled trial (RCT) was conducted in a sample of 120 HIV positive patients on ART in an urban clinic in Mombasa, Kenya. The intervention was a minimum of seven sessions of multidimensional, person-centred care, given by HIV nurses trained in the palliative care approach over a period of 5 months. Rates of recruitment and refusal, the effectiveness of the randomisation procedure, trial follow-up and attrition and extent of missing data are reported.120 patients (60 randomised to control arm, 60 randomised to intervention arm) were recruited over 5.5 months, with a refusal rate of 55.7%. During the study period, three participants died from cancer, three withdrew (two moved away and one withdrew due to time constraints). All of these patients were in the intervention arm: details are reported. There were five additional missing monthly interviews in both the control and intervention study arm, bringing the total of missing data to 26 data points (4.3%). The quality and implications of these data are discussed extensively and openly, including the effect of full and ethical consent procedures, respondent burden, HIV stigma, accurate randomisation, patient safety and the impact of the intervention. Data on recruitment randomisation, attrition and missing data in clinical trials should be routinely reported, in conjunction with the now established practice of publishing study protocols to enhance research integrity, transparency and quality. Transparency is especially important in cross cultural settings, in which the sources of funding and trial design are often not based in the country of data collection. Findings reported can be used to inform future RCTs in this area. Clinicaltrials.gov NCT01608802.

Behavioral Outcome Effects of Serious Gaming as an Adjunct to Treatment for Children With Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial

PubMed Central

2016-01-01

Background The need for accessible and motivating treatment approaches within mental health has led to the development of an Internet-based serious game intervention (called “Plan-It Commander”) as an adjunct to treatment as usual for children with attention-deficit/hyperactivity disorder (ADHD). Objective The aim was to determine the effects of Plan-It Commander on daily life skills of children with ADHD in a multisite randomized controlled crossover open-label trial. Methods Participants (N=170) in this 20-week trial had a diagnosis of ADHD and ranged in age from 8 to 12 years (male: 80.6%, 137/170; female: 19.4%, 33/170). They were randomized to a serious game intervention group (group 1; n=88) or a treatment-as-usual crossover group (group 2; n=82). Participants randomized to group 1 received a serious game intervention in addition to treatment as usual for the first 10 weeks and then received treatment as usual for the next 10 weeks. Participants randomized to group 2 received treatment as usual for the first 10 weeks and crossed over to the serious game intervention in addition to treatment as usual for the subsequent 10 weeks. Primary (parent report) and secondary (parent, teacher, and child self-report) outcome measures were administered at baseline, 10 weeks, and 10-week follow-up. Results After 10 weeks, participants in group 1 compared to group 2 achieved significantly greater improvements on the primary outcome of time management skills (parent-reported; P=.004) and on secondary outcomes of the social skill of responsibility (parent-reported; P=.04), and working memory (parent-reported; P=.02). Parents and teachers reported that total social skills improved over time within groups, whereas effects on total social skills and teacher-reported planning/organizing skills were nonsignificant between groups. Within group 1, positive effects were maintained or further improved in the last 10 weeks of the study. Participants in group 2, who played the serious game during the second period of the study (weeks 10 to 20), improved on comparable domains of daily life functioning over time. Conclusions Plan-It Commander offers an effective therapeutic approach as an adjunct intervention to traditional therapeutic ADHD approaches that improve functional outcomes in daily life. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 62056259; http://www.controlled-trials.com/ISRCTN62056259 (Archived by WebCite at http://www.webcitation.org/6eNsiTDJV). PMID:26883052

Two Randomized Controlled Pilot Trials of Social Forces to Improve Statin Adherence among Patients with Diabetes.

PubMed

Reese, Peter P; Kessler, Judd B; Doshi, Jalpa A; Friedman, Joelle; Mussell, Adam S; Carney, Caroline; Zhu, Jingsan; Wang, Wenli; Troxel, Andrea; Young, Peinie; Lawnicki, Victor; Rajpathak, Swapnil; Volpp, Kevin

2016-04-01

Medication nonadherence is an important obstacle to cardiovascular disease management. To improve adherence through real-time feedback based on theories of how social forces influence behavior. Two randomized controlled pilot trials called PROMOTE and SUPPORT. Participants stored statin medication in wireless-enabled pill bottles that transmitted adherence data to researchers. Adults with diabetes and a history of low statin adherence based on pharmacy refills (i.e., Medication Possession Ratio [MPR] <80% in the pre-randomization screening period). In PROMOTE, each participant was randomized to 1) weekly messages in which that participant's statin adherence was compared to that of other participants (comparison), 2) weekly summaries of that participant's statin adherence (summary), or 3) control. In SUPPORT, each participant identified another person (the Medication Adherence Partner [MAP]) to receive reports about that participant's adherence, and was randomized to 1) daily reports to MAP, 2) weekly reports to MAP, 3) reports to MAP only if dose was missed, or 4) control. Adherence measured by pill bottle. Among 45,000 health plan members contacted by mail, <1% joined the trial. Participants had low baseline MPRs (median = 60%, IQR 41-72%) but high pill-bottle adherence (90% in PROMOTE, 92% in SUPPORT) during the trial. In PROMOTE (n = 201) and SUPPORT (n = 200), no intervention demonstrated significantly better adherence vs. In a subgroup of PROMOTE participants with the lowest pre-study MPR, pill-bottle-measured adherence in the comparison arm (89%) was higher than the control (86%) and summary (76%) arms, but differences were non-significant (p = 0.10). Interventions based on social forces did not improve medication adherence vs. control over a 3-month period. Given the low percentage of invited individuals who enrolled, the studies may have attracted participants who required little encouragement to improve adherence other than study participation.

CONSORT in China: past development and future direction.

PubMed

Song, Tian-Jiao; Leng, Hou-Fu; Zhong, Linda Ld; Wu, Tai-Xiang; Bian, Zhao-Xiang

2015-06-01

The Consolidated Standards of Reporting Trials (CONSORT) Statement was published in 1996, and first introduced to China in 2001. Although CONSORT has been widely accepted in high-quality international journals, we still need to have more investigation on how many Chinese journals have adopted the CONSORT Statement, and whether the quality of reporting has improved. A systematic search of the "Instructions to authors" in all Chinese medical journals in China Academic Journals (CAJ) Full-text Database was conducted up to February 2012 and only 7 journals officially listed the requirements of the CONSORT Statement. The research articles about randomized controlled trials (RCTs) published in 2002, 2004, 2006, 2008, and 2010 from journals which had specifically adopted the CONSORT Statement, and from 30 top journals based on the Chinese Science Citation Index (CSCI) 2011 as the control group, were identified. The quality of both cohorts of articles was assessed using the revised CONSORT Checklist and Jadad scale. A total of 1221 Chinese medical journals was identified. Only seven journals stated clearly in the "Instructions to authors" that authors should adopt the CONSORT requirement in the clinical trial paper. None of these journals is among the control group in the CSCI 2011. In the selected years, a total of 171 articles from 7 journals which had adopted CONSORT and 232 articles in the control were identified as including RCT trials. The average scores according to the revised CONSORT Checklist were 29.47 for the CONSORT-adopting journals and 25.57 for the control group; while the average scores based on the Jadad scale were 2.53 for CONSORT-adopting journals and 1.97 for the control group. Few journals among Chinese medical journals have adopted the CONSORT Statement. The overall quality of RCT reports in the 7 journals which have adopted CONSORT was better than those in the top 30 journals which have not adopted CONSORT. The quality of RCT reports in Chinese journals needs further improvement, and the CONSORT Statement could be a very helpful guideline.

Theory-based behavioral intervention increases self-reported physical activity in South African men: a cluster-randomized controlled trial.

PubMed

Jemmott, John B; Jemmott, Loretta S; Ngwane, Zolani; Zhang, Jingwen; Heeren, G Anita; Icard, Larry D; O'Leary, Ann; Mtose, Xoliswa; Teitelman, Anne; Carty, Craig

2014-07-01

To determine whether a health-promotion intervention increases South African men's adherence to physical-activity guidelines. We utilized a cluster-randomized controlled trial design. Eligible clusters, residential neighborhoods near East London, South Africa, were matched in pairs. Within randomly selected pairs, neighborhoods were randomized to theory-based, culturally congruent health-promotion intervention encouraging physical activity or attention-matched HIV/STI risk-reduction control intervention. Men residing in the neighborhoods and reporting coitus in the previous 3 months were eligible. Primary outcome was self-reported individual-level adherence to physical-activity guidelines averaged over 6-month and 12-month post-intervention assessments. Data were collected in 2007-2010. Data collectors, but not facilitators or participants, were blind to group assignment. Primary outcome intention-to-treat analysis included 22 of 22 clusters and 537 of 572 men in the health-promotion intervention and 22 of 22 clusters and 569 of 609 men in the attention-control intervention. Model-estimated probability of meeting physical-activity guidelines was 51.0% in the health-promotion intervention and 44.7% in attention-matched control (OR=1.34; 95% CI, 1.09-1.63), adjusting for baseline prevalence and clustering from 44 neighborhoods. A theory-based culturally congruent intervention increased South African men's self-reported physical activity, a key contributor to deaths from non-communicable diseases in South Africa. ClinicalTrials.gov Identifier: NCT01490359. Copyright © 2014 Elsevier Inc. All rights reserved.

Autologous serum eye drops for dry eye

PubMed Central

Pan, Qing; Angelina, Adla; Zambrano, Andrea; Marrone, Michael; Stark, Walter J; Heflin, Thomas; Tang, Li; Akpek, Esen K

2014-01-01

Background Theoretically, autologous serum eye drops (AS) have a potential advantage over traditional therapies based on the assumption that AS serve not only as a lacrimal substitute to provide lubrication, but also contain other biochemical components mimicking natural tears more closely. The application of AS in dry eye treatment has gained popularity as a second-line therapy in the treatment of dry eye. Published studies on the subject indicate that autologous serum could be an effective treatment for dry eye. Objectives To evaluate the efficacy and safety of AS compared to artificial tears for treating dry eye. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLD MEDLINE, (January 1950 to April 2013), EMBASE (January 1980 to April 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to April 2013), the meta Register of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We also searched the Science Citation Index Expanded database (September 2013) and reference lists of included studies. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 April 2013. Selection criteria We included randomized controlled trials (RCTs) in which AS was compared to artificial tears in the treatment of dry eye in adults. Data collection and analysis Two review authors independently screened all titles and abstracts and assessed full-text articles of potentially eligible trials. Two review authors extracted data and assessed the methodological quality and characteristics of the included trials.We contacted investigators for missing data. For both primary and secondary outcomes, we reported mean differences with corresponding 95% confidence intervals (CIs) for continuous outcomes. Main results We identified four eligible RCTs in which AS was compared with artificial tear treatment or saline in individuals (n = 72 participants) with dry eye of various etiologies (Sjögren’s syndrome-related dry eye, non-Sjögren’s syndrome dry eye and postoperative dry eye induced by laser-assisted in situ keratomileusis (LASIK)). The quality of the evidence provided by these trials was variable. A majority of the risk of bias domains were judged to have an unclear risk of bias in two trials owing to insufficient reporting of trial characteristics. One trial was considered to have a low risk of bias for most domains while another was considered to have a high risk of bias for most domains. Incomplete outcome reporting and heterogeneity in the participant populations and follow-up periods prevented the inclusion of these trials in a summary meta-analysis. For the primary outcome, improvement in participant-reported symptoms at one month, one trial (12 participants) showed no difference in participant-reported symptoms between 20% AS and artificial tears. Based on the results of two trials in 32 participants, 20% AS may provide some improvement in participant-reported symptoms compared to traditional artificial tears after two weeks of treatment. One trial also showed positive results with a mean difference in tear breakup time (TBUT) of 2.00 seconds (95% CI 0.99 to 3.01 seconds) between 20% AS and artificial tears after two weeks, which were not similar to findings from the other trials. Based on all other objective clinical assessments included in this review, AS was not associated with improvements in aqueous tear production measured by Schirmer’s test (two trials, 33 participants), ocular surface condition with fluorescein (four trials, 72 participants) or Rose Bengal staining (three trials, 60 participants), and epithelial metaplasia by impression cytology compared to artificial tears (one trial, 12 participants). Data on adverse effects were not reported by three of the included studies. In one study, there were no serious adverse events reported with the collection of and treatment with AS. Authors’ conclusions Overall there was inconsistency in the possible benefits of AS in improving participant-reported symptoms and TBUT and lack of effect based on other objective clinical measures. Well-planned, large, high-quality RCTs are warranted, in different severities of dry eye and using standardized questionnaires to measure participant-reported outcomes and objective clinical tests as well as objective biomarkers to assess the benefit of AS therapy for dry eye. PMID:23982997

The effects of mental practice in neurological rehabilitation; a systematic review and meta-analysis

PubMed Central

Braun, Susy; Kleynen, Melanie; van Heel, Tessa; Kruithof, Nena; Wade, Derick; Beurskens, Anna

2013-01-01

Objective: To investigate the beneficial and adverse effects of a mental practice intervention on activities, cognition, and emotion in patients after stroke, patients with Parkinson's disease or multiple sclerosis. Methods: Electronic databases PubMed/Medline, PEDro, Science Direct, Cochrane Library, PsycINFO, Rehadat, Embase, and Picarta were searched until June 2012. Fourteen randomized controlled trials in stroke and two randomized controlled trials in Parkinson's disease were included, representing 491 patients (421 with stroke). No randomized controlled trials in multiple sclerosis were identified. The methodologic quality of the included trials was assessed with the Amsterdam-Maastricht-Consensus-List (AMCL). Information on study characteristics and outcomes was summarized and evidence for effects described. Data from individual studies in stroke with same outcome measures were pooled. Results: The included 16 randomized controlled trials were heterogeneous and methodologic quality varied. Ten trials reported significant effects in favor of mental practice in patients with stroke (n = 9) and Parkinson's disease (n = 1). In six studies mental practice had similar effects as therapy as usual (n = 5 in stroke and n = 1 in Parkinson's disease). Of six performed meta-analyses with identical measures in stroke studies only two showed significant effects of mental practice: short-term improvement of arm-hand-ability (ARAT: SMD 0.62; 95% CI: 0.05 to 1.19) and improvement of performance of activities (NRS: SMD 0.9; 95% CI: 0.04 to 1.77). Five studies found effects on cognition (e.g., effects on attention, plan actions in unfamiliar surroundings) and four reported observed side-effects, both positive (e.g., might increase motivation and arousal and reduce depression) and negative (e.g., diminished concentration, irritation). Conclusions: Mental practice might have positive effects on performance of activities in patients with neurological diseases, but this review reports less positive results than earlier published ones. Strengths and limitations of past studies are pointed out. Methodologic recommendations for future studies are given. PMID:23935572

Reporting of embryo transfer methods in IVF research: a cross-sectional study.

PubMed

Gambadauro, Pietro; Navaratnarajah, Ramesan

2015-02-01

The reporting of embryo transfer methods in IVF research was assessed through a cross-sectional analysis of randomized controlled trials (RCTs) published between 2010 and 2011. A systematic search identified 325 abstracts; 122 RCTs were included in the study. Embryo transfer methods were described in 42 out of 122 articles (34%). Catheters (32/42 [76%]) or ultrasound guidance (31/42 [74%]) were most frequently mentioned. Performer 'blinding' (12%) or technique standardization (7%) were seldom reported. The description of embryo transfer methods was significantly more common in trials published by journals with lower impact factor (less than 3, 39.6%; 3 or greater, 21.5%; P = 0.037). Embryo transfer methods were reported more often in trials with pregnancy as the main end-point (33% versus 16%) or with positive outcomes (37.8% versus 25.0%), albeit not significantly. Multivariate logistic regression confirmed that RCTs published in higher impact factor journals are less likely to describe embryo transfer methods (OR 0.371; 95% CI 0.143 to 0.964). Registered trials, trials conducted in an academic setting, multi-centric studies or full-length articles were not positively associated with embryo transfer methods reporting rate. Recent reports of randomized IVF trials rarely describe embryo transfer methods. The under-reporting of research methods might compromise reproducibility and suitability for meta-analysis. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Reporting quality of randomized controlled trials in patients with HIV on antiretroviral therapy: a systematic review.

PubMed

Nagai, Kaori; Saito, Akiko M; Saito, Toshiki I; Kaneko, Noriyo

2017-12-28

To allow for correct evaluation of clinical trial results, readers require comprehensive, clear, and highly transparent information on the methodology used and the results obtained. This study aimed to evaluate the quality of reporting in articles on randomized controlled trials (RCTs) of antiretroviral therapy (ART) in the field of HIV/AIDS. We searched for original articles on RCTs of ART developed in the field of HIV/AIDS in PubMed database by 5 April 2016. Searched articles were divided into three groups based on the revision year in which the Consolidated Standards of Reporting Trials (CONSORT) guidelines were published: Period 1 (1996-2001); Period 2 (2002-2010); and Period 3 (2011-2016). We evaluated the articles using the reporting rates of the 37 items in the CONSORT 2010 checklist, five items in the protocol deviation, and the three items in the ethics. Fifty-two articles were extracted and included in this study. Many of the reporting rates calculated using the CONSORT 2010 checklist showed a significantly increasing trend over the successive periods (65% in Period 1, 67% in Period 2, 79% in Period 3; p < 0.0001). The items with reporting rates < 50% were "the presence or absence of a protocol change and the reason for such a change," "randomization and blinding," and "where the full trial protocol can be accessed." Reporting rates of deviations were as low as < 30%, while the reporting rates for patient compliance were the highest (>80% in Period 3) among the five items. The reporting rates for obtaining informed consent and approval by the ethics committee or institutional review board were high (>88%), regardless of the time period assessed. In terms of representative RCT articles in the field of HIV/AIDS, the reporting rate of the items defined by CONSORT was approximately 70%, improving over the successive CONSORT statement revision periods.

Does the CONSORT checklist for abstracts improve the quality of reports of randomized controlled trials on clinical pathways?

PubMed

Cui, Qi; Tian, Jinhui; Song, Xuping; Yang, Kehu

2014-12-01

The extension of the Consolidated Standards of Reporting Trials (CONSORT) statement provides reporting guidelines to improve the reporting quality of randomized controlled trials (RCTs). This present study was aim to assess the reporting quality of abstracts of RCTs on clinical pathway. Eight databases were searched from inception to November 2012 to identify RCTs. We extracted basic information and CONSORT items from abstracts. Each abstract was assessed independently by two reviewers. Statistical analyses were performed with SPSS 13.0. Level of significance was set at P < 0.05. 328 abstracts were included. 300 (91.5%) were published in Chinese, of which 292 were published on high impact factor journals. 28 English abstracts were all published on Science Citation Index (SCI) journals. (1) Intervention, objective and outcome were almost fully reported in all abstracts, while recruitment and funding were never reported. (2) There are nine items (P < 0.05) in Chinese that were of low quality compared with in English. There was statistically difference on total score between Chinese and English abstracts (P < 0.00001). (3) There was no difference in any items between high and low impact factor journal in China. (4) In SCI journals, there were significant changes in reporting for three items trial design (P = 0.026), harms (P = 0.039) and trial registration (P = 0.019) in different periods (pre- and post-CONSORT), but only the numbers of randomized (P = 0.003) changed in Chinese abstracts. The reporting quality of abstracts of RCTs on clinical pathway still should be improved. After the publication of CONSORT for abstracts guideline, the RCT abstracts reporting quality were improvement to some extent. The abstracts in Chinese journals showed non-adherence to the CONSORT for abstracts guidelines. © 2014 John Wiley & Sons, Ltd.

Dengzhanhua preparations for acute cerebral infarction.

PubMed

Cao, Wenzhai; Liu, Weimin; Wu, Taixiang; Zhong, Dechao; Liu, Guanjian

2008-10-08

Dengzhanhua preparations are widely used in China. Many controlled trials have been undertaken to investigate the efficacy of dengzhanhua preparations in the treatment of acute cerebral infarction. To assess whether dengzhanhua preparations are effective and safe at improving outcomes in patients with acute cerebral infarction. We searched the Cochrane Stroke Group Trials Register (last searched October 2007), the Chinese Stroke Trials Register (last searched June 2006), the trials register of the Cochrane Complementary Medicine Field (last searched June 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2 2006), MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), AMED (the Allied and Complementary Medicine Database, 1985 to June 2006), the China Biological Medicine Database (CBM-disc, 1979 to June 2006), and Chinese Knowledge Infrastructure (CNKI,1994 to October 2007). We also searched the reference lists of relevant articles. Randomised and quasi-randomised controlled clinical trials of dengzhanhua preparations regardless of duration, dosage and route of administration in patients with confirmed acute cerebral infarction. Two review authors independently applied the inclusion criteria, assessed trial quality, and extracted the data. We included nine trials, all conducted in China, involving 723 participants. The method of randomisation and concealment was poorly described. The included trials compared dengzhanhua injection plus routine therapy with routine therapy alone. Patients were enrolled up to one week after the onset of stroke. No trials reported data on the pre-specified primary or secondary outcomes. In a post-hoc comparison of dengzhanhua injection plus routine therapy versus routine therapy alone, dengzhanhua injection showed a statistically significant benefit on the outcome 'marked neurologic improvement' (relative risk 1.53; 95% confidence interval 1.36 to 1.72). No serious adverse effects were reported. Due to the generally low methodological quality and small sample size of the included trials in this systematic review, we could not draw a firm conclusion.

Internet-based randomised controlled trials for the evaluation of complementary and alternative medicines: probiotics in spondyloarthropathy

PubMed Central

Brophy, Sinead; Burrows, Claire L; Brooks, Caroline; Gravenor, Michael B; Siebert, Stefan; Allen, Stephen J

2008-01-01

Background The clinical effectiveness of complementary and alternative medicines (CAMs) is widely debated because of a lack of clinical trials. The internet may provide an effective and economical approach for undertaking randomised controlled trials (RCTs) of low-risk interventions. We investigated whether the internet could be used to perform an internet-based RCT of a CAM fulfilling the revised CONSORT (Consolidated Standards of Reporting Trials) statement quality checklist for reporting of RCTs. A secondary aim was to examine the effect of probiotics compared to placebo in terms of well-being over 12 weeks. Methods People aged ≥18 years with confirmed spondyloarthropathy living in the United Kingdom with internet access were invited to participate in an internet-based RCT of probiotic compared to placebo for improving well-being and bowel symptoms. The intervention was a probiotic containing 4 strains of live bacteria or identical placebo taken by mouth daily for 3 months. The primary outcome measure was the performance of the trial according to the revised CONSORT statement. Results 147 people were randomised into the trial. The internet-based trial of the CAM fulfilled the revised CONSORT statement such as efficient blinding, allocation concealment, intention to treat analysis and flow of participants through the trial. Recruitment of the required number of participants was completed in 19 months. Sixty-five percent (96/147) completed the entire 3 months of the trial. The trial was low cost and demonstrated that in an intention to treat analysis, probiotics did not improve well-being or bowel symptoms. Conclusion The internet-based RCT proved to be a successful and economical method for examining this CAM intervention. Recruitment, adherence and completion rate were all similar to those reported with conventional RCTs but at a fraction of the cost. Internet-based RCTs can fulfil all the criteria of the revised CONSORT statement and are an appropriate method for studying low-risk interventions. Trial registration ISRCTN36133252 PMID:18190710

A Randomized Controlled Trial of the First Step to Success Early Intervention: Demonstration of Program Efficacy Outcomes in a Diverse, Urban School District

ERIC Educational Resources Information Center

Walker, Hill M.; Seeley, John R.; Small, Jason; Severson, Herbert H.; Graham, Bethany A.; Feil, Edward G.; Serna, Loretta; Golly, Annemieke M.; Forness, Steven R.

2009-01-01

This article reports on a randomized controlled trial of the First Step to Success early intervention that was conducted over a 4-year period in Albuquerque Public Schools. First Step is a selected intervention for students in Grades 1 through 3 with externalizing behavior problems, and it addresses secondary prevention goals and objectives. It…

Pragmatic Pilot Cluster Randomised Control Trial of a School-Based Peer-Led Anti-Smoking Intervention for 13-14 Year Olds in Malaysia: Process Evaluation

ERIC Educational Resources Information Center

Melson, Elniee; Bridle, Christopher; Markham, Wolfgang

2017-01-01

Purpose: The purpose of this paper is to report the process evaluation of a pilot randomised control trial of an anti-smoking intervention for Malaysian 13-14-year olds, conducted in 2011/2012. It was hypothesised that trained peer supporters would promote non-smoking among classmates through informal conversations. Design/methodology/approach:…

Association between berries intake and cardiovascular diseases risk factors: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials.

PubMed

Luís, Ângelo; Domingues, Fernanda; Pereira, Luísa

2018-02-21

The main goal of this work was to clarify the effects of the consumption of berries on cardiovascular disease (CVD) risk factors by performing a systematic review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, followed by a meta-analysis and a trial sequential analysis (TSA) of randomized controlled trials (RCTs). The electronic search was conducted in PubMed, Scopus, SciELO, Web of Science and Cochrane Library between April and June 2016. To be included, RCTs had to report 1 or more of the following outcomes: total cholesterol (TC), HDL-cholesterol (HDL), LDL-cholesterol (LDL), triglycerides (TG), blood pressure (BP), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM), intercellular adhesion molecule-1 (ICAM), glucose, insulin, apolipoprotein A-I (Apo A-I) or apolipoprotein B (Apo B). It was observed that the intake of berries reduces TC, LDL, TG, and BP while increasing the level of HDL, suggesting a beneficial effect on the control of CVDs' risk factors. Thus, the intake of berries as nutraceuticals or functional foods could be suggested for the prevention and control of CVDs.

Systematic Review of Interventions to Improve the Provision of Information for Adults with Primary Brain Tumors and Their Caregivers

PubMed Central

Langbecker, Danette; Janda, Monika

2014-01-01

Background: Adults with primary brain tumors and their caregivers have significant information needs. This review assessed the effect of interventions to improve information provision for adult primary brain tumor patients and/or their caregivers. Methods: We included randomized or non-randomized trials testing educational interventions that had outcomes of information provision, knowledge, understanding, recall, or satisfaction with the intervention, for adults diagnosed with primary brain tumors and/or their family or caregivers. PubMed, MEDLINE, EMBASE, and Cochrane Reviews databases were searched for studies published between 1980 and June 2014. Results: Two randomized controlled, 1 non-randomized controlled, and 10 single group pre–post trials enrolled more than 411 participants. Five group, four practice/process change, and four individual interventions assessed satisfaction (12 studies), knowledge (4 studies), and information provision (2 studies). Nine studies reported high rates of satisfaction. Three studies showed statistically significant improvements over time in knowledge and two showed greater information was provided to intervention than control group participants, although statistical testing was not performed. Discussion: The trials assessed intermediate outcomes such as satisfaction, and only 4/13 reported on knowledge improvements. Few trials had a randomized controlled design and risk of bias was either evident or could not be assessed in most domains. PMID:25667919

Clinical Trials of Aspirin Treatment After Desensitization in Aspirin-Exacerbated Respiratory Disease.

PubMed

Kowalski, Marek L; Wardzyńska, Aleksandra; Makowska, Joanna S

2016-11-01

The clinical efficacy of aspirin treatment after desensitization in patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs has been documented in observational studies and in double-blind placebo-controlled trials. There is no general agreement with regard to the optimal maintenance dose or duration of treatment with acetylsalicylic acid after desensitization, thus further studies are necessary to offer clear guidelines to clinicians. This article summarizes data from noncontrolled, active-control, and placebo-controlled trials assessing clinical effectiveness and reporting on safety of treatment with acetylsalicylic acid in desensitized patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

Modified versus standard intention-to-treat reporting: are there differences in methodological quality, sponsorship, and findings in randomized trials? A cross-sectional study.

PubMed

Montedori, Alessandro; Bonacini, Maria Isabella; Casazza, Giovanni; Luchetta, Maria Laura; Duca, Piergiorgio; Cozzolino, Francesco; Abraha, Iosief

2011-02-28

Randomized controlled trials (RCTs) that use the modified intention-to-treat (mITT) approach are increasingly being published. Such trials have a preponderance of post-randomization exclusions, industry sponsorship, and favourable findings, and little is known whether in terms of these items mITT trials are different with respect to trials that report a standard intention-to-treat. To determine differences in the methodological quality, sponsorship, authors' conflicts of interest, and findings among trials with different "types" of intention-to-treat, we undertook a cross-sectional study of RCTs published in 2006 in three general medical journals (the Journal of the American Medical Association, the New England Journal of Medicine and the Lancet) and three specialty journals (Antimicrobial Agents and Chemotherapy, the American Heart Journal and the Journal of Clinical Oncology). Trials were categorized based on the "type" of intention-to-treat reporting as follows: ITT, trials reporting the use of standard ITT approach; mITT, trials reporting the use of a "modified intention-to-treat" approach; and "no ITT", trials not reporting the use of any intention-to-treat approach. Two pairs of reviewers independently extracted the data in duplicate. The strength of the associations between the "type" of intention-to-treat reporting and the quality of reporting (sample size calculation, flow-chart, lost to follow-up), the methodological quality of the trials (sequence generation, allocation concealment, and blinding), the funding source, and the findings was determined. Odds ratios (OR) were calculated with 95% confidence intervals (CI). Of the 367 RCTs included, 197 were classified as ITT, 56 as mITT, and 114 as "no ITT" trials. The quality of reporting and the methodological quality of the mITT trials were similar to those of the ITT trials; however, the mITT trials were more likely to report post-randomization exclusions (adjusted OR 3.43 [95%CI, 1.70 to 6.95]; P < 0.001). We found a strong association between trials classified as mITT and for-profit agency sponsorship (adjusted OR 7.41 [95%CI, 3.14 to 17.48]; P < .001) as well as the presence of authors' conflicts of interest (adjusted OR 5.14 [95%CI, 2.12 to 12.48]; P < .001). There was no association between mITT reporting and favourable results; in general, however, trials with for-profit agency sponsorship were significantly associated with favourable results (adjusted OR 2.30; [95%CI, 1.28 to 4.16]; P = 0.006). We found that the mITT trials were significantly more likely to perform post-randomization exclusions and were strongly associated with industry funding and authors' conflicts of interest.

Physiotherapy for sleep disturbance in chronic low back pain: a feasibility randomised controlled trial

PubMed Central

2010-01-01

Background Sleep disturbance is becoming increasingly recognised as a clinically important symptom in people with chronic low back pain (CLBP, low back pain >12 weeks), associated with physical inactivity and depression. Current research and international clinical guidelines recommend people with CLBP assume a physically active role in their recovery to prevent chronicity, but the high prevalence of sleep disturbance in this population may be unknowingly limiting their ability to participate in exercise-based rehabilitation programmes and contributing to poor outcomes. There is currently no knowledge concerning the effectiveness of physiotherapy on sleep disturbance in people with chronic low back pain and no evidence of the feasibility of conducting randomized controlled trials that comprehensively evaluate sleep as an outcome measure in this population. Methods/Design This study will evaluate the feasibility of a randomised controlled trial (RCT), exploring the effects of three forms of physiotherapy (supervised general exercise programme, individualized walking programme and usual physiotherapy, which will serve as the control group) on sleep quality in people with chronic low back pain. A presenting sample of 60 consenting patients will be recruited in the physiotherapy department of Beaumont Hospital, Dublin, Ireland, and randomly allocated to one of the three groups in a concealed manner. The main outcomes will be sleep quality (self-report and objective measurement), and self-reported functional disability, pain, quality of life, fear avoidance, anxiety and depression, physical activity, and patient satisfaction. Outcome will be evaluated at baseline, 3 months and 6 months. Qualitative telephone interviews will be embedded in the research design to obtain feedback from a sample of participants' about their experiences of sleep monitoring, trial participation and interventions, and to inform the design of a fully powered future RCT. Planned analysis will explore trends in the data, effect sizes and clinically important effects (quantitative data), and thematic analysis (qualitative data). Discussion This study will evaluate the feasibility of a randomised controlled trial exploring the effects of three forms of physiotherapy (supervised general exercise programme, individualized walking programme and usual physiotherapy, which will serve as the control group) on sleep quality in people with chronic low back pain. Trial Registration Current controlled trial ISRCTN54009836 PMID:20398349

Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy.

PubMed

Shang, Aijing; Huwiler-Müntener, Karin; Nartey, Linda; Jüni, Peter; Dörig, Stephan; Sterne, Jonathan A C; Pewsner, Daniel; Egger, Matthias

Homoeopathy is widely used, but specific effects of homoeopathic remedies seem implausible. Bias in the conduct and reporting of trials is a possible explanation for positive findings of trials of both homoeopathy and conventional medicine. We analysed trials of homoeopathy and conventional medicine and estimated treatment effects in trials least likely to be affected by bias. Placebo-controlled trials of homoeopathy were identified by a comprehensive literature search, which covered 19 electronic databases, reference lists of relevant papers, and contacts with experts. Trials in conventional medicine matched to homoeopathy trials for disorder and type of outcome were randomly selected from the Cochrane Controlled Trials Register (issue 1, 2003). Data were extracted in duplicate and outcomes coded so that odds ratios below 1 indicated benefit. Trials described as double-blind, with adequate randomisation, were assumed to be of higher methodological quality. Bias effects were examined in funnel plots and meta-regression models. 110 homoeopathy trials and 110 matched conventional-medicine trials were analysed. The median study size was 65 participants (range ten to 1573). 21 homoeopathy trials (19%) and nine (8%) conventional-medicine trials were of higher quality. In both groups, smaller trials and those of lower quality showed more beneficial treatment effects than larger and higher-quality trials. When the analysis was restricted to large trials of higher quality, the odds ratio was 0.88 (95% CI 0.65-1.19) for homoeopathy (eight trials) and 0.58 (0.39-0.85) for conventional medicine (six trials). Biases are present in placebo-controlled trials of both homoeopathy and conventional medicine. When account was taken for these biases in the analysis, there was weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects.

Assessment of generalizability, applicability and predictability (GAP) for evaluating external validity in studies of universal family-based prevention of alcohol misuse in young people: systematic methodological review of randomized controlled trials.

PubMed

Fernandez-Hermida, Jose Ramon; Calafat, Amador; Becoña, Elisardo; Tsertsvadze, Alexander; Foxcroft, David R

2012-09-01

To assess external validity characteristics of studies from two Cochrane Systematic Reviews of the effectiveness of universal family-based prevention of alcohol misuse in young people. Two reviewers used an a priori developed external validity rating form and independently assessed three external validity dimensions of generalizability, applicability and predictability (GAP) in randomized controlled trials. The majority (69%) of the included 29 studies were rated 'unclear' on the reporting of sufficient information for judging generalizability from sample to study population. Ten studies (35%) were rated 'unclear' on the reporting of sufficient information for judging applicability to other populations and settings. No study provided an assessment of the validity of the trial end-point measures for subsequent mortality, morbidity, quality of life or other economic or social outcomes. Similarly, no study reported on the validity of surrogate measures using established criteria for assessing surrogate end-points. Studies evaluating the benefits of family-based prevention of alcohol misuse in young people are generally inadequate at reporting information relevant to generalizability of the findings or implications for health or social outcomes. Researchers, study authors, peer reviewers, journal editors and scientific societies should take steps to improve the reporting of information relevant to external validity in prevention trials. © 2012 The Authors. Addiction © 2012 Society for the Study of Addiction.

Safety monitoring of ophthalmic biologics: a systematic review of pre- and postmarketing safety data.

PubMed

Penedones, Ana; Mendes, Diogo; Alves, Carlos; Batel Marques, Francisco

2014-11-01

The present study evaluates the safety of the biologics approved for the treatment of ocular diseases. The European medicines agency Website was searched to identify biologics with approved ophthalmologic therapeutic indications. A systematic search was performed using MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and the International Clinical Trials Registry Platform up to December 2013. Pre-marketing, phase III randomized controlled trials (RCT), postmarketing clinical trials, observational longitudinal studies, and case reports involving adverse events (AE) were included. Methodological quality was assessed by Downs & Black checklist. All European spontaneous reports of AE included in the Eudravigilance up to December 2013 were also considered. AE were classified as ocular (related and non-related with the injection procedure) and non-ocular (related or non-related with vascular endothelial growth factor inhibition). Incidences of all reported AEs were estimated. Pegaptanib, ranibizumab, and aflibercept were identified as ophthalmic biologics. Fourteen premarketing RCT, 7 postmarketing clinical trials, 31 observational studies, along with 31 case reports and 7,720 spontaneous reports were identified and included in this study. Both in pre- and postmarketing settings, ocular AEs were more frequent than non-ocular AEs. Premarketing safety data inform the most common AEs. Postmarketing studies suggest an increased number of events such as retinal pigmented epithelium tears (0.6%-24%), thromboembolic events (0.8%-5%), and mortality (2.8%-4%). This study highlights the need to properly evaluate the risk for rare, serious, and long-term AEs, such as thromboembolic events, since they can lead to imbalances in the benefit-risk ratio of biologics in ophthalmology.

The use of subdissociative-dose ketamine for acute pain in the emergency department.

PubMed

Sin, Billy; Ternas, Theologia; Motov, Sergey M

2015-03-01

Ketamine is a well-known anesthetic with its use trailing back to the 1960s. It has antagonistic effects at the N-methyl-d-aspartate receptor. There is emerging literature to suggest the use of subdissociative-dose ketamine (SDDK) for pain reduction. This evidence-based review evaluates the evidence regarding the use of SDDK for acute pain control in the emergency department (ED). The MEDLINE and EMBASE databases were searched. Randomized controlled trials (RCTs) that described or evaluated the use of SDDK for acute pain in the ED were included. Literature was excluded if it was not published in English. Duplicate articles, unpublished reports, abstracts, and review articles were also excluded. Quality assessment and evaluation of literature were evaluated based on the GRADE criteria. The primary outcome of interest in this review was the difference in pain score from baseline to cutoff time as specified in the studies. Secondary outcome measures were the incidence of adverse events and reduction in the amount of adjuvant opioids consumed by patients who received SDDK. Four RCTs met the inclusion criteria, which enrolled a total of 428 patients. Three adult trials and one pediatric trial were identified. The level of evidence for the individual trials ranged from low to moderate. A significant reduction in pain scores was only found in two of the four trials. One trial found a significant reduction in mean pain scores when ketamine was compared to morphine (p < 0.05). Another trial reported a significant decrease in mean distress scores, favoring SDDK over fentanyl (1.0 vs. 2.7, p < 0.05). One trial found a significant reduction in the amount of morphine consumed, favoring ketamine over placebo (0.14 mg/kg, 95% confidence interval [CI] = 0.13 to 0.16 mg/kg vs. 0.2 mg/kg, 95% CI = 0.18 to 0.22 mg/kg; p < 0.001). An emergence phenomenon was reported in one trial. Four RCTs with methodologic limitations failed to provide convincing evidence to either support or refute the use of SDDK for acute pain control in the ED. © 2015 by the Society for Academic Emergency Medicine.

Specialist teams for neonatal transport to neonatal intensive care units for prevention of morbidity and mortality.

PubMed

Chang, Alvin S M; Berry, Andrew; Jones, Lisa J; Sivasangari, Subramaniam

2015-10-28

Maternal antenatal transfers provide better neonatal outcomes. However, there will inevitably be some infants who require acute transport to a neonatal intensive care unit (NICU). Because of this, many institutions develop services to provide neonatal transport by specially trained health personnel. However, few studies report on relevant clinical outcomes in infants requiring transport to NICU. To determine the effects of specialist transport teams compared with non-specialist transport teams on the risk of neonatal mortality and morbidity among high-risk newborn infants requiring transport to neonatal intensive care. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE (1966 to 31 July 2015), EMBASE (1980 to 31 July 2015), CINAHL (1982 to 31 July 2015), conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. randomised, quasi-randomised or cluster randomised controlled trials. neonates requiring transport to a neonatal intensive care unit. transport by a specialist team compared to a non-specialist team. any of the following outcomes - death; adverse events during transport leading to respiratory compromise; and condition on admission to the neonatal intensive care unit. The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the author. Data on relevant outcomes were extracted and the effect size estimated and reported as risk ratio (RR), risk difference (RD), number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH) and mean difference (MD) for continuous outcomes. Data from cluster randomised trials were not combined for analysis. One trial met the inclusion criteria of this review but was considered ineligible owing to serious bias in the reporting of the results. There is no reliable evidence from randomised trials to support or refute the effects of specialist neonatal transport teams for neonatal retrieval on infant morbidity and mortality. Cluster randomised trial study designs may be best suited to provide us with answers on effectiveness and clinical outcomes.

Impact of industry collaboration on randomised controlled trials in oncology.

PubMed

Linker, Anne; Yang, Annie; Roper, Nitin; Whitaker, Evans; Korenstein, Deborah

2017-02-01

Industry funders can simply provide money or collaborate in trial design, analysis or reporting of clinical trials. Our aim was to assess the impact of industry collaboration on trial methodology and results of randomised controlled trials (RCT). We searched PubMed for oncology RCTs published May 2013 to December 2015 in peer-reviewed journals with impact factor > 5 requiring reporting of funder role. Two authors extracted methodologic (primary end-point; blinding of the patient, clinician and outcomes assessor; and analysis) and outcome data. We used descriptive statistics and two-sided Fisher exact tests to compare characteristics of trials with collaboration, with industry funding only, and without industry funding. We included 224 trials. Compared to those without industry funding, trials with collaboration used more placebo control (RR 3·59, 95% CI [1·88-6·83], p < 0001), intention-to-treat analysis (RR 1·32, 95% CI [1·04-1·67], p = 02), and blinding of patients (RR 3·05, 95% CI [1·71-5·44], p < 0001), clinicians (RR 3·36, 95% CI [1·83-6·16], p≤·001) and outcomes assessors (RR 3·03, 95% CI [1·57-5·83], p = 0002). They did not differ in use of overall survival as a primary end-point (RR 1·27 95% CI [0·72-2·24]) and were similarly likely to report positive results (RR 1·11 95% CI [0·85-1·46], p = 0.45). Studies with funding only did not differ from those without funding. Oncology RCTs with industry collaboration were more likely to use some high-quality methods than those without industry funding, with similar rates of positive results. Our findings suggest that collaboration is not associated with trial outcomes and that mandatory disclosure of funder roles may mitigate bias. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quality of Reporting Nutritional Randomized Controlled Trials in Patients With Cystic Fibrosis.

PubMed

Daitch, Vered; Babich, Tanya; Singer, Pierre; Leibovici, Leonard

2016-08-01

Randomized controlled trials (RCTs) have a major role in the making of evidence-based guidelines. The aim of the present study was to critically appraise the RCTs that addressed nutritional interventions in patients with cystic fibrosis. Embase, PubMed, and the Cochrane Library were systematically searched until July 2015. Methodology and reporting of nutritional RCTs were evaluated by the Consolidated Standards of Reporting Trials (CONSORT) checklist and additional dimensions relevant to patients with CF. Fifty-one RCTs were included. Full details on methods were provided in a minority of studies. The mean duration of intervention was <6 months. 56.9% of the RCTs did not define a primary outcome; 70.6% of studies did not provide details on sample size calculation; and only 31.4% reported on the subgroup or separated between important subgroups. The examined RCTs were characterized by a weak methodology, a small number of patients with no sample size calculations, a relatively short intervention, and many times did not examine the outcomes that are important to the patient. Improvement over the years has been minor.

Intensified hand-hygiene campaign including soap-and-water wash may prevent acute infections in office workers, as shown by a recognized-exposure -adjusted analysis of a randomized trial.

PubMed

Hovi, Tapani; Ollgren, Jukka; Savolainen-Kopra, Carita

2017-01-09

Variable exposure to causative agents of acute respiratory (RTI) or gastrointestinal tract infections (GTI) is a significant confounding factor in the analysis of the efficacy of interventions concerning these infections. We had an exceptional opportunity to reanalyze a previously published dataset from a trial assessing the effect of enhanced hand hygiene on the occurrence of RTI or GTI in adults, after adjustment for reported exposure and other covariates. Twenty-one working units (designated clusters) each including at least 50 office employees, totaling 1,270 persons, were randomized into two intervention arms (either using water-and-soap or alcohol-rub in hand cleansing), or in the control arm. Self-reported data was collected through weekly emails and included own symptoms of RTI or GTI, and exposures to other persons with similar symptoms. Differences in the weekly occurrences of RTI and GTI symptoms between the arms were analyzed using multilevel binary regression model with log link with personal and cluster specific random effects, self-reported exposure to homologous disease, randomization triplet, and seasonality as covariates in the Bayesian framework. Over the 16 months duration of the trial, 297 persons in the soap and water arm, 238 persons in the alcohol-based hand rub arm, and 230 controls sent reports. The arms were similar in age distribution and gender ratios. A temporally-associated reported exposure strongly increased the risk of both types of infection in all trial arms. Persons in the soap-and-water arm reported a significantly - about 24% lower weekly prevalence of GTI than the controls whether they had observed an exposure or not during the preceding week, while for RTI, this intervention reduced the prevalence only during weeks without a reported exposure. Alcohol-rub did not affect the symptom prevalence. We conclude that while frequent and careful hand washing with soap and water partially protected office-working adults from GTI, the effect on RTI was only marginal in this study. Potential reasons for this difference include partially different transmission routes and a difference in the virus load. In this trial, frequent standardized hand rubbing with ethanol-based disinfectant did not reduce the weekly prevalence of either type of infections. ClinicalTrials.gov Identifier: NCT00821509, 12 March 2009.

Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus: a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials

PubMed Central

Kähler, Pernille; Grevstad, Berit; Almdal, Thomas; Gluud, Christian; Wetterslev, Jørn; Vaag, Allan; Hemmingsen, Bianca

2014-01-01

Objective To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus. Design A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. Data sources The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS to January 2013. Study selection Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included. Data extraction Two authors independently assessed studies for inclusion and extracted data. Results 18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all-cause mortality (risk ratio 1.16, 95% CI 0.65 to 2.08) or cardiovascular mortality (0.49, 0.19 to 1.24). Targeting intensive glycaemic control reduced the relative risks for the composite macrovascular outcome (0.63, 0.41 to 0.96; p=0.03), and nephropathy (0.37, 0.27 to 0.50; p<0.00001. The effect estimates of retinopathy, ketoacidosis and retinal photocoagulation were not consistently statistically significant between random and fixed effects models. The risk of severe hypoglycaemia was significantly increased with intensive glycaemic targets (1.40, 1.01 to 1.94). Trial sequential analyses showed that the amount of data needed to demonstrate a relative risk reduction of 10% were, in general, inadequate. Conclusions There was no significant effect towards improved all-cause mortality when targeting intensive glycaemic control compared with conventional glycaemic control. However, there may be beneficial effects of targeting intensive glycaemic control on the composite macrovascular outcome and on nephropathy, and detrimental effects on severe hypoglycaemia. Notably, the data for retinopathy and ketoacidosis were inconsistent. There was a severe lack of reporting on patient relevant outcomes, and all trials had poor bias control. PMID:25138801

Reconciling the influence of task-set switching and motor inhibition processes on stop signal after-effects.

PubMed

Anguera, Joaquin A; Lyman, Kyle; Zanto, Theodore P; Bollinger, Jacob; Gazzaley, Adam

2013-01-01

Executive response functions can be affected by preceding events, even if they are no longer associated with the current task at hand. For example, studies utilizing the stop signal task have reported slower response times to "GO" stimuli when the preceding trial involved the presentation of a "STOP" signal. However, the neural mechanisms that underlie this behavioral after-effect are unclear. To address this, behavioral and electroencephalography (EEG) measures were examined in 18 young adults (18-30 years) on "GO" trials following a previously "Successful Inhibition" trial (pSI), a previously "Failed Inhibition" trial (pFI), and a previous "GO" trial (pGO). Like previous research, slower response times were observed during both pSI and pFI trials (i.e., "GO" trials that were preceded by a successful and unsuccessful inhibition trial, respectively) compared to pGO trials (i.e., "GO" trials that were preceded by another "GO" trial). Interestingly, response time slowing was greater during pSI trials compared to pFI trials, suggesting executive control is influenced by both task set switching and persisting motor inhibition processes. Follow-up behavioral analyses indicated that these effects resulted from between-trial control adjustments rather than repetition priming effects. Analyses of inter-electrode coherence (IEC) and inter-trial coherence (ITC) indicated that both pSI and pFI trials showed greater phase synchrony during the inter-trial interval compared to pGO trials. Unlike the IEC findings, differential ITC was present within the beta and alpha frequency bands in line with the observed behavior (pSI > pFI > pGO), suggestive of more consistent phase synchrony involving motor inhibition processes during the ITI at a regional level. These findings suggest that between-trial control adjustments involved with task-set switching and motor inhibition processes influence subsequent performance, providing new insights into the dynamic nature of executive control.

Relevance of randomised controlled trials in oncology.

PubMed

Tannock, Ian F; Amir, Eitan; Booth, Christopher M; Niraula, Saroj; Ocana, Alberto; Seruga, Bostjan; Templeton, Arnoud J; Vera-Badillo, Francisco

2016-12-01

Well-designed randomised controlled trials (RCTs) can prevent bias in the comparison of treatments and provide a sound basis for changes in clinical practice. However, the design and reporting of many RCTs can render their results of little relevance to clinical practice. In this Personal View, we discuss the limitations of RCT data and suggest some ways to improve the clinical relevance of RCTs in the everyday management of patients with cancer. RCTs should ask questions of clinical rather than commercial interest, avoid non-validated surrogate endpoints in registration trials, and have entry criteria that allow inclusion of all patients who are fit to receive treatment. Furthermore, RCTs should be reported with complete accounting of frequency and management of toxicities, and with strict guidelines to ensure freedom from bias. Premature reporting of results should be avoided. The bar for clinical benefit should be raised for drug registration, which should require publication and review of mature data from RCTs, post-marketing health outcome studies, and value-based pricing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Omitted data in randomized controlled trials for anxiety and depression: A systematic review of the inclusion of sexual orientation and gender identity.

PubMed

Heck, Nicholas C; Mirabito, Lucas A; LeMaire, Kelly; Livingston, Nicholas A; Flentje, Annesa

2017-01-01

The current study examined the frequency with which randomized controlled trials (RCTs) of behavioral and psychological interventions for anxiety and depression include data pertaining to participant sexual orientation and nonbinary gender identities. Using systematic review methodology, the databases PubMed and PsycINFO were searched to identify RCTs published in 2004, 2009, and 2014. Random selections of 400 articles per database per year (2,400 articles in total) were considered for inclusion in the review. Articles meeting inclusion criteria were read and coded by the research team to identify whether the trial reported data pertaining to participant sexual orientation and nonbinary gender identities. Additional trial characteristics were also identified and indexed in our database (e.g., sample size, funding source). Of the 232 articles meeting inclusion criteria, only 1 reported participants' sexual orientation, and zero articles included nonbinary gender identities. A total of 52,769 participants were represented in the trials, 93 of which were conducted in the United States, and 43 acknowledged the National Institutes of Health as a source of funding. Despite known mental health disparities on the basis of sexual orientation and nonbinary gender identification, researchers evaluating interventions for anxiety and depression are not reporting on these important demographic characteristics. Reporting practices must change to ensure that our interventions generalize to lesbian, gay, bisexual, and transgender persons. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

DeLLITE depression in late life: an intervention trial of exercise. Design and recruitment of a randomised controlled trial.

PubMed

Kerse, Ngaire; Falloon, Karen; Moyes, Simon A; Hayman, Karen J; Dowell, Tony; Kolt, Gregory S; Elley, C Raina; Hatcher, Simon; Peri, Kathy; Keeling, Sally; Robinson, Elizabeth; Parsons, John; Wiles, Janine; Arroll, Bruce

2008-05-24

Physical activity shows potential in combating the poor outcomes associated with depression in older people. Meta-analyses show gaps in the research with poor trial design compromising certainty in conclusions and few programmes showing sustained effects. The Depression in Late Life: an Intervention Trial of Exercise (DeLLITE) is a 12 month randomised controlled trial of a physical activity intervention to increase functional status in people aged 75 years and older with depressive symptoms. The intervention involves an individualised activity programme based on goal setting and progression of difficulty of activities delivered by a trained nurse during 8 home visits over 6 months. The control group received time matched home visits to discuss social contacts and networks. Baseline, 6 and 12 months measures were assessed in face to face visits with the primary outcome being functional status (SPPB, NEADL). Secondary outcomes include depressive symptoms (Geriatric Depression Scale), quality of life (SF-36), physical activity (AHS Physical Activity Questionnaire) and falls (self report). Due to report in 2008 the DeLLITE study has recruited 70% of those eligible and tests the efficacy of a home based, goal setting physical activity programme in improving function, mood and quality of life in older people with depressive symptomatology. If successful in improving function and mood this trial could prove for the first time that there are long term health benefit of physical activity, independent of social activity, in this high risk group who consume excess health related costs. Australian and New Zealand Clinical Trials Register ACTRN12605000475640.

DeLLITE Depression in late life: an intervention trial of exercise. Design and recruitment of a randomised controlled trial

PubMed Central

Kerse, Ngaire; Falloon, Karen; Moyes, Simon A; Hayman, Karen J; Dowell, Tony; Kolt, Gregory S; Elley, C Raina; Hatcher, Simon; Peri, Kathy; Keeling, Sally; Robinson, Elizabeth; Parsons, John; Wiles, Janine; Arroll, Bruce

2008-01-01

Background Physical activity shows potential in combating the poor outcomes associated with depression in older people. Meta-analyses show gaps in the research with poor trial design compromising certainty in conclusions and few programmes showing sustained effects. Methods/design The Depression in Late Life: an Intervention Trial of Exercise (DeLLITE) is a 12 month randomised controlled trial of a physical activity intervention to increase functional status in people aged 75 years and older with depressive symptoms. The intervention involves an individualised activity programme based on goal setting and progression of difficulty of activities delivered by a trained nurse during 8 home visits over 6 months. The control group received time matched home visits to discuss social contacts and networks. Baseline, 6 and 12 months measures were assessed in face to face visits with the primary outcome being functional status (SPPB, NEADL). Secondary outcomes include depressive symptoms (Geriatric Depression Scale), quality of life (SF-36), physical activity (AHS Physical Activity Questionnaire) and falls (self report). Discussion Due to report in 2008 the DeLLITE study has recruited 70% of those eligible and tests the efficacy of a home based, goal setting physical activity programme in improving function, mood and quality of life in older people with depressive symptomatology. If successful in improving function and mood this trial could prove for the first time that there are long term health benefit of physical activity, independent of social activity, in this high risk group who consume excess health related costs. Trial registration Australian and New Zealand Clinical Trials Register ACTRN12605000475640 PMID:18501008

A literature review of applied adaptive design methodology within the field of oncology in randomised controlled trials and a proposed extension to the CONSORT guidelines.

PubMed

Mistry, Pankaj; Dunn, Janet A; Marshall, Andrea

2017-07-18

The application of adaptive design methodology within a clinical trial setting is becoming increasingly popular. However the application of these methods within trials is not being reported as adaptive designs hence making it more difficult to capture the emerging use of these designs. Within this review, we aim to understand how adaptive design methodology is being reported, whether these methods are explicitly stated as an 'adaptive design' or if it has to be inferred and to identify whether these methods are applied prospectively or concurrently. Three databases; Embase, Ovid and PubMed were chosen to conduct the literature search. The inclusion criteria for the review were phase II, phase III and phase II/III randomised controlled trials within the field of Oncology that published trial results in 2015. A variety of search terms related to adaptive designs were used. A total of 734 results were identified, after screening 54 were eligible. Adaptive designs were more commonly applied in phase III confirmatory trials. The majority of the papers performed an interim analysis, which included some sort of stopping criteria. Additionally only two papers explicitly stated the term 'adaptive design' and therefore for most of the papers, it had to be inferred that adaptive methods was applied. Sixty-five applications of adaptive design methods were applied, from which the most common method was an adaptation using group sequential methods. This review indicated that the reporting of adaptive design methodology within clinical trials needs improving. The proposed extension to the current CONSORT 2010 guidelines could help capture adaptive design methods. Furthermore provide an essential aid to those involved with clinical trials.

Effectiveness of a Web-Based Self-Help Program for Suicidal Thinking in an Australian Community Sample: Randomized Controlled Trial

PubMed Central

van Spijker, Bregje AJ; Werner-Seidler, Aliza; Batterham, Philip J; Mackinnon, Andrew; Calear, Alison L; Gosling, John A; Reynolds, Julia; Kerkhof, Ad JFM; Solomon, Daniela; Shand, Fiona

2018-01-01

Background Treatment for suicidality can be delivered online, but evidence for its effectiveness is needed. Objective The goal of our study was to examine the effectiveness of an online self-help intervention for suicidal thinking compared to an attention-matched control program. Methods A 2-arm randomized controlled trial was conducted with assessment at postintervention, 6, and, 12 months. Through media and community advertizing, 418 suicidal adults were recruited to an online portal and were delivered the intervention program (Living with Deadly Thoughts) or a control program (Living Well). The primary outcome was severity of suicidal thinking, assessed using the Columbia Suicide Severity Rating Scale. Results Intention-to-treat analyses showed significant reductions in the severity of suicidal thinking at postintervention, 6, and 12 months. However, no overall group differences were found. Conclusions Living with Deadly Thoughts was of no greater effectiveness than the control group. Further investigation into the conditions under which this program may be beneficial is now needed. Limitations of this trial include it being underpowered given the effect size ultimately observed, a high attrition rate, and the inability of determining suicide deaths or of verifying self-reported suicide attempts. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12613000410752; https://www.anzctr.org.au/ Trial/Registration/TrialReview.aspx?id=364016 (Archived by WebCite at http://www.webcitation.org/6vK5FvQXy); Universal Trial Number U1111-1141-6595 PMID:29444769

The impact of growth hormone therapy on adult height in noonan syndrome: a systematic review.

PubMed

Giacomozzi, Claudio; Deodati, Annalisa; Shaikh, Mohamad Guftar; Ahmed, Syed Faisal; Cianfarani, Stefano

2015-01-01

Recombinant human growth hormone (rhGH) is being used to promote linear growth in short children with Noonan syndrome. However, its efficacy is still controversial. To systematically determine the impact of rhGH therapy on adult height in children with Noonan syndrome. We searched the Cochrane Central Register of Controlled Trials, ISI Web of Science, MEDLINE, and the bibliographic references from all retrieved articles published until April 2014. Studies reporting adult/near-adult height in children with Noonan syndrome treated with rhGH or reporting at least a 3-year follow-up were analysed. Quality and strength of recommendation were assessed according to the Endocrine Society criteria. No controlled trials reporting adult height were available. Five studies were identified reporting adult height or near adult height. Data comparison showed inter-individual variability in the response to rhGH, mean height gain standard deviation score ranging between 0.6 and 1.4 according to national standards, and between 0.6 and 2 according to Noonan standards. Significant biases affected all the studies. High-quality controlled trials on the impact of rhGH therapy on adult height are lacking, and the robustness of available data is not sufficient to recommend such therapy in children with Noonan syndrome. © 2015 S. Karger AG, Basel.

A randomized controlled trial of an electronic informed consent process.

PubMed

Rothwell, Erin; Wong, Bob; Rose, Nancy C; Anderson, Rebecca; Fedor, Beth; Stark, Louisa A; Botkin, Jeffrey R

2014-12-01

A pilot study assessed an electronic informed consent model within a randomized controlled trial (RCT). Participants who were recruited for the parent RCT project were randomly selected and randomized to either an electronic consent group (n = 32) or a simplified paper-based consent group (n = 30). Results from the electronic consent group reported significantly higher understanding of the purpose of the study, alternatives to participation, and who to contact if they had questions or concerns about the study. However, participants in the paper-based control group reported higher mean scores on some survey items. This research suggests that an electronic informed consent presentation may improve participant understanding for some aspects of a research study. © The Author(s) 2014.

Effects of web-based instruction and patient preferences on patient-reported outcomes and learning for women with advanced ovarian cancer: A randomized controlled trial.

PubMed

Petzel, Sue V; Isaksson Vogel, Rachel; Cragg, Julie; McClellan, Molly; Chan, Daniel; Jacko, Julie A; Sainfort, François; Geller, Melissa A

2018-05-23

A randomized controlled trial was conducted of a web-based intervention to improve advanced care planning in women with ovarian cancer. A secondary analysis of 35 randomized women focused on changes in distress and knowledge about ovarian cancer through distress monitoring and information tailored to patients' cognitive coping style (monitoring, blunting). Pre-/postresults indicated the Intervention group demonstrated lower distress (p = 0.06); blunting was associated with lower depression (p = 0.04); knowledge in both groups was unchanged. Women in the Intervention vs. Control group reported their family was less likely to be upset by cancer information (p = 0.0004). This intervention reduced distress while incorporating patient preferences.

Interventions to Promote Colorectal Cancer Screening: An Integrative Review

PubMed Central

Rawl, Susan M.; Menon, Usha; Burness, Allison; Breslau, Erica S.

2012-01-01

Behavior change interventions to promote colorectal cancer (CRC) screening have targeted people in community and primary care settings, health care providers, and health systems. Randomized controlled trials provide the strongest evidence of intervention efficacy. The purpose of this integrative review was to evaluate trials of CRC screening interventions published between 1997 and 2007 and to identify knowledge gaps and future directions for research. Thirty-three randomized trials that met inclusion criteria were evaluated using a modified version of the TREND criteria. Significant intervention effects were reported in six out of ten trials focused on increasing fecal occult blood testing, four of seven trials focused on sigmoidoscopy or colonoscopy completion, and nine of 16 focused on completion of any screening test. Several effective interventions to promote CRC screening were identified. Future trials need to use theory to guide interventions, examine moderators and mediators, consistently report results, and use comparable outcome measures. PMID:22261002

Evolution of poor reporting and inadequate methods over time in 20 920 randomised controlled trials included in Cochrane reviews: research on research study.

PubMed

Dechartres, Agnes; Trinquart, Ludovic; Atal, Ignacio; Moher, David; Dickersin, Kay; Boutron, Isabelle; Perrodeau, Elodie; Altman, Douglas G; Ravaud, Philippe

2017-06-08

Objective  To examine how poor reporting and inadequate methods for key methodological features in randomised controlled trials (RCTs) have changed over the past three decades. Design  Mapping of trials included in Cochrane reviews. Data sources  Data from RCTs included in all Cochrane reviews published between March 2011 and September 2014 reporting an evaluation of the Cochrane risk of bias items: sequence generation, allocation concealment, blinding, and incomplete outcome data. Data extraction  For each RCT, we extracted consensus on risk of bias made by the review authors and identified the primary reference to extract publication year and journal. We matched journal names with Journal Citation Reports to get 2014 impact factors. Main outcomes measures  We considered the proportions of trials rated by review authors at unclear and high risk of bias as surrogates for poor reporting and inadequate methods, respectively. Results  We analysed 20 920 RCTs (from 2001 reviews) published in 3136 journals. The proportion of trials with unclear risk of bias was 48.7% for sequence generation and 57.5% for allocation concealment; the proportion of those with high risk of bias was 4.0% and 7.2%, respectively. For blinding and incomplete outcome data, 30.6% and 24.7% of trials were at unclear risk and 33.1% and 17.1% were at high risk, respectively. Higher journal impact factor was associated with a lower proportion of trials at unclear or high risk of bias. The proportion of trials at unclear risk of bias decreased over time, especially for sequence generation, which fell from 69.1% in 1986-1990 to 31.2% in 2011-14 and for allocation concealment (70.1% to 44.6%). After excluding trials at unclear risk of bias, use of inadequate methods also decreased over time: from 14.8% to 4.6% for sequence generation and from 32.7% to 11.6% for allocation concealment. Conclusions  Poor reporting and inadequate methods have decreased over time, especially for sequence generation and allocation concealment. But more could be done, especially in lower impact factor journals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cardiovascular safety of linagliptin in type 2 diabetes: a comprehensive patient-level pooled analysis of prospectively adjudicated cardiovascular events.

PubMed

Rosenstock, Julio; Marx, Nikolaus; Neubacher, Dietmar; Seck, Thomas; Patel, Sanjay; Woerle, Hans-Juergen; Johansen, Odd Erik

2015-05-21

The cardiovascular (CV) safety of linagliptin was evaluated in subjects with type 2 diabetes (T2DM). Pre-specified patient-level pooled analysis of all available double-blind, randomized, controlled trials, ≥ 12 weeks' duration (19 trials, 9459 subjects) of linagliptin versus placebo/active treatment. Primary end point: composite of prospectively adjudicated CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for unstable angina (4P-MACE). Hospitalization for congestive heart failure (CHF) was also evaluated; adjudication of CHF was introduced during the phase 3 program (8 trials; 3314 subjects). 4P-MACE was assessed in placebo-controlled trials (subgroup of 18 trials; 7746 subjects). Investigator-reported events suggestive of CHF from 24 placebo-controlled trials (including trials <12 weeks' duration, 8778 subjects) were also analyzed. 5847 patients received linagliptin (5 mg: 5687, 10 mg: 160) and 3612 comparator (glimepiride: 775, voglibose: 162, placebo: 2675); cumulative exposure, 4421.3 and 3254.7 patient-years, respectively. 4P-MACE incidence rates: 13.4 per 1000 patient-years, linagliptin (60 events), 18.9, total comparators (62 events); overall hazard ratio (HR), 0.78 (95% confidence interval [CI], 0.55-1.12). HR for adjudicated hospitalization for CHF (n = 21): 1.04 (0.43-2.47). For placebo-controlled trials, 4P-MACE incidence rates: 14.9 per 1000 patient-years, linagliptin (43 events), 16.4, total comparators (29 events); overall HR, 1.09 (95% CI, 0.68-1.75). Occurrence of investigator-reported events suggestive of CHF was low for linagliptin- (26 events, 0.5%; serious: 16 events, 0.3%) and placebo-treated (8 events, 0.2%; serious: 6 events, 0.2%) patients. Linagliptin is not associated with increased CV risk versus pooled active comparators or placebo in patients with T2DM.

Systematic evaluation of the methodology of randomized controlled trials of anticoagulation in patients with cancer.

PubMed

Rada, Gabriel; Schünemann, Holger J; Labedi, Nawman; El-Hachem, Pierre; Kairouz, Victor F; Akl, Elie A

2013-02-14

Randomized controlled trials (RCTs) that are inappropriately designed or executed may provide biased findings and mislead clinical practice. In view of recent interest in the treatment and prevention of thrombotic complications in cancer patients we evaluated the characteristics, risk of bias and their time trends in RCTs of anticoagulation in patients with cancer. We conducted a comprehensive search, including a search of four electronic databases (MEDLINE, EMBASE, ISI the Web of Science, and CENTRAL) up to February 2010. We included RCTs in which the intervention and/or comparison consisted of: vitamin K antagonists, unfractionated heparin (UFH), low molecular weight heparin (LMWH), direct thrombin inhibitors or fondaparinux. We performed descriptive analyses and assessed the association between the variables of interest and the year of publication. We included 67 RCTs with 24,071 participants. In twenty one trials (31%) DVT diagnosis was triggered by clinical suspicion; the remaining trials either screened for DVT or were unclear about their approach. 41 (61%), 22 (33%), and 11 (16%) trials respectively reported on major bleeding, minor bleeding, and thrombocytopenia. The percentages of trials satisfying risk of bias criteria were: adequate sequence generation (85%), adequate allocation concealment (61%), participants' blinding (39%), data collectors' blinding (44%), providers' blinding (41%), outcome assessors' blinding (75%), data analysts' blinding (15%), intention to treat analysis (57%), no selective outcome reporting (12%), no stopping early for benefit (97%). The mean follow-up rate was 96%. Adequate allocation concealment and the reporting of intention to treat analysis were the only two quality criteria that improved over time. Many RCTs of anticoagulation in patients with cancer appear to use insufficiently rigorous outcome assessment methods and to have deficiencies in key methodological features. It is not clear whether this reflects a problem in the design, conduct or the reporting of these trials, or both. Future trials should avoid the shortcomings described in this article.

Adverse effects of homeopathy, what do we know? A systematic review and meta-analysis of randomized controlled trials.

PubMed

Stub, Trine; Musial, Frauke; Kristoffersen, Agnete A; Alræk, Terje; Liu, Jianping

2016-06-01

Homeopathy is a popular treatment modality among patient, however there is sparse research about adverse effects of homeopathy. A concept unique for homeopathy, is homeopathic aggravation that is understood as a transient worsening of the patients' symptoms before an expected improvement occurs. From a risk perspective it is vital that a distinction between homeopathic aggravations and adverse effects is established. There is a lack of systematic information on how frequent adverse effects and homeopathic aggravations are reported in studies. Therefore, a systematic review and meta-analysis were performed. Sixteen electronic databases were searched for Randomized Controlled Trials (RCTs). The searches were limited from the year 1995 to January 2011. Forty-one RCTs, with a total of 6.055 participants were included. A subtotal of 39 studies was included in the additional meta-analysis. A total of 28 trials (68%) reported adverse effects and five trials (12%) reported homeopathic aggravations. The meta-analysis (including six subgroup comparisons) demonstrated that no significant difference was found between homeopathy and control with OR 0.99, 95% CI 0.86-1.14, I(2)=54%. More than two third of the adverse effects were classified as grade 1 (68%) and two third were classified as grade 2 (25%) and grade 3 (6%) according to the Common Terminology Criteria for Adverse Effects. Homeopathic aggravation was classified as grade 1 (98%) and grade 3 (2%), suggesting that homeopathic aggravations were reported to be less severe than adverse effects. The methodological quality according to a method recommended in the Cochrane handbook for RCTs, was high. Adverse effects including the concept of homeopathic aggravations are commonly reported in trials. The meta-analysis demonstrated that the proportion of patients experiencing adverse effects to be similar for patients randomized to homeopathic treatment compared to patients randomized to placebo and conventional medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Short-acting insulin analogues versus regular human insulin for adults with type 1 diabetes mellitus.

PubMed

Fullerton, Birgit; Siebenhofer, Andrea; Jeitler, Klaus; Horvath, Karl; Semlitsch, Thomas; Berghold, Andrea; Plank, Johannes; Pieber, Thomas R; Gerlach, Ferdinand M

2016-06-30

Short-acting insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. To assess the effects of short-acting insulin analogues versus regular human insulin in adults with type 1 diabetes. We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues with regular human insulins in the treatment of adults with type 1 diabetes who were not pregnant. Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results.The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the insulin analogue, insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable.We also found no clear evidence for a substantial effect of insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Our analysis suggests only a minor benefit of short-acting insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of short acting insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

Reporting adverse events in randomized controlled trials in periodontology: a systematic review.

PubMed

Faggion, Clovis M; Tu, Yu-Kang; Giannakopoulos, Nikolaos N

2013-09-01

Reporting of adverse events is of paramount importance in randomized controlled trials (RCTs) to guide the implementation of new therapeutic approaches in clinical practice. The aim of this study was to assess the quality of adverse events reporting in RCTs published in the periodontal literature. Two authors (CMF and NNG) searched the PubMed and LILACS electronic databases independently and in duplicate to identify RCTs published in periodontology from 2002 to 2003 and from 2011 to 2012. Reporting quality in RCTs was assessed with reference to the 2004 CONSORT Extension for Harms checklist. Differences in adverse events reporting between industry- and non-industry-funded RCTs were also determined. Cohen's kappa statistic was used to determine the extent of inter-reviewer agreement. Fischer's exact test was used to assess differences in reporting between the two samples. The analysis included 246 publications. One hundred twenty-four of 990 (13%) items and 223 of 1460 (15%) items were adequately reported in publications from 2002 to 2003 and from 2011 to 2012 respectively. Three checklist topics were significantly better reported in the 2011-2012 sample; two recommendations were better reported in non-industry-funded trials in publications from both periods. Improvement and standardization of adverse events reporting in periodontology are needed. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Professional medical writing support and the quality of randomised controlled trial reporting: a cross-sectional study

PubMed Central

Gattrell, William T; Hopewell, Sally; Young, Kate; Farrow, Paul; White, Richard; Winchester, Christopher C

2016-01-01

Objectives Authors may choose to work with professional medical writers when writing up their research for publication. We examined the relationship between medical writing support and the quality and timeliness of reporting of the results of randomised controlled trials (RCTs). Design Cross-sectional study. Study sample Primary reports of RCTs published in BioMed Central journals from 2000 to 16 July 2014, subdivided into those with medical writing support (n=110) and those without medical writing support (n=123). Main outcome measures Proportion of items that were completely reported from a predefined subset of the Consolidated Standards of Reporting Trials (CONSORT) checklist (12 items known to be commonly poorly reported), overall acceptance time (from manuscript submission to editorial acceptance) and quality of written English as assessed by peer reviewers. The effect of funding source and publication year was examined. Results The number of articles that completely reported at least 50% of the CONSORT items assessed was higher for those with declared medical writing support (39.1% (43/110 articles); 95% CI 29.9% to 48.9%) than for those without (21.1% (26/123 articles); 95% CI 14.3% to 29.4%). Articles with declared medical writing support were more likely than articles without such support to have acceptable written English (81.1% (43/53 articles); 95% CI 67.6% to 90.1% vs 47.9% (23/48 articles); 95% CI 33.5% to 62.7%). The median time of overall acceptance was longer for articles with declared medical writing support than for those without (167 days (IQR 114.5–231 days) vs 136 days (IQR 77–193 days)). Conclusions In this sample of open-access journals, declared professional medical writing support was associated with more complete reporting of clinical trial results and higher quality of written English. Medical writing support may play an important role in raising the quality of clinical trial reporting. PMID:26899254

Treating Acute Insomnia: A Randomized Controlled Trial of a “Single-Shot” of Cognitive Behavioral Therapy for Insomnia

PubMed Central

Ellis, Jason G.; Cushing, Toby; Germain, Anne

2015-01-01

Study Objectives: Despite considerable evidence supporting cognitive behavioral therapy for insomnia (CBT-I) for chronic insomnia, it remains untested within the context of acute insomnia. This study examined the efficacy of a single session of CBT-I, with an accompanying self-help pamphlet, for individuals with acute insomnia. Design: A pragmatic parallel group randomized controlled trial. Setting: Community. Participants: Forty adults (mean age 32.9 ± 13.72 y) with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) defined insomnia disorder, except a self-reported duration of less than 3 mo (i.e., acute insomnia), who reported no previous exposure to CBT-I and were not currently taking medication for sleep. Interventions: A single 60- to 70-min session of CBT-I (n = 20), with an accompanying self-help pamphlet, or wait list control group (n = 20). All subjects were offered a full individual course of CBT-I on completion of the study, regardless of group allocation. Measurements and Results: Subjects completed sleep diaries and the Insomnia Severity Index (ISI) pretreatment and 1 mo following treatment. There were no between-group differences on baseline ISI scores or subjective sleep continuity. The intervention group reported significantly lower ISI scores than controls (t(38) 2.24, P < 0.05) at follow-up. Further, using proposed ISI scores for identifying insomnia caseness (i.e., ≥ 10), 60% of those in the CBT-I group had remitted by 1 mo compared to 15% of those in the control group. Conclusions: This single session of cognitive behavioral therapy for insomnia (CBT-I) is sufficiently efficacious for a significant proportion of those with acute insomnia. The results are discussed in terms of integrating this brief form of CBT-I into the “stepped care” model of insomnia. Trial Registration: Testing the efficacy of an early intervention for acute insomnia (SRCTN05891695) http://www.controlled-trials.com/ISRCTN05891695. Citation: Ellis JG, Cushing T, Germain A. Treating acute insomnia: a randomized controlled trial of a “single-shot” of cognitive behavioral therapy for insomnia. SLEEP 2015;38(6):971–978. PMID:25515106

Different intensities of glycaemic control for women with gestational diabetes mellitus.

PubMed

Martis, Ruth; Brown, Julie; Alsweiler, Jane; Crawford, Tineke J; Crowther, Caroline A

2016-04-07

Gestational diabetes mellitus (GDM) has major short- and long-term implications for both the mother and her baby. GDM is defined as a carbohydrate intolerance resulting in hyperglycaemia or any degree of glucose intolerance with onset or first recognition during pregnancy from 24 weeks' gestation onwards and which resolves following the birth of the baby. Rates for GDM can be as high as 25% depending on the population and diagnostic criteria used and rates are increasing globally. Risk factors associated with GDM include advanced maternal age, obesity, ethnicity, family history of diabetes, and a previous history of GDM, macrosomia or unexplained stillbirth. There is wide variation internationally in glycaemic treatment target recommendations for women with GDM that are based on consensus rather than high-quality trials. To assess the effect of different intensities of glycaemic control in pregnant women with GDM on maternal and infant health outcomes. We searched the Cochrane Pregancy and Childbirth Group's Trials Register (31 January 2016), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (1 February 2016) and reference lists of the retrieved studies. We included one randomised controlled trial. Cluster-randomised and quasi-randomised controlled trials were eligible for inclusion. We used the methods described in the Cochrane Handbook for Systematic Reviews of Interventions for carrying out data collection, assessing study quality and analysing results. Two review authors independently assessed trial eligibility for inclusion, evaluated methodological quality and extracted data for the one included study. We sought additional information from one trial author but had no response. We assessed the quality of evidence for selected outcomes using the GRADE approach. We included one Canadian trial of 180 women, recruited between 20 to 32 weeks' gestation, who had been diagnosed with GDM. Data from 171 of the 180 women were published as a conference abstract and no full report has been identified. The overall risk of bias of the single included study was judged to be unclear.The included trial did not report on any of this review's primary outcomes. For the mother, these were hypertension disorders of pregnancy or subsequent development of type 2 diabetes. For the infant, our primary outcomes were (perinatal (fetal and neonatal) mortality; large-for-gestational age; composite of death or severe morbidity or later childhood neurosensory disability).The trial did report data relating to some of this review's secondary outcomes. There was no clear difference in caesarean section rates for women assigned to using strict glycaemic targets (pre-prandial 5.0 mmol/L (90 mg/L) and at one-hour postprandial 6.7 mmol/L (120 mg/dL)) (28/85, 33%) when compared with women assigned to using liberal glycaemic targets (pre-prandial 5.8 mmol/L (103 mg/dL) and at one-hour postprandial 7.8 mmol/L (140 mg/dL)) (21/86, 24%) (risk ratio (RR) 1.35, 95% confidence interval (CI) 0.83 to 2.18, one trial, 171 women; very low quality). Using the GRADE approach, we found the quality of the evidence to bevery low for caesarean section due to poor reporting of risk of bias, imprecision and publication bias. Strict glycaemic targets were associated with an increase in the use of pharmacological therapy (identified as the use of insulin in this study) (33/85; 39%) compared with liberal glycaemic targets (18/86; 21%) (RR 1.85, 95% CI 1.14 to 3.03; one trial, 171 women). CIs are wide suggesting imprecision and caution is required when interpreting the data. No other secondary maternal outcome data relevant to this review were reported. For the infant, there were no clear differences between the groups of women receiving strict and liberal glycaemic targets for macrosomia (birthweight greater than 4000 g) (RR 1.35, 95% CI 0.31 to 5.85, one trial, 171 babies); small-for-gestational age (RR 1.12, 95% CI 0.48 to 2.63, one trial, 171 babies); birthweight (mean difference (MD) -92.00 g, 95% CI -241.97 to 57.97, one trial, 171 babies) or gestational age (MD -0.30 weeks, 95% CI -0.73 to 0.13, one trial, 171 babies). Adverse effects data were not reported. No other secondary neonatal outcomes relevant to this review were reported. This review is based on a single study (involving 180 women) with an unclear risk of bias. The trial (which was only reported in a conference abstract) did not provide data for any of this review's primary outcomes but did provide data for a limited number of our secondary outcomes. There is insufficient evidence to guide clinical practice for targets for glycaemic control for women with GDM to minimise adverse effects on maternal and fetal health. Glycaemic target recommendations from international professional organisations for maternal glycaemic control vary widely and are reliant on consensus given the lack of high-quality evidence.Further high-quality trials are needed, and these should compare different glycaemic targets for guiding treatment of women with GDM, assess both short-term and long-term health outcomes for women and their babies, include women's experiences and assess health services costs. Four studies are ongoing.

Quality of patient-reported outcome reporting across cancer randomized controlled trials according to the CONSORT patient-reported outcome extension: A pooled analysis of 557 trials.

PubMed

Efficace, Fabio; Fayers, Peter; Pusic, Andrea; Cemal, Yeliz; Yanagawa, Jane; Jacobs, Marc; la Sala, Andrea; Cafaro, Valentina; Whale, Katie; Rees, Jonathan; Blazeby, Jane

2015-09-15

The main objectives of this study were to identify the number of randomized controlled trials (RCTs) including a patient-reported outcome (PRO) endpoint across a wide range of cancer specialties and to evaluate the completeness of PRO reporting according to the Consolidated Standards of Reporting Trials (CONSORT) PRO extension. RCTs with a PRO endpoint that had been performed across several cancer specialties and published between 2004 and 2013 were considered. Studies were evaluated on the basis of previously defined criteria, including the CONSORT PRO extension and the Cochrane Collaboration's tool for assessing the risk of bias of RCTs. Analyses were also conducted by the type of PRO endpoint (primary vs secondary) and by the cancer disease site. A total of 56,696 potentially eligible records were scrutinized, and 557 RCTs with a PRO evaluation, enrolling 254,677 patients overall, were identified. PROs were most frequently used in RCTs of breast (n = 123), lung (n = 85), and colorectal cancer (n = 66). Overall, PROs were secondary endpoints in 421 RCTs (76%). Four of 6 evaluated CONSORT PRO items were documented in less than 50% of the RCTs. The level of reporting was higher in RCTs with a PRO as a primary endpoint. The presence of a supplementary report was the only statistically significant factor associated with greater completeness of reporting for both RCTs with PROs as primary endpoints (β = .19, P = .001) and RCTs with PROs as secondary endpoints (β = .30, P < .001). Implementation of the CONSORT PRO extension is equally important across all cancer specialties. Its use can also contribute to revealing the robust PRO design of some studies, which might be obscured by poor outcome reporting. © 2015 American Cancer Society.

Inclusion and definition of acute renal dysfunction in critically ill patients in randomized controlled trials: a systematic review.

PubMed

da Hora Passos, Rogerio; Ramos, Joao Gabriel Rosa; Gobatto, André; Caldas, Juliana; Macedo, Etienne; Batista, Paulo Benigno

2018-04-24

In evidence-based medicine, multicenter, prospective, randomized controlled trials (RCTs) are the gold standard for evaluating treatment benefits and ensuring the effectiveness of interventions. Patient-centered outcomes, such as mortality, are most often the preferred evaluated outcomes. While there is currently agreement on how to classify renal dysfunction in critically ill patients , the application frequency of this new classification system in RCTs has not previously been evaluated. In this study, we aim to assess the definition of renal dysfunction in multicenter RCTs involving critically ill patients that included mortality as a primary endpoint. A comprehensive search was conducted for publications reporting multicenter randomized controlled trials (RCTs) involving adult patients in intensive care units (ICUs) that included mortality as a primary outcome. MEDLINE and PUBMED were queried for relevant articles in core clinical journals published between May 2004 and December 2017. Of 418 articles reviewed, 46 multicenter RCTs with a primary endpoint related to mortality were included. Thirty-six (78.3%) of the trial reports provided information on renal function in the participants. Only seven articles (15.2%) included mean or median serum creatinine levels, mean creatinine clearance or estimated glomerular filtration rates. Sequential organ failure assessment (SOFA) score was the most commonly used definition of renal dysfunction (20 studies; 43.5%). Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease Improving Global Outcomes (KDIGO) criteria were used in five (10.9%) trials. In thirteen trials (28.3%), no renal dysfunction criteria were reported. Only one trial excluded patients with renal dysfunction, and it used urinary output or need for renal replacement therapy (RRT) as criteria for this diagnosis. The presence of renal dysfunction was included as a baseline patient characteristic in most RCTs. The RIFLE, AKIN and KDIGO classification systems were infrequently used; renal dysfunction was generally defined using the SOFA score.

Quality of Reporting Randomized Controlled Trials in Five Leading Neurology Journals in 2008 and 2013 Using the Modified "Risk of Bias" Tool.

PubMed

Zhai, Xiao; Cui, Jin; Wang, Yiran; Qu, Zhiquan; Mu, Qingchun; Li, Peiwen; Zhang, Chaochao; Yang, Mingyuan; Chen, Xiao; Chen, Ziqiang; Li, Ming

2017-03-01

To examine the risk of bias of methodological quality of reporting randomized clinical trials (RCTs) in major neurology journals before and after the update (2011) of Cochrane risk of bias tool. RCTs in 5 leading neurology journals in 2008 and 2013 were searched systematically. Characteristics were extracted based on the list of the modified Cochrane Collaboration's tool. Country, number of patients, type of intervention, and funding source also were examined for further analysis. A total of 138 RCTs were enrolled in this study. The rates of following a trial plan were 61.6% for the allocation generation, 52.9% for the allocation concealment, 84.8% for the blinding of the participants or the personnel, 34.8% for the blinding of outcome assessment, 78.3% for the incomplete outcome data, and 67.4% for the selective reporting. A significant setback was found in "the selective reporting" in 2013 than that in 2008. Trials performed by multi-centers and on a large scale had significantly more "low risk of bias" trials. Not only the number of surgical trials (5.8%) was much less than that of trials using drugs (73.9%), but also the reporting quality of surgical trials were worse (P = 0.008). Finally, only 17.4% trials met the criterion of "low risk of bias." The modified "risk of bias" tool is an improved version for assessment. Methodological quality of reporting RCTs in the 5neurology journals is unsatisfactory, especially that for surgical RCTs, and it could be further improved. Copyright © 2017 Elsevier Inc. All rights reserved.

Internet treatment for social anxiety disorder in Romania: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Social anxiety disorder (SAD) is one of the most common anxiety disorders and is associated with marked impairments. However, a small proportion of individuals with SAD seek and receive treatment. Internet-administrated cognitive behavior therapy (iCBT) has been found to be an effective treatment for SAD. This trial will be the first Internet-delivered guided self-help intervention for SAD in Romania. Methods Participants with social anxiety disorder (N = 96) will be recruited via newspapers, online banners and Facebook. Participants will be randomized to either: a) an active treatment, or b) a waiting list control group. The treatment will have a guided iCBT format and will last for nine weeks. Self-report questionnaires on social phobia, anxiety, depression, treatment credibility and irrational thinking will be used. All assessments will be collected pre, post and at follow-up (six months after intervention). Liebowitz Social Anxiety Scale – Self-Report version (LSAS-SR) will be the primary outcome measure and will be administrated on a weekly basis in both conditions. Discussion The present randomized controlled trial investigates the efficacy of an Internet-administered intervention in reducing social anxiety symptoms in a culture where this form of treatment has not been tested. This trial will add to the body of knowledge on the efficacy of iCBT, and the results might lead to an increase of the accessibility of evidence-based psychological treatment in Romania. Trial registration ClinicalTrials.gov: NCT01557894 PMID:23111108

Quality of natural product clinical trials: a comparison of those published in alternative medicine versus conventional medicine journals.

PubMed

Cochrane, Zara Risoldi; Gregory, Philip; Wilson, Amy

2011-06-01

To compare the quality of natural product clinical trials published in alternative medicine journals versus those published in conventional medicine journals. Systematic search and review of the literature. Randomized controlled trials of natural products were included if they were published in English between 2003 and 2008. Articles were categorized by their journal of publication (alternative medicine versus conventional medicine). Two independent reviewers evaluated study quality using guidelines from the Cochrane Collaboration. The results with respect to the primary outcome (positive or negative) were also assessed. Thirty articles were evaluated, 15 published in alternative medicine journals and 15 in conventional medicine journals. Of articles published in alternative medicine journals, 33.33% (n = 5) were considered low quality, and none were considered high quality. Of articles published in conventional medicine journals, 26.67% (n = 4) were considered low quality and 6.67% (n = 1) were considered high quality. Two thirds of all trials reviewed were of unclear quality, due to inadequate reporting of information relating to the study's methodology. Similar proportions of positive and negative primary outcomes were found in alternative and conventional medicine journals, and low-quality articles were not more likely to report a positive primary outcome (Fisher's exact test, two-tailed p = .287). The quality of natural product randomized controlled trials was similar among alternative and conventional medicine journals. Efforts should be made to improve the reporting of natural product clinical trials for accurate determinations of study quality to be possible.

Small studies may overestimate the effect sizes in critical care meta-analyses: a meta-epidemiological study

PubMed Central

2013-01-01

Introduction Small-study effects refer to the fact that trials with limited sample sizes are more likely to report larger beneficial effects than large trials. However, this has never been investigated in critical care medicine. Thus, the present study aimed to examine the presence and extent of small-study effects in critical care medicine. Methods Critical care meta-analyses involving randomized controlled trials and reported mortality as an outcome measure were considered eligible for the study. Component trials were classified as large (≥100 patients per arm) and small (<100 patients per arm) according to their sample sizes. Ratio of odds ratio (ROR) was calculated for each meta-analysis and then RORs were combined using a meta-analytic approach. ROR<1 indicated larger beneficial effect in small trials. Small and large trials were compared in methodological qualities including sequence generating, blinding, allocation concealment, intention to treat and sample size calculation. Results A total of 27 critical care meta-analyses involving 317 trials were included. Of them, five meta-analyses showed statistically significant RORs <1, and other meta-analyses did not reach a statistical significance. Overall, the pooled ROR was 0.60 (95% CI: 0.53 to 0.68); the heterogeneity was moderate with an I2 of 50.3% (chi-squared = 52.30; P = 0.002). Large trials showed significantly better reporting quality than small trials in terms of sequence generating, allocation concealment, blinding, intention to treat, sample size calculation and incomplete follow-up data. Conclusions Small trials are more likely to report larger beneficial effects than large trials in critical care medicine, which could be partly explained by the lower methodological quality in small trials. Caution should be practiced in the interpretation of meta-analyses involving small trials. PMID:23302257

Development and Evaluation of a Pedagogical Tool to Improve Understanding of a Quality Checklist: A Randomised Controlled Trial

PubMed Central

Fourcade, Lola; Boutron, Isabelle; Moher, David; Ronceray, Lucie; Baron, Gabriel; Ravaud, Philippe

2007-01-01

Objective: The aim of this study was to develop and evaluate a pedagogical tool to enhance the understanding of a checklist that evaluates reports of nonpharmacological trials (CLEAR NPT). Design: Paired randomised controlled trial. Participants: Clinicians and systematic reviewers. Interventions: We developed an Internet-based computer learning system (ICLS). This pedagogical tool used many examples from published randomised controlled trials to demonstrate the main coding difficulties encountered when using this checklist. Randomised participants received either a specific Web-based training with the ICLS (intervention group) or no specific training. Outcome measures: The primary outcome was the rate of correct answers compared to a criterion standard for coding a report of randomised controlled trials with the CLEAR NPT. Results: Between April and June 2006, 78 participants were randomly assigned to receive training with the ICLS (39) or no training (39). Participants trained by the ICLS did not differ from the control group in performance on the CLEAR NPT. The mean paired difference and corresponding 95% confidence interval was 0.5 (−5.1 to 6.1). The rate of correct answers did not differ between the two groups regardless of the CLEAR NPT item. Combining both groups, the rate of correct answers was high or items related to allocation sequence (79.5%), description of the intervention (82.0%), blinding of patients (79.5%), and follow-up schedule (83.3%). The rate of correct answers was low for items related to allocation concealment (46.1%), co-interventions (30.3%), blinding of outcome assessors (53.8%), specific measures to avoid ascertainment bias (28.6%), and intention-to-treat analysis (60.2%). Conclusions: Although we showed no difference in effect between the intervention and control groups, our results highlight the gap in knowledge and urgency for education on important aspects of trial conduct. PMID:17479163

Implementation of an educational intervention to improve hand washing in primary schools: process evaluation within a randomised controlled trial.

PubMed

Chittleborough, Catherine R; Nicholson, Alexandra L; Young, Elaine; Bell, Sarah; Campbell, Rona

2013-08-15

Process evaluations are useful for understanding how interventions are implemented in trial settings. This is important for interpreting main trial results and indicating how the intervention might function beyond the trial. The purpose of this study was to examine the reach, dose, fidelity, acceptability, and sustainability of the implementation of an educational hand washing intervention in primary schools, and to explore views regarding acceptability and sustainability of the intervention. Process evaluation within a cluster randomised controlled trial, including focus groups with pupils aged 6 to 11, semi-structured interviews with teachers and external staff who coordinated the intervention delivery, and school reports and direct observations of the intervention delivery. The educational package was delivered in 61.4% of schools (85.2% of intervention schools, 37.8% of control schools following completion of the trial). Teachers and pupils reacted positively to the intervention, although concerns were raised about the age-appropriateness of the resources. Teachers adapted the resources to suit their school setting and pupils. Staff coordinating the intervention delivery had limited capacity to follow up and respond to schools. The hand washing intervention was acceptable to schools, but its reach outside of a randomised trial, evidenced in the low proportion of schools in the control arm who received it after the trial had ended, suggests that the model of delivery may not be sustainable. ISRCTN: ISRCTN93576146.

Randomized controlled trials in pediatric complementary and alternative medicine: Where can they be found?

PubMed Central

Sampson, Margaret; Campbell, Kaitryn; Ajiferuke, Isola; Moher, David

2003-01-01

Background The safety and effectiveness of CAM interventions are of great relevance to pediatric health care providers. The objective of this study is to identify sources of reported randomized controlled trials (RCTs) in the field of pediatric complementary and alternative medicine (CAM). Methods Reports of RCTs were identified by searching Medline and 12 additional bibliographic databases and by reviewing the reference lists of previously identified pediatric CAM systematic reviews. Results We identified 908 reports of RCTs that included children under 18 and investigated a CAM therapy. Since 1965, there has been a steady growth in the number of these trials that are being published. The four journals that published the most reported RCTs are The American Journal of Clinical Nutrition, Pediatrics, Journal of Pediatrics, and Lancet. Medline, CAB Health, and Embase were the best database sources for identifying these studies; they indexed 93.2%, 58.4% and 42.2 % respectively of the journals publishing reports of pediatric CAM RCTs. Conclusions Those working or interested in the field of pediatric CAM should routinely search Medline, CAB Health and Embase for literature in the field. The four core journals identified above should be included in their collection. PMID:12589711

Psychosocial consequences of allocation to lung cancer screening: a randomised controlled trial.

PubMed

Aggestrup, Louise Mosborg; Hestbech, Mie Sara; Siersma, Volkert; Pedersen, Jesper Holst; Brodersen, John

2012-01-01

To examine the psychosocial consequences of being allocated to the control group as compared with the screen group in a randomised lung cancer screening trial. The Danish Lung Cancer Screening Trial, a randomised controlled trial, ran from 2004 to 2010 with the purpose of investigating the benefits and harms of lung cancer screening. The participants in Danish Lung Cancer Screening Trial were randomised to either the control group or the screen group and were asked to complete the questionnaires Consequences Of Screening and Consequences Of Screening in Lung Cancer (COS-LC). The Consequences Of Screening and the COS-LC were used to examine the psychosocial consequences of participating in the study, by comparing the control and the screen groups' responses at the prevalence and at the incidence round. There was no statistically significant difference in socio-demographic characteristics or smoking habits between the two groups. Responses to the COS-LC collected before the incidence round were statistically significantly different on the scales 'anxiety', 'behaviour', 'dejection', 'self-blame', 'focus on airway symptoms' and 'introvert', with the control group reporting higher negative psychosocial consequences. Furthermore, the participants in both the control and the screen groups exhibited a mean increase in negative psychosocial consequences when their responses from the prevalence round were compared with their responses from the first incidence round. Participation in a randomised controlled trial on lung cancer screening has negative psychosocial consequences for the apparently healthy participants-both the participants in the screen group and the control group. This negative impact was greatest for the control group.

Can a documentary increase help-seeking intentions in men? A randomised controlled trial

PubMed Central

Schlichthorst, Marisa; Spittal, Matthew J; Phelps, Andrea; Pirkis, Jane

2018-01-01

Background We investigated whether a public health intervention—a three-part documentary called Man Up which explored the relationship between masculinity and mental health, well-being and suicidality—could increase men’s intentions to seek help for personal and emotional problems. Methods We recruited men aged 18 years or over who were not at risk of suicide to participate in a double-blind randomised controlled trial. Participants were randomly assigned (1:1) via computer randomisation to view Man Up (the intervention) or a control documentary. We hypothesised that 4 weeks after viewing Man Up participants would report higher levels of intention to seek help than those who viewed the control documentary. Our primary outcome was assessed using the General Help Seeking Questionnaire, and was analysed for all participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001169437, Universal Trial Number: U1111-1186-1459) and was funded by the Movember Foundation. Results Three hundred and fifty-four men were assessed for eligibility for the trial and randomised to view Man Up or the control documentary. Of these, 337 completed all stages (nine participants were lost to follow-up in the intervention group and eight in the control group). Linear regression analysis showed a significant increase in intentions to seek help in the intervention group, but not in the control group (coef.=2.06, 95% CI 0.48 to 3.63, P=0.01). Conclusions Our trial demonstrates the potential for men’s health outcomes to be positively impacted by novel, media-based public health interventions that focus on traditional masculinity. Trial registration number ACTRN12616001169437, Results. PMID:29101215

Garlic powder intake and cardiovascular risk factors: a meta-analysis of randomized controlled clinical trials

PubMed Central

Kwak, Jin Sook; Kim, Ji Yeon; Paek, Ju Eun; Lee, You Jin; Kim, Haeng-Ran; Park, Dong-Sik

2014-01-01

BACKGROUND/OBJECTIVES Although preclinical studies suggest that garlic has potential preventive effects on cardiovascular disease (CVD) risk factors, clinical trials and reports from systematic reviews or meta-analyses present inconsistent results. The contradiction might be attributed to variations in the manufacturing process that can markedly influence the composition of garlic products. To investigate this issue further, we performed a meta-analysis of the effects of garlic powder on CVD risk factors. MATERIALS/METHODS We searched PubMed, Cochrane, Science Direct and EMBASE through May 2014. A random-effects meta-analysis was performed on 22 trials reporting total cholesterol (TC), 17 trials reporting LDL cholesterol (LDL-C), 18 trials reporting HDL cholesterol (HDL-C), 4 trials reporting fasting blood glucose (FBG), 9 trials reporting systolic blood pressure (SBP) and 10 trials reporting diastolic blood pressure (DBP). RESULTS The overall garlic powder intake significantly reduced blood TC and LDL-C by -0.41 mmol/L (95% confidence interval [CI], -0.69, -0.12) (-15.83 mg/dL [95% CI, -26.64, -4.63]) and -0.21 mmol/L (95% CI, -0.40, -0.03) (-8.11 mg/dL [95% CI, -15.44, -1.16]), respectively. The mean difference in the reduction of FBG levels was -0.96 mmol/L (95% CI, -1.91, -0.01) (-17.30 mg/dL [95% CI, -34.41, -0.18]). Evidence for SBP and DBP reduction in the garlic supplementation group was also demonstrated by decreases of -4.34 mmHg (95% CI, -8.38, -0.29) and -2.36 mmHg (95% CI, -4.56, -0.15), respectively. CONCLUSIONS This meta-analysis provides consistent evidence that garlic powder intake reduces the CVD risk factors of TC, LDL-C, FBG and BP. PMID:25489404

Garlic powder intake and cardiovascular risk factors: a meta-analysis of randomized controlled clinical trials.

PubMed

Kwak, Jin Sook; Kim, Ji Yeon; Paek, Ju Eun; Lee, You Jin; Kim, Haeng-Ran; Park, Dong-Sik; Kwon, Oran

2014-12-01

Although preclinical studies suggest that garlic has potential preventive effects on cardiovascular disease (CVD) risk factors, clinical trials and reports from systematic reviews or meta-analyses present inconsistent results. The contradiction might be attributed to variations in the manufacturing process that can markedly influence the composition of garlic products. To investigate this issue further, we performed a meta-analysis of the effects of garlic powder on CVD risk factors. We searched PubMed, Cochrane, Science Direct and EMBASE through May 2014. A random-effects meta-analysis was performed on 22 trials reporting total cholesterol (TC), 17 trials reporting LDL cholesterol (LDL-C), 18 trials reporting HDL cholesterol (HDL-C), 4 trials reporting fasting blood glucose (FBG), 9 trials reporting systolic blood pressure (SBP) and 10 trials reporting diastolic blood pressure (DBP). The overall garlic powder intake significantly reduced blood TC and LDL-C by -0.41 mmol/L (95% confidence interval [CI], -0.69, -0.12) (-15.83 mg/dL [95% CI, -26.64, -4.63]) and -0.21 mmol/L (95% CI, -0.40, -0.03) (-8.11 mg/dL [95% CI, -15.44, -1.16]), respectively. The mean difference in the reduction of FBG levels was -0.96 mmol/L (95% CI, -1.91, -0.01) (-17.30 mg/dL [95% CI, -34.41, -0.18]). Evidence for SBP and DBP reduction in the garlic supplementation group was also demonstrated by decreases of -4.34 mmHg (95% CI, -8.38, -0.29) and -2.36 mmHg (95% CI, -4.56, -0.15), respectively. This meta-analysis provides consistent evidence that garlic powder intake reduces the CVD risk factors of TC, LDL-C, FBG and BP.

The effects of computer-based mindfulness training on Self-control and Mindfulness within Ambulatorily assessed network Systems across Health-related domains in a healthy student population (SMASH): study protocol for a randomized controlled trial.

PubMed

Rowland, Zarah; Wenzel, Mario; Kubiak, Thomas

2016-12-01

Self-control is an important ability in everyday life, showing associations with health-related outcomes. The aim of the Self-control and Mindfulness within Ambulatorily assessed network Systems across Health-related domains (SMASH) study is twofold: first, the effectiveness of a computer-based mindfulness training will be evaluated in a randomized controlled trial. Second, the SMASH study implements a novel network approach in order to investigate complex temporal interdependencies of self-control networks across several domains. The SMASH study is a two-armed, 6-week, non-blinded randomized controlled trial that combines seven weekly laboratory meetings and 40 days of electronic diary assessments with six prompts per day in a healthy undergraduate student population at the Johannes Gutenberg University Mainz, Germany. Participants will be randomly assigned to (1) receive a computer-based mindfulness intervention or (2) to a wait-list control condition. Primary outcomes are self-reported momentary mindfulness and self-control assessed via electronic diaries. Secondary outcomes are habitual mindfulness and habitual self-control. Further measures include self-reported behaviors in specific self-control domains: emotion regulation, alcohol consumption and eating behaviors. The effects of mindfulness training on primary and secondary outcomes are explored using three-level mixed models. Furthermore, networks will be computed with vector autoregressive mixed models to investigate the dynamics at participant and group level. This study was approved by the local ethics committee (reference code 2015_JGU_psychEK_011) and follows the standards laid down in the Declaration of Helsinki (2013). This randomized controlled trial combines an intensive Ambulatory Assessment of 40 consecutive days and seven laboratory meetings. By implementing a novel network approach, underlying processes of self-control within different health domains will be identified. These results will deepen the understanding of self-control performance and will guide to just-in-time individual interventions for several health-related behaviors. ClinicalTrials.gov, NCT02647801 . Registered on 15 December 2015 (registered retrospectively). .

Routine blood cultures in the management of pyelonephritis in pregnancy for improving outcomes.

PubMed

Gomi, Harumi; Goto, Yoshihito; Laopaiboon, Malinee; Usui, Rie; Mori, Rintaro

2015-02-13

Pyelonephritis is a type of urinary tract infection (UTI) that affects the upper urinary tract and kidneys, and is one of the most common conditions for hospitalisation among pregnant women, aside from delivery. Samples of urine and blood are obtained and used for cultures as part of the diagnosis and management of the condition. Acute pyelonephritis requires hospitalisation with intravenous administration of antimicrobial agents. Several studies have questioned the necessity of obtaining blood cultures in addition to urine cultures, citing cost and questioning whether blood testing is superfluous. Pregnant women with bacteraemia require a change in the initial empirical treatment based on the blood culture. However, these cases are not common, and represent approximately 15% to 20% of cases. It is unclear whether blood cultures are essential for the effective management of the condition. To assess the effectiveness of routine blood cultures to improve health outcomes in the management of pyelonephritis in pregnant women. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register without language or date restrictions (31 December 2014). Randomised controlled trials and quasi-randomised trials comparing outcomes among pregnant women with pyelonephritis who received initial management with or without blood cultures. Cluster-randomised trials were eligible for inclusion in this review but none were identified. Clinical trials using a cross-over design were not eligible for inclusion. Two review authors independently assessed one trial report for inclusion. We identified one trial report but this was excluded. No clinical trials met the inclusion criteria for this review. There are no large-scale randomised controlled trials to assess outcomes in the management of pyelonephritis in pregnancy with or without blood cultures. Randomised controlled trials are needed to evaluate the effectiveness of managing pyelonephritis in pregnant women with or without blood cultures, and to assess any adverse outcomes as well as the cost-effectiveness of excluding blood cultures from treatment.

A systematic review of randomized controlled trials with herbal medicine on chronic rhinosinusitis.

PubMed

Anushiravani, Majid; Bakhshaee, Mahdi; Taghipour, Ali; Naghedi-Baghdar, Hamideh; Farshchi, Masoumeh Kaboli; Hoseini, Seyed Saeed; Mehri, Mohammad Reza

2018-03-01

Chronic rhinosinusitis (CRS) is a common disease with evidence to show that its incidence and prevalence are increasing. Medicinal plants are commonly used to treat CRS. This systematic review aimed to assess the effectiveness and safety of herbal preparations for treatment of the patients with CRS. Cochran, Embase, ISI, PubMed, and Scopus databases were searched until August 1, 2016. Only randomized controlled trials were included. Four randomized controlled trials were included in this systematic review. Various medicinal plants were studied in each article. Inclusion and exclusion criteria, and outcome measures varied among different articles. The results of this trials showed that this special medicinal plants may be effective in the treatment of CRS. No serious reactions were reported during the administration of herbal remedies in the 4 studies. However, trials with a well-designed approach are needed to study the actual safety and efficacy of herbs in the treatment of CRS. Copyright © 2017 John Wiley & Sons, Ltd.

A Pilot Randomized Controlled Trial of the ACCESS Program: A Group Intervention to Improve Social, Adaptive Functioning, Stress Coping, and Self-Determination Outcomes in Young Adults with Autism Spectrum Disorder.

PubMed

Oswald, Tasha M; Winder-Patel, Breanna; Ruder, Steven; Xing, Guibo; Stahmer, Aubyn; Solomon, Marjorie

2018-05-01

The purpose of this pilot randomized controlled trial was to investigate the acceptability and efficacy of the Acquiring Career, Coping, Executive control, Social Skills (ACCESS) Program, a group intervention tailored for young adults with autism spectrum disorder (ASD) to enhance critical skills and beliefs that promote adult functioning, including social and adaptive skills, self-determination skills, and coping self-efficacy. Forty-four adults with ASD (ages 18-38; 13 females) and their caregivers were randomly assigned to treatment or waitlist control. Compared to controls, adults in treatment significantly improved in adaptive and self-determination skills, per caregiver report, and self-reported greater belief in their ability to access social support to cope with stressors. Results provide evidence for the acceptability and efficacy of the ACCESS Program.

A critical appraisal of the reporting quality of published randomized controlled trials in the fall injuries.

PubMed

Asghari Jafarabadi, Mohammad; Sadeghi-Bazrgani, Homayoun; Dianat, Iman

2018-06-01

To evaluate the quality of reporting in published randomized controlled trials (RTCs) in the field of fall injuries. The 188 RTCs published between 2001 and 2011, indexed in EMBASE and Medline databases were extracted through searching by appropriate keywords and EMTree classification terms. The evaluation trustworthiness was assured through parallel evaluations of two experts in epidemiology and biostatistics. About 40%-75% of papers had problems in reporting random allocation method, allocation concealment, random allocation implementation, blinding and similarity among groups, intention to treat and balancing benefits and harms. Moreover, at least 10% of papers inappropriately/not reported the design, protocol violations, sample size justification, subgroup/adjusted analyses, presenting flow diagram, drop outs, recruitment time, baseline data, suitable effect size on outcome, ancillary analyses, limitations and generalizability. Considering the shortcomings found and due to the importance of the RCTs for fall injury prevention programmes, their reporting quality should be improved.

An Efficacy Trial of Carescapes: Home-Based Child-Care Practices and Children's Social Outcomes.

PubMed

Rusby, Julie C; Jones, Laura B; Crowley, Ryann; Smolkowski, Keith

2016-07-01

This study reported findings from a longitudinal randomized controlled trial of Carescapes, a professional development program for home-based child-care providers in promoting children's social competence. Participants included 134 child-care providers and 310 children, ages 3-5 years, in Oregon. The Carescapes intervention group made significant improvements in observed caregiver responsiveness and monitoring, and showed decreased caregiver-reported child problem behavior and improved parent-reported peer relationships compared to the control group. Increased caregiver-reported cooperation skills were found for the intervention group at follow-up. No differences in condition were found for kindergarten teacher-reported social-behavioral, classroom, and academic skills. Moderation effects on children's behavior and peer relations were found for child age and exposure to the intervention child care. © 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.

Effects of nitrates on mortality in acute myocardial infarction and in heart failure

PubMed Central

Held, P.

1992-01-01

1 Seven randomized controlled trials of intravenous nitroglycerin in a total of about 850 patients have been reported. Overall, there were 51 deaths (12.5%) in the nitroglycerin group and 87 (20%) in the control group. This indicates a 48% reduction in the odds of death (P < 0.001, 95% confidence limits (25% to 64%)). 2 There are five randomized trials of oral nitrates after acute myocardial infarction. In these trials, 11.8% of the patients in the nitrate group compared with 13.3% in the control group died. This indicates a nonsignificant 12% reduction in the odds of death but the 95% confidence interval overlaps widely with the i.v. trials. If all trials of i.v. or oral nitrates are considered the reduction in the odds of death is 32% (P < 0.01). 3 Nitrates have a beneficial effect on haemodynamics in heart failure but the data on mortality effects are sparse. In combination with hydralazine, however, long-term mortality was reduced in the V-HEFT trial of chronic heart failure. PMID:1633075

Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

DTIC Science & Technology

2017-10-01

Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704...penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR...TERMS Breast cancer, adjuvant treatment, aspirin, randomized controlled trial 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF

A Randomised Controlled Trial of the Use of a Piece of Commercial Software for the Acquisition of Reading Skills

ERIC Educational Resources Information Center

Khan, Muhammad Ahmad; Gorard, Stephen

2012-01-01

We report here the overall results of a cluster randomised controlled trial of the use of computer-aided instruction with 672 Year 7 pupils in 23 secondary school classes in the north of England. A new piece of commercial software, claimed on the basis of publisher testing to be effective in improving reading after just six weeks of use in the…

The Impact of Achieve3000 on Elementary Literacy Outcomes: Randomized Control Trial Evidence, 2013-14 to 2014-15. Eye on Evaluation. DRA Report No. 16.02

ERIC Educational Resources Information Center

Hill, Darryl V.; Lenard, Matthew A.

2016-01-01

In 2013-14, the Wake County Public School System (WCPSS) launched Achieve3000 as a randomized controlled trial in 16 elementary schools. Achieve3000 is an early literacy program that differentiates non-fiction reading passages based on individual students' Lexile scores. Twoyear results show that Achieve3000 did not have a significant impact on…

Promoting Recruitment using Information Management Efficiently (PRIME): a stepped-wedge, cluster randomised trial of a complex recruitment intervention embedded within the REstart or Stop Antithrombotics Randomised Trial.

PubMed

Maxwell, Amy E; Parker, Richard A; Drever, Jonathan; Rudd, Anthony; Dennis, Martin S; Weir, Christopher J; Al-Shahi Salman, Rustam

2017-12-28

Few interventions are proven to increase recruitment in clinical trials. Recruitment to RESTART, a randomised controlled trial of secondary prevention after stroke due to intracerebral haemorrhage, has been slower than expected. Therefore, we sought to investigate an intervention to boost recruitment to RESTART. We conducted a stepped-wedge, cluster randomised trial of a complex intervention to increase recruitment, embedded within the RESTART trial. The primary objective was to investigate if the PRIME complex intervention (a recruitment co-ordinator who conducts a recruitment review, provides access to bespoke stroke audit data exports, and conducts a follow-up review after 6 months) increases the recruitment rate to RESTART. We included 72 hospital sites located in England, Wales, or Scotland that were active in RESTART in June 2015. All sites began in the control state and were allocated using block randomisation stratified by hospital location (Scotland versus England/Wales) to start the complex intervention in one of 12 different months. The primary outcome was the number of patients randomised into RESTART per month per site. We quantified the effect of the complex intervention on the primary outcome using a negative binomial, mixed model adjusting for site, December/January months, site location, and background time trends in recruitment rate. We recruited and randomised 72 sites and recorded their monthly recruitment to RESTART over 24 months (March 2015 to February 2017 inclusive), providing 1728 site-months of observations for the primary analysis. The adjusted rate ratio for the number of patients randomised per month after allocation to the PRIME complex intervention versus control time before allocation to the PRIME complex intervention was 1.06 (95% confidence interval 0.55 to 2.03, p = 0.87). Although two thirds of respondents to the 6-month follow-up questionnaire agreed that the audit reports were useful, only six patients were reported to have been randomised using the audit reports. Respondents frequently reported resource and time pressures as being key barriers to running the audit reports. The PRIME complex intervention did not significantly improve the recruitment rate to RESTART. Further research is needed to establish if PRIME might be beneficial at an earlier stage in a prevention trial or for prevention dilemmas that arise more often in clinical practice.

Feasibility of a multicentre, randomised controlled trial of laparoscopic versus open colorectal surgery in the acute setting: the LaCeS feasibility trial protocol.

PubMed

Harji, Deena; Marshall, Helen; Gordon, Katie; Crow, Hannah; Hiley, Victoria; Burke, Dermot; Griffiths, Ben; Moriarty, Catherine; Twiddy, Maureen; O'Dwyer, John L; Verjee, Azmina; Brown, Julia; Sagar, Peter

2018-02-22

Acute colorectal surgery forms a significant proportion of emergency admissions within the National Health Service. There is limited evidence to suggest minimally invasive surgery may be associated with improved clinical outcomes in this cohort of patients. Consequently, there is a need to assess the clinical effectiveness and cost-effectiveness of laparoscopic surgery in the acute colorectal setting. However,emergency colorectal surgical trials have previously been difficult to conduct due to issues surrounding recruitment and equipoise. The LaCeS (randomised controlled trial of Laparoscopic versus open Colorectal Surgery in the acute setting) feasibility trial will determine the feasibility of conducting a definitive, phase III trial of laparoscopic versus open acute colorectal resection. The LaCeS feasibility trial is a prospective, multicentre, single-blinded, parallel group, pragmatic randomised controlled feasibility trial. Patients will be randomised on a 1:1 basis to receive eitherlaparoscopic or open surgery. The trial aims to recruit at least 66 patients from five acute general surgical units across the UK. Patients over the age of 18 with a diagnosis of acute colorectal pathology requiring resection on clinical and radiological/endoscopic investigations, with a National Confidential Enquiry into Patient Outcome and Death classification of urgent will be considered eligible for participation. The primary outcome is recruitment. Secondary outcomes include assessing the safety profile of laparoscopic surgery using intraoperative and postoperative complication rates, conversion rates and patient-safety indicators as surrogate markers. Clinical and patient-reported outcomes will also be reported. The trial will contain an embedded qualitative study to assess clinician and patient acceptability of trial processes. The LaCeS feasibility trial is approved by the Yorkshire and The Humber, Bradford Leeds Research Ethics Committee (REC reference: 15/ YH/0542). The results from the trial will be presented at national and international colorectal conferences and will be submitted for publication to peer-reviewed journals. ISRCTN15681041; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). A randomized controlled trial

PubMed Central

Damiani, Lucas Petri; Berwanger, Otavio; Paisani, Denise; Laranjeira, Ligia Nasi; Suzumura, Erica Aranha; Amato, Marcelo Britto Passos; Carvalho, Carlos Roberto Ribeiro; Cavalcanti, Alexandre Biasi

2017-01-01

Background The Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) is an international multicenter randomized pragmatic controlled trial with allocation concealment involving 120 intensive care units in Brazil, Argentina, Colombia, Italy, Poland, Portugal, Malaysia, Spain, and Uruguay. The primary objective of ART is to determine whether maximum stepwise alveolar recruitment associated with PEEP titration, adjusted according to the static compliance of the respiratory system (ART strategy), is able to increase 28-day survival in patients with acute respiratory distress syndrome compared to conventional treatment (ARDSNet strategy). Objective To describe the data management process and statistical analysis plan. Methods The statistical analysis plan was designed by the trial executive committee and reviewed and approved by the trial steering committee. We provide an overview of the trial design with a special focus on describing the primary (28-day survival) and secondary outcomes. We describe our data management process, data monitoring committee, interim analyses, and sample size calculation. We describe our planned statistical analyses for primary and secondary outcomes as well as pre-specified subgroup analyses. We also provide details for presenting results, including mock tables for baseline characteristics, adherence to the protocol and effect on clinical outcomes. Conclusion According to best trial practice, we report our statistical analysis plan and data management plan prior to locking the database and beginning analyses. We anticipate that this document will prevent analysis bias and enhance the utility of the reported results. Trial registration ClinicalTrials.gov number, NCT01374022. PMID:28977255

Study participant reported outcomes of mental health interventions: results from a randomized controlled trial among survivors of systematic violence in southern Iraq.

PubMed

Mahmooth, Z; Weiss, W M; Zangana, G A S; Bolton, P

2018-01-01

Common mental health problems experienced by survivors of systematic violence include trauma, depression, and anxiety. A trial of mental health interventions by community mental health workers for survivors of systematic violence in southern Iraq showed benefits from two psychotherapies on trauma, depression, anxiety, and function: Common Elements Treatment Approach (CETA) and cognitive processing therapy (CPT). This study assessed whether other non-predetermined changes reported by intervention participants were more common than in the control group. The trial involved 342 participants (CETA: 99 intervention, 50 control; CPT: 129 intervention, 64 control). Sixteen intervention-related changes since enrollment were identified from free-listing interviews of 15 early therapy completers. The changes were then added as a new quantitative module to the follow-up questionnaire. The changes were organized into eight groupings by thematic analysis - family, social standing, anger management, interest in regular activities, optimism, feeling close to God, avoiding smoking and drugs, and physical health. All participants were interviewed with this module and responses were compared between intervention and control participants. Multi-level, multi-variate regression models showed CETA intervention subjects with significant, positive changes relative to CETA controls on most themes. CPT intervention subjects showed little to no change compared with CPT controls in most themes. Participants receiving CETA reported more positive changes from therapy compared with controls than did participants receiving CPT. This study suggests differential effects of psychotherapy beyond the predetermined clinical outcome measures and that identification of these effects should be part of intervention evaluations.

Moving Beyond Conventional Clinical Trial End Points in Treatment-refractory Metastatic Colorectal Cancer: A Composite Quality-of-life and Symptom Control End Point.

PubMed

Gong, Jun; Wu, Daniel; Chuang, Jeremy; Tuli, Richard; Simard, John; Hendifar, Andrew

2017-11-01

This review highlights the evidence supporting symptom control and quality-of-life (QOL) measures as predictors of survival in treatment-refractory metastatic colorectal cancer (mCRC) and describes a composite symptom control and QOL end point recently reported in a Phase III trial that may serve as a more reasonable end point of efficacy in this population. A literature search was conducted using MEDLINE to identify clinical studies (including case series and observational, retrospective, and prospective studies) that reported the predictive value of QOL measures for survival in mCRC. The search was limited by the following key words: quality of life, survival, and colorectal cancer. We then performed a second search limited to studies of randomized and Phase III design in mCRC to identify studies that used QOL assessments as their primary end points. A manual search was also performed to include additional studies of potential relevance. There is increasing evidence to support that symptom control and QOL measures are predictors of survival in treatment-refractory mCRC and can serve as an alternative but equally as important end point to survival in this population. A recent large, randomized Phase III trial using a composite primary end point of lean body mass, pain, anorexia, and fatigue reported the feasibility in evaluating benefit in mCRC beyond conventional clinical trial end points. Future studies in treatment-refractory mCRC may be better served by evaluating improvement in symptom control and QOL, which may otherwise serve as the best predictor of survival in last-line treatment settings. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Area-wide traffic calming for preventing traffic related injuries.

PubMed

Bunn, F; Collier, T; Frost, C; Ker, K; Roberts, I; Wentz, R

2003-01-01

It is estimated that by 2020 road traffic crashes will have moved from ninth to third in the world disease burden ranking, as measured in disability adjusted life years, and second in developing countries. The identification of effective strategies for the prevention of traffic related injuries is of global health importance. Area-wide traffic calming schemes that discourage through traffic on residential roads is one such strategy. To evaluate the effectiveness of area-wide traffic calming in preventing traffic related crashes, injuries, and deaths. We searched the following electronic databases: Cochrane Injuries Group's Specialised Register, Cochrane Controlled Trials Register, MEDLINE, EMBASE and TRANSPORT (NTIS, TRIS, TRANSDOC). We searched the web sites of road safety organisations, handsearched conference proceedings, checked reference lists of relevant papers and contacted experts in the area. The search was not restricted by language or publication status. Randomised controlled trials, and controlled before-after studies of area-wide traffic calming schemes. Two reviewers independently extracted data on type of study, characteristics of intervention and control areas, and length of data collection periods. Before and after data were collected on the total number of road traffic crashes, all road user deaths and injuries, pedestrian-motor vehicle collisions and road user deaths. The statistical package STATA was used to calculate rate ratios for each study, which were then pooled to give an overall estimate using a random effects model. We found no randomised controlled trials, but 16 controlled before-after trials met our inclusion criteria. Seven studies were done in Germany, six in the UK, two in Australia and one in the Netherlands. There were no studies in low or middle income countries. Eight trials reported the number of road traffic crashes resulting in deaths. The pooled rate ratio was 0.63 (0.14, 2.59 95% CI). Sixteen studies reported the number of road traffic crashes resulting in injuries (fatal and non fatal). The pooled rate ratio was 0.89 (0.80, 1.00 95% CI). Nine studies reported the total number of road traffic crashes. The pooled rate ratio was 0.95 (0.81, 1.11 95% CI). Thirteen trials reported the number of pedestrian-motor vehicle collisions. The pooled rate ratio was 1.00 (0.84, 1.18). There was significant heterogeneity for the total number of crashes and deaths and injuries. The results from this review suggest that area-wide traffic calming in towns and cities may be a promising intervention for reducing the number of road traffic injuries, and deaths. However, further rigorous evaluations of this intervention are needed.

Aquatic exercise for the treatment of knee and hip osteoarthritis.

PubMed

Bartels, Else Marie; Juhl, Carsten B; Christensen, Robin; Hagen, Kåre Birger; Danneskiold-Samsøe, Bente; Dagfinrud, Hanne; Lund, Hans

2016-03-23

Osteoarthritis is a chronic disease characterized by joint pain, tenderness, and limitation of movement. At present, no cure is available. Thus only treatment of the person's symptoms and treatment to prevent further development of the disease are possible. Clinical trials indicate that aquatic exercise may have advantages for people with osteoarthritis. This is an update of a published Cochrane review. To evaluate the effects of aquatic exercise for people with knee or hip osteoarthritis, or both, compared to no intervention. We searched the following databases up to 28 April 2015: the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library Issue 1, 2014), MEDLINE (from 1949), EMBASE (from 1980), CINAHL (from 1982), PEDro (Physiotherapy Evidence Database), and Web of Science (from 1945). There was no language restriction. Randomized controlled clinical trials of aquatic exercise compared to a control group (e.g. usual care, education, social attention, telephone call, waiting list for surgery) of participants with knee or hip osteoarthritis. Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias of the included trials. We analysed the pooled results using standardized mean difference (SMD) values. Nine new trials met the inclusion criteria and we excluded two earlier included trials. Thus the number of participants increased from 800 to 1190 and the number of included trials increased from six to 13. Most participants were female (75%), with an average age of 68 years and a body mass index (BMI) of 29.4. Osteoarthritis duration was 6.7 years, with a great variation of the included participants. The mean aquatic exercise duration was 12 weeks. We found 12 trials at low to unclear risk of bias for all domains except blinding of participants and personnel. They showed that aquatic exercise caused a small short term improvement compared to control in pain (SMD -0.31, 95% CI -0.47 to -0.15; 12 trials, 1076 participants) and disability (SMD -0.32, 95% CI -0.47 to -0.17; 12 trials, 1059 participants). Ten trials showed a small effect on quality of life (QoL) (SMD -0.25, 95% CI -0.49 to -0.01; 10 trials, 971 participants). These effects on pain and disability correspond to a five point lower (95% CI three to eight points lower) score on mean pain and mean disability compared to the control group (scale 0 to 100), and a seven point higher (95% CI 0 to 13 points higher) score on mean QoL compared with control group (scale 0 to 100). No included trials performed a radiographic evaluation. No serious adverse events were reported in the included trials with relation to aquatic exercise. There is moderate quality evidence that aquatic exercise may have small, short-term, and clinically relevant effects on patient-reported pain, disability, and QoL in people with knee and hip OA. The conclusions of this review update does not change those of the previous published version of this Cochrane review.

Effectiveness and cost effectiveness of counselling in primary care.

PubMed

Bower, P; Rowland, N; Mellor, C l; Heywood, P; Godfrey, C; Hardy, R

2002-01-01

Counsellors are prevalent in primary care settings. However, there are concerns about the clinical and cost-effectiveness of the treatments they provide, compared with alternatives such as usual care from the general practitioner, medication or other psychological therapies. To assess the effectiveness and cost effectiveness of counselling in primary care by reviewing cost and outcome data in randomised controlled trials, controlled clinical trials and controlled patient preference trials of counselling interventions in primary care, for patients with psychological and psychosocial problems considered suitable for counselling. The original search strategy included electronic searching of databases (including the CCDAN Register of RCTs and CCTs) along with handsearching of a specialist journal. Published and unpublished sources (clinical trials, books, dissertations, agency reports etc.) were searched, and their reference lists scanned to uncover further controlled trials. Contact was made with subject experts and CCDAN members in order to uncover further trials. For the updated review, searches were restricted to those databases judged to be high yield in the first version of the review: MEDLINE, EMBASE, PSYCLIT and CINAHL, the Cochrane Controlled Trials register and the CCDAN trials register. All controlled trials comparing counselling in primary care with other treatments for patients with psychological and psychosocial problems considered suitable for counselling. Trials completed before the end of June 2001 were included in the review. Data were extracted using a standardised data extraction sheet. The relevant data were entered into the Review Manager software. Trials were quality rated, using CCDAN criteria, to assess the extent to which their design and conduct were likely to have prevented systematic error. Continuous measures of outcome were combined using standardised mean differences. An overall effect size was calculated for each outcome with 95% confidence intervals. Continuous data from different measuring instruments were transformed into a standard effect size by dividing mean values by standard deviations. In view of the diversity of counselling services in primary care (the range of treatments, patients and practitioners) tests of heterogeneity were done to assess the feasibility of aggregating measures of outcome from trials. Sensitivity analyses were undertaken to test the robustness of the results. Seven trials were included in the review. The main analyses showed significantly greater clinical effectiveness in the counselling group compared with 'usual care' in the short-term (standardised mean difference -0.28, 95% CI -0.43 to -0.13, n=772, 6 trials) but not the long-term (standardised mean difference -0.09, 95% CI -0.27 to 0.10, n=475, 4 trials). Levels of satisfaction with counselling were high. Four studies reported similar total costs associated with counselling and usual care over the long-term. However, the economic analyses were likely to be underpowered. Counselling is associated with modest improvement in short-term outcome compared to 'usual care', but provides no additional advantages in the long-term. Patients are satisfied with counselling, and it may not be associated with increased costs.

Effects of digital Cognitive Behavioural Therapy for Insomnia on cognitive function: study protocol for a randomised controlled trial.

PubMed

Kyle, Simon D; Hurry, Madeleine E D; Emsley, Richard; Luik, Annemarie I; Omlin, Ximena; Spiegelhalder, Kai; Espie, Colin A; Sexton, Claire E

2017-06-17

The daytime effects of insomnia pose a significant burden to patients and drive treatment seeking. In addition to subjective deficits, meta-analytic data show that patients experience reliable objective impairments across several cognitive domains. While Cognitive Behavioural Therapy for Insomnia (CBT-I) is an effective and scalable treatment, we know little about its impact upon cognitive function. Trials of CBT-I have typically used proxy measures for cognitive functioning, such as fatigue or work performance scales, and no study has assessed self-reported impairment in cognitive function as a primary outcome. Moreover, only a small number of studies have assessed objective cognitive performance, pre-to-post CBT-I, with mixed results. This study specifically aims to (1) investigate the impact of CBT-I on cognitive functioning, assessed through both self-reported impairment and objective performance measures, and (2) examine whether change in sleep mediates this impact. We propose a randomised controlled trial of 404 community participants meeting criteria for Insomnia Disorder. In the DISCO trial (D efining the I mpact of improved S leep on CO gnitive function (DISCO)) participants will be randomised to digital automated CBT-I delivered by a web and/or mobile platform (in addition to treatment as usual (TAU)) or to a wait-list control (in addition to TAU). Online assessments will take place at 0 (baseline), 10 (post-treatment), and 24 (follow-up) weeks. At week 25, all participants allocated to the wait-list group will be offered digital CBT-I, at which point the controlled element of the trial will be complete. The primary outcome is self-reported cognitive impairment at post-treatment (10 weeks). Secondary outcomes include objective cognitive performance, insomnia severity, sleepiness, fatigue, and self-reported cognitive failures and emotional distress. All main analyses will be carried out on completion of follow-up assessments and will be based on the intention-to-treat principle. Further analyses will determine to what extent observed changes in self-reported cognitive impairment and objective cognitive performance are mediated by changes in sleep. The trial is supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) based at Oxford University Hospitals NHS Trust and University of Oxford, and by the NIHR Oxford Health BRC. This study will be the first large-scale examination of the impact of digital CBT-I on self-reported cognitive impairment and objective cognitive performance. ISRCTN, ID: ISRCTN89237370 . Registered on 17 October 2016.

Snow and Ice Control Materials for Texas Roads; VOLUME 1: Literature and Best Practices Review; VOLUME 2: Field Trials and Laboratory Study

DOT National Transportation Integrated Search

2017-03-01

This report provides findings from a four-year research study of snow and ice control materials for winter weather roadway maintenance applications in Texas. The report is presented in two volumes. Volume 1 is a literature review and best practices r...

Maximising the value of combining qualitative research and randomised controlled trials in health research: the QUAlitative Research in Trials (QUART) study--a mixed methods study.

PubMed

O'Cathain, Alicia; Thomas, Kate J; Drabble, Sarah J; Rudolph, Anne; Goode, Jackie; Hewison, Jenny

2014-06-01

Researchers sometimes undertake qualitative research with randomised controlled trials (RCTs) of health interventions. To systematically explore how qualitative research is being used with trials and identify ways of maximising its value to the trial aim of providing evidence of effectiveness of health interventions. A sequential mixed methods study with four components. (1) Database search of peer-reviewed journals between January 2008 and September 2010 for articles reporting the qualitative research undertaken with specific trials, (2) systematic search of database of registered trials to identify studies combining qualitative research and trials, (3) survey of 200 lead investigators of trials with no apparent qualitative research and (4) semistructured telephone interviews with 18 researchers purposively sampled from the first three methods. Qualitative research was undertaken with at least 12% of trials. A large number of articles reporting qualitative research undertaken with trials (n=296) were published between 2008 and 2010. A total of 28% (82/296) of articles reported qualitative research undertaken at the pre-trial stage and around one-quarter concerned drugs or devices. The articles focused on 22 aspects of the trial within five broad categories. Some focused on more than one aspect of the trial, totalling 356 examples. The qualitative research focused on the intervention being trialled (71%, 254/356), the design and conduct of the trial (15%, 54/356), the outcomes of the trial (1%, 5/356), the measures used in the trial (3%, 10/356), and the health condition in the trial (9%, 33/356). The potential value of the qualitative research to the trial endeavour included improving the external validity of trials and facilitating interpretation of trial findings. This value could be maximised by using qualitative research more at the pre-trial stage and reporting findings with explicit attention to the implications for the trial endeavour. During interviews, three models of study were identified: qualitative research as peripheral to the trial, qualitative research as an 'add-on' to the trial and a study with qualitative research and trial as essential components, with the third model offering more opportunity to maximise the value of the qualitative research. Interviewees valued the use of qualitative research with trials and identified team structures and wider structural issues which gave more value to the trial than the qualitative research as barriers to maximising the value of the qualitative research. A large number of articles were published between 2008 and 2010, addressing a wide range of aspects of trials. There were examples of this research affecting the trial by facilitating interpretation of trial findings, developing and refining interventions for testing in the trial and changing the measures used in the trial. However, researchers were not necessarily maximising the value of qualitative research undertaken with trials to the endeavour of generating evidence of effectiveness of health interventions. Researchers can maximise value by promoting its use at the pre-trial stage to ensure that the intervention and trial conduct is optimised at the main trial stage, being explicit about the conclusions for the trial endeavour in peer-reviewed journal articles reporting the qualitative research and valuing the contribution of the qualitative research as much as the trial. Future recommendations for researchers include: plan the qualitative research, design and implement studies not trials, use qualitative research at the feasibility and pilot stage of trials, be explicit in publications about the impact of the qualitative research on the trial and implications for the trial endeavour, undertake in-depth qualitative research, allow qualitative research to take a challenging role and develop a learning environment around the use of qualitative research and trials. This project was funded by the Medical Research Council (MRC) as part of the MRC-National Institute for Health Research Methodology Research programme.

Progressive resistance strength training for improving physical function in older adults

PubMed Central

Liu, Chiung-ju; Latham, Nancy K

2014-01-01

Background Muscle weakness in old age is associated with physical function decline. Progressive resistance strength training (PRT) exercises are designed to increase strength. Objectives To assess the effects of PRT on older people and identify adverse events. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialized Register (to March 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to May 01, 2008), EMBASE (1980 to February 06 2007), CINAHL (1982 to July 01 2007) and two other electronic databases. We also searched reference lists of articles, reviewed conference abstracts and contacted authors. Selection criteria Randomised controlled trials reporting physical outcomes of PRT for older people were included. Data collection and analysis Two review authors independently selected trials, assessed trial quality and extracted data. Data were pooled where appropriate. Main results One hundred and twenty one trials with 6700 participants were included. In most trials, PRT was performed two to three times per week and at a high intensity. PRT resulted in a small but significant improvement in physical ability (33 trials, 2172 participants; SMD 0.14, 95% CI 0.05 to 0.22). Functional limitation measures also showed improvements: e.g. there was a modest improvement in gait speed (24 trials, 1179 participants, MD 0.08 m/s, 95% CI 0.04 to 0.12); and a moderate to large effect for getting out of a chair (11 trials, 384 participants, SMD -0.94, 95% CI -1.49 to -0.38). PRT had a large positive effect on muscle strength (73 trials, 3059 participants, SMD 0.84, 95% CI 0.67 to 1.00). Participants with osteoarthritis reported a reduction in pain following PRT (6 trials, 503 participants, SMD -0.30, 95% CI -0.48 to -0.13). There was no evidence from 10 other trials (587 participants) that PRT had an effect on bodily pain. Adverse events were poorly recorded but adverse events related to musculoskeletal complaints, such as joint pain and muscle soreness, were reported in many of the studies that prospectively defined and monitored these events. Serious adverse events were rare, and no serious events were reported to be directly related to the exercise programme. Authors' conclusions This review provides evidence that PRT is an effective intervention for improving physical functioning in older people, including improving strength and the performance of some simple and complex activities. However, some caution is needed with transferring these exercises for use with clinical populations because adverse events are not adequately reported. PMID:19588334

Reporting outcomes of definitive radiation-based treatment for esophageal cancer: a review of the literature.

PubMed

Main, B G; Strong, S; McNair, A G; Falk, S J; Crosby, T; Blazeby, J M

2015-01-01

Accurate evaluation of radical radiotherapy requires well designed research with valid and appropriate outcomes. This study reviewed standards of outcome reporting and study design in randomized controlled trials (RCTs) of radiation-based therapy for esophageal cancer and made recommendations for future work. Randomized controlled trials reporting outcomes of definitive radiation-based treatment alone or in combination with chemotherapy were systematically identified and summarized. The types, frequency, and definitions of all clinical and patient-reported outcomes (PROs) reported in the methods and results sections of papers were examined. Studies providing a definition for at least one outcome and presenting all outcomes reported in the methods were classified as high quality. From 1425 abstracts, 16 RCTs including 1803 patients were identified. The primary outcome was overall survival in 13 studies, but five different definitions were reported. Outcomes for treatment failure included local, regional, and distant failures, and inconsistent definitions were applied. An observer assessment of dysphagia was reported in seven RCTs but PROs were reported in only one. Only three RCTs were at low risk of bias, with all lacking reports of sequence generation and only a minority reporting allocation concealment. The quality of outcome reporting in RCTs was inconsistent and risked bias. A core outcome set including clinical and PROs is needed to improve reporting of trials of definitive radiation-based treatment for esophageal cancer. © 2014 International Society for Diseases of the Esophagus.

Implementation of an educational intervention to improve hand washing in primary schools: process evaluation within a randomised controlled trial

PubMed Central

2013-01-01

Background Process evaluations are useful for understanding how interventions are implemented in trial settings. This is important for interpreting main trial results and indicating how the intervention might function beyond the trial. The purpose of this study was to examine the reach, dose, fidelity, acceptability, and sustainability of the implementation of an educational hand washing intervention in primary schools, and to explore views regarding acceptability and sustainability of the intervention. Methods Process evaluation within a cluster randomised controlled trial, including focus groups with pupils aged 6 to 11, semi-structured interviews with teachers and external staff who coordinated the intervention delivery, and school reports and direct observations of the intervention delivery. Results The educational package was delivered in 61.4% of schools (85.2% of intervention schools, 37.8% of control schools following completion of the trial). Teachers and pupils reacted positively to the intervention, although concerns were raised about the age-appropriateness of the resources. Teachers adapted the resources to suit their school setting and pupils. Staff coordinating the intervention delivery had limited capacity to follow up and respond to schools. Conclusions The hand washing intervention was acceptable to schools, but its reach outside of a randomised trial, evidenced in the low proportion of schools in the control arm who received it after the trial had ended, suggests that the model of delivery may not be sustainable. Trial registration ISRCTN: ISRCTN93576146 PMID:23947388

The feasibility of a randomized controlled trial of esophagectomy for esophageal cancer - the ROMIO (Randomized Oesophagectomy: Minimally Invasive or Open) study: protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background There is a need for evidence of the clinical effectiveness of minimally invasive surgery for the treatment of esophageal cancer, but randomized controlled trials in surgery are often difficult to conduct. The ROMIO (Randomized Open or Minimally Invasive Oesophagectomy) study will establish the feasibility of a main trial which will examine the clinical and cost-effectiveness of minimally invasive and open surgical procedures for the treatment of esophageal cancer. Methods/Design A pilot randomized controlled trial (RCT), in two centers (University Hospitals Bristol NHS Foundation Trust and Plymouth Hospitals NHS Trust) will examine numbers of incident and eligible patients who consent to participate in the ROMIO study. Interventions will include esophagectomy by: (1) open gastric mobilization and right thoracotomy, (2) laparoscopic gastric mobilization and right thoracotomy, and (3) totally minimally invasive surgery (in the Bristol center only). The primary outcomes of the feasibility study will be measures of recruitment, successful development of methods to monitor quality of surgery and fidelity to a surgical protocol, and development of a core outcome set to evaluate esophageal cancer surgery. The study will test patient-reported outcomes measures to assess recovery, methods to blind participants, assessments of surgical morbidity, and methods to capture cost and resource use. ROMIO will integrate methods to monitor and improve recruitment using audio recordings of consultations between recruiting surgeons, nurses, and patients to provide feedback for recruiting staff. Discussion The ROMIO study aims to establish efficient methods to undertake a main trial of minimally invasive surgery versus open surgery for esophageal cancer. Trial registration The pilot trial has Current Controlled Trials registration number ISRCTN59036820(25/02/2013) at http://www.controlled-trials.com; the ROMIO trial record at that site gives a link to the original version of the study protocol. PMID:24888266

Conflict Adaptation Depends on Task Structure

ERIC Educational Resources Information Center

Akcay, Caglar; Hazeltine, Eliot

2008-01-01

The dependence of the Simon effect on the correspondence of the previous trial can be explained by the conflict-monitoring theory, which holds that a control system adjusts automatic activation from irrelevant stimulus information (conflict adaptation) on the basis of the congruency of the previous trial. The authors report on 4 experiments…

A systematic review of randomised controlled trials on the effectiveness of exercise programs on Lumbo Pelvic Pain among postnatal women.

PubMed

Tseng, Pei-Ching; Puthussery, Shuby; Pappas, Yannis; Gau, Meei-Ling

2015-11-26

A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group's Trials Register, and electronic libraries of authors'institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of 'good' methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment.

Care delivery and self-management strategies for children with epilepsy.

PubMed

Lindsay, Bruce; Bradley, Peter M

2010-12-08

Epilepsy care for children has been criticised for its lack of impact. Various service models and strategies have been developed in response to perceived inadequacies in care provision for children and their families. We set out to compare the effectiveness of specialist or dedicated teams or individuals in the care of children with epilepsy with usual care services. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library February issue, 2010), MEDLINE (1950 to March 2010), EMBASE (1988 to May 2006*), PsycINFO (1806 to March 2010) and CINAHL (1982 to March 2010).*Please note that as we currently do not have access to EMBASE, we have been unable to update this aspect of our searching. We included randomised controlled trials, controlled or matched trials, cohort studies or other prospective studies with a control group, or time series studies. Each review author independently selected studies, extracted data and assessed the quality of included studies. Four trials and five reports are included in this review. They report on four different education and counselling programmes for children, children and parents, or teenagers and parents. Each programme showed some benefits for the well-being of children with epilepsy, but each trial had methodological flaws and no single programme was evaluated by more than one study. While each of the programmes in this review showed some benefit to children with epilepsy their impacts were extremely variable. No programme showed benefits across the full range of outcomes. No study appears to have demonstrated any detrimental effects but the evidence in favour of any single programme is insufficient to make it possible to recommend one programme rather than another. More trials, carried out by independent research teams, are needed.

Clinical trial design for orthodontists.

PubMed

Pandis, Nikolaos; Cobourne, Martyn T

2013-06-01

High-quality research should form the basis of all clinical practice. Randomized controlled trials currently provide the gold standard for investigating the effectiveness of treatment interventions and these are increasingly being used in orthodontics. Here we discuss the reasons why this form of investigation provides the most useful evidence for assessing treatment outcome. The methods available to achieve true randomization, a fundamental component in the design of these trials, are also discussed. In addition, we focus on how to minimize bias in clinical research, not only during the design and management of a trial, but also when disseminating results. We focus on the importance of using control groups correctly and describe methods that are available to adequately power a trial. Finally, we emphasise the importance of accurate and transparent reporting, which facilitates correct communication and assessment of the evidence.

The Conduct and Reporting of Child Health Research: An Analysis of Randomized Controlled Trials Published in 2012 and Evaluation of Change over 5 Years.

PubMed

Gates, Allison; Hartling, Lisa; Vandermeer, Ben; Caldwell, Patrina; Contopoulos-Ioannidis, Despina G; Curtis, Sarah; Fernandes, Ricardo M; Klassen, Terry P; Williams, Katrina; Dyson, Michele P

2018-02-01

For child health randomized controlled trials (RCTs) published in 2012, we aimed to describe design and reporting characteristics and evaluate changes since 2007; assess the association between trial design and registration and risk of bias (RoB); and assess the association between RoB and effect size. For 300 RCTs, we extracted design and reporting characteristics and assessed RoB. We assessed 5-year changes in design and reporting (based on 300 RCTs we had previously analyzed) using the Fisher exact test. We tested for associations between design and reporting characteristics and overall RoB and registration using the Fisher exact, Cochran-Armitage, Kruskal-Wallis, and Jonckheere-Terpstra tests. We pooled effect sizes and tested for differences by RoB using the χ 2 test for subgroups in meta-analysis. The 2012 and 2007 RCTs differed with respect to many design and reporting characteristics. From 2007 to 2012, RoB did not change for random sequence generation and improved for allocation concealment (P < .001). Fewer 2012 RCTs were rated high overall RoB and more were rated unclear (P = .03). Only 7.3% of 2012 RCTs were rated low overall RoB. Trial registration doubled from 2007 to 2012 (23% to 46%) (P < .001) and was associated with lower RoB (P = .009). Effect size did not differ by RoB (P = .43) CONCLUSIONS: Random sequence generation and allocation concealment were not often reported, and selective reporting was prevalent. Measures to increase trialists' awareness and application of existing reporting guidance, and the prospective registration of RCTs is needed to improve the trustworthiness of findings from this field. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Zhen gan xi feng decoction, a traditional chinese herbal formula, for the treatment of essential hypertension: a systematic review of randomized controlled trials.

PubMed

Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

2013-01-01

Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use.

A Randomized trial of an Asthma Internet Self-management Intervention (RAISIN): study protocol for a randomized controlled trial.

PubMed

Morrison, Deborah; Wyke, Sally; Thomson, Neil C; McConnachie, Alex; Agur, Karolina; Saunderson, Kathryn; Chaudhuri, Rekha; Mair, Frances S

2014-05-24

The financial costs associated with asthma care continue to increase while care remains suboptimal. Promoting optimal self-management, including the use of asthma action plans, along with regular health professional review has been shown to be an effective strategy and is recommended in asthma guidelines internationally. Despite evidence of benefit, guided self-management remains underused, however the potential for online resources to promote self-management behaviors is gaining increasing recognition. The aim of this paper is to describe the protocol for a pilot evaluation of a website 'Living well with asthma' which has been developed with the aim of promoting self-management behaviors shown to improve outcomes. The study is a parallel randomized controlled trial, where adults with asthma are randomly assigned to either access to the website for 12 weeks, or usual asthma care for 12 weeks (followed by access to the website if desired). Individuals are included if they are over 16-years-old, have a diagnosis of asthma with an Asthma Control Questionnaire (ACQ) score of greater than, or equal to 1, and have access to the internet. Primary outcomes for this evaluation include recruitment and retention rates, changes at 12 weeks from baseline for both ACQ and Asthma Quality of Life Questionnaire (AQLQ) scores, and quantitative data describing website usage (number of times logged on, length of time logged on, number of times individual pages looked at, and for how long). Secondary outcomes include clinical outcomes (medication use, health services use, lung function) and patient reported outcomes (including adherence, patient activation measures, and health status). Piloting of complex interventions is considered best practice and will maximise the potential of any future large-scale randomized controlled trial to successfully recruit and be able to report on necessary outcomes. Here we will provide results across a range of outcomes which will provide estimates of efficacy to inform the design of a future full-scale randomized controlled trial of the 'Living well with asthma' website. This trial is registered with Current Controlled Trials ISRCTN78556552 on 18/06/13.

Momordica charantia for type 2 diabetes mellitus.

PubMed

Ooi, Cheow Peng; Yassin, Zaitun; Hamid, Tengku-Aizan

2010-02-17

Momordica charantia is not only a nutritious vegetable, but is also used in traditional medical practices to treat type 2 diabetes mellitus. Experimental studies with animals and humans suggested that the vegetable has a possible role in glycaemic control. To assess the effects of mormodica charantia for type 2 diabetes mellitus. Several electronic databases were searched, among these The Cochrane Library (issue 4, 2009), MEDLINE, EMBASE, CINAHL, SIGLE and LILACS (all up to November 2009), combined with handsearches. No language restriction was used. Randomized controlled trials that compared momordica charantia with a placebo or a control intervention with or without pharmacological or non-pharmacological interventions were included. Two authors independently extracted the data. Risk of bias of trials was evaluated using the parameters of randomization, allocation concealment, blinding, completeness of outcome data, selective reporting and other potential sources of bias. A meta-analysis was not performed given the quality of data and the variability of preparations of momordica charantia used in interventions (no similar preparation was tested twice). Three randomised controlled trials with up to three months duration and investigating 350 participants met the inclusion criteria. Risk of bias of these trials (only one study was published as a full peer-reviewed publication) was generally high. Two RCTs compared the effect of preparations from different parts of the momordica charantia plants and placebo on the glycemic control in type 2 diabetes mellitus. There was no statistically significant difference compared to placebo. The effects of preparation from the leaves of the plant and glibenclamide were comparable in the third trial. No serious adverse effects were reported in all the trials. There were no documentations of death from any cause, morbidity, (health-related) quality of life and costs. There is insufficient evidence to recommend momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice.

A theory-based online health behaviour intervention for new university students (U@Uni:LifeGuide): results from a repeat randomized controlled trial.

PubMed

Cameron, David; Epton, Tracy; Norman, Paul; Sheeran, Paschal; Harris, Peter R; Webb, Thomas L; Julious, Steven A; Brennan, Alan; Thomas, Chloe; Petroczi, Andrea; Naughton, Declan; Shah, Iltaf

2015-12-07

This paper reports the results of a repeat trial assessing the effectiveness of an online theory-based intervention to promote healthy lifestyle behaviours in new university students. The original trial found that the intervention reduced the number of smokers at 6-month follow-up compared with the control condition, but had non-significant effects on the other targeted health behaviours. However, the original trial suffered from low levels of engagement, which the repeat trial sought to rectify. Three weeks before staring university, all incoming undergraduate students at a large university in the UK were sent an email inviting them to participate in the study. After completing a baseline questionnaire, participants were randomly allocated to intervention or control conditions. The intervention consisted of a self-affirmation manipulation, health messages based on the theory of planned behaviour and implementation intention tasks. Participants were followed-up 1 and 6 months after starting university. The primary outcome measures were portions of fruit and vegetables consumed, physical activity levels, units of alcohol consumed and smoking status at 6-month follow-up. The study recruited 2,621 students (intervention n=1346, control n=1275), of whom 1495 completed at least one follow-up (intervention n=696, control n=799). Intention-to-treat analyses indicated that the intervention had a non-significant effect on the primary outcomes, although the effect of the intervention on fruit and vegetable intake was significant in the per-protocol analyses. Secondary analyses revealed that the intervention had significant effects on having smoked at university (self-report) and on a biochemical marker of alcohol use. Despite successfully increasing levels of engagement, the intervention did not have a significant effect on the primary outcome measures. The relatively weak effects of the intervention, found in both the original and repeat trials, may be due to the focus on multiple versus single health behaviours. Future interventions targeting the health behaviour of new university students should therefore focus on single health behaviours. Current Controlled Trials ISRCTN07407344 .

The quality of reporting of randomized controlled trials of traditional Chinese medicine: a survey of 13 randomly selected journals from mainland China.

PubMed

Wang, Gang; Mao, Bing; Xiong, Ze-Yu; Fan, Tao; Chen, Xiao-Dong; Wang, Lei; Liu, Guan-Jian; Liu, Jia; Guo, Jia; Chang, Jing; Wu, Tai-Xiang; Li, Ting-Qian

2007-07-01

The number of randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) is increasing. However, there have been few systematic assessments of the quality of reporting of these trials. This study was undertaken to evaluate the quality of reporting of RCTs in TCM journals published in mainland China from 1999 to 2004. Thirteen TCM journals were randomly selected by stratified sampling of the approximately 100 TCM journals published in mainland China. All issues of the selected journals published from 1999 to 2004 were hand-searched according to guidelines from the Cochrane Centre. All reviewers underwent training in the evaluation of RCTs at the Chinese Centre of Evidence-based Medicine. A comprehensive quality assessment of each RCT was completed using a modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist (total of 30 items) and the Jadad scale. Disagreements were resolved by consensus. Seven thousand four hundred twenty-two RCTs were identified. The proportion of published RCTs relative to all types of published clinical trials increased significantly over the period studied, from 18.6% in 1999 to 35.9% in 2004 (P < 0.001). The mean (SD) Jadad score was 1.03 (0.61) overall. One RCT had a Jadad score of 5 points; 14 had a score of 4 points; and 102 had a score of 3 points. The mean (SD) Jadad score was 0.85 (0.53) in 1999 (746 RCTs) and 1.20 (0.62) in 2004 (1634 RCTs). Across all trials, 39.4% of the items on the modified CONSORT checklist were reported, which was equivalent to 11.82 (5.78) of the 30 items. Some important methodologic components of RCTs were incompletely reported, such as sample-size calculation (reported in 1.1% of RCTs), randomization sequence (7.9%), allocation concealment (0.3 %), implementation of the random-allocation sequence (0%), and analysis of intention to treat (0%). The findings of this study indicate that the quality of reporting of RCTs of TCM has improved, but remains poor.

Primary care research: difficulties recruiting preschool children to clinical trials.

PubMed

Chadwick, B L; Treasure, E T

2005-05-01

The aims of the present study were to report difficulties experienced recruiting preschool children to a clinical trial and to report the acceptability of a dental intervention to their parents. The study was a randomized controlled trial (RCT). The study took place in community dental clinics, health centres and patient homes. Health visitors were used to recruit 508 children aged between 18 and 30 months from high caries areas of South Wales. Children with caries-free first primary molars were entered into a placebo-controlled individual RCT of fissure sealants. All children received a standard package of dental health education. Children in the test group had their first primary molars sealed with glass ionomer. All children were reviewed once. Families were asked to rate the acceptability of procedures. Health visitors referred 1228 children for screening, but only 547 were seen (44.5%) and 508 subjects were recruited to the trial. Of these, 449 (88.4%) were seen at follow-up. Some 667 children missed 1610 visits at baseline, and 373 of those recruited missed an appointment. At follow-up, 1056 appointments were staffed to review 449 children. Three-quarters of parents reported the examination to be very easy. Preschool children are difficult to access for community trials. Dental examinations and sealant placement were acceptable to the majority of families who were seen.

Excessive drinking--brief intervention by a primary health care nurse. A randomized controlled trial.

PubMed

Tomson, Y; Romelsjö, A; Aberg, H

1998-09-01

To evaluate the effect of a nurse-conducted intervention on excessive drinkers. Randomized, controlled trial. Vårby Health Centre, Stockholm. The intervention group visited a nurse three times during a 12-month period. The controls met once with a general practitioner (GP). Patients were recruited at a health screening on the basis of a raised gamma-glutamyl transferase (GGT). Of 2338 subjects, aged 25-54 years, 222 had a screening GGT of > or = 0.9 mukat/l. 100 were randomized to the treatment and 122 to the control group. GGT, self-reported alcohol consumption (g/week), sickness allowance and use of health care. After 2 years a reduction of GGT from 1.52 to 1.21 mukat/l (p = 0.02) had occurred in the treatment group. The controls increased their mean level of GGT from 1.75 to 2.16 mukat/l. Mean weekly alcohol consumption in the intervention group was reduced from 337 to 228 g/week (p = 0.02). The controls did not quantify their alcohol consumption initially, but reported a reduced weekly consumption at follow-up. The intervention had an impact on GGT and self-reported consumption. The controls also reported decreased consumption possibly because their appointment with the GP functioned as a very brief intervention.

Statistical analysis plan for the family-led rehabilitation after stroke in India (ATTEND) trial: A multicenter randomized controlled trial of a new model of stroke rehabilitation compared to usual care.

PubMed

Billot, Laurent; Lindley, Richard I; Harvey, Lisa A; Maulik, Pallab K; Hackett, Maree L; Murthy, Gudlavalleti Vs; Anderson, Craig S; Shamanna, Bindiganavale R; Jan, Stephen; Walker, Marion; Forster, Anne; Langhorne, Peter; Verma, Shweta J; Felix, Cynthia; Alim, Mohammed; Gandhi, Dorcas Bc; Pandian, Jeyaraj Durai

2017-02-01

Background In low- and middle-income countries, few patients receive organized rehabilitation after stroke, yet the burden of chronic diseases such as stroke is increasing in these countries. Affordable models of effective rehabilitation could have a major impact. The ATTEND trial is evaluating a family-led caregiver delivered rehabilitation program after stroke. Objective To publish the detailed statistical analysis plan for the ATTEND trial prior to trial unblinding. Methods Based upon the published registration and protocol, the blinded steering committee and management team, led by the trial statistician, have developed a statistical analysis plan. The plan has been informed by the chosen outcome measures, the data collection forms and knowledge of key baseline data. Results The resulting statistical analysis plan is consistent with best practice and will allow open and transparent reporting. Conclusions Publication of the trial statistical analysis plan reduces potential bias in trial reporting, and clearly outlines pre-specified analyses. Clinical Trial Registrations India CTRI/2013/04/003557; Australian New Zealand Clinical Trials Registry ACTRN1261000078752; Universal Trial Number U1111-1138-6707.

Radiation-Induced Cardiac Toxicity After Therapy for Breast Cancer: Interaction Between Treatment Era and Follow-Up Duration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demirci, Senem; Department of Radiation Oncology, Duke University Medical Center, Durham, NC; Nam, Jiho

2009-03-15

Purpose: Cardiac toxicity after breast radiotherapy (RT) has been widely described in 'older' RT trials (i.e., using larger fraction sizes, wide RT fields, and orthovoltage energy). The results from more 'modern' RT trials have shown less cardiac toxicity. The comparisons between the 'older' and 'modern' trials are confounded by the longer follow-up time in the 'older' trials. We systematically assessed the effect of treatment era and follow-up duration on the reported rates of cardiac toxicity associated with RT. Methods and Materials: The published data were surveyed using PubMed to identify studies using 'breast cancer,' 'irradiation/radiotherapy,' 'cardiac/heart,' and 'toxicity/morbidity/mortality' in amore » keyword search. Relevant data were extracted from the identified trials. The trials were defined as 'older' (patient accrual start year before 1980) and 'modern' (patient accrual start year in or after 1980) to segregate the trials and assess the treatment era effect. A 10-year follow-up duration was used as a cutoff to segregate and analyze trials with varying lengths of follow-up. Results: We analyzed 19 published reports of patients treated between 1968 and 2002 (5 randomized controlled trials, 5 single- or multi-institutional studies, and 9 national cancer registry database reviews). In the reviewed trials, all the older trials reported excess cardiac toxicity, typically with a median of >10-15 years of follow-up. However, the vast majority of modern RT trials had shorter median follow-up durations, typically {<=}10 years and did not report an excess toxicity risk. The modern studies lacked longer follow-up. Conclusion: Additional follow-up is needed to ensure that modern methods effectively reduce cardiac toxicity. Continued diligence to minimize cardiac exposure remains prudent.« less

Accounting for sequential trial effects in the flanker task: conflict adaptation or associative priming?

PubMed

Nieuwenhuis, Sander; Stins, John F; Posthuma, Danielle; Polderman, Tinca J C; Boomsma, Dorret I; de Geus, Eco J

2006-09-01

The conflict-control loop theory proposes that the detection of conflict in information processing triggers an increase in cognitive control, resulting in improved performance on the subsequent trial. This theory seems consistent with the robust finding that conflict susceptibility is reduced following correct trials associated with high conflict: the conflict adaptation effect. However, despite providing favorable conditions for eliciting and detecting conflict-triggered performance adjustments, none of the five experiments reported here provide unequivocal evidence of such adjustments. Instead, the results corroborate and extend earlier findings by demonstrating that the conflict adaptation effect, at least in the flanker task, is only present for a specific subset of trial sequences that is characterized by a response repetition. This pattern of results provides strong evidence that the conflict adaptation effect reflects associative stimulus-response priming instead of conflict-driven adaptations in cognitive control.

Self-Control Strength Depletion Reduces Self-Efficacy and Impairs Exercise Performance.

PubMed

Graham, Jeffrey D; Bray, Steven R

2015-10-01

The purpose of this study was to investigate the role of task self-efficacy as a psychological factor involved in the relationship between self-control depletion and physical endurance. Participants (N = 37) completed two isometric handgrip endurance trials, separated by a Stroop task, which was either congruent (control) or incongruent (causing depletion). Task self-efficacy for the second endurance trial was measured following the Stroop task. Participants in the depletion condition reported lower task self-efficacy and showed a greater reduction in performance on the second endurance trial when compared with controls. Task self-efficacy also mediated the relationship between self-control depletion and endurance performance. The results of this study provide evidence that task self-efficacy is negatively affected following self-control depletion. We recommend that task self-efficacy be further investigated as a psychological factor accounting for the negative change in self-control performance of physical endurance and sport tasks following self-control strength depletion.

Patient and Partner Feedback Reports to Improve Statin Medication Adherence: A Randomized Control Trial.

PubMed

Reddy, Ashok; Huseman, Tiffany L; Canamucio, Anne; Marcus, Steven C; Asch, David A; Volpp, Kevin; Long, Judith A

2017-03-01

Simple nudges such as reminders and feedback reports to either a patient or a partner may facilitate improved medication adherence. To test the impact of a pill bottle used to monitor adherence, deliver a daily alarm, and generate weekly medication adherence feedback reports on statin adherence. Three-month, three-arm randomized clinical trial (ClinicalTrials.gov identifier: NCT02480530). One hundred and twenty-six veterans with known coronary artery disease and poor adherence (medication possession ratio <80 %). Patients were randomized to one of three groups: (1) a control group (n = 36) that received a pill-monitoring device with no alarms or feedback; (2) an individual feedback group (n = 36) that received a daily alarm and a weekly medication adherence feedback report; and (3) a partner feedback group (n = 54) that received an alarm and a weekly feedback report that was shared with a friend, family member, or a peer. The intervention continued for 3 months, and participants were followed for an additional 3 months after the intervention period. Adherence as measured by pill bottle. Secondary outcomes included change in LDL (mg/dl), patient activation, and social support. During the 3-month intervention period, medication adherence was higher in both feedback arms than in the control arm (individual feedback group 89 %, partner feedback group 86 %, control group 67 %; p < 0.001 and = 0.001). At 6 months, there was no difference in medication adherence between either of the feedback groups and the control (individual feedback 60 %, partner feedback 52 %, control group 54 %; p = 0.75 and 0.97). Daily alarms combined with individual or partner feedback reports improved statin medication adherence. While neither an individual feedback nor partner feedback strategy created a sustainable medication adherence habit, the intervention itself is relatively easy to implement and low cost.

Massage, reflexology and other manual methods for pain management in labour.

PubMed

Smith, Caroline A; Levett, Kate M; Collins, Carmel T; Jones, Leanne

2012-02-15

Many women would like to avoid pharmacological or invasive methods of pain management in labour, and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of manual healing methods including massage and reflexology for pain management in labour. To examine the effects of manual healing methods including massage and reflexology for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2 of 4), MEDLINE (1966 to 30 June 2011), CINAHL (1980 to 30 June 2011), the Australian and New Zealand Clinical Trial Registry (30 June 2011), Chinese Clinical Trial Register (30 June 2011), Current Controlled Trials (30 June 2011), ClinicalTrials.gov, (30 June 2011) ISRCTN Register (30 June 2011), National Centre for Complementary and Alternative Medicine (NCCAM) (30 June 2011) and the WHO International Clinical Trials Registry Platform (30 June 2011). Randomised controlled trials comparing manual healing methods with standard care, no treatment, other non-pharmacological forms of pain management in labour or placebo. Two authors independently assessed trial quality and extracted data. We attempted to contact study authors for additional information. We included six trials, with data reporting on five trials and 326 women in the meta-analysis. We found trials for massage only. Less pain during labour was reported from massage compared with usual care during the first stage of labour (standardised mean difference (SMD) -0.82, 95% confidence interval (CI) -1.17 to -0.47), four trials, 225 women), and labour pain was reduced in one trial of massage compared with music (risk ratio (RR) 0.40, 95% CI 0.18 to 0.89, 101 women). One trial of massage compared with usual care found reduced anxiety during the first stage of labour (MD -16.27, 95% CI -27.03 to -5.51, 60 women). No trial was assessed as being at a low risk of bias for all quality domains. Massage may have a role in reducing pain, and improving women's emotional experience of labour. However, there is a need for further research.

Exercise therapy for fatigue in multiple sclerosis.

PubMed

Heine, Martin; van de Port, Ingrid; Rietberg, Marc B; van Wegen, Erwin E H; Kwakkel, Gert

2015-09-11

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system affecting an estimated 1.3 million people worldwide. It is characterised by a variety of disabling symptoms of which excessive fatigue is the most frequent. Fatigue is often reported as the most invalidating symptom in people with MS. Various mechanisms directly and indirectly related to the disease and physical inactivity have been proposed to contribute to the degree of fatigue. Exercise therapy can induce physiological and psychological changes that may counter these mechanisms and reduce fatigue in MS. To determine the effectiveness and safety of exercise therapy compared to a no-exercise control condition or another intervention on fatigue, measured with self-reported questionnaires, of people with MS. We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Trials Specialised Register, which, among other sources, contains trials from: the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 10), MEDLINE (from 1966 to October 2014), EMBASE (from 1974 to October 2014), CINAHL (from 1981 to October 2014), LILACS (from 1982 to October 2014), PEDro (from 1999 to October 2014), and Clinical trials registries (October 2014). Two review authors independently screened the reference lists of identified trials and related reviews. We included randomized controlled trials (RCTs) evaluating the efficacy of exercise therapy compared to no exercise therapy or other interventions for adults with MS that included subjective fatigue as an outcome. In these trials, fatigue should have been measured using questionnaires that primarily assessed fatigue or sub-scales of questionnaires that measured fatigue or sub-scales of questionnaires not primarily designed for the assessment of fatigue but explicitly used as such. Two review authors independently selected the articles, extracted data, and determined methodological quality of the included trials. Methodological quality was determined by means of the Cochrane 'risk of bias' tool and the PEDro scale. The combined body of evidence was summarised using the GRADE approach. The results were aggregated using meta-analysis for those trials that provided sufficient data to do so. Forty-five trials, studying 69 exercise interventions, were eligible for this review, including 2250 people with MS. The prescribed exercise interventions were categorised as endurance training (23 interventions), muscle power training (nine interventions), task-oriented training (five interventions), mixed training (15 interventions), or 'other' (e.g. yoga; 17 interventions). Thirty-six included trials (1603 participants) provided sufficient data on the outcome of fatigue for meta-analysis. In general, exercise interventions were studied in mostly participants with the relapsing-remitting MS phenotype, and with an Expanded Disability Status Scale less than 6.0. Based on 26 trials that used a non-exercise control, we found a significant effect on fatigue in favour of exercise therapy (standardized mean difference (SMD) -0.53, 95% confidence interval (CI) -0.73 to -0.33; P value < 0.01). However, there was significant heterogeneity between trials (I(2) > 58%). The mean methodological quality, as well as the combined body of evidence, was moderate. When considering the different types of exercise therapy, we found a significant effect on fatigue in favour of exercise therapy compared to no exercise for endurance training (SMDfixed effect -0.43, 95% CI -0.69 to -0.17; P value < 0.01), mixed training (SMDrandom effect -0.73, 95% CI -1.23 to -0.23; P value < 0.01), and 'other' training (SMDfixed effect -0.54, 95% CI -0.79 to -0.29; P value < 0.01). Across all studies, one fall was reported. Given the number of MS relapses reported for the exercise condition (N = 25) and non-exercise control condition (N = 26), exercise does not seem to be associated with a significant risk of a MS relapse. However, in general, MS relapses were defined and reported poorly. Exercise therapy can be prescribed in people with MS without harm. Exercise therapy, and particularly endurance, mixed, or 'other' training, may reduce self reported fatigue. However, there are still some important methodological issues to overcome. Unfortunately, most trials did not explicitly include people who experienced fatigue, did not target the therapy on fatigue specifically, and did not use a validated measure of fatigue as the primary measurement of outcome.

Methodological reporting of randomized clinical trials in respiratory research in 2010.

PubMed

Lu, Yi; Yao, Qiuju; Gu, Jie; Shen, Ce

2013-09-01

Although randomized controlled trials (RCTs) are considered the highest level of evidence, they are also subject to bias, due to a lack of adequately reported randomization, and therefore the reporting should be as explicit as possible for readers to determine the significance of the contents. We evaluated the methodological quality of RCTs in respiratory research in high ranking clinical journals, published in 2010. We assessed the methodological quality, including generation of the allocation sequence, allocation concealment, double-blinding, sample-size calculation, intention-to-treat analysis, flow diagrams, number of medical centers involved, diseases, funding sources, types of interventions, trial registration, number of times the papers have been cited, journal impact factor, journal type, and journal endorsement of the CONSORT (Consolidated Standards of Reporting Trials) rules, in RCTs published in 12 top ranking clinical respiratory journals and 5 top ranking general medical journals. We included 176 trials, of which 93 (53%) reported adequate generation of the allocation sequence, 66 (38%) reported adequate allocation concealment, 79 (45%) were double-blind, 123 (70%) reported adequate sample-size calculation, 88 (50%) reported intention-to-treat analysis, and 122 (69%) included a flow diagram. Multivariate logistic regression analysis revealed that journal impact factor ≥ 5 was the only variable that significantly influenced adequate allocation sequence generation. Trial registration and journal impact factor ≥ 5 significantly influenced adequate allocation concealment. Medical interventions, trial registration, and journal endorsement of the CONSORT statement influenced adequate double-blinding. Publication in one of the general medical journal influenced adequate sample-size calculation. The methodological quality of RCTs in respiratory research needs improvement. Stricter enforcement of the CONSORT statement should enhance the quality of RCTs.

Effectiveness of an HIV/STD risk-reduction intervention for adolescents when implemented by community-based organizations: a cluster-randomized controlled trial.

PubMed

Jemmott, John B; Jemmott, Loretta S; Fong, Geoffrey T; Morales, Knashawn H

2010-04-01

We evaluated the effectiveness of an HIV/STD risk-reduction intervention when implemented by community-based organizations (CBOs). In a cluster-randomized controlled trial, 86 CBOs that served African American adolescents aged 13 to 18 years were randomized to implement either an HIV/STD risk-reduction intervention whose efficacy has been demonstrated or a health-promotion control intervention. CBOs agreed to implement 6 intervention groups, a random half of which completed 3-, 6-, and 12-month follow-up assessments. The primary outcome was consistent condom use in the 3 months prior to each follow-up assessment, averaged over the follow-up assessments. Participants were 1707 adolescents, 863 in HIV/STD-intervention CBOs and 844 in control-intervention CBOs. HIV/STD-intervention participants were more likely to report consistent condom use (odds ratio [OR] = 1.39; 95% confidence interval [CI] = 1.06, 1.84) than were control-intervention participants. HIV/STD-intervention participants also reported a greater proportion of condom-protected intercourse (beta = 0.06; 95% CI = 0.00, 0.12) than did the control group. This is the first large, randomized intervention trial to demonstrate that CBOs can successfully implement an HIV/STD risk-reduction intervention whose efficacy has been established.

Effectiveness of an HIV/STD Risk-Reduction Intervention for Adolescents When Implemented by Community-Based Organizations: A Cluster-Randomized Controlled Trial

PubMed Central

Jemmott, Loretta S.; Fong, Geoffrey T.; Morales, Knashawn H.

2010-01-01

Objectives. We evaluated the effectiveness of an HIV/STD risk-reduction intervention when implemented by community-based organizations (CBOs). Methods. In a cluster-randomized controlled trial, 86 CBOs that served African American adolescents aged 13 to 18 years were randomized to implement either an HIV/STD risk-reduction intervention whose efficacy has been demonstrated or a health-promotion control intervention. CBOs agreed to implement 6 intervention groups, a random half of which completed 3-, 6-, and 12-month follow-up assessments. The primary outcome was consistent condom use in the 3 months prior to each follow-up assessment, averaged over the follow-up assessments. Results. Participants were 1707 adolescents, 863 in HIV/STD-intervention CBOs and 844 in control-intervention CBOs. HIV/STD-intervention participants were more likely to report consistent condom use (odds ratio [OR] = 1.39; 95% confidence interval [CI] = 1.06, 1.84) than were control-intervention participants. HIV/STD-intervention participants also reported a greater proportion of condom-protected intercourse (β = 0.06; 95% CI = 0.00, 0.12) than did the control group. Conclusions. This is the first large, randomized intervention trial to demonstrate that CBOs can successfully implement an HIV/STD risk-reduction intervention whose efficacy has been established. PMID:20167903

COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): statistical and economic analysis plan for a randomised controlled trial.

PubMed

Robinson, Emily J; Goldstein, Laura H; McCrone, Paul; Perdue, Iain; Chalder, Trudie; Mellers, John D C; Richardson, Mark P; Murray, Joanna; Reuber, Markus; Medford, Nick; Stone, Jon; Carson, Alan; Landau, Sabine

2017-06-06

Dissociative seizures (DSs), also called psychogenic non-epileptic seizures, are a distressing and disabling problem for many patients in neurological settings with high and often unnecessary economic costs. The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES) trial is an evaluation of a specifically tailored psychological intervention with the aims of reducing seizure frequency and severity and improving psychological well-being in adults with DS. The aim of this paper is to report in detail the quantitative and economic analysis plan for the CODES trial, as agreed by the trial steering committee. The CODES trial is a multicentre, pragmatic, parallel group, randomised controlled trial performed to evaluate the clinical effectiveness and cost-effectiveness of 13 sessions of cognitive behavioural therapy (CBT) plus standardised medical care (SMC) compared with SMC alone for adult outpatients with DS. The objectives and design of the trial are summarised, and the aims and procedures of the planned analyses are illustrated. The proposed analysis plan addresses statistical considerations such as maintaining blinding, monitoring adherence with the protocol, describing aspects of treatment and dealing with missing data. The formal analysis approach for the primary and secondary outcomes is described, as are the descriptive statistics that will be reported. This paper provides transparency to the planned inferential analyses for the CODES trial prior to the extraction of outcome data. It also provides an update to the previously published trial protocol and guidance to those conducting similar trials. ISRCTN registry ISRCTN05681227 (registered on 5 March 2014); ClinicalTrials.gov NCT02325544 (registered on 15 December 2014).

Published methodological quality of randomized controlled trials does not reflect the actual quality assessed in protocols.

PubMed

Mhaskar, Rahul; Djulbegovic, Benjamin; Magazin, Anja; Soares, Heloisa P; Kumar, Ambuj

2012-06-01

To assess whether the reported methodological quality of randomized controlled trials (RCTs) reflects the actual methodological quality and to evaluate the association of effect size (ES) and sample size with methodological quality. Systematic review. This is a retrospective analysis of all consecutive phase III RCTs published by eight National Cancer Institute Cooperative Groups up to 2006. Data were extracted from protocols (actual quality) and publications (reported quality) for each study. Four hundred twenty-nine RCTs met the inclusion criteria. Overall reporting of methodological quality was poor and did not reflect the actual high methodological quality of RCTs. The results showed no association between sample size and actual methodological quality of a trial. Poor reporting of allocation concealment and blinding exaggerated the ES by 6% (ratio of hazard ratio [RHR]: 0.94; 95% confidence interval [CI]: 0.88, 0.99) and 24% (RHR: 1.24; 95% CI: 1.05, 1.43), respectively. However, actual quality assessment showed no association between ES and methodological quality. The largest study to date shows that poor quality of reporting does not reflect the actual high methodological quality. Assessment of the impact of quality on the ES based on reported quality can produce misleading results. Copyright © 2012 Elsevier Inc. All rights reserved.

Household costs for personal protection against mosquitoes: secondary outcomes from a randomised controlled trial of dengue prevention in Guerrero state, Mexico.

PubMed

Legorreta-Soberanis, José; Paredes-Solís, Sergio; Morales-Pérez, Arcadio; Nava-Aguilera, Elizabeth; Serrano-de Los Santos, Felipe René; Sánchez-Gervacio, Belén Madeline; Ledogar, Robert J; Cockcroft, Anne; Andersson, Neil

2017-05-30

Dengue is a serious public health issue that affects households in endemic areas in terms of health and also economically, imposing costs for prevention and treatment of cases. The Camino Verde cluster-randomised controlled trial in Mexico and Nicaragua assessed the impact of evidence-based community engagement in dengue prevention. The Mexican arm of the trial was conducted in 90 randomly selected communities in three coastal regions of Guerrero State. This study reports an analysis of a secondary outcome of the trial: household use of and expenditure on anti-mosquito products. We examined whether the education and mobilisation activities of the trial motivated people to spend less on anti-mosquito products. We carried out a household questionnaire survey in the trial communities in 2010 (12,312 households) and 2012 (5349 households in intervention clusters, 5142 households in control clusters), including questions about socio-economic status, self-reported dengue illness, and purchase of and expenditure on insecticide anti-mosquito products in the previous month. We examined expenditures on anti-mosquito products at baseline in relation to social vulnerability and we compared use of and expenditures on these products between intervention and control clusters in 2012. In 2010, 44.2% of 12,312 households reported using anti-mosquito products, with a mean expenditure of USD4.61 per month among those who used them. Socially vulnerable households spent less on the products. In 2012, after the intervention, the proportion of households who purchased anti-mosquito products in the last month was significantly lower in intervention clusters (47.8%; 2503/5293) than in control clusters (53.3%; 2707/5079) (difference - 0.05, 95% CIca -0.100 to -0.010). The mean expenditure on the products, among those households who bought them, was USD6.43; 30.4% in the intervention clusters and 36.7% in the control clusters spent more than this (difference - 0.06, 95% CIca -0.12 to -0.01). These expenditures on anti-mosquito products represent 3.3% and 3.8% respectively of monthly household income for the poorest 10% of the population in 2012. The Camino Verde community mobilisation intervention, as well as being effective in reducing dengue infections, was effective in reducing household use of and expenditure on insecticide anti-mosquito products. ( ISRCTN27581154 ).

The impact of a computerised test of attention and activity (QbTest) on diagnostic decision-making in children and young people with suspected attention deficit hyperactivity disorder: single-blind randomised controlled trial.

PubMed

Hollis, Chris; Hall, Charlotte L; Guo, Boliang; James, Marilyn; Boadu, Janet; Groom, Madeleine J; Brown, Nikki; Kaylor-Hughes, Catherine; Moldavsky, Maria; Valentine, Althea Z; Walker, Gemma M; Daley, David; Sayal, Kapil; Morriss, Richard

2018-04-26

Diagnosis of attention deficit hyperactivity disorder (ADHD) relies on subjective methods which can lead to diagnostic uncertainty and delay. This trial evaluated the impact of providing a computerised test of attention and activity (QbTest) report on the speed and accuracy of diagnostic decision-making in children with suspected ADHD. Randomised, parallel, single-blind controlled trial in mental health and community paediatric clinics in England. Participants were 6-17 years-old and referred for ADHD diagnostic assessment; all underwent assessment-as-usual, plus QbTest. Participants and their clinician were randomised to either receive the QbTest report immediately (QbOpen group) or the report was withheld (QbBlind group). The primary outcome was number of consultations until a diagnostic decision confirming/excluding ADHD within 6-months from baseline. Health economic cost-effectiveness and cost utility analysis was conducted. Assessing QbTest Utility in ADHD: A Randomised Controlled Trial was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02209116). One hundred and thirty-two participants were randomised to QbOpen group (123 analysed) and 135 to QbBlind group (127 analysed). Clinicians with access to the QbTest report (QbOpen) were more likely to reach a diagnostic decision about ADHD (hazard ratio 1.44, 95% CI 1.04-2.01). At 6-months, 76% of those with a QbTest report had received a diagnostic decision, compared with 50% without. QbTest reduced appointment length by 15% (time ratio 0.85, 95% CI 0.77-0.93), increased clinicians' confidence in their diagnostic decisions (odds ratio 1.77, 95% CI 1.09-2.89) and doubled the likelihood of excluding ADHD. There was no difference in diagnostic accuracy. Health economic analysis showed a position of strict dominance; however, cost savings were small suggesting that the impact of providing the QbTest report within this trial can best be viewed as 'cost neutral'. QbTest may increase the efficiency of ADHD assessment pathway allowing greater patient throughput with clinicians reaching diagnostic decisions faster without compromising diagnostic accuracy. © 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

An Australian general practice based strategy to improve chronic disease prevention, and its impact on patient reported outcomes: evaluation of the preventive evidence into practice cluster randomised controlled trial.

PubMed

Harris, Mark Fort; Parker, Sharon M; Litt, John; van Driel, Mieke; Russell, Grant; Mazza, Danielle; Jayasinghe, Upali W; Smith, Jane; Del Mar, Chris; Lane, Riki; Denney-Wilson, Elizabeth

2017-09-08

Implementing evidence-based chronic disease prevention with a practice-wide population is challenging in primary care. PEP Intervention practices received education, clinical audit and feedback and practice facilitation. Patients (40‑69 years) without chronic disease from trial and control practices were invited to participate in baseline and 12 month follow up questionnaires. Patient-recalled receipt of GP services and referral, and the proportion of patients at risk were compared over time and between intervention and control groups. Mean difference in BMI, diet and physical activity between baseline and follow up were calculated and compared using a paired t-test. Change in the proportion of patients meeting the definition for physical activity diet and weight risk was calculated using McNemar's test and multilevel analysis was used to determine the effect of the intervention on follow-up scores. Five hundred eighty nine patients completed both questionnaires. No significant changes were found in the proportion of patients reporting a BP, cholesterol, glucose or weight check in either group. Less than one in six at-risk patients reported receiving lifestyle advice or referral at baseline with little change at follow up. More intervention patients reported attempts to improve their diet and reduce weight. Mean score improved for diet in the intervention group (p = 0.04) but self-reported BMI and PA risk did not significantly change in either group. There was no significant change in the proportion of patients who reported being at-risk for diet, PA or weight, and no changes in PA, diet and BMI in multilevel linear regression adjusted for patient age, sex, practice size and state. There was good fidelity to the intervention but practices varied in their capacity to address changes. The lack of measurable effect within this trial may be attributable to the complexities around behaviour change and/or system change. This trial highlights some of the challenges in providing suitable chronic disease preventive interventions which are both scalable to whole practice populations and meet the needs of diverse practice structures. Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000578808 (29/5/2012). This trial registration is retrospective as our first patient returned their consent on the 21/5/2012. Patient recruitment was ongoing until 31/10/2012.

The effect of replacing saturated fat with mostly n-6 polyunsaturated fat on coronary heart disease: a meta-analysis of randomised controlled trials.

PubMed

Hamley, Steven

2017-05-19

A cornerstone of conventional dietary advice is the recommendation to replace saturated fatty acids (SFA) with mostly n-6 polyunsaturated fatty acids (PUFA) to reduce the risk of coronary heart disease (CHD). Many clinical trials aimed to test this advice and have had their results pooled in several meta-analyses. However, earlier meta-analyses did not sufficiently account for major confounding variables that were present in some of those trials. Therefore, the aim of the study was to account for the major confounding variables in the diet heart trials, and emphasise the results from those trials that most accurately test the effect of replacing SFA with mostly n-6 PUFA. Clinical trials were identified from earlier meta-analyses. Relevant trials were categorised as 'adequately controlled' or 'inadequately controlled' depending on whether there were substantial dietary or non-dietary differences between the experimental and control groups that were not related to SFA or mostly n-6 PUFA intake, then were subject to different subgroup analyses. When pooling results from only the adequately controlled trials there was no effect for major CHD events (RR = 1.06, CI = 0.86-1.31), total CHD events (RR = 1.02, CI = 0.84-1.23), CHD mortality (RR = 1.13, CI = 0.91-1.40) and total mortality (RR = 1.07, CI = 0.90-1.26). Whereas, the pooled results from all trials, including the inadequately controlled trials, suggested that replacing SFA with mostly n-6 PUFA would significantly reduce the risk of total CHD events (RR = 0.80, CI = 0.65-0.98, P = 0.03), but not major CHD events (RR = 0.87, CI = 0.70-1.07), CHD mortality (RR = 0.90, CI = 0.70-1.17) and total mortality (RR = 1.00, CI = 0.90-1.10). Available evidence from adequately controlled randomised controlled trials suggest replacing SFA with mostly n-6 PUFA is unlikely to reduce CHD events, CHD mortality or total mortality. The suggestion of benefits reported in earlier meta-analyses is due to the inclusion of inadequately controlled trials. These findings have implications for current dietary recommendations.

ClinicalTrials.gov registration can supplement information in abstracts for systematic reviews: a comparison study.

PubMed

Scherer, Roberta W; Huynh, Lynn; Ervin, Ann-Margret; Taylor, Jakeisha; Dickersin, Kay

2013-06-18

The inclusion of randomized controlled trials (RCTs) reported in conference abstracts in systematic reviews is controversial, partly because study design information and risk of bias is often not fully reported in the abstract. The Association for Research in Vision and Ophthalmology (ARVO) requires trial registration of abstracts submitted for their annual conference as of 2007. Our goal was to assess the feasibility of obtaining study design information critical to systematic reviews, but not typically included in conference abstracts, from the trial registration record. We reviewed all conference abstracts presented at the ARVO meetings from 2007 through 2009, and identified 496 RCTs; 154 had a single matching registration record in ClinicalTrials.gov. Two individuals independently extracted information from the abstract and the ClinicalTrials.gov record, including study design, sample size, inclusion criteria, masking, interventions, outcomes, funder, and investigator name and contact information. Discrepancies were resolved by consensus. We assessed the frequencies of reporting variables appearing in the abstract and the trial register and assessed agreement of information reported in both sources. We found a substantial amount of study design information in the ClinicalTrials.gov record that was unavailable in the corresponding conference abstract, including eligibility criteria associated with gender (83%; 128/154); masking or blinding of study participants (53%, 82/154), persons administering treatment (30%, 46/154), and persons measuring the outcomes (40%, 61/154)); and number of study centers (58%; 90/154). Only 34% (52/154) of abstracts explicitly described a primary outcome, but a primary outcome was included in the "Primary Outcome" field in the ClinicalTrials.gov record for 82% (126/154) of studies. One or more study interventions were reported in each abstract, but agreed exactly with those reported in ClinicalTrials.gov only slightly more than half the time (88/154, 56%). We found no contact information for study investigators in the abstract, but this information was available in less than one quarter of ClinicalTrial.gov records (17%; 26/154). RCT design information not reported in conference abstracts is often available in the corresponding ClinicalTrials.gov registration record. Sometimes there is conflicting information reported in the two sources and further contact with the trial investigators may still be required.

ClinicalTrials.gov registration can supplement information in abstracts for systematic reviews: a comparison study

PubMed Central

2013-01-01

Background The inclusion of randomized controlled trials (RCTs) reported in conference abstracts in systematic reviews is controversial, partly because study design information and risk of bias is often not fully reported in the abstract. The Association for Research in Vision and Ophthalmology (ARVO) requires trial registration of abstracts submitted for their annual conference as of 2007. Our goal was to assess the feasibility of obtaining study design information critical to systematic reviews, but not typically included in conference abstracts, from the trial registration record. Methods We reviewed all conference abstracts presented at the ARVO meetings from 2007 through 2009, and identified 496 RCTs; 154 had a single matching registration record in ClinicalTrials.gov. Two individuals independently extracted information from the abstract and the ClinicalTrials.gov record, including study design, sample size, inclusion criteria, masking, interventions, outcomes, funder, and investigator name and contact information. Discrepancies were resolved by consensus. We assessed the frequencies of reporting variables appearing in the abstract and the trial register and assessed agreement of information reported in both sources. Results We found a substantial amount of study design information in the ClinicalTrials.gov record that was unavailable in the corresponding conference abstract, including eligibility criteria associated with gender (83%; 128/154); masking or blinding of study participants (53%, 82/154), persons administering treatment (30%, 46/154), and persons measuring the outcomes (40%, 61/154)); and number of study centers (58%; 90/154). Only 34% (52/154) of abstracts explicitly described a primary outcome, but a primary outcome was included in the “Primary Outcome” field in the ClinicalTrials.gov record for 82% (126/154) of studies. One or more study interventions were reported in each abstract, but agreed exactly with those reported in ClinicalTrials.gov only slightly more than half the time (88/154, 56%). We found no contact information for study investigators in the abstract, but this information was available in less than one quarter of ClinicalTrial.gov records (17%; 26/154). Conclusion RCT design information not reported in conference abstracts is often available in the corresponding ClinicalTrials.gov registration record. Sometimes there is conflicting information reported in the two sources and further contact with the trial investigators may still be required. PMID:23773868

Effect of cinnamon on glucose control and lipid parameters.

PubMed

Baker, William L; Gutierrez-Williams, Gabriela; White, C Michael; Kluger, Jeffrey; Coleman, Craig I

2008-01-01

To perform a meta-analysis of randomized controlled trials of cinnamon to better characterize its impact on glucose and plasma lipids. A systematic literature search through July 2007 was conducted to identify randomized placebo-controlled trials of cinnamon that reported data on A1C, fasting blood glucose (FBG), or lipid parameters. The mean change in each study end point from baseline was treated as a continuous variable, and the weighted mean difference was calculated as the difference between the mean value in the treatment and control groups. A random-effects model was used. Five prospective randomized controlled trials (n = 282) were identified. Upon meta-analysis, the use of cinnamon did not significantly alter A1C, FBG, or lipid parameters. Subgroup and sensitivity analyses did not significantly change the results. Cinnamon does not appear to improve A1C, FBG, or lipid parameters in patients with type 1 or type 2 diabetes.

The influence of emotional interference on cognitive control: A meta-analysis of neuroimaging studies using the emotional Stroop task.

PubMed

Song, Sensen; Zilverstand, Anna; Song, Hongwen; d'Oleire Uquillas, Federico; Wang, Yongming; Xie, Chao; Cheng, Li; Zou, Zhiling

2017-05-18

The neural correlates underlying the influence of emotional interference on cognitive control remain a topic of discussion. Here, we assessed 16 neuroimaging studies that used an emotional Stroop task and that reported a significant interaction effect between emotion (stimulus type) and cognitive conflict. There were a total of 330 participants, equaling 132 foci for an activation likelihood estimation (ALE) analysis. Results revealed consistent brain activation patterns related to emotionally-salient stimuli (as compared to emotionally-neutral trials) during cognitive conflict trials [incongruent trials (with task-irrelevant information interfering), versus congruent/baseline trials (less disturbance from task-irrelevant information)], that span the lateral prefrontal cortex (dorsolateral prefrontal cortex and inferior frontal gyrus), the medial prefrontal cortex, and the dorsal anterior cingulate cortex. Comparing mild emotional interference trials (without semantic conflict) versus intense emotional interference trials (with semantic conflict), revealed that while concurrent activation in similar brain regions as mentioned above was found for intense emotional interference trials, activation for mild emotional interference trials was only found in the precentral/postcentral gyrus. These data provide evidence for the potential neural mechanisms underlying emotional interference on cognitive control, and further elucidate an important distinction in brain activation patterns for different levels of emotional conflict across emotional Stroop tasks.

Resolving ethical issues in stem cell clinical trials: the example of Parkinson disease.

PubMed

Lo, Bernard; Parham, Lindsay

2010-01-01

Clinical trials of stem cell transplantation raise ethical issues that are intertwined with scientific and design issues, including choice of control group and intervention, background interventions, endpoints, and selection of subjects. We recommend that the review and IRB oversight of stem cell clinical trials should be strengthened. Scientific and ethics review should be integrated in order to better assess risks and potential benefits. Informed consent should be enhanced by assuring that participants comprehend key aspects of the trial. For the trial to yield generalizable knowledge, negative findings and serious adverse events must be reported.

Statins as antiarrhythmics: a systematic review part I: effects on risk of atrial fibrillation.

PubMed

Abuissa, Hussam; O'Keefe, James H; Bybee, Kevin A

2009-10-01

Recent studies have demonstrated that statins may possess antiarrhythmic properties in addition to their lipid-lowering effects. Studies which reported the association of statins with the incidence of atrial arrhythmias were identified through a systematic review of published literature. One randomized, placebo-controlled trial of 200 patients undergoing cardiac surgery showed that atorvastatin decreased the incidence of postoperative atrial fibrillation by 61%. Observational studies in patients with stable coronary disease, left ventricular dysfunction, or those undergoing cardiac or noncardiac surgery show that statin therapy is associated with an approximately 50% lower rate of atrial fibrillation. Two small randomized trials reported conflicting results: one showing that atorvastatin reduced the recurrence of AF after electrical cardioversion and the other finding that pravastatin did not. Published data suggests that statins may possess antiarrhythmic properties that reduce the propensity for atrial fibrillation. Most of this data is observational; more randomized, placebo-controlled trials are needed.

Assessing the impact of scaling-up bednet coverage through agricultural loan programmes: evidence from a cluster randomised controlled trial in Katete, Zambia.

PubMed

Fink, Günther; Masiye, Felix

2012-11-01

To investigate the effectiveness of scaling-up existing bednet distribution campaigns, a randomised controlled trial with 516 farming households in Katete District, a rural area with highly endemic malaria in Zambia's Eastern Province, was evaluated. In the trial, selected farmers were assigned to bednet programmes that allowed them to obtain additional bednets for free or at subsidised prices through agricultural loan programmes. On average, 2.4 nets were distributed in the free distribution group and 0.9 in the net loan group. The marginal health impact of additional nets appears large, reducing the odds of self-reported all-cause morbidity by 40-42% and the odds of self-reported confirmed malaria by 53-60%. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Have CONSORT guidelines improved the quality of reporting of randomised controlled trials published in public health dentistry journals?

PubMed

Savithra, Prakash; Nagesh, Lakshminarayan Shetty

2013-01-01

To assess a) whether the quality of reporting of randomised controlled trials (RCTs) has improved since the formulation of the Consolidated Standards of Reporting Trials (CONSORT) statement and b) whether there is any difference in reporting of RCTs between the selected public health dentistry journals. A hand search of the journals of public health dentistry was performed and four journals were identified for the study. They were Community Dentistry and Oral Epidemiology (CDOE), Community Dental Health (CDH), Journal of Public Health Dentistry (JPHD) and Oral Health and Preventive Dentistry (OHPD). A total of 114 RCTs published between 1990 and 2009 were selected. CONSORT guidelines were applied to each selected article in order to assess and determine any improvement since the publication of CONSORT guidelines. The chi-square test was employed to determine any statistical significant difference in quality of reporting of RCTs before and after the publication of the CONSORT guidelines. A comparison was also done to determine any statistically significant difference in quality of reporting of RCTs between the selected journals. Title, abstract, discussion and conclusion sections of the selected articles showed adherence to the CONSORT guidelines, whereas the compliance was poor with respect to the methodology section. The quality of reporting of RCTs is generally poor in public health dentistry journals. Overall, the quality of reporting has not substantially improved since the publication of CONSORT guidelines.

Reporting of Telehealth-Delivered Dietary Intervention Trials in Chronic Disease: Systematic Review.

PubMed

Warner, Molly M; Kelly, Jaimon T; Reidlinger, Dianne P; Hoffmann, Tammy C; Campbell, Katrina L

2017-12-11

Telehealth-delivered dietary interventions are effective for chronic disease management and are an emerging area of clinical practice. However, to apply interventions from the research setting in clinical practice, health professionals need details of each intervention component. The aim of this study was to evaluate the completeness of intervention reporting in published dietary chronic disease management trials that used telehealth delivery methods. Eligible randomized controlled trial publications were identified through a systematic review. The completeness of reporting of experimental and comparison interventions was assessed by two independent assessors using the Template for Intervention Description and Replication (TIDieR) checklist that consists of 12 items including intervention rationale, materials used, procedures, providers, delivery mode, location, when and how much intervention delivered, intervention tailoring, intervention modifications, and fidelity. Where reporting was incomplete, further information was sought from additional published material and through email correspondence with trial authors. Within the 37 eligible trials, there were 49 experimental interventions and 37 comparison interventions. One trial reported every TIDieR item for their experimental intervention. No publications reported every item for the comparison intervention. For the experimental interventions, the most commonly reported items were location (96%), mode of delivery (98%), and rationale for the essential intervention elements (96%). Least reported items for experimental interventions were modifications (2%) and intervention material descriptions (39%) and where to access them (20%). Of the 37 authors, 14 responded with further information, and 8 could not be contacted. Many details of the experimental and comparison interventions in telehealth-delivered dietary chronic disease management trials are incompletely reported. This prevents accurate interpretation of trial results and implementation of effective interventions in clinical practice. ©Molly M Warner, Jaimon T Kelly, Dianne P Reidlinger, Tammy C Hoffmann, Katrina L Campbell. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 11.12.2017.

Quality of Radiotherapy Reporting in Randomized Controlled Trials of Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma: A Systematic Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bekelman, Justin E.; Yahalom, Joachim

2009-02-01

Purpose: Standards for the reporting of radiotherapy details in randomized controlled trials (RCTs) are lacking. Although radiotherapy (RT) is an important component of curative therapy for Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), we postulated that RT reporting may be inadequate in Phase III HL and NHL trials. Methods and Materials: We searched PubMed and the Cochrane registry for reports of RCTs involving RT and either HL or NHL published between 1998 and 2007. We screened 133 titles and abstracts to identify relevant studies. We included a total of 61 reports. We assessed these reports for the presence of sixmore » quality measures: target volume, radiation dose, fractionation, radiation prescription, quality assurance (QA) process use, and adherence to QA (i.e., reporting of major or minor deviations). Results: Of 61 reports, 23 (38%) described the target volume. Of the 42 reports involving involved-field RT alone, only 8 (19%) adequately described the target volume. The radiation dose and fractionation was described in most reports (54 reports [89%] and 39 reports [64%], respectively). Thirteen reports specified the RT prescription point (21%). Only 12 reports (20%) described using a RT QA process, and 7 reports (11%) described adherence to the QA process. Conclusion: Reporting of RT in HL and NHL RCTs is deficient. Because the interpretation, replication, and application of RCT results depend on adequate description and QA of therapeutic interventions, consensus standards for RT reporting should be developed and integrated into the peer-review process.« less

The Men's Safer Sex (MenSS) trial: protocol for a pilot randomised controlled trial of an interactive digital intervention to increase condom use in men

PubMed Central

Bailey, Julia V; Webster, Rosie; Hunter, Rachael; Freemantle, Nick; Rait, Greta; Michie, Susan; Estcourt, Claudia; Anderson, Jane; Gerressu, Makeda; Stephenson, Judith; Ang, Chee Siang; Hart, Graham; Dhanjal, Sacha; Murray, Elizabeth

2015-01-01

Introduction Sexually transmitted infections (STI) are a major public health problem. Condoms provide effective protection but there are many barriers to use. Face-to-face health promotion interventions are resource-intensive and show mixed results. Interactive digital interventions may provide a suitable alternative, allowing private access to personally tailored behaviour change support. We have developed an interactive digital intervention (the Men's Safer Sex (MenSS) website) which aims to increase condom use in men. We describe the protocol for a pilot trial to assess the feasibility of a full-scale randomised controlled trial of the MenSS website in addition to usual sexual health clinical care. Methods and analysis Participants: Men aged 16 or over who report female sexual partners and recent unprotected sex or suspected acute STI. Participants (N=166) will be enrolled using a tablet computer in clinic waiting rooms. All trial procedures will be online, that is, eligibility checks; study consent; trial registration; automated random allocation; and data submission. At baseline and at 3, 6 and 12 months, an online questionnaire will assess condom use, self-reported STI diagnoses, and mediators of condom use (eg, knowledge, intention). Reminders will be by email and mobile phone. The primary outcome is condom use, measured at 3 months. STI rates will be recorded from sexual health clinic medical records at 12 months. The feasibility of a cost-effectiveness analysis will be assessed, to calculate incremental cost per STI prevented (Chlamydia or Gonorrhoea), from the NHS perspective. Ethics and dissemination Ethical approval: City and East NHS Research Ethics Committee (reference number 13 LO 1801). Findings will be made available through publication in peer-reviewed journals, and to participants and members of the public via Twitter and from the University College London eHealth Unit website. Raw data will be made available on request. Trial registration number Current Controlled Trials. ISRCTN18649610. Registered 15 October 2013 http://www.controlled-trials.com/ISRCTN18649610. PMID:25687900

The efficacy of computer-enabled discharge communication interventions: a systematic review.

PubMed

Motamedi, Soror Mona; Posadas-Calleja, Juan; Straus, Sharon; Bates, David W; Lorenzetti, Diane L; Baylis, Barry; Gilmour, Janet; Kimpton, Shandra; Ghali, William A

2011-05-01

Traditional manual/dictated discharge summaries are inaccurate, inconsistent and untimely. Computer-enabled discharge communications may improve information transfer by providing a standardised document that immediately links acute and community healthcare providers. To conduct a systematic review evaluating the efficacy of computer-enabled discharge communication compared with traditional communication for patients discharged from acute care hospitals. MEDLINE, EMBASE, Cochrane CENTRAL Register of Controlled Trials and MEDLINE In-Process. Keywords from three themes were combined: discharge communication, electronic/online/web-based and controlled interventional studies. Study types included: clinical trials, quasiexperimental studies with concurrent controls and controlled before--after studies. Interventions included: (1) automatic population of a discharge document by computer database(s); (2) transmission of discharge information via computer technology; or (3) computer technology providing a 'platform' for dynamic discharge communication. Controls included: no intervention or traditional manual/dictated discharge summaries. Primary outcomes included: mortality, readmission and adverse events/near misses. Secondary outcomes included: timeliness, accuracy, quality/completeness and physician/patient satisfaction. Description of interventions and study outcomes were extracted by two independent reviewers. 12 unique studies were identified: eight randomised controlled trials and four quasi-experimental studies. Pooling/meta-analysis was not possible, given the heterogeneity of measures and outcomes reported. The primary outcomes of mortality and readmission were inconsistently reported. There was no significant difference in mortality, and one study reported reduced long-term readmission. Intervention groups experienced reductions in perceived medical errors/adverse events, and improvements in timeliness and physician/patient satisfaction. Computer-enabled discharge communications appear beneficial with respect to a number of important secondary outcomes. Primary outcomes of mortality and readmission are less commonly reported in this literature and require further study.

Steering teens safe: a randomized trial of a parent-based intervention to improve safe teen driving.

PubMed

Peek-Asa, Corinne; Cavanaugh, Joseph E; Yang, Jingzhen; Chande, Vidya; Young, Tracy; Ramirez, Marizen

2014-07-31

Crashes are the leading cause of death for teens, and parent-based interventions are a promising approach. We assess the effectiveness of Steering Teens Safe, a parent-focused program to increase safe teen driving. Steering Teens Safe aimed to improve parental communication with teens about safe driving using motivational interviewing techniques in conjunction with 19 safe driving lessons. A randomized controlled trial involved 145 parent-teen dyads (70 intervention and 75 control). Intervention parents received a 45-minute session to learn the program with four follow-up phone sessions, a DVD, and a workbook. Control parents received a standard brochure about safe driving. Scores were developed to measure teen-reported quantity and quality of parental communication about safe driving. The main outcome measure was a previously validated Risky Driving Score reported by teens. Because the Score was highly skewed, a generalized linear model based on a gamma distribution was used for analysis. Intervention teens ranked their parent's success in talking about driving safety higher than control teens (p = 0.035) and reported that their parents talked about more topics (non-significant difference). The Risky Driving Score was 21% lower in intervention compared to control teens (85% CI = 0.60, 1.00). Interaction between communication quantity and the intervention was examined. Intervention teens who reported more successful communication had a 42% lower Risky Driving Score (95% CI = 0.37, 0.94) than control parents with less successful communication. This program had a positive although not strong effect, and it may hold the most promise in partnership with other programs, such as Driver's Education or Graduated Driver's License policies. ClinicalTrials.gov NCT01014923. Registered Nov. 16, 2009.

The Effectiveness of Mobile-Health Technologies to Improve Health Care Service Delivery Processes: A Systematic Review and Meta-Analysis

PubMed Central

Free, Caroline; Phillips, Gemma; Watson, Louise; Galli, Leandro; Felix, Lambert; Edwards, Phil; Patel, Vikram; Haines, Andy

2013-01-01

Background Mobile health interventions could have beneficial effects on health care delivery processes. We aimed to conduct a systematic review of controlled trials of mobile technology interventions to improve health care delivery processes. Methods and Findings We searched for all controlled trials of mobile technology based health interventions using MEDLINE, EMBASE, PsycINFO, Global Health, Web of Science, Cochrane Library, UK NHS HTA (Jan 1990–Sept 2010). Two authors independently extracted data on allocation concealment, allocation sequence, blinding, completeness of follow-up, and measures of effect. We calculated effect estimates and we used random effects meta-analysis to give pooled estimates. We identified 42 trials. None of the trials had low risk of bias. Seven trials of health care provider support reported 25 outcomes regarding appropriate disease management, of which 11 showed statistically significant benefits. One trial reported a statistically significant improvement in nurse/surgeon communication using mobile phones. Two trials reported statistically significant reductions in correct diagnoses using mobile technology photos compared to gold standard. The pooled effect on appointment attendance using text message (short message service or SMS) reminders versus no reminder was increased, with a relative risk (RR) of 1.06 (95% CI 1.05–1.07, I 2 = 6%). The pooled effects on the number of cancelled appointments was not significantly increased RR 1.08 (95% CI 0.89–1.30). There was no difference in attendance using SMS reminders versus other reminders (RR 0.98, 95% CI 0.94–1.02, respectively). To address the limitation of the older search, we also reviewed more recent literature. Conclusions The results for health care provider support interventions on diagnosis and management outcomes are generally consistent with modest benefits. Trials using mobile technology-based photos reported reductions in correct diagnoses when compared to the gold standard. SMS appointment reminders have modest benefits and may be appropriate for implementation. High quality trials measuring clinical outcomes are needed. Please see later in the article for the Editors' Summary PMID:23458994

The effectiveness of mobile-health technologies to improve health care service delivery processes: a systematic review and meta-analysis.

PubMed

Free, Caroline; Phillips, Gemma; Watson, Louise; Galli, Leandro; Felix, Lambert; Edwards, Phil; Patel, Vikram; Haines, Andy

2013-01-01

Mobile health interventions could have beneficial effects on health care delivery processes. We aimed to conduct a systematic review of controlled trials of mobile technology interventions to improve health care delivery processes. We searched for all controlled trials of mobile technology based health interventions using MEDLINE, EMBASE, PsycINFO, Global Health, Web of Science, Cochrane Library, UK NHS HTA (Jan 1990-Sept 2010). Two authors independently extracted data on allocation concealment, allocation sequence, blinding, completeness of follow-up, and measures of effect. We calculated effect estimates and we used random effects meta-analysis to give pooled estimates. We identified 42 trials. None of the trials had low risk of bias. Seven trials of health care provider support reported 25 outcomes regarding appropriate disease management, of which 11 showed statistically significant benefits. One trial reported a statistically significant improvement in nurse/surgeon communication using mobile phones. Two trials reported statistically significant reductions in correct diagnoses using mobile technology photos compared to gold standard. The pooled effect on appointment attendance using text message (short message service or SMS) reminders versus no reminder was increased, with a relative risk (RR) of 1.06 (95% CI 1.05-1.07, I(2) = 6%). The pooled effects on the number of cancelled appointments was not significantly increased RR 1.08 (95% CI 0.89-1.30). There was no difference in attendance using SMS reminders versus other reminders (RR 0.98, 95% CI 0.94-1.02, respectively). To address the limitation of the older search, we also reviewed more recent literature. The results for health care provider support interventions on diagnosis and management outcomes are generally consistent with modest benefits. Trials using mobile technology-based photos reported reductions in correct diagnoses when compared to the gold standard. SMS appointment reminders have modest benefits and may be appropriate for implementation. High quality trials measuring clinical outcomes are needed. Please see later in the article for the Editors' Summary.

Primary outcomes reporting in trials of paediatric type 1 diabetes mellitus: a systematic review.

PubMed

Khanpour Ardestani, Samaneh; Karkhaneh, Mohammad; Yu, Hai Chuan; Hydrie, Muhammad Zafar Iqbal; Vohra, Sunita

2017-12-19

Our objective was to systematically review randomised clinical trials (RCTs) of paediatric type 1 diabetes mellitus (T1DM) to assess reporting of (1) primary outcome, (2) outcome measurement properties and (3) presence or absence of adverse events. Electronic searches in MEDLINE, EMBASE, CINAHL, Cochrane SR and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were undertaken. The search period was between 2001 and 2017. English-language RCTs on children younger than 21 years with T1DM were selected. We excluded studies of diagnostic or screening tools, multiple phase studies, protocols, and follow-up or secondary analysis of data. Of 11 816 unique references, 231 T1DM RCTs were included. Of total 231 included studies, 117 (50.6%) trials failed to report what their primary outcome was. Of 114 (49.4%) studies that reported primary outcome, 88 (77.2%) reported one and 26 (22.8%) more than one primary outcomes. Of 114 studies that clearly stated their primary outcome, 101 (88.6%) used biological/physiological measurements and 13 (11.4%) used instruments (eg, questionnaires, scales, etc) to measure their primary outcome; of these, 12 (92.3%) provided measurement properties or related citation. Of the 231 included studies, 105 (45.5%) reported that adverse events occurred, 39 (16.9%) reported that no adverse events were identified and 87 (37.7%) did not report on the presence or absence of adverse events. Despite tremendous efforts to improve reporting of clinical trials, clear reporting of primary outcomes of RCTs for paediatric T1DM is still lacking. Adverse events due to DM interventions were often not reported in the included trials. Transparent reporting of primary outcome, validity of measurement tools and adverse events need to be improved in paediatric T1DM trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Variability in the reporting of renal function endpoints in immunosuppression trials in renal transplantation: time for consensus?

PubMed

Knight, Simon R; Hussain, Samia

2016-12-01

Early measures of graft function are increasingly used to assess efficacy in clinical trials of kidney transplant immunosuppression. This study aimed to assess the variability and quality of reporting of these endpoints in contemporary trials. Data regarding renal function endpoints were extracted from 213 reports from randomized controlled trials comparing immunosuppressive interventions in renal transplant recipients published between 2010 and 2014. A total of 174 (81.7%) reports included a measure of renal function; in 44 (20.7%), this was the primary endpoint. A total of 103 manuscripts (48.4%) reported serum creatinine, 142 (66.6%) reported estimated glomerular filtration rate (eGFR), and 26 (12.2%) reported measured GFR. Formulas used for GFR estimation were modification of diet in renal disease (42.3%), Cockroft-Gault (23.5%), Nankivell (15.0%), and CKD-EPI (0.9%). Six studies (2.8%) did not report the formula used to estimate GFR. A total of 13.9% of endpoints had missing data. In 10 studies, disagreement was found in the significance of findings using different measures of renal function. There is a great deal of variability in the reporting of renal function endpoints, with a significant proportion of studies using underperforming or inappropriate estimates. There is a need for consensus as to the best tool for monitoring and reporting renal function post-transplant, and in particular for use in clinical trials and registries. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Culturally adaptive storytelling intervention versus didactic intervention to improve hypertension control in Vietnam: a cluster-randomized controlled feasibility trial.

PubMed

Nguyen, Hoa L; Allison, Jeroan J; Ha, Duc A; Chiriboga, Germán; Ly, Ha N; Tran, Hanh T; Nguyen, Cuong K; Dang, Diem M; Phan, Ngoc T; Vu, Nguyen C; Nguyen, Quang P; Goldberg, Robert J

2017-01-01

Vietnam is experiencing an epidemiologic transition with an increased prevalence of non-communicable diseases. Novel, large-scale, effective, and sustainable interventions to control hypertension in Vietnam are needed. We report the results of a cluster-randomized feasibility trial at 3 months follow-up conducted in Hung Yen province, Vietnam, designed to evaluate the feasibility and acceptability of two community-based interventions to improve hypertension control: a "storytelling" intervention, "We Talk about Our Hypertension," and a didactic intervention. The storytelling intervention included stories about strategies for coping with hypertension, with patients speaking in their own words, and didactic content about the importance of healthy lifestyle behaviors including salt reduction and exercise. The didactic intervention included only didactic content. The storytelling intervention was delivered by two DVDs at 3-month intervals; the didactic intervention included only one installment. The trial was conducted in four communes, equally randomized to the two interventions. The mean age of the 160 study patients was 66 years, and 54% were men. Most participants described both interventions as understandable, informative, and motivational. Between baseline and 3 months, mean systolic blood pressure declined by 8.2 mmHg (95% CI 4.1-12.2) in the storytelling group and by 5.5 mmHg (95% CI 1.4-9.5) in the didactic group. The storytelling group also reported a significant increase in hypertension medication adherence. Both interventions were well accepted in several rural communities and were shown to be potentially effective in lowering blood pressure. A large-scale randomized trial is needed to compare the effectiveness of the two interventions in controlling hypertension. ClinicalTrials.gov, NCT02483780.

Study protocol: a randomized controlled trial investigating the effects of a psychosexual training program for adolescents with autism spectrum disorder.

PubMed

Visser, Kirsten; Greaves-Lord, Kirstin; Tick, Nouchka T; Verhulst, Frank C; Maras, Athanasios; van der Vegt, Esther J M

2015-08-28

Previous research shows that adolescents with autism spectrum disorder (ASD) run several risks in their psychosexual development and that these adolescents can have limited access to reliable information on puberty and sexuality, emphasizing the need for specific guidance of adolescents with ASD in their psychosexual development. Few studies have investigated the effects of psychosexual training programs for adolescents with ASD and to date no randomized controlled trials are available to study the effects of psychosexual interventions for this target group. The randomized controlled trial (RCT) described in this study protocol aims to investigate the effects of the Tackling Teenage Training (TTT) program on the psychosexual development of adolescents with ASD. This parallel clinical trial, conducted in the South-West of the Netherlands, has a simple equal randomization design with an intervention and a waiting-list control condition. Two hundred adolescents and their parents participate in this study. We assess the participants in both conditions using self-report as well as parent-report questionnaires at three time points during 1 year: at baseline (T1), post-treatment (T2), and for follow-up (T3). To our knowledge, the current study is the first that uses a randomized controlled design to study the effects of a psychosexual training program for adolescents with ASD. It has a number of methodological strengths, namely a large sample size, a wide range of functionally relevant outcome measures, the use of multiple informants, and a standardized research and intervention protocol. Also some limitations of the described study are identified, for instance not making a comparison between two treatment conditions, and no use of blinded observational measures to investigate the ecological validity of the research results. Dutch Trial Register NTR2860. Registered on 20 April 2011.

Enhancing the quality of antibiotic prescribing in Primary Care: Qualitative evaluation of a blended learning intervention

PubMed Central

2010-01-01

Background The Stemming the Tide of Antibiotic Resistance (STAR) Educational Program aims to enhance the quality of antibiotic prescribing and raise awareness about antibiotic resistance among general medical practitioners. It consists of a seven part, theory-based blended learning program that includes online reflection on clinicians' own practice, presentation of research evidence and guidelines, a practice-based seminar focusing on participants' own antibiotic prescribing and resistance rates in urine samples sent from their practice, communication skills training using videos of simulated patients in routine surgeries, and participation in a web forum. Effectiveness was evaluated in a randomised controlled trial in which 244 GPs and Nurse Practitioners and 68 general practices participated. This paper reports part of the process evaluation of that trial. Methods Semi-structured, digitally recorded, and transcribed telephone interviews with 31 purposively sampled trial participants analysed using thematic content analysis. Results The majority of participants reported increased awareness of antibiotic resistance, greater self-confidence in reducing antibiotic prescribing and at least some change in consultation style and antibiotic prescribing behaviour. Reported practical changes included adopting a practice-wide policy of antibiotic prescription reduction. Many GPs also reported increased insight into patients' expectations, ultimately contributing to improved doctor-patient rapport. The components of the intervention put forward as having the greatest influence on changing clinician behaviour were the up-to-date research evidence resources, simple and effective communication skills presented in on-line videos, and presentation of the practice's own antibiotic prescribing levels combined with an overview of local resistance data. Conclusion Participants regarded this complex blended learning intervention acceptable and feasible, and reported wide-ranging, positive changes in attitudes and clinical practice as a result of participating in the STAR Educational Program. Trial registration Current Controlled Trials ISRCTN63355948 PMID:20459655

Pre-cue Fronto-Occipital Alpha Phase and Distributed Cortical Oscillations Predict Failures of Cognitive Control

PubMed Central

Hamm, Jordan P.; Dyckman, Kara A.; McDowell, Jennifer E.; Clementz, Brett A.

2012-01-01

Cognitive control is required for correct performance on antisaccade tasks, including the ability to inhibit an externally driven ocular motor repsonse (a saccade to a peripheral stimulus) in favor of an internally driven ocular motor goal (a saccade directed away from a peripheral stimulus). Healthy humans occasionally produce errors during antisaccade tasks, but the mechanisms associated with such failures of cognitive control are uncertain. Most research on cognitive control failures focuses on post-stimulus processing, although a growing body of literature highlights a role of intrinsic brain activity in perceptual and cognitive performance. The current investigation used dense array electroencephalography and distributed source analyses to examine brain oscillations across a wide frequency bandwidth in the period prior to antisaccade cue onset. Results highlight four important aspects of ongoing and preparatory brain activations that differentiate error from correct antisaccade trials: (i) ongoing oscillatory beta (20–30Hz) power in anterior cingulate prior to trial initiation (lower for error trials), (ii) instantaneous phase of ongoing alpha-theta (7Hz) in frontal and occipital cortices immediately before trial initiation (opposite between trial types), (iii) gamma power (35–60Hz) in posterior parietal cortex 100 ms prior to cue onset (greater for error trials), and (iv) phase locking of alpha (5–12Hz) in parietal and occipital cortices immediately prior to cue onset (lower for error trials). These findings extend recently reported effects of pre-trial alpha phase on perception to cognitive control processes, and help identify the cortical generators of such phase effects. PMID:22593071

Serenoa repens (saw palmetto): a systematic review of adverse events.

PubMed

Agbabiaka, Taofikat B; Pittler, Max H; Wider, Barbara; Ernst, Edzard

2009-01-01

Serenoa repens (W. Bartram) Small, also known as saw palmetto, is one of the most widely used herbal preparations for the treatment of lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Although a number of randomized controlled trials (RCTs) and systematic reviews of the efficacy of S. repens for the treatment of LUTS and BPH have been published, no systematic review on its drug interactions or adverse events currently exists. This review assesses all available human safety data of S. repens monopreparations. Systematic literature searches were conducted from date of inception to February 2008 in five electronic databases; reference lists and our departmental files were checked for further relevant publications. Information was requested from spontaneous reporting schemes of the WHO and national safety bodies. Twenty-four manufacturers/distributors of S. repens preparations and four herbalist organizations were contacted for additional information. No language restrictions were imposed. Only reports of adverse events in humans from monopreparations of S. repens were included. Data from all articles, regardless of study design, reporting adverse events or interactions were independently extracted by the first author and validated by the second. Forty articles (26 randomized controlled trials, 4 non-randomized controlled trials, 6 uncontrolled trials and 4 case reports/series) were included. They suggest that adverse events associated with the use of S. repens are mild and similar to those with placebo. The most frequently reported adverse events are abdominal pain, diarrhoea, nausea, fatigue, headache, decreased libido and rhinitis. More serious adverse events such as death and cerebral haemorrhage are reported in isolated case reports and data from spontaneous reporting schemes, but causality is questionable. No drug interactions were reported. Currently available data suggest that S. repens is well tolerated by most users and is not associated with serious adverse events. The majority of adverse events are mild, infrequent and reversible, and include abdominal pain, diarrhoea, nausea and fatigue, headache, decreased libido and rhinitis. We found no evidence for drug interactions with S. repens. However, higher quality reporting of adverse events is essential if safety assessments are to be improved in future.

Participant recruitment into a randomised controlled trial of exercise therapy for people with multiple sclerosis.

PubMed

Carter, Anouska; Humphreys, Liam; Snowdon, Nicky; Sharrack, Basil; Daley, Amanda; Petty, Jane; Woodroofe, Nicola; Saxton, John

2015-10-15

The success of a clinical trial is often dependant on whether recruitment targets can be met in the required time frame. Despite an increase in research into the benefits of exercise in people with multiple sclerosis (PwMS), no trial has reported detailed data on effective recruitment strategies for large-scale randomised controlled trials. The main purpose of this report is to provide a detailed outline of recruitment strategies, rates and estimated costs in the Exercise Intervention for Multiple Sclerosis (ExIMS) trial to identify best practices for future trials involving multiple sclerosis (MS) patient recruitment. The ExIMS researchers recruited 120 PwMS to participate in a 12-week exercise intervention. Participants were randomly allocated to either exercise or usual-care control groups. Participants were sedentary, aged 18-65 years and had Expanded Disability Status Scale scores of 1.0-6.5. Recruitment strategies included attendance at MS outpatient clinics, consultant mail-out and trial awareness-raising activities. A total of 120 participants were recruited over the course of 34 months. To achieve this target, 369 potentially eligible and interested participants were identified. A total of 60 % of participants were recruited via MS clinics, 29.2 % from consultant mail-outs and 10.8 % through trial awareness. The randomisation yields were 33.2 %, 31.0 % and 68.4 % for MS clinic, consultant mail-outs and trial awareness strategies, respectively. The main reason for ineligibility was being too active (69.2 %), whilst for eligible participants the most common reason for non-participation was the need to travel to the study site (15.8 %). Recruitment via consultant mail-out was the most cost-effective strategy, with MS clinics being the most time-consuming and most costly. To reach recruitment targets in a timely fashion, a variety of methods were employed. Although consultant mail-outs were the most cost-effective recruitment strategy, use of this method alone would not have allowed us to obtain the predetermined number of participants in the required time period, thus leading to costly extensions of the project or failure to reach the number of participants required for sufficient statistical power. Thus, a multifaceted approach to recruitment is recommended for future trials. International Standard Randomised Controlled Trial Registry number: ISRCTN41541516 ; date registered: 5 February 2009.

Diet, physical activity, and behavioural interventions for the treatment of overweight or obesity in preschool children up to the age of 6 years.

PubMed

Colquitt, Jill L; Loveman, Emma; O'Malley, Claire; Azevedo, Liane B; Mead, Emma; Al-Khudairy, Lena; Ells, Louisa J; Metzendorf, Maria-Inti; Rees, Karen

2016-03-10

Child overweight and obesity has increased globally, and can be associated with short- and long-term health consequences. To assess the effects of diet, physical activity, and behavioural interventions for the treatment of overweight or obesity in preschool children up to the age of 6 years. We performed a systematic literature search in the databases Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, and LILACS, as well as in the trial registers ClinicalTrials.gov and ICTRP Search Portal. We also checked references of identified trials and systematic reviews. We applied no language restrictions. The date of the last search was March 2015 for all databases. We selected randomised controlled trials (RCTs) of diet, physical activity, and behavioural interventions for treating overweight or obesity in preschool children aged 0 to 6 years. Two review authors independently assessed risk of bias, evaluated the overall quality of the evidence using the GRADE instrument, and extracted data following the Cochrane Handbook for Systematic Reviews of Interventions. We contacted trial authors for additional information. We included 7 RCTs with a total of 923 participants: 529 randomised to an intervention and 394 to a comparator. The number of participants per trial ranged from 18 to 475. Six trials were parallel RCTs, and one was a cluster RCT. Two trials were three-arm trials, each comparing two interventions with a control group. The interventions and comparators in the trials varied. We categorised the comparisons into two groups: multicomponent interventions and dietary interventions. The overall quality of the evidence was low or very low, and six trials had a high risk of bias on individual 'Risk of bias' criteria. The children in the included trials were followed up for between six months and three years.In trials comparing a multicomponent intervention with usual care, enhanced usual care, or information control, we found a greater reduction in body mass index (BMI) z score in the intervention groups at the end of the intervention (6 to 12 months): mean difference (MD) -0.3 units (95% confidence interval (CI) -0.4 to -0.2); P < 0.00001; 210 participants; 4 trials; low-quality evidence, at 12 to 18 months' follow-up: MD -0.4 units (95% CI -0.6 to -0.2); P = 0.0001; 202 participants; 4 trials; low-quality evidence, and at 2 years' follow-up: MD -0.3 units (95% CI -0.4 to -0.1); 96 participants; 1 trial; low-quality evidence.One trial stated that no adverse events were reported; the other trials did not report on adverse events. Three trials reported health-related quality of life and found improvements in some, but not all, aspects. Other outcomes, such as behaviour change and parent-child relationship, were inconsistently measured.One three-arm trial of very low-quality evidence comparing two types of diet with control found that both the dairy-rich diet (BMI z score change MD -0.1 units (95% CI -0.11 to -0.09); P < 0.0001; 59 participants) and energy-restricted diet (BMI z score change MD -0.1 units (95% CI -0.11 to -0.09); P < 0.0001; 57 participants) resulted in greater reduction in BMI than the comparator at the end of the intervention period, but only the dairy-rich diet maintained this at 36 months' follow-up (BMI z score change in MD -0.7 units (95% CI -0.71 to -0.69); P < 0.0001; 52 participants). The energy-restricted diet had a worse BMI outcome than control at this follow-up (BMI z score change MD 0.1 units (95% CI 0.09 to 0.11); P < 0.0001; 47 participants). There was no substantial difference in mean daily energy expenditure between groups. Health-related quality of life, adverse effects, participant views, and parenting were not measured.No trial reported on all-cause mortality, morbidity, or socioeconomic effects.All results should be interpreted cautiously due to their low quality and heterogeneous interventions and comparators. Muticomponent interventions appear to be an effective treatment option for overweight or obese preschool children up to the age of 6 years. However, the current evidence is limited, and most trials had a high risk of bias. Most trials did not measure adverse events. We have identified four ongoing trials that we will include in future updates of this review.The role of dietary interventions is more equivocal, with one trial suggesting that dairy interventions may be effective in the longer term, but not energy-restricted diets. This trial also had a high risk of bias.

‘Trial Exegesis’: Methods for Synthesizing Clinical and Patient Reported Outcome (PRO) Data in Trials to Inform Clinical Practice. A Systematic Review

PubMed Central

Macefield, Rhiannon C.; Blencowe, Natalie S.; Brookes, Sara T.; Blazeby, Jane M.

2016-01-01

Purpose The CONSORT extension for patient reported outcomes (PROs) aims to improve reporting, but guidance on the optimal integration with clinical data is lacking. This study examines in detail the reporting of PROs and clinical data from randomized controlled trials (RCTs) in gastro-intestinal cancer to inform design and reporting of combined PRO and clinical data from trials to improve the ‘take home’ message for clinicians to use in practice. Materials and Methods The case study was undertaken in gastro-intestinal cancer trials. Well-conducted RCTs reporting PROs with validated instruments were identified and categorized into those combining PRO and clinical data in a single paper, or those separating data into linked primary and supplemental papers. Qualitative methods were developed to examine reporting of the critical interpretation of the trial results (trial exegesis) in the papers in relation of the PRO and clinical outcomes and applied to each publication category. Results were used to inform recommendations for practice. Results From 1917 screened abstracts, 49 high quality RCTs were identified reported in 36 combined and 15 linked primary and supplemental papers. In-depth analysis of manuscript text identified three categories for understanding trial exegesis: where authors reported a “detailed”, “general”, or absent PRO rationale and integrated interpretation of clinical and PRO results. A total of 11 (30%) and 6 (16%) combined papers reported “detailed” PRO rationale and integrated interpretation of results although only 2 (14%) and 1 (7%) primary papers achieved the same standard respectively. Supplemental papers provide better information with 11 (73%) and 3 (20%) achieving “detailed” rationale and integrated interpretation of results. Supplemental papers, however, were published a median of 20 months after the primary RCT data in lower impact factor journals (median 16.8 versus 5.2). Conclusion It is recommended that single papers, with detailed PRO rationale and integrated PRO and clinical data are published to optimize trial exegesis. Further work to examine whether this improves the use of PRO data to inform practice is needed. PMID:27571514

Effects of Study Design and Allocation on participant behaviour--ESDA: study protocol for a randomized controlled trial.

PubMed

Kypri, Kypros; McCambridge, Jim; Wilson, Amanda; Attia, John; Sheeran, Paschal; Bowe, Steve; Vater, Tina

2011-02-14

What study participants think about the nature of a study has been hypothesised to affect subsequent behaviour and to potentially bias study findings. In this trial we examine the impact of awareness of study design and allocation on participant drinking behaviour. A three-arm parallel group randomised controlled trial design will be used. All recruitment, screening, randomisation, and follow-up will be conducted on-line among university students. Participants who indicate a hazardous level of alcohol consumption will be randomly assigned to one of three groups. Group A will be informed their drinking will be assessed at baseline and again in one month (as in a cohort study design). Group B will be told the study is an intervention trial and they are in the control group. Group C will be told the study is an intervention trial and they are in the intervention group. All will receive exactly the same brief educational material to read. After one month, alcohol intake for the past 4 weeks will be assessed. The experimental manipulations address subtle and previously unexplored ways in which participant behaviour may be unwittingly influenced by standard practice in trials. Given the necessity of relying on self-reported outcome, it will not be possible to distinguish true behaviour change from reporting artefact. This does not matter in the present study, as any effects of awareness of study design or allocation involve bias that is not well understood. There has been little research on awareness effects, and our outcomes will provide an indication of the possible value of further studies of this type and inform hypothesis generation. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000846022.

PRagmatic trial Of Video Education in Nursing homes: The design and rationale for a pragmatic cluster randomized trial in the nursing home setting.

PubMed

Mor, Vincent; Volandes, Angelo E; Gutman, Roee; Gatsonis, Constantine; Mitchell, Susan L

2017-04-01

Background/Aims Nursing homes are complex healthcare systems serving an increasingly sick population. Nursing homes must engage patients in advance care planning, but do so inconsistently. Video decision support tools improved advance care planning in small randomized controlled trials. Pragmatic trials are increasingly employed in health services research, although not commonly in the nursing home setting to which they are well-suited. This report presents the design and rationale for a pragmatic cluster randomized controlled trial that evaluated the "real world" application of an Advance Care Planning Video Program in two large US nursing home healthcare systems. Methods PRagmatic trial Of Video Education in Nursing homes was conducted in 360 nursing homes (N = 119 intervention/N = 241 control) owned by two healthcare systems. Over an 18-month implementation period, intervention facilities were instructed to offer the Advance Care Planning Video Program to all patients. Control facilities employed usual advance care planning practices. Patient characteristics and outcomes were ascertained from Medicare Claims, Minimum Data Set assessments, and facility electronic medical record data. Intervention adherence was measured using a Video Status Report embedded into electronic medical record systems. The primary outcome was the number of hospitalizations/person-day alive among long-stay patients with advanced dementia or cardiopulmonary disease. The rationale for the approaches to facility randomization and recruitment, intervention implementation, population selection, data acquisition, regulatory issues, and statistical analyses are discussed. Results The large number of well-characterized candidate facilities enabled several unique design features including stratification on historical hospitalization rates, randomization prior to recruitment, and 2:1 control to intervention facilities ratio. Strong endorsement from corporate leadership made randomization prior to recruitment feasible with 100% participation of facilities randomized to the intervention arm. Critical regulatory issues included minimal risk determination, waiver of informed consent, and determination that nursing home providers were not engaged in human subjects research. Intervention training and implementation were initiated on 5 January 2016 using corporate infrastructures for new program roll-out guided by standardized training elements designed by the research team. Video Status Reports in facilities' electronic medical records permitted "real-time" adherence monitoring and corrective actions. The Centers for Medicare and Medicaid Services Virtual Research Data Center allowed for rapid outcomes ascertainment. Conclusion We must rigorously evaluate interventions to deliver more patient-focused care to an increasingly frail nursing home population. Video decision support is a practical approach to improve advance care planning. PRagmatic trial Of Video Education in Nursing homes has the potential to promote goal-directed care among millions of older Americans in nursing homes and establish a methodology for future pragmatic randomized controlled trials in this complex healthcare setting.

Less is More in Antidepressant Clinical Trials: A Meta-Analysis of the Effect of Visit Frequency on Treatment Response and Drop-out

PubMed Central

Rutherford, Bret R; Cooper, Timothy M.; Persaud, Amanda; Brown, Patrick J.; Sneed, Joel R.; Roose, Steven P.

2014-01-01

Objective We investigated how the number of follow-up visits affects response rates and drop-out among patients in antidepressant trials for Major Depressive Disorder (MDD). Data Sources Medline, PsycINFO, and PubMed were searched to identify trials contrasting antidepressants to placebo or active comparator in adults with depression. The index terms “depression—drug therapy,” “depressive disorder—drug therapy,” and “antidepressant agents,” in addition to the class and individual generic name of all antidepressants were combined using the ‘or’ operator. Results were limited to 1) English language articles, 2) publication year 1985 or later, 3) age group ≥ 18, and 4) publication types including clinical trials, controlled clinical trials, meta-analysis, multi-center study, randomized controlled trial, or review. Study Selection Included articles reported trials of approved antidepressant medications for MDD in outpatients aged 18–65, were 6–12 weeks in duration, and had response rates specified using a standardized measure. Trials were excluded for enrolling inpatients, pregnant women, psychotic subjects, or those with treatment-resistant depression. These criteria allowed 9,189 articles identified in the literature review to be narrowed to 111 reports. Data extraction Demographic characteristics, the number of study visits planned in each treatment cell, duration of active treatment, attrition rates, and response rates to medication and placebo were entered into a database. Results In a multilevel meta-analysis, active medication vs. placebo (OR 1.96, p < 0.001), active comparator vs. placebo-controlled study design (OR 1.82, p < 0.001), and longer vs. shorter duration (OR 1.87, p < 0.001) were associated with significantly increased odds of treatment response. After controlling for these variables, the number of study visits did not significantly influence response rates (OR 0.97, p = 0.877). The odds of drop-out were significantly decreased for active comparator vs. placebo-controlled trials (OR 0.67, p = 0.002) and longer vs. shorter duration trials (OR 0.54, p = 0.035), while increasing numbers of study visits significantly increased the odds of participant drop-out (OR 2.77, p < 0.001). Conclusion Visit schedules that are much more frequent than are commonly practiced in the community treatment of depression may increase the expense of clinical trials and make them less generalizable to standard clinical treatment. PMID:23945448

Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials.

PubMed

de Labra, Carmen; Guimaraes-Pinheiro, Christyanne; Maseda, Ana; Lorenzo, Trinidad; Millán-Calenti, José C

2015-12-02

Low physical activity has been shown to be one of the most common components of frailty, and interventions have been considered to prevent or reverse this syndrome. The purpose of this systematic review of randomized, controlled trials is to examine the exercise interventions to manage frailty in older people. The PubMed, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched using specific keywords and Medical Subject Headings for randomized, controlled trials published during the period of 2003-2015, which enrolled frail older adults in an exercise intervention program. Studies where frailty had been defined were included in the review. A narrative synthesis approach was performed to examine the results. The Physiotherapy Evidence Database (PEDro scale) was used to assess the methodological quality of the selected studies. Of 507 articles, nine papers met the inclusion criteria. Of these, six included multi-component exercise interventions (aerobic and resistance training not coexisting in the intervention), one included physical comprehensive training, and two included exercises based on strength training. All nine of these trials included a control group receiving no treatment, maintaining their habitual lifestyle or using a home-based low level exercise program. Five investigated the effects of exercise on falls, and among them, three found a positive impact of exercise interventions on this parameter. Six trials reported the effects of exercise training on several aspects of mobility, and among them, four showed enhancements in several measurements of this outcome. Three trials focused on the effects of exercise intervention on balance performance, and one demonstrated enhanced balance. Four trials investigated functional ability, and two showed positive results after the intervention. Seven trials investigated the effects of exercise intervention on muscle strength, and five of them reported increases; three trials investigated the effects of exercise training on body composition, finding improvements in this parameter in two of them; finally, one trial investigated the effects of exercise on frailty using Fried's criteria and found an improvement in this measurement. Exercise interventions have demonstrated improvement in different outcome measurements in frail older adults, however, there were large differences between studies with regard to effect sizes. This systematic review suggested that frail older adults seemed to benefit from exercise interventions, although the optimal program remains unclear. More studies of this topic and with frail populations are needed to select the most favorable exercise program.

Preventing substance misuse: study protocol for a randomised controlled trial of the Strengthening Families Programme 10–14 UK (SFP 10–14 UK)

PubMed Central

2014-01-01

Background Prevention of alcohol, drug and tobacco misuse by young people is a key public health priority. There is a need to develop the evidence base through rigorous evaluations of innovative approaches to substance misuse prevention. The Strengthening Families Programme 10–14 is a universal family-based alcohol, drugs and tobacco prevention programme, which has achieved promising results in US trials, and which now requires cross-cultural assessment. This paper therefore describes the protocol for a randomised controlled trial of the UK version of the Strengthening Families Programme 10–14 (SFP 10–14 UK). Methods/Design The trial comprises a pragmatic cluster randomised controlled effectiveness trial with families as the unit of randomisation, with embedded process and economic evaluations. Participating families will be randomised to one of two treatment groups - usual care with full access to existing services (control group), or usual care plus SFP 10–14 UK (intervention group). The trial has two primary outcomes - the number of occasions that young people report having drunk alcohol in the last 30 days, and drunkenness during the last 30 days, both dichotomised as ‘never’ and ‘1-2 times or more’. The main follow-up is at 2 years past baseline, and short-term and intermediate outcomes are also measured at 9 and 15 months. Discussion The results from this trial will provide evidence on the effectiveness and cost-effectiveness of an innovative universal family-based substance misuse prevention programme in a UK context. Trial registration Current Controlled Trials ISRCTN63550893. PMID:24438460

Changes in clinical trials methodology over time: a systematic review of six decades of research in psychopharmacology.

PubMed

Brunoni, André R; Tadini, Laura; Fregni, Felipe

2010-03-03

There have been many changes in clinical trials methodology since the introduction of lithium and the beginning of the modern era of psychopharmacology in 1949. The nature and importance of these changes have not been fully addressed to date. As methodological flaws in trials can lead to false-negative or false-positive results, the objective of our study was to evaluate the impact of methodological changes in psychopharmacology clinical research over the past 60 years. We performed a systematic review from 1949 to 2009 on MEDLINE and Web of Science electronic databases, and a hand search of high impact journals on studies of seven major drugs (chlorpromazine, clozapine, risperidone, lithium, fluoxetine and lamotrigine). All controlled studies published 100 months after the first trial were included. Ninety-one studies met our inclusion criteria. We analyzed the major changes in abstract reporting, study design, participants' assessment and enrollment, methodology and statistical analysis. Our results showed that the methodology of psychiatric clinical trials changed substantially, with quality gains in abstract reporting, results reporting, and statistical methodology. Recent trials use more informed consent, periods of washout, intention-to-treat approach and parametric tests. Placebo use remains high and unchanged over time. Clinical trial quality of psychopharmacological studies has changed significantly in most of the aspects we analyzed. There was significant improvement in quality reporting and internal validity. These changes have increased study efficiency; however, there is room for improvement in some aspects such as rating scales, diagnostic criteria and better trial reporting. Therefore, despite the advancements observed, there are still several areas that can be improved in psychopharmacology clinical trials.

Critical appraisal of clinical trials in multiple system atrophy: Toward better quality.

PubMed

Castro Caldas, Ana; Levin, Johannes; Djaldetti, Ruth; Rascol, Olivier; Wenning, Gregor; Ferreira, Joaquim J

2017-10-01

Multiple system atrophy (MSA) is a rare neurodegenerative disease of undetermined cause. Although many clinical trials have been conducted, there is still no treatment that cures the disease or slows its progression. We sought to assess the clinical trials, methodology, and quality of reporting of clinical trails conducted in MSA patients. We conducted a systematic review of all trials with at least 1 MSA patient subject to any pharmacological/nonpharmacological interventions. Two independent reviewers evaluated the methodological characteristics and quality of reporting of trials. A total of 60 clinical trials were identified, including 1375 MSA patients. Of the trials, 51% (n = 31) were single-arm studies. A total of 28% (n = 17) had a parallel design, half of which (n = 13) were placebo controlled. Of the studies, 8 (13.3%) were conducted in a multicenter setting, 3 of which were responsible for 49.3% (n = 678) of the total included MSA patients. The description of primary outcomes was unclear in 60% (n = 40) of trials. Only 10 (16.7%) clinical trials clearly described the randomization process. Blinding of the participants, personnel, and outcome assessments were at high risk of bias in the majority of studies. The number of dropouts/withdrawals was high (n = 326, 23.4% among the included patients). Overall, the design and quality of reporting of the reviewed studies is unsatisfactory. The most frequent clinical trials were small and single centered. Inadequate reporting was related to the information on the randomization process, sequence generation, allocation concealment, blinding of participants, and sample size calculations. Although improved during the recent years, methodological quality and trial design need to be optimized to generate more informative results. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Dietary interventions, lifestyle changes, and dietary supplements in preventing gestational diabetes mellitus: a literature review.

PubMed

Facchinetti, Fabio; Dante, Giulia; Petrella, Elisabetta; Neri, Isabella

2014-11-01

Gestational diabetes mellitus (GDM) is associated with increased rates of fetal morbidity and mortality, both during the pregnancy and in the postnatal life. Current treatment of GDM includes diet with or without medications, but this management is expensive and poorly cost-effective for the health care systems. Strategies to prevent such condition would be preferable with respect to its treatment. The aim of this literature review was to evaluate studies reporting the efficacy of the most used approaches to prevent GDM as well as evidences of efficacy and safety of dietary supplementations. Systematic literature searches were performed in electronic databases, covering the period January 1983 to April 2014. Randomized controlled clinical trials were included. Quality of the articles was evaluated with the Jadad scale. We did not evaluate those articles that were already entered in the most recent systematic reviews, and we completed the research with the trials published thereafter. Of 55 articles identified, 15 randomized controlled trials were eligible. Quality and heterogeneity of the studies cannot allow firm conclusions. Anyway, trials in which only intake or expenditure has been targeted mostly reported negative results. On the contrary, combined lifestyle programs including diet control (orienting food intake, restricting energy intake) associated with moderate but continuous physical activity exhibit better efficacy in reducing GDM prevalence. The results from dietary supplements with myoinositol or probiotics are promising. The actual evidences provide enough arguments for implementing large-scale, high-quality randomized controlled trials looking at the possible benefits of these new approaches for preventing GDM.

Interventions in sports settings to reduce risky alcohol consumption and alcohol-related harm: a systematic review.

PubMed

Kingsland, Melanie; Wiggers, John H; Vashum, Khanrin P; Hodder, Rebecca K; Wolfenden, Luke

2016-01-21

Elevated levels of risky alcohol consumption and alcohol-related harm have been reported for sportspeople and supporters compared to non-sporting populations. Limited systematic reviews have been conducted to assess the effect of interventions targeting such behaviours. A review was undertaken to determine if interventions implemented in sports settings decreased alcohol consumption and related harms. Studies were included that implemented interventions within sports settings; measured alcohol consumption or alcohol-related injury or violence and were either randomised controlled trials, staggered enrollment trials, stepped-wedged trials, quasi-randomised trials, quasi-experimental trials or natural experiments. Studies without a parallel comparison group were excluded. Studies from both published and grey literature were included. Two authors independently screened potential studies against the eligibility criteria, and two authors independently extracted data from included studies and assessed risk of bias. The results of included studies were synthesised narratively. The title and abstract of 6382 papers and the full text of 45 of these papers were screened for eligibility. Three studies met the inclusion criteria for the review. One of the included studies was a randomised controlled trial (RCT) of a cognitive-behavioural intervention with athletes within an Olympic training facility in the USA. The study reported a significant change in alcohol use between pre-test and follow-up between intervention and control groups. The other two studies were RCTs in community sports clubs in Ireland and Australia. The Australian study found a significant intervention effect for both risky alcohol consumption at sports clubs and overall risk of alcohol-related harm. The Irish study found no significant intervention effect. A limited number of studies have been conducted to assess the effect of interventions implemented in sports settings on alcohol consumption and related harms. While two of the three studies found significant intervention effects, it is difficult to determine the extent to which such effects are generalisable. Further controlled trials are required in this setting. PROSPERO CRD42014001739.

Figures in clinical trial reports: current practice & scope for improvement.

PubMed

Pocock, Stuart J; Travison, Thomas G; Wruck, Lisa M

2007-11-19

Most clinical trial publications include figures, but there is little guidance on what results should be displayed as figures and how. To evaluate the current use of figures in Trial reports, and to make constructive suggestions for future practice. We surveyed all 77 reports of randomised controlled trials in five general medical journals during November 2006 to January 2007. The numbers and types of figures were determined, and then each Figure was assessed for its style, content, clarity and suitability. As a consequence, guidelines are developed for presenting figures, both in general and for each specific common type of Figure. Most trial reports contained one to three figures, mean 2.3 per article. The four main types were flow diagram, Kaplan Meier plot, Forest plot (for subgroup analyses) and repeated measures over time: these accounted for 92% of all figures published. For each type of figure there is a considerable diversity of practice in both style and content which we illustrate with selected examples of both good and bad practice. Some pointers on what to do, and what to avoid, are derived from our critical evaluation of these articles' use of figures. There is considerable scope for authors to improve their use of figures in clinical trial reports, as regards which figures to choose, their style of presentation and labelling, and their specific content. Particular improvements are needed for the four main types of figures commonly used.

Clinical trials in palliative care: a systematic review of their methodological characteristics and of the quality of their reporting.

PubMed

Bouça-Machado, Raquel; Rosário, Madalena; Alarcão, Joana; Correia-Guedes, Leonor; Abreu, Daisy; Ferreira, Joaquim J

2017-01-25

Over the past decades there has been a significant increase in the number of published clinical trials in palliative care. However, empirical evidence suggests that there are methodological problems in the design and conduct of studies, which raises questions about the validity and generalisability of the results and of the strength of the available evidence. We sought to evaluate the methodological characteristics and assess the quality of reporting of clinical trials in palliative care. We performed a systematic review of published clinical trials assessing therapeutic interventions in palliative care. Trials were identified using MEDLINE (from its inception to February 2015). We assessed methodological characteristics and describe the quality of reporting using the Cochrane Risk of Bias tool. We retrieved 107 studies. The most common medical field studied was oncology, and 43.9% of trials evaluated pharmacological interventions. Symptom control and physical dimensions (e.g. intervention on pain, breathlessness, nausea) were the palliative care-specific issues most studied. We found under-reporting of key information in particular on random sequence generation, allocation concealment, and blinding. While the number of clinical trials in palliative care has increased over time, methodological quality remains suboptimal. This compromises the quality of studies. Therefore, a greater effort is needed to enable the appropriate performance of future studies and increase the robustness of evidence-based medicine in this important field.

Psychosocial consequences of allocation to lung cancer screening: a randomised controlled trial

PubMed Central

Aggestrup, Louise Mosborg; Hestbech, Mie Sara; Siersma, Volkert; Pedersen, Jesper Holst

2012-01-01

Objective To examine the psychosocial consequences of being allocated to the control group as compared with the screen group in a randomised lung cancer screening trial. Method The Danish Lung Cancer Screening Trial, a randomised controlled trial, ran from 2004 to 2010 with the purpose of investigating the benefits and harms of lung cancer screening. The participants in Danish Lung Cancer Screening Trial were randomised to either the control group or the screen group and were asked to complete the questionnaires Consequences Of Screening and Consequences Of Screening in Lung Cancer (COS-LC). The Consequences Of Screening and the COS-LC were used to examine the psychosocial consequences of participating in the study, by comparing the control and the screen groups' responses at the prevalence and at the incidence round. Results There was no statistically significant difference in socio-demographic characteristics or smoking habits between the two groups. Responses to the COS-LC collected before the incidence round were statistically significantly different on the scales ‘anxiety’, ‘behaviour’, ‘dejection’, ‘self-blame’, ‘focus on airway symptoms’ and ‘introvert’, with the control group reporting higher negative psychosocial consequences. Furthermore, the participants in both the control and the screen groups exhibited a mean increase in negative psychosocial consequences when their responses from the prevalence round were compared with their responses from the first incidence round. Conclusions Participation in a randomised controlled trial on lung cancer screening has negative psychosocial consequences for the apparently healthy participants—both the participants in the screen group and the control group. This negative impact was greatest for the control group. PMID:22382119

Effects of reiki in clinical practice: a systematic review of randomised clinical trials.

PubMed

Lee, M S; Pittler, M H; Ernst, E

2008-06-01

The aim of this systematic review is to summarise and critically evaluate the evidence for the effectiveness of reiki. We searched the literature using 23 databases from their respective inceptions through to November 2007 (search again 23 January 2008) without language restrictions. Methodological quality was assessed using the Jadad score. The searches identified 205 potentially relevant studies. Nine randomised clinical trials (RCTs) met our inclusion criteria. Two RCTs suggested beneficial effects of reiki compared with sham control on depression, while one RCT did not report intergroup differences. For pain and anxiety, one RCT showed intergroup differences compared with sham control. For stress and hopelessness a further RCT reported effects of reiki and distant reiki compared with distant sham control. For functional recovery after ischaemic stroke there were no intergroup differences compared with sham. There was also no difference for anxiety between groups of pregnant women undergoing amniocentesis. For diabetic neuropathy there were no effects of reiki on pain. A further RCT failed to show the effects of reiki for anxiety and depression in women undergoing breast biopsy compared with conventional care. In total, the trial data for any one condition are scarce and independent replications are not available for each condition. Most trials suffered from methodological flaws such as small sample size, inadequate study design and poor reporting. In conclusion, the evidence is insufficient to suggest that reiki is an effective treatment for any condition. Therefore the value of reiki remains unproven.

The Neural Substrates of Cognitive Control Deficits in Autism Spectrum Disorders

PubMed Central

Solomon, Marjorie; Ozonoff, Sally; Ursu, Stefan; Ravizza, Susan; Cummings, Neil; Ly, Stanford; Carter, Cameron

2009-01-01

Executive functions deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive functions deficits in ASDs, and only one in adolescents. The current study examined cognitive control –the ability to maintain task context online to support adaptive functioning in the face of response competition—in 22 adolescents aged 12–18 with autism spectrum disorders and 23 age, gender, and IQ matched typically developing subjects. During the cue phase of the task, where subjects must maintain information online to overcome a prepotent response tendency, typically developing subjects recruited significantly more anterior frontal (BA 10), parietal (BA 7, 40), and occipital regions (BA 18) for high control trials (25% of trials) versus low control trials (75% of trials). Both groups showed similar activation for low control cues, however the ASD group exhibited significantly less activation for high control cues. Functional connectivity analysis using time series correlation, factor analysis, and beta series correlation methods provided convergent evidence that the ASD group exhibited lower levels of functional connectivity and less network integration between frontal, parietal, and occipital regions. In the typically developing group, fronto-parietal connectivity was related to lower error rates on high control trials. In the autism group, reduced fronto-parietal connectivity was related to attention deficit hyperactivity disorder symptoms. PMID:19410583

A systematic review of RCTs and quasi-RCTs on traditional Chinese patent medicines for treatment of chronic hepatitis B.

PubMed

Zhan, Tao; Wei, Xing; Chen, Ze-Qi; Wang, Dong-Sheng; Dai, Xing-Ping

2011-12-01

Traditional Chinese patent medicines (TCPMs) are widely used for treatment of chronic hepatitis B (CHB) in China. To estimate the overall effectiveness of TCPMs for CHB, we performed a systematic review of clinical reports designed as randomized controlled trials (RCTs). One hundred and thirty-eight available RCTs and quasi-RCTs on 62 TCPMs, involving 16,393 patients, were included. The methodological quality of these trials was generally "poor". Few trials (6.52%) reported the methods of randomization correctly. Another common problem was the lack of allocation concealment, proper blinding, and the reporting of lost cases and dropouts. Forty-two trials (30.43%) on 27 TCPMs reported some anti-viral effect of TCPMs. Others reported beneficial aspects, including improvements of liver function (79.71% of the studies), liver fibrosis (29.99%), and CHB symptoms (92.75%). Forty-one articles (29.71%) reported mild adverse events with TCPMs but these occurred infrequently. In summary, the outcome of the report on currently registered TCPMs may be biased due to poor methodology. The data from these trials, therefore, is too weak to use in forming a recommendation for treatment of CHB. Nevertheless, five drugs (Dan Shen agents, Da Huang Zhe Chong pill/capsule, Shuang Hu Qing Gan granule, Fu Zheng Hua Yu granule and Cao Xian Yi Gan capsule) appear to be more effective than the other TCPMs.

Effects of Cupping Therapy in Amateur and Professional Athletes: Systematic Review of Randomized Controlled Trials.

PubMed

Bridgett, Rhianna; Klose, Petra; Duffield, Rob; Mydock, Suni; Lauche, Romy

2018-03-01

Despite the recent re-emergence of the process of cupping by athletes, supporting evidence for its efficacy and safety remains scarce. This systematic review aims to summarize the evidence of clinical trials on cupping for athletes. SCOPUS, Cochrane Library, PubMed, AMED, and CNKI databases were searched from their inception to December 10, 2016. Randomized controlled trials on cupping therapy with no restriction regarding the technique, or cointerventions, were included, if they measured the effects of cupping compared with any other intervention on health and performance outcomes in professionals, semi-professionals, and leisure athletes. Data extraction and risk of bias assessment using the Cochrane Risk of Bias Tool were conducted independently by two pairs of reviewers. Eleven trials with n = 498 participants from China, the United States, Greece, Iran, and the United Arab Emirates were included, reporting effects on different populations, including soccer, football, and handball players, swimmers, gymnasts, and track and field athletes of both amateur and professional nature. Cupping was applied between 1 and 20 times, in daily or weekly intervals, alone or in combination with, for example, acupuncture. Outcomes varied greatly from symptom intensity, recovery measures, functional measures, serum markers, and experimental outcomes. Cupping was reported as beneficial for perceptions of pain and disability, increased range of motion, and reductions in creatine kinase when compared to mostly untreated control groups. The majority of trials had an unclear or high risk of bias. None of the studies reported safety. No explicit recommendation for or against the use of cupping for athletes can be made. More studies are necessary for conclusive judgment on the efficacy and safety of cupping in athletes.

Effects of Natural Sounds on Pain: A Randomized Controlled Trial with Patients Receiving Mechanical Ventilation Support.

PubMed

Saadatmand, Vahid; Rejeh, Nahid; Heravi-Karimooi, Majideh; Tadrisi, Sayed Davood; Vaismoradi, Mojtaba; Jordan, Sue

2015-08-01

Nonpharmacologic pain management in patients receiving mechanical ventilation support in critical care units is under investigated. Natural sounds may help reduce the potentially harmful effects of anxiety and pain in hospitalized patients. The aim of this study was to examine the effect of pleasant, natural sounds on self-reported pain in patients receiving mechanical ventilation support, using a pragmatic parallel-arm, randomized controlled trial. The study was conducted in a general adult intensive care unit of a high-turnover teaching hospital, in Tehran, Iran. Between October 2011 and June 2012, we recruited 60 patients receiving mechanical ventilation support to the intervention (n = 30) and control arms (n = 30) of a pragmatic parallel-group, randomized controlled trial. Participants in both arms wore headphones for 90 minutes. Those in the intervention arm heard pleasant, natural sounds, whereas those in the control arm heard nothing. Outcome measures included the self-reported visual analog scale for pain at baseline; 30, 60, and 90 minutes into the intervention; and 30 minutes post-intervention. All patients approached agreed to participate. The trial arms were similar at baseline. Pain scores in the intervention arm fell and were significantly lower than in the control arm at each time point (p < .05). Administration of pleasant, natural sounds via headphones is a simple, safe, nonpharmacologic nursing intervention that may be used to allay pain for up to 120 minutes in patients receiving mechanical ventilation support. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Randomized controlled trial of a web-based indoor tanning intervention: Acceptability and preliminary outcomes.

PubMed

Stapleton, Jerod L; Manne, Sharon L; Darabos, Katie; Greene, Kathryn; Ray, Anne E; Turner, Amber L; Coups, Elliot J

2015-12-01

This article describes the acceptability and preliminary behavioral outcomes of a pilot randomized control trial of a web-based indoor tanning intervention for young adult women. The intervention targets indoor tanning users' perceptions of the benefits and value of tanning and addresses the role of body image-related constructs in indoor tanning. Participants were 186 young adult women who reported indoor tanning at least once in the past 12 months. The study design was a 2-arm randomized controlled trial with pre- and postintervention assessments and random assignment to an intervention or control condition. Intervention acceptability was assessed by obtaining participants' evaluation of the intervention. Regression analyses were used to test for intervention condition differences in preliminary behavioral outcomes measured at 6 weeks postintervention. Participants provided favorable evaluations of the intervention on several dimensions and a highly positive overall rating. Intervention participants were more likely to report abstaining from indoor tanning and indicated a lower likelihood of using indoor tanning in the future compared with control participants on the postintervention assessment. No differences were found for sunburns. The results of this pilot randomized controlled trial provide evidence that the indoor tanning intervention is acceptable to participants and may encourage cessation of indoor tanning behavior. The findings provide preliminary support for an indoor tanning intervention that engages tanners to challenge their beliefs about the benefits of indoor tanning. The use of a web-based indoor tanning intervention is unique and provides strong potential for dissemination. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Characteristics of funding of clinical trials: cross-sectional survey and proposed guidance

PubMed Central

Jouni, Nahla; Abou-Jaoude, Eliane A; Hasbani, Divina Justina; Abou-Jaoude, Elias A; Khaldieh, Mariam; Hammoud, Mira Zein; Al-Gibbawi, Mounir; Anouti, Sirine; Guyatt, Gordon; Akl, Elie A

2017-01-01

Objectives To provide a detailed and current characterisation of funding of a representative sample clinical trials. We also aimed to develop guidance for standardised reporting of funding information. Methods We addressed the extent to which clinical trials published in 2015 in any of the 119 Core Clinical Journals included a statement on the funding source (eg, whether a not-for-profit organisation was supported by a private-for-profit organisation), type of funding, amount and role of funder. We used a stepwise approach to develop a guidance and an instrument for standardised reporting of funding information. Results Of 200 trials, 178 (89%) included a funding statement, of which 171 (96%) reported being funded. Funding statements in the 171 funded trials indicated the source in 100%, amount in 1% and roles of funders in 50%. The most frequent sources were governmental (58%) and private-for-profit (40%). Of 54 funding statements in which the source was a not-for-profit organisation, we found evidence of undisclosed support of those from private-for-profit organisation(s) in 26 (48%). The most frequently reported roles of funders in the 171 funded trials related to study design (42%) and data analysis, interpretation or management (41%). Of 139 randomised controlled trials (RCTs) addressing pharmacological or surgical interventions, 29 (21%) reported information on the supplier of the medication or device. The proposed guidance addresses both the funding information that RCTs should report and the reporting process. Attached to the guidance is a fillable PDF document for use as an instrument for standardised reporting of funding information. Conclusion Although the majority of RCTs report funding, there is considerable variability in the reporting of funding source, amount and roles of funders. A standardised approach to reporting of funding information would address these limitations. Future research should explore the implications of funding by not-for-profit organisations that are supported by for-profit organisations. PMID:28982811

Pretravel Health Advice Among Australians Returning From Bali, Indonesia: A Randomized Controlled Trial Protocol.

PubMed

Thomson, Chloe A; Gibbs, Robyn A; Heyworth, Jane S; Giele, Carolien; Firth, Martin J; Effler, Paul V

2016-12-07

The effect of pretravel health advice (PTHA) on travel-related illness rates is poorly understood, and to date there are no published randomized controlled trials evaluating the impact of PTHA outcomes. This study aims to determine the effect of an online PTHA intervention on travel-related illness rates in Western Australians visiting Bali, Indonesia. Western Australian travelers to Bali will be recruited online before departure and will be randomly allocated to an intervention or control group by computer algorithm. The intervention in this study is a short animated video, with accompanying text, containing PTHA relevant to Bali. An online posttravel survey will be administered to all participants within two weeks of their return from Bali. The primary outcome is the difference in self-reported travel-related illness rates between control and intervention groups. Secondary outcomes include the difference in risk prevention behaviors and health risk knowledge between the control and intervention groups. Further secondary outcomes include whether individuals in the control group who sought external PTHA differ from those who did not with respect to risk prevention behaviors, health risk knowledge, and health risk perception, as well as the rate of self-reported travel-related illness. The study began recruitment in September 2016 and will conclude in September 2017. Data analysis will take place in late 2017, with results disseminated via peer-reviewed journals in early 2018. This will be the first randomized controlled trial to examine the effect of a novel PTHA intervention upon travel-related illness. In addition, this study builds upon the limited existing data on the effectiveness of PTHA on travel-related illness. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12615001230549; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369567 (Archived by WebCite at http://www.webcitation.org/6m0G7xJg1). ©Chloe Thomson, Robyn A Gibbs, Jane S Heyworth, Carolien Giele, Martin J Firth, Paul V Effler. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 07.12.2016.

Warming of intravenous and irrigation fluids for preventing inadvertent perioperative hypothermia.

PubMed

Campbell, Gillian; Alderson, Phil; Smith, Andrew F; Warttig, Sheryl

2015-04-13

Inadvertent perioperative hypothermia (a drop in core temperature to below 36°C) occurs because of interference with normal temperature regulation by anaesthetic drugs, exposure of skin for prolonged periods and receipt of large volumes of intravenous and irrigation fluids. If the temperature of these fluids is below core body temperature, they can cause significant heat loss. Warming intravenous and irrigation fluids to core body temperature or above might prevent some of this heat loss and subsequent hypothermia. To estimate the effectiveness of preoperative or intraoperative warming, or both, of intravenous and irrigation fluids in preventing perioperative hypothermia and its complications during surgery in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 2), MEDLINE Ovid SP (1956 to 4 February 2014), EMBASE Ovid SP (1982 to 4 February 2014), the Institute for Scientific Information (ISI) Web of Science (1950 to 4 February 2014), Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCOhost (1980 to 4 February 2014) and reference lists of identified articles. We also searched the Current Controlled Trials website and ClinicalTrials.gov. We included randomized controlled trials or quasi-randomized controlled trials comparing fluid warming methods versus standard care or versus other warming methods used to maintain normothermia. Two review authors independently extracted data from eligible trials and settled disputes with a third review author. We contacted study authors to ask for additional details when needed. We collected data on adverse events only if they were reported in the trials. We included in this review 24 studies with a total of 1250 participants. The trials included various numbers and types of participants. Investigators used a range of methods to warm fluids to temperatures between 37°C and 41°C. We found that evidence was of moderate quality because descriptions of trial design were often unclear, resulting in high or unclear risk of bias due to inappropriate or unclear randomization and blinding procedures. These factors may have influenced results in some way. Our protocol specified the risk of hypothermia as the primary outcome; as no trials reported this, we decided to include data related to mean core temperature. The only secondary outcome reported in the trials that provided useable data was shivering. Evidence was unclear regarding the effects of fluid warming on bleeding. No data were reported on our other specified outcomes of cardiovascular complications, infection, pressure ulcers, bleeding, mortality, length of stay, unplanned intensive care admission and adverse events.Researchers found that warmed intravenous fluids kept the core temperature of study participants about half a degree warmer than that of participants given room temperature intravenous fluids at 30, 60, 90 and 120 minutes, and at the end of surgery. Warmed intravenous fluids also further reduced the risk of shivering compared with room temperature intravenous fluidsInvestigators reported no statistically significant differences in core body temperature or shivering between individuals given warmed and room temperature irrigation fluids. Warm intravenous fluids appear to keep patients warmer during surgery than room temperature fluids. It is unclear whether the actual differences in temperature are clinically meaningful, or if other benefits or harms are associated with the use of warmed fluids. It is also unclear if using fluid warming in addition to other warming methods confers any benefit, as a ceiling effect is likely when multiple methods of warming are used.

Strategies to improve the implementation of healthy eating, physical activity and obesity prevention policies, practices or programmes within childcare services.

PubMed

Wolfenden, Luke; Jones, Jannah; Williams, Christopher M; Finch, Meghan; Wyse, Rebecca J; Kingsland, Melanie; Tzelepis, Flora; Wiggers, John; Williams, Amanda J; Seward, Kirsty; Small, Tameka; Welch, Vivian; Booth, Debbie; Yoong, Sze Lin

2016-10-04

Despite the existence of effective interventions and best-practice guideline recommendations for childcare services to implement policies, practices and programmes to promote child healthy eating, physical activity and prevent unhealthy weight gain, many services fail to do so. The primary aim of the review was to examine the effectiveness of strategies aimed at improving the implementation of policies, practices or programmes by childcare services that promote child healthy eating, physical activity and/or obesity prevention. The secondary aims of the review were to:1. describe the impact of such strategies on childcare service staff knowledge, skills or attitudes;2. describe the cost or cost-effectiveness of such strategies;3. describe any adverse effects of such strategies on childcare services, service staff or children;4. examine the effect of such strategies on child diet, physical activity or weight status. We searched the following electronic databases on 3 August 2015: the Cochrane Central Register of Controlled trials (CENTRAL), MEDLINE, MEDLINE In Process, EMBASE, PsycINFO, ERIC, CINAHL and SCOPUS. We also searched reference lists of included trials, handsearched two international implementation science journals and searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp/) and ClinicalTrials.gov (www.clinicaltrials.gov). We included any study (randomised or non-randomised) with a parallel control group that compared any strategy to improve the implementation of a healthy eating, physical activity or obesity prevention policy, practice or programme by staff of centre-based childcare services to no intervention, 'usual' practice or an alternative strategy. The review authors independently screened abstracts and titles, extracted trial data and assessed risk of bias in pairs; we resolved discrepancies via consensus. Heterogeneity across studies precluded pooling of data and undertaking quantitative assessment via meta-analysis. However, we narratively synthesised the trial findings by describing the effect size of the primary outcome measure for policy or practice implementation (or the median of such measures where a single primary outcome was not stated). We identified 10 trials as eligible and included them in the review. The trials sought to improve the implementation of policies and practices targeting healthy eating (two trials), physical activity (two trials) or both healthy eating and physical activity (six trials). Collectively the implementation strategies tested in the 10 trials included educational materials, educational meetings, audit and feedback, opinion leaders, small incentives or grants, educational outreach visits or academic detailing. A total of 1053 childcare services participated across all trials. Of the 10 trials, eight examined implementation strategies versus a usual practice control and two compared alternative implementation strategies. There was considerable study heterogeneity. We judged all studies as having high risk of bias for at least one domain.It is uncertain whether the strategies tested improved the implementation of policies, practices or programmes that promote child healthy eating, physical activity and/or obesity prevention. No intervention improved the implementation of all policies and practices targeted by the implementation strategies relative to a comparison group. Of the eight trials that compared an implementation strategy to usual practice or a no intervention control, however, seven reported improvements in the implementation of at least one of the targeted policies or practices relative to control. For these trials the effect on the primary implementation outcome was as follows: among the three trials that reported score-based measures of implementation the scores ranged from 1 to 5.1; across four trials reporting the proportion of staff or services implementing a specific policy or practice this ranged from 0% to 9.5%; and in three trials reporting the time (per day or week) staff or services spent implementing a policy or practice this ranged from 4.3 minutes to 7.7 minutes. The review findings also indicate that is it uncertain whether such interventions improve childcare service staff knowledge or attitudes (two trials), child physical activity (two trials), child weight status (two trials) or child diet (one trial). None of the included trials reported on the cost or cost-effectiveness of the intervention. One trial assessed the adverse effects of a physical activity intervention and found no difference in rates of child injury between groups. For all review outcomes, we rated the quality of the evidence as very low. The primary limitation of the review was the lack of conventional terminology in implementation science, which may have resulted in potentially relevant studies failing to be identified based on the search terms used in this review. Current research provides weak and inconsistent evidence of the effectiveness of such strategies in improving the implementation of policies and practices, childcare service staff knowledge or attitudes, or child diet, physical activity or weight status. Further research in the field is required.

The Relations among Measurements of Informant Discrepancies within a Multisite Trial of Treatments for Childhood Social Phobia

ERIC Educational Resources Information Center

De Los Reyes, Andres; Alfano, Candice A.; Beidel, Deborah C.

2010-01-01

Discrepancies between informants' reports of children's behavior are robustly observed in clinical child research and have important implications for interpreting the outcomes of controlled treatment trials. However, little is known about the basic psychometric properties of these discrepancies. This study examined the relation between…

Successful Outcomes from a Structured Curriculum Used in the Veterans Affairs Low Vision Intervention Trial

ERIC Educational Resources Information Center

Stelmack, Joan A.; Rinne, Stephen; Mancil, Rickilyn M.; Dean, Deborah; Moran, D'Anna; Tang, X. Charlene; Cummings, Roger; Massof, Robert W.

2008-01-01

A low vision rehabilitation program with a structured curriculum was evaluated in a randomized controlled trial. The treatment group demonstrated large improvements in self-reported visual function (reading, mobility, visual information processing, visual motor skills, and overall). The team approach and the protocols of the treatment program are…