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

CENTRAL, PEDro, PubMed, and EMBASE are the most comprehensive databases indexing randomized controlled trials of physical therapy interventions.

PubMed

Michaleff, Zoe A; Costa, Leonardo O P; Moseley, Anne M; Maher, Christopher G; Elkins, Mark R; Herbert, Robert D; Sherrington, Catherine

2011-02-01

Many bibliographic databases index research studies evaluating the effects of health care interventions. One study has concluded that the Physiotherapy Evidence Database (PEDro) has the most complete indexing of reports of randomized controlled trials of physical therapy interventions, but the design of that study may have exaggerated estimates of the completeness of indexing by PEDro. The purpose of this study was to compare the completeness of indexing of reports of randomized controlled trials of physical therapy interventions by 8 bibliographic databases. This study was an audit of bibliographic databases. Prespecified criteria were used to identify 400 reports of randomized controlled trials from the reference lists of systematic reviews published in 2008 that evaluated physical therapy interventions. Eight databases (AMED, CENTRAL, CINAHL, EMBASE, Hooked on Evidence, PEDro, PsycINFO, and PubMed) were searched for each trial report. The proportion of the 400 trial reports indexed by each database was calculated. The proportions of the 400 trial reports indexed by the databases were as follows: CENTRAL, 95%; PEDro, 92%; PubMed, 89%; EMBASE, 88%; CINAHL, 53%; AMED, 50%; Hooked on Evidence, 45%; and PsycINFO, 6%. Almost all of the trial reports (99%) were found in at least 1 database, and 88% were indexed by 4 or more databases. Four trial reports were uniquely indexed by a single database only (2 in CENTRAL and 1 each in PEDro and PubMed). The results are only applicable to searching for English-language published reports of randomized controlled trials evaluating physical therapy interventions. The 4 most comprehensive databases of trial reports evaluating physical therapy interventions were CENTRAL, PEDro, PubMed, and EMBASE. Clinicians seeking quick answers to clinical questions could search any of these databases knowing that all are reasonably comprehensive. PEDro, unlike the other 3 most complete databases, is specific to physical therapy, so studies not relevant to physical therapy are less likely to be retrieved. Researchers could use CENTRAL, PEDro, PubMed, and EMBASE in combination to conduct exhaustive searches for randomized trials in physical therapy.

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.

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.

Inadequacy of ethical conduct and reporting of stepped wedge cluster randomized trials: Results from a systematic review.

PubMed

Taljaard, Monica; Hemming, Karla; Shah, Lena; Giraudeau, Bruno; Grimshaw, Jeremy M; Weijer, Charles

2017-08-01

Background/aims The use of the stepped wedge cluster randomized design is rapidly increasing. This design is commonly used to evaluate health policy and service delivery interventions. Stepped wedge cluster randomized trials have unique characteristics that complicate their ethical interpretation. The 2012 Ottawa Statement provides comprehensive guidance on the ethical design and conduct of cluster randomized trials, and the 2010 CONSORT extension for cluster randomized trials provides guidelines for reporting. Our aims were to assess the adequacy of the ethical conduct and reporting of stepped wedge trials to date, focusing on research ethics review and informed consent. Methods We conducted a systematic review of stepped wedge cluster randomized trials in health research published up to 2014 in English language journals. We extracted details of study intervention and data collection procedures, as well as reporting of research ethics review and informed consent. Two reviewers independently extracted data from each trial; discrepancies were resolved through discussion. We identified the presence of any research participants at the cluster level and the individual level. We assessed ethical conduct by tabulating reporting of research ethics review and informed consent against the presence of research participants. Results Of 32 identified stepped wedge trials, only 24 (75%) reported review by a research ethics committee, and only 16 (50%) reported informed consent from any research participants-yet, all trials included research participants at some level. In the subgroup of 20 trials with research participants at cluster level, only 4 (20%) reported informed consent from such participants; in 26 trials with individual-level research participants, only 15 (58%) reported their informed consent. Interventions (regardless of whether targeting cluster- or individual-level participants) were delivered at the group level in more than two-thirds of trials; nine trials (28%) had no identifiable data collected from any research participants. Overall, only three trials (9%) indicated that a waiver of consent had been granted by a research ethics committee. When considering the combined requirement of research ethics review and informed consent (or a waiver), only one in three studies were compliant. Conclusion The ethical conduct and reporting of key ethical protections in stepped wedge trials, namely, research ethics review and informed consent, are inadequate. We recommend that stepped wedge trials be classified as research and reviewed and approved by a research ethics committee. We also recommend that researchers appropriately identify research participants (which may include health professionals), seek informed consent or appeal to an ethics committee for a waiver of consent, and include explicit details of research ethics approval and informed consent in the trial report.

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

Methodological survey of designed uneven randomization trials (DU-RANDOM): a protocol.

PubMed

Wu, Darong; Akl, Elie A; Guyatt, Gordon H; Devereaux, Philip J; Brignardello-Petersen, Romina; Prediger, Barbara; Patel, Krupesh; Patel, Namrata; Lu, Taoying; Zhang, Yuan; Falavigna, Maicon; Santesso, Nancy; Mustafa, Reem A; Zhou, Qi; Briel, Matthias; Schünemann, Holger J

2014-01-23

Although even randomization (that is, approximately 1:1 randomization ratio in study arms) provides the greatest statistical power, designed uneven randomization (DUR), (for example, 1:2 or 1:3) is used to increase participation rates. Until now, no convincing data exists addressing the impact of DUR on participation rates in trials. The objective of this study is to evaluate the epidemiology and to explore factors associated with DUR. We will search for reports of RCTs published within two years in 25 general medical journals with the highest impact factor according to the Journal Citation Report (JCR)-2010. Teams of two reviewers will determine eligibility and extract relevant information from eligible RCTs in duplicate and using standardized forms. We will report the prevalence of DUR trials, the reported reasons for using DUR, and perform a linear regression analysis to estimate the association between the randomization ratio and the associated factors, including participation rate, type of informed consent, clinical area, and so on. A clearer understanding of RCTs with DUR and its association with factors in trials, for example, participation rate, can optimize trial design and may have important implications for both researchers and users of the medical literature.

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.

Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010.

PubMed

Califf, Robert M; Zarin, Deborah A; Kramer, Judith M; Sherman, Rachel E; Aberle, Laura H; Tasneem, Asba

2012-05-02

Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0.83; 95% CI, 0.76-0.91), and mental health trials vs those in the other 2 specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials. Clinical trials registered in ClinicalTrials.gov are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs.

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.

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.

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.

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.

Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions.

PubMed

Coronado-Montoya, Stephanie; Levis, Alexander W; Kwakkenbos, Linda; Steele, Russell J; Turner, Erick H; Thombs, Brett D

2016-01-01

A large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of "positive" results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses. 108 (87%) of 124 published trials reported ≥1 positive outcome in the abstract, and 109 (88%) concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7). Of 21 trial registrations, 13 (62%) remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases. The proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice.

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

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; 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 might 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 November 18-19, 2008 in Chicago, IL, to achieve the objective. Before 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. Before the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items would 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 subitem 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 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.

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.

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.

Reporting and methodological quality of sample size calculations in cluster randomized trials could be improved: a review.

PubMed

Rutterford, Clare; Taljaard, Monica; Dixon, Stephanie; Copas, Andrew; Eldridge, Sandra

2015-06-01

To assess the quality of reporting and accuracy of a priori estimates used in sample size calculations for cluster randomized trials (CRTs). We reviewed 300 CRTs published between 2000 and 2008. The prevalence of reporting sample size elements from the 2004 CONSORT recommendations was evaluated and a priori estimates compared with those observed in the trial. Of the 300 trials, 166 (55%) reported a sample size calculation. Only 36 of 166 (22%) reported all recommended descriptive elements. Elements specific to CRTs were the worst reported: a measure of within-cluster correlation was specified in only 58 of 166 (35%). Only 18 of 166 articles (11%) reported both a priori and observed within-cluster correlation values. Except in two cases, observed within-cluster correlation values were either close to or less than a priori values. Even with the CONSORT extension for cluster randomization, the reporting of sample size elements specific to these trials remains below that necessary for transparent reporting. Journal editors and peer reviewers should implement stricter requirements for authors to follow CONSORT recommendations. Authors should report observed and a priori within-cluster correlation values to enable comparisons between these over a wider range of trials. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Description of interventions is under-reported in physical therapy clinical trials.

PubMed

Hariohm, K; Jeyanthi, S; Kumar, J Saravan; Prakash, V

Amongst several barriers to the application of quality clinical evidence and clinical guidelines into routine daily practice, poor description of interventions reported in clinical trials has received less attention. Although some studies have investigated the completeness of descriptions of non-pharmacological interventions in randomized trials, studies that exclusively analyzed physical therapy interventions reported in published trials are scarce. To evaluate the quality of descriptions of interventions in both experimental and control groups in randomized controlled trials published in four core physical therapy journals. We included all randomized controlled trials published from the Physical Therapy Journal, Journal of Physiotherapy, Clinical Rehabilitation, and Archives of Physical Medicine and Rehabilitation between June 2012 and December 2013. Each randomized controlled trial (RCT) was analyzed and coded for description of interventions using the checklist developed by Schroter et al. Out of 100 RCTs selected, only 35 RCTs (35%) fully described the interventions in both the intervention and control groups. Control group interventions were poorly described in the remaining RCTs (65%). Interventions, especially in the control group, are poorly described in the clinical trials published in leading physical therapy journals. A complete description of the intervention in a published report is crucial for physical therapists to be able to use the intervention in clinical practice. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

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.

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.

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.

Methodological reporting of randomized trials in five leading Chinese nursing journals.

PubMed

Shi, Chunhu; Tian, Jinhui; Ren, Dan; Wei, Hongli; Zhang, Lihuan; Wang, Quan; Yang, Kehu

2014-01-01

Randomized controlled trials (RCTs) are not always well reported, especially in terms of their methodological descriptions. This study aimed to investigate the adherence of methodological reporting complying with CONSORT and explore associated trial level variables in the Chinese nursing care field. In June 2012, we identified RCTs published in five leading Chinese nursing journals and included trials with details of randomized methods. The quality of methodological reporting was measured through the methods section of the CONSORT checklist and the overall CONSORT methodological items score was calculated and expressed as a percentage. Meanwhile, we hypothesized that some general and methodological characteristics were associated with reporting quality and conducted a regression with these data to explore the correlation. The descriptive and regression statistics were calculated via SPSS 13.0. In total, 680 RCTs were included. The overall CONSORT methodological items score was 6.34 ± 0.97 (Mean ± SD). No RCT reported descriptions and changes in "trial design," changes in "outcomes" and "implementation," or descriptions of the similarity of interventions for "blinding." Poor reporting was found in detailing the "settings of participants" (13.1%), "type of randomization sequence generation" (1.8%), calculation methods of "sample size" (0.4%), explanation of any interim analyses and stopping guidelines for "sample size" (0.3%), "allocation concealment mechanism" (0.3%), additional analyses in "statistical methods" (2.1%), and targeted subjects and methods of "blinding" (5.9%). More than 50% of trials described randomization sequence generation, the eligibility criteria of "participants," "interventions," and definitions of the "outcomes" and "statistical methods." The regression analysis found that publication year and ITT analysis were weakly associated with CONSORT score. The completeness of methodological reporting of RCTs in the Chinese nursing care field is poor, especially with regard to the reporting of trial design, changes in outcomes, sample size calculation, allocation concealment, blinding, and statistical methods.

What's in a title? An assessment of whether randomized controlled trial in a title means that it is one.

PubMed

Koletsi, Despina; Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2012-06-01

In this study, we aimed to investigate whether studies published in orthodontic journals and titled as randomized clinical trials are truly randomized clinical trials. A second objective was to explore the association of journal type and other publication characteristics on correct classification. American Journal of Orthodontics and Dentofacial Orthopedics, European Journal of Orthodontics, Angle Orthodontist, Journal of Orthodontics, Orthodontics and Craniofacial Research, World Journal of Orthodontics, Australian Orthodontic Journal, and Journal of Orofacial Orthopedics were hand searched for clinical trials labeled in the title as randomized from 1979 to July 2011. The data were analyzed by using descriptive statistics, and univariable and multivariable examinations of statistical associations via ordinal logistic regression modeling (proportional odds model). One hundred twelve trials were identified. Of the included trials, 33 (29.5%) were randomized clinical trials, 52 (46.4%) had an unclear status, and 27 (24.1%) were not randomized clinical trials. In the multivariable analysis among the included journal types, year of publication, number of authors, multicenter trial, and involvement of statistician were significant predictors of correctly classifying a study as a randomized clinical trial vs unclear and not a randomized clinical trial. From 112 clinical trials in the orthodontic literature labeled as randomized clinical trials, only 29.5% were identified as randomized clinical trials based on clear descriptions of appropriate random number generation and allocation concealment. The type of journal, involvement of a statistician, multicenter trials, greater numbers of authors, and publication year were associated with correct clinical trial classification. This study indicates the need of clear and accurate reporting of clinical trials and the need for educating investigators on randomized clinical trial methodology. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

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; 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, IL, 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.

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.

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.

Review and Analysis of Publication Trends over Three Decades in Three High Impact Medicine Journals.

PubMed

Ivanov, Alexander; Kaczkowska, Beata A; Khan, Saadat A; Ho, Jean; Tavakol, Morteza; Prasad, Ashok; Bhumireddy, Geetha; Beall, Allan F; Klem, Igor; Mehta, Parag; Briggs, William M; Sacchi, Terrence J; Heitner, John F

2017-01-01

Over the past three decades, industry sponsored research expanded in the United States. Financial incentives can lead to potential conflicts of interest (COI) resulting in underreporting of negative study results. We hypothesized that over the three decades, there would be an increase in: a) reporting of conflict of interest and source of funding; b) percentage of randomized control trials c) number of patients per study and d) industry funding. Original articles published in three calendar years (1988, 1998, and 2008) in The Lancet, New England Journal of Medicine and Journal of American Medical Association were collected. Studies were reviewed and investigational design categorized as prospective and retrospective clinical trials. Prospective trials were categorized into randomized or non-randomized and single-center or multi-center trials. Retrospective trials were categorized as registries, meta-analyses and other studies, mostly comprising of case reports or series. Study outcomes were categorized as positive or negative depending on whether the pre-specified hypothesis was met. Financial disclosures were researched for financial relationships and profit status, and accordingly categorized as government, non-profit or industry sponsored. Studies were assessed for reporting COI. 1,671 original articles were included in this analysis. Total number of published studies decreased by 17% from 1988 to 2008. Over 20 year period, the proportion of prospective randomized trials increased from 22 to 46% (p < 0.0001); whereas the proportion of prospective non-randomized trials decreased from 59% to 27% (p < 0.001). There was an increase in the percentage of prospective randomized multi-center trials from 11% to 41% (p < 0.001). Conversely, there was a reduction in non-randomized single-center trials from 47% to 10% (p < 0.001). Proportion of government funded studies remained constant, whereas industry funded studies more than doubled (17% to 40%; p < 0.0001). The number of studies with negative results more than doubled (10% to 22%; p<0.0001). While lack of funding disclosure decreased from 35% to 7%, COI reporting increased from 2% to 84% (p < 0.0001). Improved reporting of COI, clarity in financial sponsorship, increased publication of negative results in the setting of larger and better designed clinical trials represents a positive step forward in the scientific publications, despite the higher percentage of industry funded studies.

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…

Randomized trials published in Chinese or Western journals: comparative empirical analysis.

PubMed

Purgato, Marianna; Cipriani, Andrea; Barbui, Corrado

2012-06-01

A major concern to the inclusion in systematic reviews of studies originating in China and published in Chinese journals refers to the quality of study reporting. In this systematic survey of randomized trials, we compared the characteristics of studies published in Chinese journals with those of studies published in Western journals. We included 69 studies comparing citalopram with other antidepressant drugs in the treatment of major depression. Of these, 37 (54%) were published in Chinese journals. The standard of reporting was generally poor in both Western and Chinese studies. In some Chinese studies, the generation of the randomization sequence raised concern about their experimental nature, and in almost all included studies, the concealment of allocation was not properly described. Blinding was seldom adopted in Chinese studies, and the risk of sponsorship bias was uncertain because Chinese studies did not report any financial support. In most Western studies, outcome data were selectively and incompletely reported. Pooling together all trials revealed that citalopram was similarly effective in comparison with all other antidepressant drugs both in Western studies (standardized mean difference, -0.04; 95% confidence interval, -0.15 to 0.06) and in Chinese studies (standardized mean difference, -0.08, 95% confidence interval, -0.18 to 0.02). Randomized controlled trials published in Chinese journals represent most of the studies included in this review. This suggests that omitting to search biomedical databases originating from China would systematically exclude a relevant proportion of randomized trials published in Chinese journals, with a risk of random error or bias. The increasing inclusion of Chinese studies in systematic reviews reinforces the need to check the quality of randomized trials that are meta-analyzed.

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.

Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events?

PubMed

Als-Nielsen, Bodil; Chen, Wendong; Gluud, Christian; Kjaergard, Lise L

2003-08-20

Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions. To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events. Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication). Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not. The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events. Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data.

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.

Assessing the Eventual Publication of Clinical Trial Abstracts Submitted to a Large Annual Oncology Meeting.

PubMed

Massey, Paul R; Wang, Ruibin; Prasad, Vinay; Bates, Susan E; Fojo, Tito

2016-03-01

Despite the ethical imperative to publish clinical trials when human subjects are involved, such data frequently remain unpublished. The objectives were to tabulate the rate and ascertain factors associated with eventual publication of clinical trial results reported as abstracts in the Proceedings of the American Society of Clinical Oncology (American Society of Clinical Oncology). Abstracts describing clinical trials for patients with breast, lung, colorectal, ovarian, and prostate cancer from 2009 to 2011 were identified by using a comprehensive online database (http://meetinglibrary.asco.org/abstracts). Abstracts included reported results of a treatment or intervention assessed in a discrete, prospective clinical trial. Publication status at 4-6 years was determined by using a standardized search of PubMed. Primary outcomes were the rate of publication for abstracts of randomized and nonrandomized clinical trials. Secondary outcomes included factors influencing the publication of results. A total of 1,075 abstracts describing 378 randomized and 697 nonrandomized clinical trials were evaluated. Across all years, 75% of randomized and 54% of nonrandomized trials were published, with an overall publication rate of 61%. Sample size was a statistically significant predictor of publication for both randomized and nonrandomized trials (odds ratio [OR] per increase of 100 participants = 1.23 [1.11-1.36], p < .001; and 1.64 [1.15-2.34], p = .006, respectively). Among randomized studies, an industry coauthor or involvement of a cooperative group increased the likelihood of publication (OR 2.37, p = .013; and 2.21, p = .01, respectively). Among nonrandomized studies, phase II trials were more likely to be published than phase I (p < .001). Use of an experimental agent was not a predictor of publication in randomized (OR 0.76 [0.38-1.52]; p = .441) or nonrandomized trials (OR 0.89 [0.61-1.29]; p = .532). This is the largest reported study examining why oncology trials are not published. The data show that 4-6 years after appearing as abstracts, 39% of oncology clinical trials remain unpublished. Larger sample size and advanced trial phase were associated with eventual publication; among randomized trials, an industry-affiliated author or a cooperative group increased likelihood of publication. Unfortunately, we found that, despite widespread recognition of the problem and the creation of central data repositories, timely publishing of oncology clinical trials results remains unsatisfactory. ©AlphaMed Press.

Effect Sizes and Primary Outcomes in Large-Budget, Cardiovascular-Related Behavioral Randomized Controlled Trials Funded by NIH Since 1980

PubMed Central

Irvin, Veronica L.; Kaplan, Robert M.

2015-01-01

Purpose We reviewed large-budget, National Institutes of Health (NIH)-supported randomized controlled trials (RCTs) with behavioral interventions to assess (1) publication rates, (2) trial registration, (3) use of objective measures, (4) significant behavior and physiological change, and (5) effect sizes. Methods We identified large-budget grants (>$500,000/year) funded by NIH (National Heart Lung and Blood Institute (NHLBI) or National Institute of Diabetes & Digestive and Kidney Diseases (NIDDK)) for cardiovascular disease (dates January 1, 1980 to December 31, 2012). Among 106 grants that potentially met inclusion criteria, 20 studies were not published and 48 publications were excluded, leaving 38 publications for analysis. ClinicalTrials.gov abstracts were used to determine whether outcome measures had been pre-specified. Results Three fourths of trials were registered in ClinicalTrials.gov and all published pre-specified outcomes. Twenty-six trials reported a behavioral outcome with 81 % reporting significant improvements for the target behavior. Thirty-two trials reported a physiological outcome. All were objectively measured, and 81 % reported significant benefit. Seventeen trials reported morbidity outcomes, and seven reported a significant benefit. Nine trials assessed mortality, and all were null for this outcome. Conclusions Behavioral trials complied with trial registration standards. Most reported a physiological benefit, but few documented morbidity or mortality benefits. PMID:26507906

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.

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

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.

Best (but oft-forgotten) practices: designing, analyzing, and reporting cluster randomized controlled trials.

PubMed

Brown, Andrew W; Li, Peng; Bohan Brown, Michelle M; Kaiser, Kathryn A; Keith, Scott W; Oakes, J Michael; Allison, David B

2015-08-01

Cluster randomized controlled trials (cRCTs; also known as group randomized trials and community-randomized trials) are multilevel experiments in which units that are randomly assigned to experimental conditions are sets of grouped individuals, whereas outcomes are recorded at the individual level. In human cRCTs, clusters that are randomly assigned are typically families, classrooms, schools, worksites, or counties. With growing interest in community-based, public health, and policy interventions to reduce obesity or improve nutrition, the use of cRCTs has increased. Errors in the design, analysis, and interpretation of cRCTs are unfortunately all too common. This situation seems to stem in part from investigator confusion about how the unit of randomization affects causal inferences and the statistical procedures required for the valid estimation and testing of effects. In this article, we provide a brief introduction and overview of the importance of cRCTs and highlight and explain important considerations for the design, analysis, and reporting of cRCTs by using published examples. © 2015 American Society for Nutrition.

Assessing the Eventual Publication of Clinical Trial Abstracts Submitted to a Large Annual Oncology Meeting

PubMed Central

Wang, Ruibin; Prasad, Vinay; Bates, Susan E.; Fojo, Tito

2016-01-01

Background. Despite the ethical imperative to publish clinical trials when human subjects are involved, such data frequently remain unpublished. The objectives were to tabulate the rate and ascertain factors associated with eventual publication of clinical trial results reported as abstracts in the Proceedings of the American Society of Clinical Oncology (American Society of Clinical Oncology). Materials and Methods. Abstracts describing clinical trials for patients with breast, lung, colorectal, ovarian, and prostate cancer from 2009 to 2011 were identified by using a comprehensive online database (http://meetinglibrary.asco.org/abstracts). Abstracts included reported results of a treatment or intervention assessed in a discrete, prospective clinical trial. Publication status at 4−6 years was determined by using a standardized search of PubMed. Primary outcomes were the rate of publication for abstracts of randomized and nonrandomized clinical trials. Secondary outcomes included factors influencing the publication of results. Results. A total of 1,075 abstracts describing 378 randomized and 697 nonrandomized clinical trials were evaluated. Across all years, 75% of randomized and 54% of nonrandomized trials were published, with an overall publication rate of 61%. Sample size was a statistically significant predictor of publication for both randomized and nonrandomized trials (odds ratio [OR] per increase of 100 participants = 1.23 [1.11–1.36], p < .001; and 1.64 [1.15–2.34], p = .006, respectively). Among randomized studies, an industry coauthor or involvement of a cooperative group increased the likelihood of publication (OR 2.37, p = .013; and 2.21, p = .01, respectively). Among nonrandomized studies, phase II trials were more likely to be published than phase I (p < .001). Use of an experimental agent was not a predictor of publication in randomized (OR 0.76 [0.38–1.52]; p = .441) or nonrandomized trials (OR 0.89 [0.61–1.29]; p = .532). Conclusion. This is the largest reported study examining why oncology trials are not published. The data show that 4−6 years after appearing as abstracts, 39% of oncology clinical trials remain unpublished. Larger sample size and advanced trial phase were associated with eventual publication; among randomized trials, an industry-affiliated author or a cooperative group increased likelihood of publication. Unfortunately, we found that, despite widespread recognition of the problem and the creation of central data repositories, timely publishing of oncology clinical trials results remains unsatisfactory. Implications for Practice: The Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects notes the ethical obligation to report clinical trial data, whether positive or negative. This obligation is listed alongside requirements for risk minimization, access, confidentiality, and informed consent, all bedrocks of the clinical trial system, yet clinical trials are often not published, particularly if negative or difficult to complete. This study found that among American Society for Clinical Oncology (ASCO) Annual Meeting abstracts, 2009–2011, only 61% were published 4–6 years later: 75% of randomized trials and 54% of nonrandomized trials. Clinicians need to insist that every study in which they participate is published. PMID:26888691

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.

Methodological Reporting of Randomized Trials in Five Leading Chinese Nursing Journals

PubMed Central

Shi, Chunhu; Tian, Jinhui; Ren, Dan; Wei, Hongli; Zhang, Lihuan; Wang, Quan; Yang, Kehu

2014-01-01

Background Randomized controlled trials (RCTs) are not always well reported, especially in terms of their methodological descriptions. This study aimed to investigate the adherence of methodological reporting complying with CONSORT and explore associated trial level variables in the Chinese nursing care field. Methods In June 2012, we identified RCTs published in five leading Chinese nursing journals and included trials with details of randomized methods. The quality of methodological reporting was measured through the methods section of the CONSORT checklist and the overall CONSORT methodological items score was calculated and expressed as a percentage. Meanwhile, we hypothesized that some general and methodological characteristics were associated with reporting quality and conducted a regression with these data to explore the correlation. The descriptive and regression statistics were calculated via SPSS 13.0. Results In total, 680 RCTs were included. The overall CONSORT methodological items score was 6.34±0.97 (Mean ± SD). No RCT reported descriptions and changes in “trial design,” changes in “outcomes” and “implementation,” or descriptions of the similarity of interventions for “blinding.” Poor reporting was found in detailing the “settings of participants” (13.1%), “type of randomization sequence generation” (1.8%), calculation methods of “sample size” (0.4%), explanation of any interim analyses and stopping guidelines for “sample size” (0.3%), “allocation concealment mechanism” (0.3%), additional analyses in “statistical methods” (2.1%), and targeted subjects and methods of “blinding” (5.9%). More than 50% of trials described randomization sequence generation, the eligibility criteria of “participants,” “interventions,” and definitions of the “outcomes” and “statistical methods.” The regression analysis found that publication year and ITT analysis were weakly associated with CONSORT score. Conclusions The completeness of methodological reporting of RCTs in the Chinese nursing care field is poor, especially with regard to the reporting of trial design, changes in outcomes, sample size calculation, allocation concealment, blinding, and statistical methods. PMID:25415382

A generic minimization random allocation and blinding system on web.

PubMed

Cai, Hongwei; Xia, Jielai; Xu, Dezhong; Gao, Donghuai; Yan, Yongping

2006-12-01

Minimization is a dynamic randomization method for clinical trials. Although recommended by many researchers, the utilization of minimization has been seldom reported in randomized trials mainly because of the controversy surrounding the validity of conventional analyses and its complexity in implementation. However, both the statistical and clinical validity of minimization were demonstrated in recent studies. Minimization random allocation system integrated with blinding function that could facilitate the implementation of this method in general clinical trials has not been reported. SYSTEM OVERVIEW: The system is a web-based random allocation system using Pocock and Simon minimization method. It also supports multiple treatment arms within a trial, multiple simultaneous trials, and blinding without further programming. This system was constructed with generic database schema design method, Pocock and Simon minimization method and blinding method. It was coded with Microsoft Visual Basic and Active Server Pages (ASP) programming languages. And all dataset were managed with a Microsoft SQL Server database. Some critical programming codes were also provided. SIMULATIONS AND RESULTS: Two clinical trials were simulated simultaneously to test the system's applicability. Not only balanced groups but also blinded allocation results were achieved in both trials. Practical considerations for minimization method, the benefits, general applicability and drawbacks of the technique implemented in this system are discussed. Promising features of the proposed system are also summarized.

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.

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

Literate Language Intervention with High-Need Prekindergarten Children: A Randomized Trial

ERIC Educational Resources Information Center

Phillips, Beth M.; Tabulda, Galiya; Ingrole, Smriti A.; Webb Burris, Pam; Sedgwick, T. Kayla; Chen, Shiyi

2016-01-01

Purpose: The present article reports on the implementation and results of a randomized intervention trial targeting the literate language skills of prekindergarten children without identified language disorders but with low oral language skills. Method: Children (N = 82; 45 boys and 37 girls) were screened-in and randomized to a business-as-usual…

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…

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

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.

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.

Active implementation strategy of CONSORT adherence by a dental specialty journal improved randomized clinical trial reporting.

PubMed

Pandis, Nikolaos; Shamseer, Larissa; Kokich, Vincent G; Fleming, Padhraig S; Moher, David

2014-09-01

To describe a novel CONsolidated Standards of Reporting Trials (CONSORT) adherence strategy implemented by the American Journal of Orthodontics and Dentofacial Orthopedics (AJO-DO) and to report its impact on the completeness of reporting of published trials. The AJO-DO CONSORT adherence strategy, initiated in June 2011, involves active assessment of randomized clinical trial (RCT) reporting during the editorial process. The completeness of reporting CONSORT items was compared between trials submitted and published during the implementation period (July 2011 to September 2013) and trials published between August 2007 and July 2009. Of the 42 RCTs submitted (July 2011 to September 2013), 23 were considered for publication and assessed for completeness of reporting, seven of which were eventually published. For all published RCTs between 2007 and 2009 (n = 20), completeness of reporting by CONSORT item ranged from 0% to 100% (Median = 40%, interquartile range = 60%). All published trials in 2011-2013, reported 33 of 37 CONSORT (sub) items. Four CONSORT 2010 checklist items remained problematic even after implementation of the adherence strategy: changes to methods (3b), changes to outcomes (6b) after the trial commenced, interim analysis (7b), and trial stopping (14b), which are typically only reported when applicable. Trials published following implementation of the AJO-DO CONSORT adherence strategy completely reported more CONSORT items than those published or submitted previously. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

A Randomized Clinical Trial of the Collaborative Assessment and Management of Suicidality vs. Enhanced Care as Usual for Sucidal Soldiers

DTIC Science & Technology

2017-06-01

Research Projects : Patient Perspectives on Successful Management of Suicide Risk in Military and Civilian Samples Masters Student: Kaitlyn R. Schuler...Award Number: W81XWH-11-1-0164 TITLE: "A Randomized Clinical Trial of the Collaborative Assessment & Management of Suicidality vs. Enhanced Care...REPORT TYPE Final 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE "A Randomized Clinical Trial of the Collaborative Assessment & Management

Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals.

PubMed

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-12-01

The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration-approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article.

Industry Collaboration and Primary Guest Authorship of High-Impact Randomized Clinical Trials: A Cross-Sectional Study.

PubMed

Roper, Nitin; Korenstein, Deborah

2015-10-01

Journals have increased disclosure requirements in recent years, in part to deter guest authorship. The prevalence of guest authorship among primary authors (first and last) in the current era of increased disclosure requirements is unknown. Our aim was to examine the self-reported prevalence of guest authorship among primary authors from a sample of randomized clinical trials with and without industry funding and industry collaboration in the design, analysis or reporting of trials. Cross-sectional analysis of randomized, drug/device clinical trials with published details on the "Role of the Funding Source/Sponsor" published in high-impact biomedical journals between 1 December 2011 and 31 November 2012. Phase 1 or 2 trials, secondary trial analyses, and trials that were not listed on ClinicalTrials.gov were excluded. Primary guest authorship was defined, based on International Committee of Medical Journal Editors (ICMJE) criteria, when neither the first nor last author contributed to either of the following: 1) the design of the trial or the analysis/interpretation of data; or 2) drafting part or all of the manuscript. One hundred and sixty-eight randomized clinical trials that met inclusion criteria were included. We measured differences in the prevalence of guest authorship between trials with neither industry funding nor collaboration and 1) trials with industry funding without collaboration, and 2) trials with industry funding with collaboration. The overall prevalence of primary guest authorship was 6 % (10/168). Primary guest authorship was significantly more common in trials with industry funding with collaboration than in those with neither industry funding nor collaboration [13.2 % (10/76) vs. 0 % (0/39); p < 0.02]. Primary guest authorship did not differ between trials with industry funding without collaboration and trials with neither industry funding nor collaboration. Among a sample of randomized, drug/device clinical trials in high-impact biomedical journals, primary guest authorship was overall uncommon and occurred exclusively among trials with industry funding with collaboration.

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.

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…

Calcium plus vitamin D supplementation and joint symptoms in postmenopausal women in the women's health initiative randomized trial.

PubMed

Chlebowski, Rowan T; Pettinger, Mary; Johnson, Karen C; Wallace, Robert; Womack, Catherine; Mossavar-Rahmani, Yasmin; Stefanick, Marcia; Wactawski-Wende, Jean; Carbone, Laura; Lu, Bing; Eaton, Charles; Walitt, Brian; Kooperberg, Charles L

2013-10-01

Low vitamin D intake and levels have been associated with increased joint symptoms in some observational studies but the findings are mixed and evidence from randomized trials sparse. To evaluate the influence of supplemental calcium and vitamin D on joint symptoms in the Women's Health Initiative randomized, placebo-controlled, clinical trial. In post hoc analyses, the results of the Women's Health Initiative randomized clinical trial in which 36,282 postmenopausal women were randomized to receive calcium carbonate (1,000 mg as elemental calcium) with vitamin D-3 (400 IU) daily or placebo were examined in the 6% subgroup of 1,911 participants, oversampled for minorities, who had serial joint symptom assessment. Qualitative information on joint pain and joint swelling was collected by questionnaire before entry and 2 years after randomization. Logistic regression models were used to compare the occurrence and severity of joint symptoms across randomization groups. At baseline, total calcium and vitamin D intakes from diet and supplements were similar in the two randomization groups. In addition, both joint pain (reported by 73%) and joint swelling (reported by 34%) were commonly reported and comparable in the supplement and placebo groups. Two years after randomization, no statistically significant differences between supplement and placebo groups were seen for joint pain frequency (74.6% compared with 75.1% [P=0.79] for supplement and placebo groups, respectively) or joint swelling frequency (34.6% compared with 32.4% [P=0.29], respectively) or in severity scores for either outcome. Subgroup analyses suggested study participants also using nonprotocol calcium supplements at study entry may have less joint pain with supplement group randomization (interaction P=0.02). Joint symptoms are relatively common in postmenopausal women. However, daily supplementation with 1,000 mg calcium carbonate and 400 IU vitamin D-3 in a randomized, placebo-controlled clinical trial setting did not reduce the self-reported frequency or severity of joint symptoms. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Assessing quality of reports on randomized clinical trials in nursing journals.

PubMed

Parent, Nicole; Hanley, James A

2009-01-01

Several surveys have presented the quality of reports on randomized clinical trials (RCTs) published in general and specialty medical journals. The aim of these surveys was to raise scientific consciousness on methodological aspects pertaining to internal and external validity. These reviews have suggested that the methodological quality could be improved. We conducted a survey of reports on RCTs published in nursing journals to assess their methodological quality. The features we considered included sample size, flow of participants, assessment of baseline comparability, randomization, blinding, and statistical analysis. We collected data from all reports of RCTs published between January 1994 and December 1997 in Applied Nursing Research, Heart & Lung and Nursing Research. We hand-searched the journals and included all 54 articles in which authors reported that individuals have been randomly allocated to distinct groups. We collected data using a condensed form of the Consolidated Standards of Reporting Trials (CONSORT) statement for structured reporting of RCTs (Begg et al., 1996). Sample size calculations were included in only 22% of the reports. Only 48% of the reports provided information about the type of randomization, and a mere 22% described blinding strategies. Comparisons of baseline characteristics using hypothesis tests were abusively produced in more than 76% of the reports. Excessive use and unstructured reports of significance testing were common (59%), and all reports failed to provide magnitude of treatment differences with confidence intervals. Better methodological quality in reports of RCTs will contribute to increase the standards of nursing research.

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.

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…

Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-for-profit organizations: 2000-2005.

PubMed

Ridker, Paul M; Torres, Jose

2006-05-17

In surveys based on data available prior to 2000, clinical trials funded by for-profit organizations appeared more likely to report positive findings than those funded by not-for-profit organizations. Whether this situation has changed over the past 5 years or whether similar effects are present among jointly funded trials is unknown. To determine in contemporary randomized cardiovascular trials the association between funding source and the likelihood of reporting positive findings. We reviewed 324 consecutive superiority trials of cardiovascular medicine published between January 1, 2000, and July 30, 2005, in JAMA, The Lancet, and the New England Journal of Medicine. The proportion of trials favoring newer treatments over the standard of care was evaluated by funding source. Of the 324 superiority trials, 21 cited no funding source. Of the 104 trials funded solely by not-for-profit organizations, 51 (49%) reported evidence significantly favoring newer treatments over the standard of care, whereas 53 (51%) did not (P = .80). By contrast, 92 (67.2%) of 137 trials funded solely by for-profit organizations favored newer treatments over standard of care (P<.001). Among 62 jointly funded trials, 35 (56.5%), an intermediate proportion, favored newer treatments. For 205 randomized trials evaluating drugs, the proportions favoring newer treatments were 39.5%, not-for-profit; 54.4%, jointly funded; and 65.5%, for-profit trials (P for trend across groups = .002). For the 39 randomized trials evaluating cardiovascular devices, the proportions favoring newer treatments were 50.0%, not-for-profit; 69.2%, jointly funded; and 82.4%, for-profit trials (P for trend across groups = .07). Regardless of funding source, trials using surrogate end points, such as quantitative angiography, intravascular ultrasound, plasma biomarkers, and functional measures were more likely to report positive findings (67%) than trials using clinical end points (54.1%; P = .02). Recent cardiovascular trials funded by for-profit organizations are more likely to report positive findings than trials funded by not-for-profit organizations, as are trials using surrogate rather than clinical end points. Trials jointly funded by not-for-profit and for-profit organizations appear to report positive findings at a rate approximately midway between rates observed in trials supported solely by one or the other of these entities.

Randomized clinical trials and observational studies in the assessment of drug safety.

PubMed

Sawchik, J; Hamdani, J; Vanhaeverbeek, M

2018-05-01

Randomized clinical trials are considered as the preferred design to assess the potential causal relationships between drugs or other medical interventions and intended effects. For this reason, randomized clinical trials are generally the basis of development programs in the life cycle of drugs and the cornerstone of evidence-based medicine. Instead, randomized clinical trials are not the design of choice for the detection and assessment of rare, delayed and/or unexpected effects related to drug safety. Moreover, the highly homogeneous populations resulting from restrictive eligibility criteria make randomized clinical trials inappropriate to describe comprehensively the safety profile of drugs. In that context, observational studies have a key added value when evaluating the benefit-risk balance of the drugs. However, observational studies are more prone to bias than randomized clinical trials and they have to be designed, conducted and reported judiciously. In this article, we discuss the strengths and limitations of randomized clinical trials and of observational studies, more particularly regarding their contribution to the knowledge of medicines' safety profile. In addition, we present general recommendations for the sensible use of observational data. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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.

Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review.

PubMed

Langrand-Escure, Julien; Rivoirard, Romain; Oriol, Mathieu; Tinquaut, Fabien; Rancoule, Chloé; Chauvin, Frank; Magné, Nicolas; Bourmaud, Aurélie

2017-01-01

Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal. Objective The present study aims at estimating the quality of reporting in published oncology phase II clinical trials. A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010-2015). All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer. Quality of reporting was assessed using the Key Methodological Score. 557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001). Screening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate. This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles.

Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review

PubMed Central

Langrand-Escure, Julien; Rivoirard, Romain; Oriol, Mathieu; Tinquaut, Fabien; Rancoule, Chloé; Chauvin, Frank; Magné, Nicolas; Bourmaud, Aurélie

2017-01-01

Background Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal. Objective The present study aims at estimating the quality of reporting in published oncology phase II clinical trials. Data sources A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010–2015). Study eligibility criteria All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer. Intervention Quality of reporting was assessed using the Key Methodological Score. Results 557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001). Limitations Screening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate. Conclusions & implications of key findings This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles. PMID:29216190

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.

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications-a cross-sectional study.

PubMed

Earley, Amy; Lau, Joseph; Uhlig, Katrin

2013-01-18

A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Registry-based study of clinical trial results reporting. ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications.

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications–a cross-sectional study

PubMed Central

Earley, Amy; Lau, Joseph; Uhlig,, Katrin

2013-01-01

Context A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. Objective To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Design Registry-based study of clinical trial results reporting. Setting ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. Selection criteria A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. Main outcome measure ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. Results In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Conclusions Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications. PMID:23335556

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…

The Ecological Effects of Universal and Selective Violence Prevention Programs for Middle School Students: A Randomized Trial

ERIC Educational Resources Information Center

Simon, Thomas R.; Ikeda, Robin M.; Smith, Emilie Phillips; Reese, Le'Roy E.; Rabiner, David L.; Miller, Shari; Winn, Donna-Marie; Dodge, Kenneth A.; Asher, Steven R.; Horne, Arthur M.; Orpinas, Pamela; Martin, Roy; Quinn, William H.; Tolan, Patrick H.; Gorman-Smith, Deborah; Henry, David B.; Gay, Franklin N.; Schoeny, Michael; Farrell, Albert D.; Meyer, Aleta L.; Sullivan, Terri N.; Allison, Kevin W.

2009-01-01

This study reports the findings of a multisite randomized trial evaluating the separate and combined effects of 2 school-based approaches to reduce violence among early adolescents. A total of 37 schools at 4 sites were randomized to 4 conditions: (1) a universal intervention that involved implementing a student curriculum and teacher training…

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.

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

What Do We Really Know About the Safety of Tai Chi?: A Systematic Review of Adverse Event Reports in Randomized Trials

PubMed Central

Wayne, Peter M.; Berkowitz, Danielle L.; Litrownik, Daniel E.; Buring, Julie E.; Yeh, Gloria Y.

2014-01-01

Objective Systematically review frequency and quality of adverse event (AE) reports in randomized clinical trials (RCTs) of Tai Chi (TC). Data Sources Electronic searches of PubMed/MEDLINE and additional databases from inception through March 2013 of English-language RCTs. Search terms were tai chi, taiji, tai chi chuan. Data were independently extracted by two investigators. Study Selection We included all available randomized controlled trials (RCTs) that were published in English and used Tai Chi as an intervention. Inclusion and exclusion of studies were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data Extraction Eligible RCTs were categorized with respect to AE reporting: 1) No mention of protocols for monitoring AEs or reports of AEs; 2) Reports of AEs either with or without explicit protocols for monitoring AEs. Data Synthesis 153 eligible RCTs were identified, most targeting older adults. Only 50 eligible trials (33%) included reporting of AEs, and of these, only 18 trials (12% overall) also reported an explicit AE monitoring protocol. Protocols varied with respect to rigor of systematic monitoring in both Tai Chi and comparison groups. Reported AEs were typically minor and expected, and primarily musculoskeletal related (e.g., knee and back pain); no intervention-related serious AEs were reported. Conclusions Tai Chi is unlikely to result in serious adverse events, but may be associated with minor musculoskeletal aches and pains. However, poor and inconsistent reporting of AEs greatly limits the conclusions that can be drawn regarding the safety of Tai Chi. PMID:24878398

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

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…

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.

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.

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.

Bayesian statistical inference enhances the interpretation of contemporary randomized controlled trials.

PubMed

Wijeysundera, Duminda N; Austin, Peter C; Hux, Janet E; Beattie, W Scott; Laupacis, Andreas

2009-01-01

Randomized trials generally use "frequentist" statistics based on P-values and 95% confidence intervals. Frequentist methods have limitations that might be overcome, in part, by Bayesian inference. To illustrate these advantages, we re-analyzed randomized trials published in four general medical journals during 2004. We used Medline to identify randomized superiority trials with two parallel arms, individual-level randomization and dichotomous or time-to-event primary outcomes. Studies with P<0.05 in favor of the intervention were deemed "positive"; otherwise, they were "negative." We used several prior distributions and exact conjugate analyses to calculate Bayesian posterior probabilities for clinically relevant effects. Of 88 included studies, 39 were positive using a frequentist analysis. Although the Bayesian posterior probabilities of any benefit (relative risk or hazard ratio<1) were high in positive studies, these probabilities were lower and variable for larger benefits. The positive studies had only moderate probabilities for exceeding the effects that were assumed for calculating the sample size. By comparison, there were moderate probabilities of any benefit in negative studies. Bayesian and frequentist analyses complement each other when interpreting the results of randomized trials. Future reports of randomized trials should include both.

[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.

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.

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

Parent Stress in a Randomized Clinical Trial of Atomoxetine and Parent Training for Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Lecavalier, Luc; Pan, Xueliang; Smith, Tristram; Handen, Benjamin L.; Arnold, L. Eugene; Silverman, Laura; Tumuluru, Rameshwari V.; Hollway, Jill; Aman, Michael G.

2018-01-01

We previously reported a 2 × 2 randomized clinical trial of atomoxetine (ATX) and parent training (PT) for attention deficit hyperactivity disorder (ADHD) symptoms and behavioral noncompliance in 128 children with autism spectrum disorder, ages 5-14 years. Children were randomized to one of four conditions: ATX alone, placebo alone, ATX + PT, or…

Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals

PubMed Central

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-01-01

Background The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Conclusions Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article. Please see later in the article for the Editors' Summary PMID:24311990

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…

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.

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.

CONSORT Statement for Randomized Trials of Nonpharmacologic Treatments: A 2017 Update and a CONSORT Extension for Nonpharmacologic Trial Abstracts.

PubMed

Boutron, Isabelle; Altman, Douglas G; Moher, David; Schulz, Kenneth F; Ravaud, Philippe

2017-07-04

Incomplete and inadequate reporting is an avoidable waste that reduces the usefulness of research. The CONSORT (Consolidated Standards of Reporting Trials) Statement is an evidence-based reporting guideline that aims to improve research transparency and reduce waste. In 2008, the CONSORT Group developed an extension to the original statement that addressed methodological issues specific to trials of nonpharmacologic treatments (NPTs), such as surgery, rehabilitation, or psychotherapy. This article describes an update of that extension and presents an extension for reporting abstracts of NPT trials. To develop these materials, the authors reviewed pertinent literature published up to July 2016; surveyed authors of NPT trials; and conducted a consensus meeting with editors, trialists, and methodologists. Changes to the CONSORT Statement extension for NPT trials include wording modifications to improve readers' understanding and the addition of 3 new items. These items address whether and how adherence of participants to interventions is assessed or enhanced, description of attempts to limit bias if blinding is not possible, and specification of the delay between randomization and initiation of the intervention. The CONSORT extension for abstracts of NPT trials includes 2 new items that were not specified in the original CONSORT Statement for abstracts. The first addresses reporting of eligibility criteria for centers where the intervention is performed and for care providers. The second addresses reporting of important changes to the intervention versus what was planned. Both the updated CONSORT extension for NPT trials and the CONSORT extension for NPT trial abstracts should help authors, editors, and peer reviewers improve the transparency of NPT trial reports.

How completely are physiotherapy interventions described in reports of randomised trials?

PubMed

Yamato, Tiê P; Maher, Chris G; Saragiotto, Bruno T; Hoffmann, Tammy C; Moseley, Anne M

2016-06-01

Incomplete descriptions of interventions are a common problem in reports of randomised controlled trials. To date no study has evaluated the completeness of the descriptions of physiotherapy interventions. To evaluate the completeness of the descriptions of physiotherapy interventions in a random sample of reports of randomised controlled trials (RCTs). A random sample of 200 reports of RCTs from the PEDro database. We included full text papers, written in English, and reporting trials with two arms. We included trials evaluating any type of physiotherapy interventions and subdisciplines. The methodological quality was evaluated using the PEDro scale and completeness of intervention description using the Template for Intervention Description and Replication (TIDieR) checklist. The proportion and 95% confidence interval were calculated for intervention and control groups, and used to present the relationship between completeness and methodological quality, and subdisciplines. Completeness of intervention reporting in physiotherapy RCTs was poor. For intervention groups, 46 (23%) trials did not describe at least half of the items. Reporting was worse for control groups, 149 (75%) trials described less than half of the items. There was no clear difference in the completeness across subdisciplines or methodological quality. Our sample were restricted to trials published in English in 2013. Descriptions of interventions in physiotherapy RCTs are typically incomplete. Authors and journals should aim for more complete descriptions of interventions in physiotherapy trials. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

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.

Estimation of treatment efficacy with complier average causal effects (CACE) in a randomized stepped wedge trial.

PubMed

Gruber, Joshua S; Arnold, Benjamin F; Reygadas, Fermin; Hubbard, Alan E; Colford, John M

2014-05-01

Complier average causal effects (CACE) estimate the impact of an intervention among treatment compliers in randomized trials. Methods used to estimate CACE have been outlined for parallel-arm trials (e.g., using an instrumental variables (IV) estimator) but not for other randomized study designs. Here, we propose a method for estimating CACE in randomized stepped wedge trials, where experimental units cross over from control conditions to intervention conditions in a randomized sequence. We illustrate the approach with a cluster-randomized drinking water trial conducted in rural Mexico from 2009 to 2011. Additionally, we evaluated the plausibility of assumptions required to estimate CACE using the IV approach, which are testable in stepped wedge trials but not in parallel-arm trials. We observed small increases in the magnitude of CACE risk differences compared with intention-to-treat estimates for drinking water contamination (risk difference (RD) = -22% (95% confidence interval (CI): -33, -11) vs. RD = -19% (95% CI: -26, -12)) and diarrhea (RD = -0.8% (95% CI: -2.1, 0.4) vs. RD = -0.1% (95% CI: -1.1, 0.9)). Assumptions required for IV analysis were probably violated. Stepped wedge trials allow investigators to estimate CACE with an approach that avoids the stronger assumptions required for CACE estimation in parallel-arm trials. Inclusion of CACE estimates in stepped wedge trials with imperfect compliance could enhance reporting and interpretation of the results of such trials.

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.

Design and analysis of group-randomized trials in cancer: A review of current practices.

PubMed

Murray, David M; Pals, Sherri L; George, Stephanie M; Kuzmichev, Andrey; Lai, Gabriel Y; Lee, Jocelyn A; Myles, Ranell L; Nelson, Shakira M

2018-06-01

The purpose of this paper is to summarize current practices for the design and analysis of group-randomized trials involving cancer-related risk factors or outcomes and to offer recommendations to improve future trials. We searched for group-randomized trials involving cancer-related risk factors or outcomes that were published or online in peer-reviewed journals in 2011-15. During 2016-17, in Bethesda MD, we reviewed 123 articles from 76 journals to characterize their design and their methods for sample size estimation and data analysis. Only 66 (53.7%) of the articles reported appropriate methods for sample size estimation. Only 63 (51.2%) reported exclusively appropriate methods for analysis. These findings suggest that many investigators do not adequately attend to the methodological challenges inherent in group-randomized trials. These practices can lead to underpowered studies, to an inflated type 1 error rate, and to inferences that mislead readers. Investigators should work with biostatisticians or other methodologists familiar with these issues. Funders and editors should ensure careful methodological review of applications and manuscripts. Reviewers should ensure that studies are properly planned and analyzed. These steps are needed to improve the rigor and reproducibility of group-randomized trials. The Office of Disease Prevention (ODP) at the National Institutes of Health (NIH) has taken several steps to address these issues. ODP offers an online course on the design and analysis of group-randomized trials. ODP is working to increase the number of methodologists who serve on grant review panels. ODP has developed standard language for the Application Guide and the Review Criteria to draw investigators' attention to these issues. Finally, ODP has created a new Research Methods Resources website to help investigators, reviewers, and NIH staff better understand these issues. Published by Elsevier Inc.

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.

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.

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.

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.

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

Randomized, Controlled Trial of Behavioral Family Systems Therapy for Diabetes: Maintenance and Generalization of Effects on Parent-Adolescent Communication

ERIC Educational Resources Information Center

Wysocki, Tim; Harris, Michael A.; Buckloh, Lisa M.; Mertlich, Deborah; Lochrie, Amanda Sobel; Taylor, Alexandra; Sadler, Michelle; White, Neil H.

2008-01-01

We report a randomized trial of a revised Behavioral Family Systems Therapy for Diabetes (BFST-D) intervention. Families of 104 adolescents with diabetes were randomized to standard care (SC) or to 6 months of an educational support group (ES) or BFST-D. Family communication and problem-solving skills were assessed at 0, 6, 12, and 18 months by…

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…

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

Sample Size Estimation in Cluster Randomized Educational Trials: An Empirical Bayes Approach

ERIC Educational Resources Information Center

Rotondi, Michael A.; Donner, Allan

2009-01-01

The educational field has now accumulated an extensive literature reporting on values of the intraclass correlation coefficient, a parameter essential to determining the required size of a planned cluster randomized trial. We propose here a simple simulation-based approach including all relevant information that can facilitate this task. An…

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…

Efficacy Trial of the Second Step Early Learning (SSEL) Curriculum: Preliminary Outcomes

ERIC Educational Resources Information Center

Upshur, Carole C.; Heyman, Miriam; Wenz-Gross, Melodie

2017-01-01

A classroom randomized trial (n = 31 classrooms) was conducted using the Second Step Early Learning (SSEL) curriculum compared to usual curricula. Head Start and community preschool classrooms enrolling low income children were randomly assigned to deliver SSEL (n = 16) or usual curricula (n = 15). Data are reported for four year olds…

A Randomized Trial of Probation Case Management for Drug-Involved Women Offenders

ERIC Educational Resources Information Center

Guydish, Joseph; Chan, Monica; Bostrom, Alan; Jessup, Martha A.; Davis, Thomas B.; Marsh, Cheryl

2011-01-01

This article reports findings from a clinical trial of a probation case management (PCM) intervention for drug-involved women offenders. Participants were randomly assigned to PCM (n = 92) or standard probation (n = 91) and followed for 12 months using measures of substance abuse, psychiatric symptoms, social support, and service utilization.…

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…

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.

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.

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

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.

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.

The Effect of Sodium Hypochlorite and Chlorhexidine as Irrigant Solutions for Root Canal Disinfection: A Systematic Review of Clinical Trials.

PubMed

Gonçalves, Lucio Souza; Rodrigues, Renata Costa Val; Andrade Junior, Carlos Vieira; Soares, Renata G; Vettore, Mario Vianna

2016-04-01

This systematic review aimed to compare the effectiveness of sodium hypochlorite and chlorhexidine for root canal disinfection during root canal therapy. A literature search for clinical trials was made on the PubMed (MEDLINE), Web of Knowledge, SCOPUS, and Science Direct databases and in the reference lists of the identified articles up to January 2015. Quality assessment of the selected studies was performed according to the Consolidated Standards of Reporting Trials statement. One clinical trial and 4 randomized clinical trials were selected from the 172 articles initially identified. There was heterogeneity in the laboratory methods used to assess the root canal disinfection as well as in the concentrations of the irrigants used. Therefore, meta-analysis was not performed. Two studies reported effective and similar reductions in bacterial levels for both irrigants. Sodium hypochlorite was more effective than chlorhexidine in reducing microorganisms in 1 study, and another reported opposite findings. Both root irrigants were ineffective in eliminating endotoxins from necrotic pulp root canals in 1 study. Trial design and information regarding randomization procedures were not clearly described in the clinical trials. No study compared laboratory results with clinical outcomes. The available evidence on this topic is scarce, and the findings of studies were not consistent. Additional randomized clinical trials using clinical outcomes to compare the use of sodium hypochlorite and chlorhexidine during root canal therapy are needed. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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

Revisiting the Quality of Reporting Randomized Controlled Trials in Nursing Literature.

PubMed

Adams, Yenupini Joyce; Kamp, Kendra; Liu, Cheng Ching; Stommel, Manfred; Thana, Kanjana; Broome, Marion E; Smith, Barbara

2018-03-01

To examine and update the literature on the quality of randomized controlled trials (RCTs) as reported in top nursing journals, based on manuscripts' adherence to the CONsolidated Standards of Reporting Trials (CONSORT) guidelines. Descriptive review of adherence of RCT manuscript to CONSORT guidelines. Top 40 International Scientific Indexing (ISI) ranked nursing journals that published 20 or more RCTs between 2010 and 2014, were included in the study. Selected articles were randomly assigned to four reviewers who assessed the quality of the articles using the CONSORT checklist. Data were analyzed using descriptive and inferential statistics. A total of 119 articles were included in the review. The mean CONSORT score significantly differed by journal but did not differ based on year of publication. The least consistently reported items included random allocation, who randomly assigned participants and whether those administering the interventions were blinded to group assignment. Although progress has been made, there is still room for improvement in the quality of RCT reporting in nursing journals. Special attention must be paid to how adequately studies adhere to the CONSORT prior to publication in nursing journals. Evidence from (RCTs) are thought to provide the best evidence for evaluating the impact of treatments and interventions by the U.S. Preventive Services Task Force. Since the evidence may be used for the development of clinical practice guidelines, it is critical that RCTs be designed, conducted, and reported appropriately and precisely. © 2017 Sigma Theta Tau International.

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.

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

Trial protocol: a parallel group, individually randomized clinical trial to evaluate the effect of a mobile phone application to improve sexual health among youth in Stockholm County.

PubMed

Nielsen, Anna; De Costa, Ayesha; Bågenholm, Aspasia; Danielsson, Kristina Gemzell; Marrone, Gaetano; Boman, Jens; Salazar, Mariano; Diwan, Vinod

2018-02-05

Genital Chlamydia trachomatis infection is a major public health problem worldwide affecting mostly youth. Sweden introduced an opportunistic screening approach in 1982 accompanied by treatment, partner notification and case reporting. After an initial decline in infection rate till the mid-90s, the number of reported cases has increased over the last two decades and has now stabilized at a high level of 37,000 reported cases in Sweden per year (85% of cases in youth). Sexual risk-taking among youth is also reported to have significantly increased over the last 20 years. Mobile health (mHealth) interventions could be particularly suitable for youth and sexual health promotion as the intervention is delivered in a familiar and discrete way to a tech savvy at-risk population. This paper presents a protocol for a randomized trial to study the effect of an interactive mHealth application (app) on condom use among the youth of Stockholm. 446 youth resident in Stockholm, will be recruited in this two arm parallel group individually randomized trial. Recruitment will be from Youth Health Clinics or via the trial website. Participants will be randomized to receive either the intervention (which comprises an interactive app on safe sexual health that will be installed on their smart phones) or a control group (standard of care). Youth will be followed up for 6 months, with questionnaire responses submitted periodically via the app. Self-reported condom use over 6 months will be the primary outcome. Secondary outcomes will include presence of an infection, Chlamydia tests during the study period and proxy markers of safe sex. Analysis is by intention to treat. This trial exploits the high mobile phone usage among youth to provide a phone app intervention in the area of sexual health. If successful, the results will have implications for health service delivery and health promotion among the youth. From a methodological perspective, this trial is expected to provide information on the strength and challenges of implementing a partially app (internet) based trial in this context. ISRCTN 13212899, date of registration June 22, 2017.

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.

Cluster randomized trials utilizing primary care electronic health records: methodological issues in design, conduct, and analysis (eCRT Study)

PubMed Central

2014-01-01

Background There is growing interest in conducting clinical and cluster randomized trials through electronic health records. This paper reports on the methodological issues identified during the implementation of two cluster randomized trials using the electronic health records of the Clinical Practice Research Datalink (CPRD). Methods Two trials were completed in primary care: one aimed to reduce inappropriate antibiotic prescribing for acute respiratory infection; the other aimed to increase physician adherence with secondary prevention interventions after first stroke. The paper draws on documentary records and trial datasets to report on the methodological experience with respect to research ethics and research governance approval, general practice recruitment and allocation, sample size calculation and power, intervention implementation, and trial analysis. Results We obtained research governance approvals from more than 150 primary care organizations in England, Wales, and Scotland. There were 104 CPRD general practices recruited to the antibiotic trial and 106 to the stroke trial, with the target number of practices being recruited within six months. Interventions were installed into practice information systems remotely over the internet. The mean number of participants per practice was 5,588 in the antibiotic trial and 110 in the stroke trial, with the coefficient of variation of practice sizes being 0.53 and 0.56 respectively. Outcome measures showed substantial correlations between the 12 months before, and after intervention, with coefficients ranging from 0.42 for diastolic blood pressure to 0.91 for proportion of consultations with antibiotics prescribed, defining practice and participant eligibility for analysis requires careful consideration. Conclusions Cluster randomized trials may be performed efficiently in large samples from UK general practices using the electronic health records of a primary care database. The geographical dispersal of trial sites presents a difficulty for research governance approval and intervention implementation. Pretrial data analyses should inform trial design and analysis plans. Trial registration Current Controlled Trials ISRCTN 47558792 and ISRCTN 35701810 (both registered on 17 March 2010). PMID:24919485

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.

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.

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.

Effect of Atomoxetine on Executive Function Impairments in Adults with ADHD

ERIC Educational Resources Information Center

Brown, Thomas E.; Holdnack, James; Saylor, Keith; Adler, Lenard; Spencer, Thomas; Williams, David W.; Padival, Anoop K.; Schuh, Kory; Trzepacz, Paula T.; Kelsey, Douglas

2011-01-01

Objective: To assess the effect of atomoxetine on ADHD-related executive functions over a 6-month period using the Brown Attention-Deficit Disorder Scale (BADDS) for Adults, a normed, 40-item, self-report scale in a randomized, double-blind, placebo-controlled clinical trial. Method: In a randomized, double-blind clinical trial, adults with ADHD…

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…

Reducing Achievement Gaps in Academic Writing for Latinos and English Learners in Grades 7-12

ERIC Educational Resources Information Center

Olson, Carol Booth; Matuchniak, Tina; Chung, Huy Q.; Stumpf, Rachel; Farkas, George

2017-01-01

This study reports 2 years of findings from a randomized controlled trial designed to replicate and demonstrate the efficacy of an existing, successful professional development program, the Pathway Project, that uses a cognitive strategies approach to text-based analytical writing. Building on an earlier randomized field trial in a large, urban,…

A Randomized Effectiveness Trial of Brief Parent Training: Six-Month Follow-Up

ERIC Educational Resources Information Center

Kjøbli, John; Bjørnebekk, Gunnar

2013-01-01

Objective: To examine the follow-up effectiveness of brief parent training (BPT) for children with emerging or existing conduct problems. Method: With the use of a randomized controlled trial and parent and teacher reports, this study examined the effectiveness of BPT compared to regular services 6 months after the end of the intervention.…

Four-Year Follow-Up of Children in the Leap Randomized Trial: Some Planned and Accidental Findings

ERIC Educational Resources Information Center

Strain, Phillip S.

2017-01-01

This article reports on a 4-year follow-up study from the Learning Experiences and Alternative Program for Preschoolers and Their Parents (LEAP) randomized trial of early intervention for young children with autism. Overall, participants from LEAP classes were marginally superior to comparison class children on elementary school outcomes specific…

Four-Year Follow-Up of Children in the LEAP Randomized Trial: Some Planned and Accidental Findings

ERIC Educational Resources Information Center

Strain, Phillip S.

2017-01-01

This article reports on a 4-year follow-up study from the Learning Experiences and Alternative Program for Preschoolers and Their Parents (LEAP) randomized trial of early intervention for young children with autism. Overall, participants from LEAP classes were marginally superior to comparison class children on elementary school outcomes specific…

A Multisite Cluster Randomized Field Trial of Open Court Reading

ERIC Educational Resources Information Center

Borman, Geoffrey D.; Dowling, N. Maritza; Schneck, Carrie

2008-01-01

In this article, the authors report achievement outcomes of a multisite cluster randomized field trial of Open Court Reading 2005 (OCR), a K-6 literacy curriculum published by SRA/McGraw-Hill. The participants are 49 first-grade through fifth-grade classrooms from predominantly minority and poor contexts across the nation. Blocking by grade level…

Randomized, Controlled Trial of CBT Training for PTSD Providers

DTIC Science & Technology

2013-10-01

and Therapy, 47, 902-909. Shapiro, F. (2001). Eye movement desensitization and reprocessing ( EMDR ): Basic principles...Hopper, E. K., Korn, D. L., & Simpson, W. B. (2007). A randomized clinical trial of eye movement desensitization and reprocessing ( EMDR ), fluoxetine...Josef Ruzek, Ph.D. CONTRACTING ORGANIZATION: Palo Alto Institute for Research and Education Palo Alto, CA 94304 REPORT

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

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.

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.

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.

Statistical analysis and handling of missing data in cluster randomized trials: a systematic review.

PubMed

Fiero, Mallorie H; Huang, Shuang; Oren, Eyal; Bell, Melanie L

2016-02-09

Cluster randomized trials (CRTs) randomize participants in groups, rather than as individuals and are key tools used to assess interventions in health research where treatment contamination is likely or if individual randomization is not feasible. Two potential major pitfalls exist regarding CRTs, namely handling missing data and not accounting for clustering in the primary analysis. The aim of this review was to evaluate approaches for handling missing data and statistical analysis with respect to the primary outcome in CRTs. We systematically searched for CRTs published between August 2013 and July 2014 using PubMed, Web of Science, and PsycINFO. For each trial, two independent reviewers assessed the extent of the missing data and method(s) used for handling missing data in the primary and sensitivity analyses. We evaluated the primary analysis and determined whether it was at the cluster or individual level. Of the 86 included CRTs, 80 (93%) trials reported some missing outcome data. Of those reporting missing data, the median percent of individuals with a missing outcome was 19% (range 0.5 to 90%). The most common way to handle missing data in the primary analysis was complete case analysis (44, 55%), whereas 18 (22%) used mixed models, six (8%) used single imputation, four (5%) used unweighted generalized estimating equations, and two (2%) used multiple imputation. Fourteen (16%) trials reported a sensitivity analysis for missing data, but most assumed the same missing data mechanism as in the primary analysis. Overall, 67 (78%) trials accounted for clustering in the primary analysis. High rates of missing outcome data are present in the majority of CRTs, yet handling missing data in practice remains suboptimal. Researchers and applied statisticians should carry out appropriate missing data methods, which are valid under plausible assumptions in order to increase statistical power in trials and reduce the possibility of bias. Sensitivity analysis should be performed, with weakened assumptions regarding the missing data mechanism to explore the robustness of results reported in the primary analysis.

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

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.

Movement-Pattern Training to Improve Function in People With Chronic Hip Joint Pain: A Feasibility Randomized Clinical Trial.

PubMed

Harris-Hayes, Marcie; Czuppon, Sylvia; Van Dillen, Linda R; Steger-May, Karen; Sahrmann, Shirley; Schootman, Mario; Salsich, Gretchen B; Clohisy, John C; Mueller, Michael J

2016-06-01

Study Design Feasibility randomized clinical trial. Background Rehabilitation may be an appropriate treatment strategy for patients with chronic hip joint pain; however, the evidence related to the effectiveness of rehabilitation is limited. Objectives To assess feasibility of performing a randomized clinical trial to investigate the effectiveness of movement-pattern training (MPT) to improve function in people with chronic hip joint pain. Methods Thirty-five patients with chronic hip joint pain were randomized into a treatment (MPT) group or a control (wait-list) group. The MPT program included 6 one-hour supervised sessions and incorporated (1) task-specific training for basic functional tasks and symptom-provoking tasks, and (2) strengthening of hip musculature. The wait-list group received no treatment. Primary outcomes for feasibility were patient retention and adherence. Secondary outcomes to assess treatment effects were patient-reported function (Hip disability and Osteoarthritis Outcome Score), lower extremity kinematics, and hip muscle strength. Results Retention rates did not differ between the MPT (89%) and wait-list groups (94%, P = 1.0). Sixteen of the 18 patients (89%) in the MPT group attended at least 80% of the treatment sessions. For the home exercise program, 89% of patients reported performing their home program at least once per day. Secondary outcomes support the rationale for conduct of a superiority randomized clinical trial. Conclusion Based on retention and adherence rates, a larger randomized clinical trial appears feasible and warranted to assess treatment effects more precisely. Data from this feasibility study will inform our future clinical trial. Level of Evidence Therapy, level 2b-. J Orthop Sports Phys Ther 2016;46(6):452-461. Epub 26 Apr 2016. doi:10.2519/jospt.2016.6279.

Cluster randomized trials utilizing primary care electronic health records: methodological issues in design, conduct, and analysis (eCRT Study).

PubMed

Gulliford, Martin C; van Staa, Tjeerd P; McDermott, Lisa; McCann, Gerard; Charlton, Judith; Dregan, Alex

2014-06-11

There is growing interest in conducting clinical and cluster randomized trials through electronic health records. This paper reports on the methodological issues identified during the implementation of two cluster randomized trials using the electronic health records of the Clinical Practice Research Datalink (CPRD). Two trials were completed in primary care: one aimed to reduce inappropriate antibiotic prescribing for acute respiratory infection; the other aimed to increase physician adherence with secondary prevention interventions after first stroke. The paper draws on documentary records and trial datasets to report on the methodological experience with respect to research ethics and research governance approval, general practice recruitment and allocation, sample size calculation and power, intervention implementation, and trial analysis. We obtained research governance approvals from more than 150 primary care organizations in England, Wales, and Scotland. There were 104 CPRD general practices recruited to the antibiotic trial and 106 to the stroke trial, with the target number of practices being recruited within six months. Interventions were installed into practice information systems remotely over the internet. The mean number of participants per practice was 5,588 in the antibiotic trial and 110 in the stroke trial, with the coefficient of variation of practice sizes being 0.53 and 0.56 respectively. Outcome measures showed substantial correlations between the 12 months before, and after intervention, with coefficients ranging from 0.42 for diastolic blood pressure to 0.91 for proportion of consultations with antibiotics prescribed, defining practice and participant eligibility for analysis requires careful consideration. Cluster randomized trials may be performed efficiently in large samples from UK general practices using the electronic health records of a primary care database. The geographical dispersal of trial sites presents a difficulty for research governance approval and intervention implementation. Pretrial data analyses should inform trial design and analysis plans. Current Controlled Trials ISRCTN 47558792 and ISRCTN 35701810 (both registered on 17 March 2010).

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.

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

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.

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.

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

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.

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.

PubMed Central

Peto, R.; Pike, M. C.; Armitage, P.; Breslow, N. E.; Cox, D. R.; Howard, S. V.; Mantel, N.; McPherson, K.; Peto, J.; Smith, P. G.

1977-01-01

Part I of this report appeared in the previous issue (Br. J. Cancer (1976) 34,585), and discussed the design of randomized clinical trials. Part II now describes efficient methods of analysis of randomized clinical trials in which we wish to compare the duration of survival (or the time until some other untoward event first occurs) among different groups of patients. It is intended to enable physicians without statistical training either to analyse such data themselves using life tables, the logrank test and retrospective stratification, or, when such analyses are presented, to appreciate them more critically, but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses. PMID:831755

A Randomized Phase II Dose-Response Exercise Trial among Colon Cancer Survivors: Purpose, Study Design, Methods, and Recruitment Results

PubMed Central

Brown, Justin C.; Troxel, Andrea B.; Ky, Bonnie; Damjanov, Nevena; Zemel, Babette S.; Rickels, Michael R.; Rhim, Andrew D.; Rustgi, Anil K.; Courneya, Kerry S.; Schmitz, Kathryn H.

2016-01-01

Background Observational studies indicate that higher volumes of physical activity are associated with improved disease outcomes among colon cancer survivors. The aim of this report is to describe the purpose, study design, methods, and recruitment results of the COURAGE trial, a National Cancer Institute (NCI) sponsored, phase II, randomized, dose-response exercise trial among colon cancer survivors. Methods/Results The primary objective of the COURAGE trial is to quantify the feasibility, safety, and physiologic effects of low-dose (150 min·wk−1) and high-dose (300 min·wk−1) moderate-intensity aerobic exercise compared to usual-care control group over six months. The exercise groups are provided with in-home treadmills and heart rate monitors. Between January and July 2015, 1,433 letters were mailed using a population-based state cancer registry; 126 colon cancer survivors inquired about participation, and 39 were randomized onto the study protocol. Age was associated with inquiry about study participation (P<0.001) and randomization onto the study protocol (P<0.001). No other demographic, clinical, or geographic characteristics were associated with study inquiry or randomization. The final trial participant was randomized in August 2015. Six month endpoint data collection was completed in February 2016. Discussion The recruitment of colon cancer survivors into an exercise trial is feasible. The findings from this trial will inform key design aspects for future phase 2 and phase 3 randomized controlled trials to examine the efficacy of exercise to improve clinical outcomes among colon cancer survivors. PMID:26970181

Coordination and Management of Multisite Complementary and Alternative Medicine (CAM) Therapies: Experience from a Multisite Reflexology Intervention Trial

PubMed Central

Rahbar, Mohammad H.; Wyatt, Gwen; Sikorskii, Alla; Victorson, David; Ardjomand-Hessabi, Manouchehr

2011-01-01

Background Multisite randomized clinical trials allow for increased research collaboration among investigators and expedite data collection efforts. As a result, government funding agencies typically look favorably upon this approach. As the field of complementary and alternative medicine (CAM) continues to evolve, so do increased calls for the use of more rigorous study design and trial methodologies, which can present challenges for investigators. Purpose To describe the processes involved in the coordination and management of a multisite randomized clinical trial of a CAM intervention. Methods Key aspects related to the coordination and management of a multisite CAM randomized clinical trial are presented, including organizational and site selection considerations, recruitment concerns and issues related to data collection and randomization to treatment groups. Management and monitoring of data, as well as quality assurance procedures are described. Finally, a real world perspective is shared from a recently conducted multisite randomized clinical trial of reflexology for women diagnosed with advanced breast cancer. Results The use of multiple sites in the conduct of CAM-based randomized clinical trials can provide an efficient, collaborative and robust approach to study coordination and data collection that maximizes efficiency and ensures the quality of results. Conclusions Multisite randomized clinical trial designs can offer the field of CAM research a more standardized and efficient approach to examine the effectiveness of novel therapies and treatments. Special attention must be given to intervention fidelity, consistent data collection and ensuring data quality. Assessment and reporting of quantitative indicators of data quality should be required. PMID:21664296

Factors Associated With Time to Site Activation, Randomization, and Enrollment Performance in a Stroke Prevention Trial.

PubMed

Demaerschalk, Bart M; Brown, Robert D; Roubin, Gary S; Howard, Virginia J; Cesko, Eldina; Barrett, Kevin M; Longbottom, Mary E; Voeks, Jenifer H; Chaturvedi, Seemant; Brott, Thomas G; Lal, Brajesh K; Meschia, James F; Howard, George

2017-09-01

Multicenter clinical trials attempt to select sites that can move rapidly to randomization and enroll sufficient numbers of patients. However, there are few assessments of the success of site selection. In the CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trials), we assess factors associated with the time between site selection and authorization to randomize, the time between authorization to randomize and the first randomization, and the average number of randomizations per site per month. Potential factors included characteristics of the site, specialty of the principal investigator, and site type. For 147 sites, the median time between site selection to authorization to randomize was 9.9 months (interquartile range, 7.7, 12.4), and factors associated with early site activation were not identified. The median time between authorization to randomize and a randomization was 4.6 months (interquartile range, 2.6, 10.5). Sites with authorization to randomize in only the carotid endarterectomy study were slower to randomize, and other factors examined were not significantly associated with time-to-randomization. The recruitment rate was 0.26 (95% confidence interval, 0.23-0.28) patients per site per month. By univariate analysis, factors associated with faster recruitment were authorization to randomize in both trials, principal investigator specialties of interventional radiology and cardiology, pre-trial reported performance >50 carotid angioplasty and stenting procedures per year, status in the top half of recruitment in the CREST trial, and classification as a private health facility. Participation in StrokeNet was associated with slower recruitment as compared with the non-StrokeNet sites. Overall, selection of sites with high enrollment rates will likely require customization to align the sites selected to the factor under study in the trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02089217. © 2017 American Heart Association, Inc.

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…

A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison

ERIC Educational Resources Information Center

Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Schwartz, Robert P.; O'Grady, Kevin

2012-01-01

The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly…

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…

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…

Competitive Employment for Youth with Autism Spectrum Disorders: Early Results from a Randomized Clinical Trial

ERIC Educational Resources Information Center

Wehman, Paul H.; Schall, Carol M.; McDonough, Jennifer; Kregel, John; Brooke, Valerie; Molinelli, Alissa; Ham, Whitney; Graham, Carolyn W.; Riehle, J. Erin; Collins, Holly T.; Thiss, Weston

2014-01-01

For most youth with autism spectrum disorders (ASD), employment upon graduation from high school or college is elusive. Employment rates are reported in many studies to be very low despite many years of intensive special education services. This paper presented the preliminary results of a randomized clinical trial of Project SEARCH plus ASD…

Differing antidepressant maintenance methodologies.

PubMed

Safer, Daniel J

2017-10-01

The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM maintenance. Antidepressant maintenance research for adults with MDD should be evaluated for industry sponsorship, attrition, the impact of the switch to placebo, and major relapse differences in MDD subpopulations. Copyright © 2017. Published by Elsevier Inc.

The feasibility and acceptability of conducting a trial of specialist medical care and the Lightning Process in children with chronic fatigue syndrome: feasibility randomized controlled trial (SMILE study)

PubMed Central

2013-01-01

Background Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is relatively common in children with limited evidence for treatment. The Phil Parker Lightning Process (LP) is a trademarked intervention, which >250 children use annually. There are no reported studies investigating the effectiveness or possible side effects of LP. Methods The trial population was drawn from the Bath and Bristol NHS specialist paediatric CFS or ME service. The study was designed as a pilot randomized trial with children (aged 12 to 18 years) comparing specialist medical care with specialist medical care plus the Lightning Process. Integrated qualitative methodology was used to explore the feasibility and acceptability of the recruitment, randomization and interventions. Results A total of 56 children were recruited from 156 eligible children (1 October 2010 to 16 June 2012). Recruitment, randomization and both interventions were feasible and acceptable. Participants suggested changes to improve feasibility and acceptability and we incorporated the following in the trial protocol: stopped collecting 6-week outcomes; introduced a second reminder letter; used phone calls to collect primary outcomes from nonresponders; informed participants about different approaches of each intervention and changed our recommendation for the primary outcome for the full study from school attendance to disability (SF-36 physical function subscale) and fatigue (Chalder Fatigue Scale). Conclusions Conducting randomized controlled trials (RCTs) to investigate an alternative treatment such as LP is feasible and acceptable for children with CFS or ME. Feasibility studies that incorporate qualitative methodology enable changes to be made to trial protocols to improve acceptability to participants. This is likely to improve recruitment rate and trial retention. Trial registration Feasibility study first randomization: 29 September 2010. Trial registration: Current Controlled Trials ISRCTN81456207 (31 July 2012). Full trial first randomization: 19 September 2012. PMID:24304689

What's in a name? The challenge of describing interventions in systematic reviews: analysis of a random sample of reviews of non-pharmacological stroke interventions

PubMed Central

Hoffmann, Tammy C; Walker, Marion F; Langhorne, Peter; Eames, Sally; Thomas, Emma; Glasziou, Paul

2015-01-01

Objective To assess, in a sample of systematic reviews of non-pharmacological interventions, the completeness of intervention reporting, identify the most frequently missing elements, and assess review authors’ use of and beliefs about providing intervention information. Design Analysis of a random sample of systematic reviews of non-pharmacological stroke interventions; online survey of review authors. Data sources and study selection The Cochrane Library and PubMed were searched for potentially eligible systematic reviews and a random sample of these assessed for eligibility until 60 (30 Cochrane, 30 non-Cochrane) eligible reviews were identified. Data collection In each review, the completeness of the intervention description in each eligible trial (n=568) was assessed by 2 independent raters using the Template for Intervention Description and Replication (TIDieR) checklist. All review authors (n=46) were invited to complete a survey. Results Most reviews were missing intervention information for the majority of items. The most incompletely described items were: modifications, fidelity, materials, procedure and tailoring (missing from all interventions in 97%, 90%, 88%, 83% and 83% of reviews, respectively). Items that scored better, but were still incomplete for the majority of reviews, were: ‘when and how much’ (in 31% of reviews, adequate for all trials; in 57% of reviews, adequate for some trials); intervention mode (in 22% of reviews, adequate for all trials; in 38%, adequate for some trials); and location (in 19% of reviews, adequate for all trials). Of the 33 (71%) authors who responded, 58% reported having further intervention information but not including it, and 70% tried to obtain information. Conclusions Most focus on intervention reporting has been directed at trials. Poor intervention reporting in stroke systematic reviews is prevalent, compounded by poor trial reporting. Without adequate intervention descriptions, the conduct, usability and interpretation of reviews are restricted and therefore, require action by trialists, systematic reviewers, peer reviewers and editors. PMID:26576811

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 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.

Practices that minimize trauma to the genital tract in childbirth: a systematic review of the literature.

PubMed

Renfrew, M J; Hannah, W; Albers, L; Floyd, E

1998-09-01

Trauma to the genital tract commonly occurs at birth, and can cause short- and long-term morbidity. Clinical measures to reduce its occurrence have not been fully identified. A systematic review of the English language literature was conducted to describe the current state of knowledge on reduction of genital tract trauma before planning a large randomized controlled trial of ways to prevent such trauma. Randomized trials and other published reports were identified from relevant databases and hand searches. Studies were reviewed and assessed using a structured format. A total of 77 papers and chapters were identified and placed into 5 categories after critical review: 25 randomized trials, 4 meta-analyses, 4 prospective studies, 36 retrospective studies, and 8 descriptions of practice from textbooks. The available evidence is conclusive in favor of restricted use of episiotomy. The contribution of maternal characteristics and attitudes to intact perineum has not been investigated. Several other topics warrant further study, including maternal position, style of pushing, and antenatal perineal massage. Strong opinions and sparse data exist regarding the role of hand maneuvers by the birth attendant for perineal management and birth of the baby. This became the topic of the planned randomized controlled trial, which was completed; results will be published soon. The case for restricting the use of episiotomy is conclusive. Several other clinical factors warrant investigation, including the role of hand maneuvers by the birth attendant in preventing birth trauma. A large randomized controlled trial will report on this topic.

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.

Has the quality of reporting in periodontology changed in 14 years? A systematic review.

PubMed

Leow, Natalie M; Hussain, Zahra; Petrie, Aviva; Donos, Nikolaos; Needleman, Ian G

2016-10-01

Quality of reporting randomized controlled trials (RCTs) in periodontology has been poor. Consolidated Standards of Reporting Trials guidelines and an extension for non-pharmacologic trials (CONSORT-NPE), were introduced to aid in improving this. The aim of this study was to assess the quality of reporting in periodontology, changes over the last 14 years, and adherence to CONSORT-NPE. Randomized controlled trials in humans, published in three periodontal journals, from 2013 to 2015 were included. Search was conducted through Medline, Embase and hand searching. One hundred and seventy-three full-text articles included. Two reviewers screened for reporting quality (κ = 0.69, 95% CI 0.60-0.76). 84% of studies (n = 145) described randomization methods, 74% (n = 128) highlighted examiner blinding and 87% (n = 151) accounted for patients at study conclusion. Patient and caregiver blinding was addressed in 50% (n = 70) and 50% (n = 27) of studies respectively. 64% (n = 110) described adequate allocation concealment. Compared with Montenegro et al. (2002, Journal of Dental Research, 81, 866), improvements seen in describing randomization (2002, 16.5%; 2016, 84%), allocation concealment (2002, 6.5%; 2016, 64%), caregiver masking (2002, 17%; 2016, 50%). CONSORT-NPE; 62% (n = 107) had detailed explanations of all treatments, 88% (n = 152) lacked protocols for adherence of caregivers' to an intervention. Only 17% (n = 29) described caregivers' expertise and case volume. Substantial improvements have occurred. Attention is required for statistical analysis of patient losses and masking. CONSORT-NPE aspects were poorly reported. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Characteristics and quality of reporting of cluster randomized trials in children: reporting needs improvement.

PubMed

Walleser, Silke; Hill, Suzanne R; Bero, Lisa A

2011-12-01

To describe the characteristics and quality of reporting of cluster randomized trials (CRTs) in children published from 2004 to 2010. Four databases were searched for reports of CRTs in children (0-18 years). Characteristics of the studies were summarized and the quality of reporting assessed using consolidated standards of reporting trial-CRT (CONSORT-CRT). Of 1,949 identified references, 106 were included. The number of published CRTs in children increased since 2004. The greatest proportion of CRTs was undertaken in Europe (29%), whereas 40% was conducted in low- and middle-income countries. Most studies were of complex rather than simple interventions (83%); were preventive rather than treatment interventions (76%); and most frequently addressed infectious disease (21%), diet/physical activity interventions (19%), health-risk behaviors (15%), and undernutrition (13%). The majority used schools as units of randomization (72%) and enrolled 1,000-10,000 children per study (51%). Reporting was generally poor, with 34% of CRTs inadequately reporting on more than half of the CONSORT-CRT criteria. Although 85% of CRTs reported that they had ethics approval for the study, consent or assent was not obtained from children in most studies. Children-specific elements of reporting are needed to improve the quality of reporting of CRTs and consequently their planning and implementation. Copyright © 2011 Elsevier Inc. All rights reserved.

A quality assessment of randomized controlled trial reports in endodontics.

PubMed

Lucena, C; Souza, E M; Voinea, G C; Pulgar, R; Valderrama, M J; De-Deus, G

2017-03-01

To assess the quality of the randomized clinical trial (RCT) reports published in Endodontics between 1997 and 2012. Retrieval of RCTs in Endodontics was based on a search of the Thomson Reuters Web of Science (WoS) database (March 2013). Quality evaluation was performed using a checklist based on the Jadad criteria, CONSORT (Consolidated Standards of Reporting Trials) statement and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials). Descriptive statistics were used for frequency distribution of data. Student's t-test and Welch test were used to identify the influence of certain trial characteristics upon report quality (α = 0.05). A total of 89 RCTs were evaluated, and several methodological flaws were found: only 45% had random sequence generation at low risk of bias, 75% did not provide information on allocation concealment, and 19% were nonblinded designs. Regarding statistics, only 55% of the RCTs performed adequate sample size estimations, only 16% presented confidence intervals, and 25% did not provide the exact P-value. Also, 2% of the articles used no statistical tests, and in 87% of the RCTs, the information provided was insufficient to determine whether the statistical methodology applied was appropriate or not. Significantly higher scores were observed for multicentre trials (P = 0.023), RCTs signed by more than 5 authors (P = 0.03), articles belonging to journals ranked above the JCR median (P = 0.03), and articles complying with the CONSORT guidelines (P = 0.000). The quality of RCT reports in key areas for internal validity of the study was poor. Several measures, such as compliance with the CONSORT guidelines, are important in order to raise the quality of RCTs in Endodontics. © 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Hypertension with unsatisfactory sleep health (HUSH): study protocol for a randomized controlled trial.

PubMed

Levenson, Jessica C; Rollman, Bruce L; Ritterband, Lee M; Strollo, Patrick J; Smith, Kenneth J; Yabes, Jonathan G; Moore, Charity G; Harvey, Allison G; Buysse, Daniel J

2017-06-06

Insomnia is common in primary care medical practices. Although behavioral treatments for insomnia are safe, efficacious, and recommended in practice guidelines, they are not widely-available, and their effects on comorbid medical conditions remain uncertain. We are conducting a pragmatic clinical trial to test the efficacy of two cognitive behavioral treatments for insomnia (Brief Behavioral Treatment for Insomnia (BBTI) and Sleep Healthy Using the Internet (SHUTi)) versus an enhanced usual care condition (EUC). The study is a three-arm, parallel group, randomized controlled trial. Participants include 625 adults with hypertension and insomnia, recruited via electronic health records from primary care practices affiliated with a large academic medical center. After screening and baseline assessments, participants are randomized to treatment. BBTI is delivered individually with a live therapist via web-interface/telehealth sessions, while SHUTi is a self-guided, automated, interactive, web-based form of cognitive behavioral therapy for insomnia. Participants in EUC receive an individualized sleep report, educational resources, and an online educational video. Treatment outcomes are measured at 9 weeks, 6 months, and 12 months. The primary outcome is patient-reported sleep disturbances. Secondary outcomes include other self-reported sleep measures, home blood pressure, body mass index, quality of life, health functioning, healthcare utilization, and side effects. This randomized clinical trial compares two efficacious insomnia interventions to EUC, and provides a cost-effective and efficient examination of their similarities and differences. The pragmatic orientation of this trial may impact sleep treatment delivery in real world clinical settings and advance the dissemination and implementation of behavioral sleep interventions. ClinicalTrials.gov (Identifier: NCT02508129 ; Date Registered: July 21, 2015).

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.

A reanalysis of the Cu-7 intrauterine contraceptive device clinical trial and the incidence of pelvic inflammatory disease: a paradigm for assessing intrauterine contraceptive device safety.

PubMed

Roy, S; Azen, C

1994-06-01

We calculated and compared the incidence of pelvic inflammatory disease in a 10% random sample of the Cu-7 intrauterine contraceptive device (G.D. Searle & Co., Skokie, Ill.) clinical trial with the rates reported to the Food and Drug Administration and those in subsequent trials published in the world literature. A 10% random sample of the Cu-7 clinical trial was examined because calculations had demonstrated this random sample to be sufficient in size (n = 1614) to detect a difference in rates of pelvic inflammatory disease from those reported to the Food and Drug Administration. An audit of a subset of the patient files, compared with the original files in Skokie, Illinois, confirmed that the files available for analysis were complete. Standard definitions were used to identify cases of pelvic inflammatory disease and to calculate rates of pelvic inflammatory disease. The world literature on Cu-7 clinical trials was reviewed. The calculated crude and Pearl index rates of pelvic inflammatory disease were consistent with those rates previously reported to the Food and Drug Administration and published in the medical literature. Life-table pelvic inflammatory disease rates were not different between nulliparous and parous women and pelvic inflammatory disease did not differ from basal annual rates in fecund women. On the basis of the analysis of this 10% sample, the pelvic inflammatory disease patient rates reported to the Food and Drug Administration for the entire Cu-7 clinical trial are accurate and are similar to those published in the world literature.

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

Last-observation-carried-forward imputation method in clinical efficacy trials: review of 352 antidepressant studies.

PubMed

Woolley, Stephen B; Cardoni, Alex A; Goethe, John W

2009-12-01

To determine the prevalence, over 40 years, of using the last-observation-carried-forward (LOCF) imputation method in clinical trials, the association between use of LOCF and how the trials were conducted, and the extent of information about attrition and LOCF use in published reports. Retrospective analysis of the reports of randomized antidepressant efficacy trials published over a 40-year period (1965-2004). MEDLINE database, Cochrane reviews, reference- and bibliography-based manual search, and publication list services. A total of 352 trials met the following criteria for analysis: antidepressant comparative efficacy trial, randomized design, patients with major depressive disorder, English-language article, published during 1965-2004, and first report of a trial. Design, attrition, and data analysis characteristics were recorded by investigators and trained assistants. Analyses included descriptive statistics of the trial size, duration, and number of patients who dropped out in LOCF versus non-LOCF studies, as well as the extent to which dropouts and the potential bias associated with attrition was discussed in the published report. The frequency of published antidepressant clinical trials increased from less than 1 trial/year (1965-1974) to 19 trials/year (1990-1994). Trials using the LOCF method were significantly larger than non-LOCF trials (p<0.01), and the proportion of subjects dropping out was significantly greater (p<0.05) in LOCF versus non-LOCF trials. The proportion of subjects dropping out remained relatively constant over time (approximately 30%) but was significantly greater among LOCF (30.9%) than non-LOCF (28.8%) trials (p<0.01). The LOCF study articles were more likely to report dropouts, but only 7% of these articles reported outcomes recorded for subjects before they dropped out. Less than 16% of articles discussed bias associated with dropouts, 6.8% discussed the direction of bias, and only about 2% suggested the magnitude of the bias. The percentage of clinical antidepressant trials using the LOCF method and the percentage of study subjects' data imputed by using LOCF increased many-fold during 1965-2004. Published reports of trials provided little information to allow readers to assess possible bias introduced by use of the LOCF method.

EXERCISE AND STRESS MANAGEMENT TRAINING PRIOR TO HEMATOPOIETIC CELL TRANSPLANTATION: BLOOD AND MARROW TRANSPLANT CLINICAL TRIALS NETWORK (BMT CTN) 0902

PubMed Central

Jacobsen, Paul B.; Le-Rademacher, Jennifer; Jim, Heather; Syrjala, Karen; Wingard, John R.; Logan, Brent; Wu, Juan; Majhail, Navneet S.; Wood, William; Rizzo, J. Douglas; Geller, Nancy L.; Kitko, Carrie; Faber, Edward; Abidi, Muneer H.; Slater, Susan; Horowitz, Mary M.; Lee, Stephanie J.

2014-01-01

Studies show that engaging patients in exercise and/or stress management techniques during hematopoietic cell transplantation (HCT) improves quality of life. The Blood and Marrow Transplant Clinical Trials Network tested the efficacy of training patients to engage in self-directed exercise and stress management during their HCTs. The study randomized 711 patients at 21 centers to receive one of four training interventions before HCT: a self-directed exercise program, a self-administered stress management program, both or neither. Participants completed self-reported assessments at enrollment and up to 180 days after transplant. Randomization was stratified by center and transplant type. There were no differences in the primary endpoints of the physical (PCS) and mental (MCS) component scales of the SF36 at day 100 among the groups based on an intention-to-treat analysis. There were no differences observed in overall survival, hospital days through day 100 post-HCT, or in other patient-reported outcomes, including treatment-related distress, sleep quality, pain, and nausea. Patient randomized to training in stress management reported more use of those techniques; patients randomized to training in exercise did not report more physical activity. Although other studies have reported efficacy of more intensive interventions, brief training in an easy-to-disseminate format for either self-directed exercise or stress management was not effective in our trial. PMID:24910380

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

Recruitment to and pilot results of the PACES randomized trial of physical exercise during adjuvant chemotherapy for colon cancer.

PubMed

van Waart, Hanna; Stuiver, Martijn M; van Harten, Wim H; Geleijn, Edwin; de Maaker-Berkhof, Marianne; Schrama, Jolanda; Geenen, Maud M; Meerum Terwogt, Jetske M; van den Heiligenberg, Simone M; Hellendoorn-van Vreeswijk, Jeannette A J H; Sonke, Gabe S; Aaronson, Neil K

2018-01-01

We report the recruitment rate, reasons for and factors influencing non-participation, and descriptive results of a randomized controlled trial of two different exercise programs for patients with colon cancer undergoing adjuvant chemotherapy. Participants were randomized to a low-intensity, home-based program (Onco-Move), a moderate- to high-intensity, combined supervised resistance and aerobic exercise program (OnTrack), or Usual Care. Non-participants provided reasons for non-participation and were asked to complete a questionnaire assessing behavioral and attitudinal variables. Trial participants completed performance-based and self-reported outcome measures prior to randomization, at the end of chemotherapy, and at the 6-month follow-up. Twenty-three of 63 referred patients agreed to participate in the trial. All 40 non-participants provided reasons for non-participation. Forty-five percent of the non-participants completed the questionnaire. Those who did not want to exercise had higher fatigue scores at baseline and a more negative attitude toward exercise. Compliance to both programs was high and no adverse events occurred. On average, the colon cancer participants were able to maintain or improve their physical fitness levels and maintain or decrease their fatigue levels during chemotherapy and follow-up. Recruitment of patients with colon cancer to a physical exercise trial during adjuvant chemotherapy proved to be difficult, underscoring the need to develop more effective strategies to increase participation rates. Both home-based and supervised programs are safe and feasible in patients with colon cancer undergoing chemotherapy. Effectiveness needs to be established in a larger trial. Netherlands Trial Register - NTR2159.

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).

The breast reconstruction evaluation of acellular dermal matrix as a sling trial (BREASTrial): design and methods of a prospective randomized trial.

PubMed

Agarwal, Jayant P; Mendenhall, Shaun D; Anderson, Layla A; Ying, Jian; Boucher, Kenneth M; Liu, Ting; Neumayer, Leigh A

2015-01-01

Recent literature has focused on the advantages and disadvantages of using acellular dermal matrix in breast reconstruction. Many of the reported data are from low level-of-evidence studies, leaving many questions incompletely answered. The present randomized trial provides high-level data on the incidence and severity of complications in acellular dermal matrix breast reconstruction between two commonly used types of acellular dermal matrix. A prospective randomized trial was conducted to compare outcomes of immediate staged tissue expander breast reconstruction using either AlloDerm or DermaMatrix. The impact of body mass index, smoking, diabetes, mastectomy type, radiation therapy, and chemotherapy on outcomes was analyzed. Acellular dermal matrix biointegration was analyzed clinically and histologically. Patient satisfaction was assessed by means of preoperative and postoperative surveys. Logistic regression models were used to identify predictors of complications. This article reports on the study design, surgical technique, patient characteristics, and preoperative survey results, with outcomes data in a separate report. After 2.5 years, we successfully enrolled and randomized 128 patients (199 breasts). The majority of patients were healthy nonsmokers, with 41 percent of patients receiving radiation therapy and 49 percent receiving chemotherapy. Half of the mastectomies were prophylactic, with nipple-sparing mastectomy common in both cancer and prophylactic cases. Preoperative survey results indicate that patients were satisfied with their premastectomy breast reconstruction education. Results from the Breast Reconstruction Evaluation Using Acellular Dermal Matrix as a Sling Trial will assist plastic surgeons in making evidence-based decisions regarding acellular dermal matrix-assisted tissue expander breast reconstruction. Therapeutic, II.

WWC Review of the Report "Interactive Learning Online at Public Universities: Evidence from a Six-Campus Randomized Trial." What Works Clearinghouse Single Study Review

ERIC Educational Resources Information Center

What Works Clearinghouse, 2014

2014-01-01

The 2013 study, "Interactive Learning Online at Public Universities: Evidence From a Six-Campus Randomized Trial," examined the impact of interactive learning online (ILO) on the pass rates of 605 students enrolled in introductory statistics courses at six public universities. ILO is a form of online course instruction in which…

Clinical effectiveness of garlic (Allium sativum).

PubMed

Pittler, Max H; Ernst, Edzard

2007-11-01

The objective of this review is to update and assess the clinical evidence based on rigorous trials of the effectiveness of garlic (A. sativum). Systematic searches were carried out in Medline, Embase, Amed, the Cochrane Database of Systematic Reviews, Natural Standard, and the Natural Medicines Comprehensive Database (search date December 2006). Our own files, the bibliographies of relevant papers and the contents pages of all issues of the review journal FACT were searched for further studies. No language restrictions were imposed. To be included, trials were required to state that they were randomized and double blind. Systematic reviews and meta-analyses of garlic were included if based on the results of randomized, double-blind trials. The literature searches identified six relevant systematic reviews and meta-analysis and double-blind randomized trials (RCT) that were published subsequently. These relate to cancer, common cold, hypercholesterolemia, hypertension, peripheral arterial disease and pre-eclampsia. The evidence based on rigorous clinical trials of garlic is not convincing. For hypercholesterolemia, the reported effects are small and may therefore not be of clinical relevance. For reducing blood pressure, few studies are available and the reported effects are too small to be clinically meaningful. For all other conditions not enough data are available for clinical recommendations.

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.

Outcomes of a pilot hand hygiene randomized cluster trial to reduce communicable infections among US office-based employees.

PubMed

Stedman-Smith, Maggie; DuBois, Cathy L Z; Grey, Scott F; Kingsbury, Diana M; Shakya, Sunita; Scofield, Jennifer; Slenkovich, Ken

2015-04-01

To determine the effectiveness of an office-based multimodal hand hygiene improvement intervention in reducing self-reported communicable infections and work-related absence. A randomized cluster trial including an electronic training video, hand sanitizer, and educational posters (n = 131, intervention; n = 193, control). Primary outcomes include (1) self-reported acute respiratory infections (ARIs)/influenza-like illness (ILI) and/or gastrointestinal (GI) infections during the prior 30 days; and (2) related lost work days. Incidence rate ratios calculated using generalized linear mixed models with a Poisson distribution, adjusted for confounders and random cluster effects. A 31% relative reduction in self-reported combined ARI-ILI/GI infections (incidence rate ratio: 0.69; 95% confidence interval, 0.49 to 0.98). A 21% nonsignificant relative reduction in lost work days. An office-based multimodal hand hygiene improvement intervention demonstrated a substantive reduction in self-reported combined ARI-ILI/GI infections.

Carotid artery stenting vs. carotid endarterectomy in the management of carotid artery stenosis: Lessons learned from randomized controlled trials

PubMed Central

Salem, Mohamed M.; Alturki, Abdulrahman Y.; Fusco, Matthew R.; Thomas, Ajith J.; Carter, Bob S.; Chen, Clark C.; Kasper, Ekkehard M.

2018-01-01

Background: Carotid artery stenosis, both symptomatic and asymptomatic, has been well studied with several multicenter randomized trials. The superiority of carotid endarterectomy (CEA) to medical therapy alone in both symptomatic and asymptomatic carotid artery stenosis has been well established in previous trials in the 1990s. The consequent era of endovascular carotid artery stenting (CAS) has offered another option for treating carotid artery stenosis. A series of randomized trials have now been conducted to compare CEA and CAS in the treatment of carotid artery disease. The large number of similar trials has created some confusion due to inconsistent results. Here, the authors review the trials that compare CEA and CAS in the management of carotid artery stenosis. Methods: The PubMed database was searched systematically for randomized controlled trials published in English that compared CEA and CAS. Only human studies on adult patients were assessed. The references of identified articles were reviewed for additional manuscripts to be included if inclusion criteria were met. The following terms were used during search: carotid stenosis, endarterectomy, stenting. Retrospective or single-center studies were excluded from the review. Results: Thirteen reports of seven large-scale prospective multicenter studies, comparing both interventions for symptomatic or asymptomatic extracranial carotid artery stenosis, were identified. Conclusions: While the superiority of intervention to medical management for symptomatic patients has been well established in the literatures, careful selection of asymptomatic patients for intervention should be undertaken and only be pursued after institution of appropriate medical therapy until further reports on trials comparing medical therapy to intervention in this patient group are available. PMID:29740506

Hierarchy of evidence: differences in results between non-randomized studies and randomized trials in patients with femoral neck fractures.

PubMed

Bhandari, Mohit; Tornetta, Paul; Ellis, Thomas; Audige, Laurent; Sprague, Sheila; Kuo, Jonathann C; Swiontkowski, Marc F

2004-01-01

There have been a number of non-randomized studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. However, there remains considerable debate about whether the results of non-randomized studies are consistent with the results of randomized, controlled trials. Given the economic burden of hip fractures, it remains essential to identify therapies to improve outcomes; however, whether data from non-randomized studies of an intervention should be used to guide patient care remains unclear. We aimed to determine whether the pooled results of mortality and revision surgery among non-randomized studies were similar to those of randomized trials in studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. We conducted a Medline search from 1969 to June 2002, identifying both randomized and non-randomized studies comparing internal fixation with arthroplasty in patients with femoral neck fractures. Additional strategies to identify relevant articles included Cochrane database, SCISEARCH, textbooks, annual meeting programs, and content experts. We abstracted information on mortality and revision rates in each study and compared the pooled results between non-randomized and randomized studies. In addition, we explored potential reasons for dissimilar results between the two study designs. We identified 140 citations that addressed the general topic of comparison of arthroplasty and internal fixation for hip fracture. Of these, 27 studies met the eligibility criteria, 13 of which were non-randomized studies and 14 of which were randomized trials. Mortality data was available in all 13 non-randomized studies ( n=3108 patients) and in 12 randomized studies ( n=1767 patients). Non-randomized studies overestimated the risk of mortality by 40% when compared with the results of randomized trials (relative risk 1.44 vs 1.04, respectively). Information on revision risk was available in 9 non-randomized studies ( n=2764 patients) and all 14 randomized studies ( n=1901 patients). Both estimates from non-randomized and randomized studies revealed a significant reduction in the risk of revision surgery with arthroplasty compared with internal fixation (relative risk 0.38 vs 0.23, respectively). The reduction in the risk of revision surgery with arthroplasty compared with internal fixation was 62% for non-randomized studies and 77% for randomized trials. Thus, non-randomized studies underestimated the relative benefit of arthroplasty by 19.5%. Non-randomized studies with point estimates of relative risk similar to the pooled estimate for randomized trials all controlled for patient age, gender, and fracture displacement in their comparisons of mortality. We were unable to identify reasons for differences in the revision rate results between the study designs. Similar to other reports in medical subspecialties, non-randomized studies provided results dissimilar to randomized trials of arthroplasty vs internal fixation for mortality and revision rates in patients with femoral neck fractures. Investigators should be aware of these discrepancies when evaluating the merits of alternative surgical interventions, especially when both randomized trials and non-randomized comparative studies are available.

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.

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.

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.

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.

Trends in the application of dynamic allocation methods in multi-arm cancer clinical trials.

PubMed

Pond, Gregory R; Tang, Patricia A; Welch, Stephen A; Chen, Eric X

2010-06-01

Dynamic allocation (DA) methods which attempt to balance baseline prognostic factors between treatment arms, can be used in multi-arm clinical trials to sequentially allocate patients to treatment. Although some experts express concern regarding the validity of inference from trials using DA, others believe DA methods produce more credible results. A review of published multi-arm cancer clinical trials was conducted to explore the frequency of DA use in oncology. Multi-arm phase III clinical trials of at least 100 patients per arm, published in 13 major oncology journals from 1995-2005 were manually reviewed. Information about reported use of DA methods, or randomization via random permuted blocks (PB), was extracted along with trial characteristics. Of 476 published clinical trials, 112 (23.5%) reported using some form of DA method, while 103 (21.6%) reported using PB methods. Most trials (403 or 84.7%) reported stratifying on at least one baseline factor. The mean number of stratification factors was 2.70 per trial, and 78.6% of DA trials reported 3 or more stratification factors compared with 30.2% of non-DA trials (p < 0.001). The frequency of DA use increased over time, with 20.2%, 21.3%, 25.8%, 28.8% and 38.9% of trials reported use in 1995-2001, 2002, 2003, 2004, and 2005, respectively. Use of DA methods was more frequently reported in trials involving an academic co-operative group (28.4% vs. 13.8%), however, no difference was observed between industry-funded and other-funded trials (24.0% vs. 23.2%) or geographical region (19.7% of North American trials, 26.2% of European trials and 21.7% of multinational/other trials). As a retrospective analysis, the true frequency of DA use is likely underreported. Few trials gave complete details of the allocation method used, thus it is possible some manuscripts reported incorrect allocation methods. Journals were selected which were assumed to publish most large, multi-arm clinical trials in cancer from 1995-2005, however, some trials were likely reported in journals other than what was reviewed. DA methods are frequently used in multi-arm cancer clinical trials. The use of DA appears to becoming more common over time and are used more frequently when an academic cooperative group is involved. No relationship between industry funded trials or geographic region and allocation method was observed. Clinical Trials 2010; 7: 227-234. http://ctj.sagepub.com.

Permissive or Trophic Enteral Nutrition and Full Enteral Nutrition Had Similar Effects on Clinical Outcomes in Intensive Care: A Systematic Review of Randomized Clinical Trials.

PubMed

Silva, Camila F A; de Vasconcelos, Simone G; da Silva, Thales A; Silva, Flávia M

2018-01-26

The aim of this study was to systematically review the effect of permissive underfeeding/trophic feeding on the clinical outcomes of critically ill patients. A systematic review of randomized clinical trials to evaluate the mortality, length of stay, and mechanical ventilation duration in patients randomized to either hypocaloric or full-energy enteral nutrition was performed. Data sources included PubMed and Scopus and the reference lists of the articles retrieved. Two independent reviewers participated in all phases of this systematic review as proposed by the Cochrane Handbook, and the review was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 7 randomized clinical trials that included a total of 1,717 patients were reviewed. Intensive care unit length of stay and mechanical ventilation duration were not statistically different between the intervention and control groups in all randomized clinical trials, and mortality rate was also not different between the groups. In conclusion, hypocaloric enteral nutrition had no significantly different effects on morbidity and mortality in critically ill patients when compared with full-energy nutrition. It is still necessary to determine the safety of this intervention in this group of patients, the optimal amount of energy provided, and the duration of this therapy. © 2018 American Society for Parenteral and Enteral Nutrition.

Pregnancy occurring during or following adjuvant trastuzumab in patients enrolled in the HERA trial (BIG 01-01).

PubMed

Azim, Hatem A; Metzger-Filho, Otto; de Azambuja, Evandro; Loibl, Sibylle; Focant, Florine; Gresko, Ekaterina; Arfi, Mounir; Piccart-Gebhart, Martine

2012-05-01

Only few case reports describe the pregnancy course and outcome of breast cancer patients, who were under treatment with trastuzumab at the time of conception or who have completed trastuzumab therapy before becoming pregnant. The HERA trial is a large phase III randomized clinical trial in which patients with early HER2-positive breast cancer were randomized to receive 1 or 2 years of trastuzumab or observation following completion of primary chemotherapy. To examine the effect of trastuzumab on pregnancy outcome, we report all pregnancy events that occurred until March 2010 in patients enrolled in the study. For the sake of this analysis, patients were assigned to three groups: (1) pregnancy occurring during and up to 3 months after trastuzumab exposure (group 1); (2) pregnancy occurring >3 months of last trastuzumab dose (group 2); and (3) pregnancy occurring in patients without prior exposure to trastuzumab (group 3). Sixteen, 45 and 9 pregnancies took place in groups 1, 2, and 3, respectively. 25 and 16% of patients in groups 1 and 2 experienced spontaneous abortion, the former being higher than figures reported in the general population. However, short-term fetal outcome appeared normal across the three groups. Only 2 congenital anomalies were reported, one in group 2 and one in group 3. No congenital anomalies were reported in those exposed to trastuzumab in utero. This is the first report from a large randomized trial assessing the effect of trastuzumab on pregnancy course and outcome. Based on our results, trastuzumab does not appear to affect fetal outcome in patients who manage to complete their pregnancy. We are currently initiating a collaboration to collect similar data from the other large adjuvant trastuzumab trials to confirm these findings.

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.

Disappointment and adherence among parents of newborns allocated to the control group: a qualitative study of a randomized clinical trial.

PubMed

Meinich Petersen, Sandra; Zoffmann, Vibeke; Kjærgaard, Jesper; Graff Stensballe, Lone; Graff Steensballe, Lone; Greisen, Gorm

2014-04-15

When a child participates in a clinical trial, informed consent has to be given by the parents. Parental motives for participation are complex, but the hope of getting a new and better treatment for the child is important. We wondered how parents react when their child is allocated to the control group of a randomized controlled trial, and how it will affect their future engagement in the trial. We included parents of newborns randomized to the control arm in the Danish Calmette study at Rigshospitalet in Copenhagen. The Calmette study is a randomized clinical trial investigating the non-specific effects of early BCG-vaccine to healthy neonates. Randomization is performed immediately after birth and parents are not blinded to the allocation. We set up a semi-structured focus group with six parents from four families. Afterwards we telephone-interviewed another 19 mothers to achieve saturation. Thematic analysis was used to identify themes across the data sets. The parents reported good understanding of the randomization process. Their most common reaction to allocation was disappointment, though relief was also seen. A model of reactions to being allocated to the control group was developed based on the participants' different positions along two continuities from 'Our participation in trial is not important' to 'Our participation in trial is important', and 'Vaccine not important to us' to 'Vaccine important to us'. Four very disappointed families had thought of getting the vaccine elsewhere, and one had actually had their child vaccinated. All parents involved in the focus group and the telephone interviews wanted to participate in the follow-ups planned for the Calmette study. This study identified an almost universal experience of disappointment among parents of newborns who were randomized to the control group, but also a broad expression of understanding and accepting the idea of randomization. The trial staff might use the model of reactions in understanding the parents' disappointment and in this way support their motives for participation. A generalized version might be applicable across randomized controlled trials at large. The Calmette study is registered in EudraCT (https://eudract.ema.europa.eu/) with trial number 2010-021979-85.

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.

[Evidence-based quality assessment of 10-year orthodontic clinical trials in 4 major dental journals].

PubMed

Sun, Yan-nan; Lei, Fei-fei; Cao, Yan-li; Fu, Min-kui

2010-02-01

To assess the quality of orthodontic clinical trials published in 4 major dental journals in the past 10 years and establish the reference standard for orthodontic clinical trials and quality control of dental journals. All the clinical trials published in Chinese Journal of Stomatology, West China Journal of Stomatology, Journal of Practice Stomatology and Chinese Journal of Orthodontics from 1999 to 2008 were searched. The demographic information of the papers was extracted and the quality of the clinical trials according to the consolidated standards of reporting trials (CONSORT) was assessed. Four hundred and ninety-four clinical trials were retrieved, and 21.3% (105/494) of them were supported by grants. For the study design, only 26.1% (129/494) were prospective studies, and 3.8% (19/494) were randomized clinical trials. It was hard to evaluate precisely due to the lack of information about the details of the study designs. For the randomized clinical trials, the lack of details for randomization, allocation concealment, blinding and intention to treat compromised the quality. The general quality of clinical trials in orthodontics is poor. It needs to be improved both in the clinical study design and the paper writing.

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.

Randomized clinical trial of bright light therapy for antepartum depression: preliminary findings.

PubMed

Epperson, C Neill; Terman, Michael; Terman, Jiuan Su; Hanusa, Barbara H; Oren, Dan A; Peindl, Kathleen S; Wisner, Katherine L

2004-03-01

Bright light therapy was shown to be a promising treatment for depression during pregnancy in a recent open-label study. In an extension of this work, we report findings from a double-blind placebo-controlled pilot study. Ten pregnant women with DSM-IV major depressive disorder were randomly assigned from April 2000 to January 2002 to a 5-week clinical trial with either a 7000 lux (active) or 500 lux (placebo) light box. At the end of the randomized controlled trial, subjects had the option of continuing in a 5-week extension phase. The Structured Interview Guide for the Hamilton Depression Scale-Seasonal Affective Disorder Version was administered to assess changes in clinical status. Salivary melatonin was used to index circadian rhythm phase for comparison with antidepressant results. Although there was a small mean group advantage of active treatment throughout the randomized controlled trial, it was not statistically significant. However, in the longer 10-week trial, the presence of active versus placebo light produced a clear treatment effect (p =.001) with an effect size (0.43) similar to that seen in antidepressant drug trials. Successful treatment with bright light was associated with phase advances of the melatonin rhythm. These findings provide additional evidence for an active effect of bright light therapy for antepartum depression and underscore the need for an expanded randomized clinical trial.

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

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.

Behavioral Outcome Effects of Serious Gaming as an Adjunct to Treatment for Children With Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial.

PubMed

Bul, Kim C M; Kato, Pamela M; Van der Oord, Saskia; Danckaerts, Marina; Vreeke, Leonie J; Willems, Annik; van Oers, Helga J J; Van Den Heuvel, Ria; Birnie, Derk; Van Amelsvoort, Thérèse A M J; Franken, Ingmar H A; Maras, Athanasios

2016-02-16

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). 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. 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. 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. Plan-It Commander offers an effective therapeutic approach as an adjunct intervention to traditional therapeutic ADHD approaches that improve functional outcomes in daily life. International Standard Randomized Controlled Trial Number (ISRCTN): 62056259; http://www.controlled-trials.com/ISRCTN62056259 (Archived by WebCite at http://www.webcitation.org/6eNsiTDJV).

The effects of Sahaja Yoga meditation on mental health: a systematic review.

PubMed

Hendriks, Tom

2018-05-30

Objectives To determine the efficacy of Sahaja Yoga (SY) meditation on mental health among clinical and healthy populations. Methods All publications on SY were eligible. Databases were searched up to November 2017, namely PubMed, MEDLINE (NLM), PsychINFO, and Scopus. An internet search (Google Scholar) was also conducted. The quality of the randomized controlled trails was assessed using the Cochrane Risk Assessment for Bias. The quality of cross-sectional studies, a non-randomized controlled trial and a cohort study was assessed with the Newcastle-Ottawa Quality Assessment Scale. Results We included a total of eleven studies; four randomized controlled trials, one non-randomized controlled trial, five cross-sectional studies, and one prospective cohort study. The studies included a total of 910 participants. Significant findings were reported in relation to the following outcomes: anxiety, depression, stress, subjective well-being, and psychological well-being. Two randomized studies were rated as high quality studies, two randomized studies as low quality studies. The quality of the non-randomized trial, the cross-sectional studies and the cohort study was high. Effect sizes could not be calculated in five studies due to unclear or incomplete reporting. Conclusions After reviewing the articles and taking the quality of the studies into account, it appears that SY may reduce depression and possibly anxiety. In addition, the practice of SY is also associated with increased subjective wellbeing and psychological well-beng. However, due to the limited number of publications, definite conclusions on the effects of SY cannot be made and more high quality randomized studies are needed to justify any firm conclusions on the beneficial effects of SY on mental health.

Improving the Reporting Quality of Nonrandomized Evaluations of Behavioral and Public Health Interventions: The TREND Statement

PubMed Central

Des Jarlais, Don C.; Lyles, Cynthia; Crepaz, Nicole

2004-01-01

Developing an evidence base for making public health decisions will require using data from evaluation studies with randomized and nonrandomized designs. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study, with sufficient detail and clarity to readily see differences and similarities among studies in the same area. The Consolidated Standards of Reporting Trials (CONSORT) statement provides guidelines for transparent reporting of randomized clinical trials. We present the initial version of the Transparent Reporting of Evaluations with Nonrandomized Designs (TREND) statement. These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions, research design, and methods of adjusting for possible biases in evaluation studies that use nonrandomized designs. PMID:14998794

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.

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.

Assessment and prevalence of pulmonary oedema in contemporary acute heart failure trials: a systematic review.

PubMed

Platz, Elke; Jhund, Pardeep S; Campbell, Ross T; McMurray, John J

2015-09-01

Pulmonary oedema is a common and important finding in acute heart failure (AHF). We conducted a systematic review to describe the methods used to assess pulmonary oedema in recent randomized AHF trials and report its prevalence in these trials. Of 23 AHF trials published between 2002 and 2013, six were excluded because they were very small or not randomized, or missing full-length publications. Of the remaining 17 (n = 200-7141) trials, six enrolled patients with HF and reduced ejection fraction (HF-REF) and 11, patients with both HF-REF and HF with preserved ejection fraction (HF-PEF). Pulmonary oedema was an essential inclusion criterion, in most trials, based upon findings on physical examination ('rales'), radiographic criteria ('signs of congestion'), or both. The prevalence of pulmonary oedema in HF-REF trials ranged from 75% to 83% and in combined HF-REF and HF-PEF trials from 51% to 100%. Five trials did not report the prevalence or extent of pulmonary oedema assessed by either clinical examination or chest x-ray. Improvement of pulmonary congestion with treatment was inconsistently reported and commonly grouped with other signs of congestion into a score. One trial suggested that patients with rales over >2/3 of the lung fields on admission were at higher risk of adverse outcomes than those without. Although pulmonary oedema is a common finding in AHF, represents a therapeutic target, and may be of prognostic importance, recent trials used inconsistent criteria to define it, and did not consistently report its severity at baseline or its response to treatment. Consistent and ideally quantitative, methods for the assessment of pulmonary oedema in AHF trials are needed. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Cluster randomised trials in the medical literature: two bibliometric surveys

PubMed Central

Bland, J Martin

2004-01-01

Background Several reviews of published cluster randomised trials have reported that about half did not take clustering into account in the analysis, which was thus incorrect and potentially misleading. In this paper I ask whether cluster randomised trials are increasing in both number and quality of reporting. Methods Computer search for papers on cluster randomised trials since 1980, hand search of trial reports published in selected volumes of the British Medical Journal over 20 years. Results There has been a large increase in the numbers of methodological papers and of trial reports using the term 'cluster random' in recent years, with about equal numbers of each type of paper. The British Medical Journal contained more such reports than any other journal. In this journal there was a corresponding increase over time in the number of trials where subjects were randomised in clusters. In 2003 all reports showed awareness of the need to allow for clustering in the analysis. In 1993 and before clustering was ignored in most such trials. Conclusion Cluster trials are becoming more frequent and reporting is of higher quality. Perhaps statistician pressure works. PMID:15310402

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.

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.

Existing reporting guidelines for clinical trials are not completely relevant for implantable medical devices: a systematic review.

PubMed

Motte, Anne-France; Diallo, Stéphanie; van den Brink, Hélène; Châteauvieux, Constance; Serrano, Carole; Naud, Carole; Steelandt, Julie; Alsac, Jean-Marc; Aubry, Pierre; Cour, Florence; Pellerin, Olivier; Pineau, Judith; Prognon, Patrice; Borget, Isabelle; Bonan, Brigitte; Martelli, Nicolas

2017-11-01

The aim of this study was to determine relevant items for reporting clinical trials on implantable medical devices (IMDs) and to identify reporting guidelines which include these items. A panel of experts identified the most relevant items for evaluating IMDs from an initial list based on reference papers. We then conducted a systematic review of articles indexed in MEDLINE. We retrieved reporting guidelines from the EQUATOR network's library for health research reporting. Finally, we screened these reporting guidelines to find those using our set of reporting items. Seven relevant reporting items were selected that related to four topics: randomization, learning curve, surgical setting, and device information. A total of 348 reporting guidelines were identified, among which 26 met our inclusion criteria. However, none of the 26 reporting guidelines presented all seven items together. The most frequently reported item was timing of randomization (65%). On the contrary, device information and learning curve effects were poorly specified. To our knowledge, this study is the first to identify specific items related to IMDs in reporting guidelines for clinical trials. We have shown that no existing reporting guideline is totally suitable for these devices. Copyright © 2017 Elsevier Inc. All rights reserved.

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…

Rapid Extremity Pain Relief by Battlefield Acupuncture after Orthopedic Surgery: A Randomized Clinical Trial

DTIC Science & Technology

2017-03-21

FINAL REPORT Project Title: Rapid Extremity Pain Relief by Battlefield Acupuncture after Orthopedic Surgery: A Randomized Clinical Trial...Center ATTN: DTIC-OA 8725 John J. Kingman Rd Fort Belvoir, VA 22060-6218 Submitted by: Jill M. Clark, MBA/HCM, CCRP, CCRC Senior Research ...Associate/ Research Manager Clinical Investigation Program Mike O’Callaghan Federal Medical Center (MOFMC) 4700 Las Vegas Blvd North, Bldg 1300, Room

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

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

[Evaluation of methodological quality in published RCTs on cataract surgery : Pilot study on the degree of adherence to CONSORT statement requirements and their qualitative validity].

PubMed

Baulig, C; Krummenauer, F; Knippschild, S

2018-01-01

The CONSORT statement can be considered as a guideline to ensure transparency in the reporting of randomized clinical trials (RCT), in addition to specific author instructions and requirements of journals. It provides a total of 25 criteria and 12 additional subcriteria on methodological and regulatorical determinants of clinical trials. The availability of the CONSORT recommendations, however, does not necessarily imply adherence to their obligations and correct realisation of the latter from a methodological perspective, so that even in ophthalmology a lack of transparency in trial reporting cannot be excluded. The question was whether a consistent consideration of the CONSORT checklist criteria by authors actually implied transparent reporting of underlying study results. This pilot study was based on a random sample of six published RCTs on cataract surgery extracted from an existing trial publication register. Compliance with each of the 25 CONSORT criteria and its 12 subcriteria and the content accuracy of the latter were independently assessed by two parallel raters for the six trial publications. The median compliance with the 37 CONSORT criteria and subcriteria was 62% [min-max 48-81%]; the median fraction of their correct implementation was 47% [min-max 34-69%]. Promotion of transparent reporting by means of the CONSORT statement appears to be problematic in implementation. There is a discrepancy between information as required by CONSORT and the content accuracy of its actual presentation. Thus, in particular, reviewers of clinical trial publications should not only check for the presence of data to be provided according to CONSORT, but also verify the meaningfulness in the respective context, at least on a random basis.

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.

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.

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

Challenges and Recommendations for Placebo Controls in Randomized Trials in Physical and Rehabilitation Medicine

PubMed Central

Fregni, Felipe; Imamura, Marta; Chien, Hsin Fen; Lew, Henry L.; Boggio, Paulo; Kaptchuk, Ted J; Riberto, Marcelo; Hsing, Wu Tu; Battistella, Linamara Rizzo; Furlan, Andrea

2010-01-01

Compared to other specialties, the field of Physical and Rehabilitation Medicine (PRM) has not received the deserved recognition from clinicians and researchers in the scientific community. One of the reasons is the lack of sound evidence to support the traditional PRM treatments. The best way to change this disadvantage is through well-conducted clinical research, such as the standard placebo or sham-controlled randomized clinical trials. Therefore, having placebo groups in clinical trials is essential to improve the level of evidence-based practice in PRM that ultimately translates in a better clinical care. To address the challenges for the use of placebo in PRM randomized clinical trials, and to create useful recommendations, we convened a working group during the inaugural International Symposium in Placebo (February 2009, in Sao Paulo, Brazil) in which the following topics were discussed: (1) current status of randomized clinical trials in PRM, (2) challenges for the use of placebo in PRM, (3) bioethical issues, (4) use of placebo in acupuncture trials and for the treatment of low-back pain, (5) mechanisms of placebo, and (6) insights from other specialties. The current article represents the consensus report from the working group. PMID:20090428

Interventional radiology and the use of metal stents in nonvascular clinical practice: a systematic overview.

PubMed

Pron, G; Common, A; Simons, M; Ho, C S

1999-05-01

The intent of this systematic overview was to describe the clinical role of metal stents in nonvascular health care interventions and the level of evidence supporting their use. Structured searches of Medline were conducted and limited to original peer-reviewed articles published in English. Clinical practice involving metal stents was reported in more than 109 clinical series involving 4,753 patients. Stents were placed mainly for palliation of malignant biliary, esophageal, and airway obstruction in patients who were untreatable or had surgically unresectable lesions. Assessment of these interventions has so far centered on safety and technical success. Efficacy, quality of life, and costing factors were not routinely reported. Randomized trial evidence was available but limited; six randomized trials involving metal stents have been reported. Three trials involved biliary malignant obstruction, and all three reported metal stent (132 patients) palliation to be superior to plastic stent palliation (136 patients) based on longer patency and lower reintervention costs. Safety and complication differences between stents, however, were inconsistent across trials. In three trials involving esophageal malignant obstruction, metal stent (82 patients) palliation was reported to be superior to plastic stent (41 patients), based on lower complication and reintervention rates, and superior to laser therapy (18 patients), based on better dysphagia relief. Use of metal stents has been reported for obstructed ducts and passageways of most body systems. There is, however, limited controlled trial evidence confirming the advantages of their use over plastic stents or other forms of treatment.

10-year trend in quantity and quality of pediatric randomized controlled trials published in mainland China: 2002–2011

PubMed Central

2013-01-01

Background Quality assessment of pediatric randomized controlled trials (RCTs) in China is limited. The aim of this study was to evaluate the quantitative trends and quality indicators of RCTs published in mainland China over a recent 10-year period. Methods We individually searched all 17 available pediatric journals published in China from January 1, 2002 to December 30, 2011 to identify RCTs of drug treatment in participants under the age of 18 years. The quality was evaluated according to the Cochrane quality assessment protocol. Results Of 1287 journal issues containing 44398 articles, a total of 2.4% (1077/44398) articles were included in the analysis. The proportion of RCTs increased from 0.28% in 2002 to 0.32% in 2011. Individual sample sizes ranged from 10 to 905 participants (median 81 participants); 2.3% of the RCTs were multiple center trials; 63.9% evaluated Western medicine, 32.5% evaluated traditional Chinese medicine; 15% used an adequate method of random sequence generation; and 10.4% used a quasi-random method for randomization. Only 1% of the RCTs reported adequate allocation concealment and 0.6% reported the method of blinding. The follow-up period was from 7 days to 96 months, with a median of 7.5 months. There was incomplete outcome data reported in 8.3%, of which 4.5% (4/89) used intention-to-treat analysis. Only 0.4% of the included trials used adequate random sequence allocation, concealment and blinding. The articles published from 2007 to 2011 revealed an improvement in the randomization method compared with articles published from 2002 to 2006 (from 2.7% to 23.6%, p = 0.000). Conclusions In mainland China, the quantity of RCTs did not increase in the pediatric population, and the general quality was relatively poor. Quality improvements were suboptimal in the later 5 years. PMID:23914882

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.

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.

Exploring the transparency mechanism and evaluating the effect of public reporting on prescription: a protocol for a cluster randomized controlled trial.

PubMed

Du, Xin; Wang, Dan; Wang, Xuan; Yang, Shiru; Zhang, Xinping

2015-03-21

The public reporting of health outcomes has become one of the most popular topics and is accepted as a quality improvement method in the healthcare field. However, little research has been conducted on the transparency mechanism, and results are mixed with regard to the evaluation of the effect of public reporting on quality improvement. The objectives of this trial are to investigate the transparency mechanism and to evaluate the effect of public reporting on prescription at the level of individual participants. This study involves a cluster randomized controlled trial conducted in 20 primary-care facilities (clusters). Eligible clusters are those facilities with excellent hospital information systems and that have agreed to participate in the trial. The 20 clusters are matched into 10 pairs according to Technique for Order Preference by Similarity to Ideal Solution score. As the unit of randomization, each pair of facilities is assigned at random to a control or an intervention group through coin flipping. Prescribed ranking information is publicly reported in the intervention group. The public materials include the posters of individuals and of facilities, the ranking lists of general practitioners, and brochures of patients, which are updated monthly. The intervention began on 13th November 2013 and lasted for one year. Specifically, participants are surveyed at five points in time (baseline, quarterly following the intervention) through questionnaires, interviews, and observations. These participants include an average of 600 patients, 300 general practitioners, 15 directors, and 6 health bureau administrators. The primary outcomes are the transparency mechanism model and the changes in medicine-prescribe. Subsequently, the modifications in the transparency mechanism constructs are evaluated. The outcomes are measured at the individual participant level, and the professional who analyzes the data is blind to the randomization status. This study protocol outlines a design that aims to examine the transparency mechanism and to evaluate the effect of public reporting on prescription. The research design is significant in the field of public policy. Furthermore, this study intends to fill the gap of the investigation of the transparency mechanism and the evaluation of public reporting on prescription.

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.

Carnitine for fatigue in multiple sclerosis.

PubMed

Tejani, Aaron M; Wasdell, Michael; Spiwak, Rae; Rowell, Greg; Nathwani, Shabita

2012-05-16

Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose. A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied. Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included. Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up. The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active-comparator, cross-over trial. In the completed study, adult patients with relapsing-remitting and secondary progressive MS were exposed to both acetyl L-carnitine 2 grams daily and amantadine 200 mg daily The effects of carnitine on fatigue are unclear. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55) and no patients experienced a serious adverse event in either treatment group. Mortality and quality of life were not reported. There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity.

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.

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.

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

Methods for a multicenter randomized trial for mixed urinary incontinence: rationale and patient-centeredness of the ESTEEM trial.

PubMed

Sung, Vivian W; Borello-France, Diane; Dunivan, Gena; Gantz, Marie; Lukacz, Emily S; Moalli, Pamela; Newman, Diane K; Richter, Holly E; Ridgeway, Beri; Smith, Ariana L; Weidner, Alison C; Meikle, Susan

2016-10-01

Mixed urinary incontinence (MUI) can be a challenging condition to manage. We describe the protocol design and rationale for the Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence (ESTEEM) trial, designed to compare a combined conservative and surgical treatment approach versus surgery alone for improving patient-centered MUI outcomes at 12 months. ESTEEM is a multisite, prospective, randomized trial of female participants with MUI randomized to a standardized perioperative behavioral/pelvic floor exercise intervention plus midurethral sling versus midurethral sling alone. We describe our methods and four challenges encountered during the design phase: defining the study population, selecting relevant patient-centered outcomes, determining sample size estimates using a patient-reported outcome measure, and designing an analysis plan that accommodates MUI failure rates. A central theme in the design was patient centeredness, which guided many key decisions. Our primary outcome is patient-reported MUI symptoms measured using the Urogenital Distress Inventory (UDI) score at 12 months. Secondary outcomes include quality of life, sexual function, cost-effectiveness, time to failure, and need for additional treatment. The final study design was implemented in November 2013 across eight clinical sites in the Pelvic Floor Disorders Network. As of 27 February 2016, 433 total/472 targeted participants had been randomized. We describe the ESTEEM protocol and our methods for reaching consensus for methodological challenges in designing a trial for MUI by maintaining the patient perspective at the core of key decisions. This trial will provide information that can directly impact patient care and clinical decision making.

Methods for increasing upper airway muscle tonus in treating obstructive sleep apnea: systematic review.

PubMed

Valbuza, Juliana Spelta; de Oliveira, Márcio Moysés; Conti, Cristiane Fiquene; Prado, Lucila Bizari F; de Carvalho, Luciane Bizari Coin; do Prado, Gilmar Fernandes

2010-12-01

Treatment of obstructive sleep apnea (OSA) using methods for increasing upper airway muscle tonus has been controversial and poorly reported. Thus, a review of the evidence is needed to evaluate the effectiveness of these methods. The design used was a systematic review of randomized controlled trials. Data sources are from the Cochrane Library, Medline, Embase and Scielo, registries of ongoing trials, theses indexed at Biblioteca Regional de Medicina/Pan-American Health Organization of the World Health Organization and the reference lists of all the trials retrieved. This was a review of randomized or quasi-randomized double-blind trials on OSA. Two reviewers independently applied eligibility criteria. One reviewer assessed study quality and extracted data, and these processes were checked by a second reviewer. The primary outcome was a decrease in the apnea/hypopnea index (AHI) of below five episodes per hour. Other outcomes were subjective sleep quality, sleep quality measured by night polysomnography, quality of life measured subjectively and adverse events associated with the treatments. Three eligible trials were included. Two studies showed improvements through the objective and subjective analyses, and one study showed improvement of snoring, but not of AHI while the subjective analyses showed no improvement. The adverse events were reported and they were not significant. There is no accepted scientific evidence that methods aiming to increase muscle tonus of the stomatognathic system are effective in reducing AHI to below five events per hour. Well-designed randomized controlled trials are needed to assess the efficacy of such methods.

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.

Randomized Trials Built on Sand: Examples from COPD, Hormone Therapy, and Cancer

PubMed Central

Suissa, Samy

2012-01-01

The randomized controlled trial is the fundamental study design to evaluate the effectiveness of medications and receive regulatory approval. Observational studies, on the other hand, are essential to address post-marketing drug safety issues but have also been used to uncover new indications or new benefits for already marketed drugs. Hormone replacement therapy (HRT) for instance, effective for menopausal symptoms, was reported in several observational studies during the 1980s and 1990s to also significantly reduce the incidence of coronary heart disease. This claim was refuted in 2002 by the large-scale Women’s Health Initiative randomized trial. An example of a new indication for an old drug is that of metformin, an anti-diabetic medication, which is being hailed as a potential anti-cancer agent, primarily on the basis of several recent observational studies that reported impressive reductions in cancer incidence and mortality with its use. These observational studies have now sparked the conduct of large-scale randomized controlled trials currently ongoing in cancer. We show in this paper that the spectacular effects on new indications or new outcomes reported in many observational studies in chronic obstructive pulmonary disease (COPD), HRT, and cancer are the result of time-related biases, such as immortal time bias, that tend to seriously exaggerate the benefits of a drug and that eventually disappear with the proper statistical analysis. In all, while observational studies are central to assess the effects of drugs, their proper design and analysis are essential to avoid bias. The scientific evidence on the potential beneficial effects in new indications of existing drugs will need to be more carefully assessed before embarking on long and expensive unsubstantiated trials. PMID:23908838

Designing and conducting a randomized trial for pandemic critical illness: the 2009 H1N1 influenza pandemic.

PubMed

Annane, Djillali; Antona, Marion; Lehmann, Blandine; Kedzia, Cecile; Chevret, Sylvie

2012-01-01

To analyze the hurdles in implementing a randomized trial of corticosteroids for severe 2009 H1N1 influenza infections. This was an investigator-led, multicenter, randomized, placebo-controlled, double-blind trial of corticosteroids in ICU patients with 2009 H1N1 influenza pneumonia requiring mechanical ventilation. The feasibility of and hurdles in designing and initiating a phase III trial in a short-lived pandemic crisis were analyzed. The regulatory agency and ethics committee approved the study's scientific, financial, and ethical aspects within 4 weeks. Hydrocortisone and placebo were prepared centrally and shipped to participating hospitals within 6 weeks. The inclusion period started on November 9, 2009. From August 1, 2009 to March 8, 2010, only 205/224 ICU patients with H1N1 infections required mechanical ventilation. The peak of the wave was missed by 2-3 weeks and only 26 patients were randomized. The two main reasons for non-inclusion were patients' admission before the beginning of the trial and ICU personnel overwhelmed by clinical duties. Parallel rather than sequential regulatory and ethics approval, and preparation and masking of study drugs by local pharmacists would have allowed the study to start 1 month earlier and before the peak of the "flu" wave. A dedicated research team in each participating center would have increased the ratio of screened to randomized patients. This report highlights the main hurdles in implementing a randomized trial for a pandemic critical illness and proposes solutions for future trials.

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.

Effects of beta-blocker therapy on mortality in patients with heart failure. A systematic overview of randomized controlled trials.

PubMed

Doughty, R N; Rodgers, A; Sharpe, N; MacMahon, S

1997-04-01

Several randomized trials have reported that beta-blocker therapy improves left ventricular function and reduces the rate of hospitalization in patients with congestive heart failure. However, most trials were individually too small to assess reliably the effects of treatment on mortality. In these circumstances a systematic overview of all trials of beta-blocker therapy in patients with congestive heart failure may provide the most reliable guide to treatment effects. Details were sought from all completed randomized trials of oral beta-blocker therapy in patients with heart failure of any aetiology. In particular, data on mortality were sought from all randomized patients for the scheduled treatment period. The typical effect of treatment on mortality was estimated from an overview in which the results of all individual trials were combined using standard statistical methods. Twenty-four randomized trials, involving 3141 patients with stable congestive heart failure were identified. Complete data on mortality were obtained from all studies, and a total of 297 deaths were documented during an average of 13 months of follow-up. Overall, there was a 31% reduction in the odds of death among patients assigned a beta-blocker (95% confidence interval 11 to 46%, 2P = 0.0035), representing an absolute reduction in mean annual mortality from 9.7% to 7.5%. The effects on mortality of vasodilating beta-blockers (47% reduction SD 15), principally carvedilol, were non-significantly greater (2P = 0.09) than those of standard agents (18% reduction SD 15), principally metoprolol. Beta-blocker therapy is likely to reduce mortality in patients with heart failure. However, large-scale, long-term randomized trials are still required to confirm and quantify more precisely the benefit suggested by this overview.

Over the counter (OTC) artificial tear drops for dry eye syndrome.

PubMed

Pucker, Andrew D; Ng, Sueko M; Nichols, Jason J

2016-02-23

Over the counter (OTC) artificial tears historically have been the first line of treatment for dry eye syndrome and dry eye-related conditions like contact lens discomfort, yet currently we know little regarding the overall efficacy of individual, commercially available artificial tears. This review provides a much needed meta-analytical look at all randomized and quasi-randomized clinical trials that have analyzed head-to-head comparisons of OTC artificial tears. To evaluate the effectiveness and toxicity of OTC artificial tear applications in the treatment of dry eye syndrome compared with another class of OTC artificial tears, no treatment, or placebo. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 4 December 2015. We searched reference lists of included trials for any additional trials not identified by the electronic searches. This review includes randomized controlled trials with adult participants who were diagnosed with dry eye, regardless of race and gender. We included trials in which the age of participants was not reported, and clinical trials comparing OTC artificial tears with another class of OTC artificial tears, placebo, or no treatment. This review did not consider head-to-head comparisons of artificial tears with another type of dry-eye therapy. We followed the standard methodological procedures expected by Cochrane. Two authors independently screened the search results, reviewed full-text copies for eligibility, examined risk of bias, and extracted data. We performed meta-analysis for trials that compared similar interventions and reported comparable outcomes with sufficient data. We summarized all other included trial results in the text. We included 43 randomized controlled trials (3497 participants with dry eye). Due to the heterogeneity of study characteristics among the included trials with respect to types of diagnostic criteria, interventions, comparisons, and measurements taken, our ability to perform meta-analyses was limited. The review found that, in general, there was uncertainty whether different OTC artificial tears provide similar relief of signs and symptoms when compared with each other or placebo. Nevertheless, we found that 0.2% polyacrylic acid-based artificial tears were consistently more effective at treating dry eye symptoms than 1.4% polyvinyl alcohol-based artificial tears in two trials assessing this comparison (175 participants). All other included artificial tears produced contradictory between-group results or found no between-group differences. Our review also found that OTC artificial tears may be generally safe, but not without adverse events. Overall, we assessed the quality of evidence as low due to high risks of bias among included trials and poor reporting of outcome measures which were insufficient for quantitative analysis. Furthermore, we identified an additional 18 potentially eligible trials that were reported only in clinical trial registers with no associated results or publications. These trials reportedly enrolled 2079 total participants for whom no data are available. Such lack of reporting of trial results represents a high risk of publication bias. OTC artificial tears may be safe and effective means for treating dry eye syndrome; the literature indicates that the majority of OTC artificial tears may have similar efficacies. This conclusion could be greatly skewed by the inconsistencies in study designs and inconsistencies in reporting trial results. Additional research is therefore needed before we can draw robust conclusions about the effectiveness of individual OTC artificial tear formulations.

The efficacy and safety of Fufangdanshen tablets (Radix Salviae miltiorrhizae formula tablets) for mild to moderate vascular dementia: a study protocol for a randomized controlled trial.

PubMed

Tian, Jinzhou; Shi, Jing; Wei, Mingqing; Qin, Renan; Ni, Jingnian; Zhang, Xuekai; Li, Ting; Wang, Yongyan

2016-06-08

Vascular dementia (VaD) is the second most common subtype of dementia after Alzheimer's disease (AD). Currently, there are no medications approved for treating patients with VaD. Fufangdanshen (FFDS) tablets (Radix Salviae miltiorrhizae formula tablets) are a traditional Chinese medicine that has been reported to improve memory. However, the existing evidence for FFDS tablets in clinical practice derives from methodologically flawed studies. To further investigate the safety, tolerability, and efficacy of FFDS tables in the treatment of mild to moderate VaD, we designed and reported the methodology for a 24-week randomized, double-blind, parallel, multicenter study. This ongoing study is a double-blind, randomized, parallel placebo-controlled trial. A total of 240 patients with mild to moderate VaD will be enrolled. After a 2-week run-in period, the eligible patients will be randomized to receive either three FFDS or placebo tablets three times per day for 24 weeks, with a follow-up 12 weeks after the last treatment. The primary efficacy measurement will be the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician Interview-Based Impression of Change (CIBIC-plus). The secondary efficacy measurements will include the Mini Mental State Examination (MMSE) and activities of daily living (ADL). Adverse events will also be reported. This randomized trial will be the first rigorous study on the efficacy and safety of FFDS tablets for treating cognitive symptoms in patients with VaD using a rational design. ClinicalTrials.gov: NCT01761227 . Registered on 2 January 2013.

Effect of magnesium added to local anesthetics for caudal anesthesia on postoperative pain in pediatric surgical patients: A systematic review and meta-analysis with Trial Sequential Analysis.

PubMed

Kawakami, Hiromasa; Mihara, Takahiro; Nakamura, Nobuhito; Ka, Koui; Goto, Takahisa

2018-01-01

Magnesium has been investigated as an adjuvant for neuraxial anesthesia, but the effect of caudal magnesium on postoperative pain is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of caudal magnesium. We searched six databases, including trial registration sites. Randomized clinical trials reporting the effect of caudal magnesium on postoperative pain after general anesthesia were eligible. The risk ratio for use of rescue analgesics after surgery was combined using a random-effects model. We also assessed adverse events. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. Four randomized controlled trials (247 patients) evaluated the need for rescue analgesics. In all four trials, 50 mg of magnesium was administered with caudal ropivacaine. The results suggested that the need for rescue analgesia was reduced significantly by caudal magnesium administration (risk ratio 0.45; 95% confidence interval 0.24-0.86). There was considerable heterogeneity as indicated by an I2 value of 62.5%. The Trial Sequential Analysis-adjusted confidence interval was 0.04-5.55, indicating that further trials are required. The quality of evidence was very low. The rate of adverse events was comparable between treatment groups. Caudal magnesium may reduce the need for rescue analgesia after surgery, but further randomized clinical trials with a low risk of bias and a low risk of random errors are necessary to assess the effect of caudal magnesium on postoperative pain and adverse events. University Hospital Medical Information Network Clinical Trials Registry UMIN000025344.

Tai Chi Improves Sleep Quality in Healthy Adults and Patients with Chronic Conditions: A Systematic Review and Meta-analysis

PubMed Central

Raman, Gowri; Zhang, Yuan; Minichiello, Vincent J; D'Ambrosio, Carolyn M.; Wang, Chenchen

2017-01-01

Background Physical activity and exercise appear to improve sleep quality. However, the quantitative effects of Tai Chi on sleep quality in the adult population have rarely been examined. We conducted a systematic review and meta-analysis evaluating the effects of Tai Chi on sleep quality in healthy adults and disease populations. Methods Medline, Cochrane Central databases, and review of references were searched through July 31, 2013. English-language studies of all designs evaluating Tai Chi’s effect on sleep outcomes in adults were examined. Data were extracted and verified by 2 reviewers. Extracted information included study setting and design, population characteristics, type and duration of interventions, outcomes, risk of bias and main results. Random effect models meta-analysis was used to assess the magnitude of treatment effect when at least 3 trials reported on the same sleep outcomes. Results Eleven studies (9 randomized and 2 non-randomized trials) totaling 994 subjects published between 2004 and 2012 were identified. All studies except one reported Pittsburg Sleep Quality Index. Nine randomized trials reported that 1.5 to 3 hour each week for a duration of 6 to 24 weeks of Tai Chi significantly improved sleep quality (Effect Size, 0.89; 95% confidence interval [CI], 0.28 to 1.50), in community-dwelling healthy participants and in patients with chronic conditions. Improvement in health outcomes including physical performance, pain reduction, and psychological well-being occurred in the Tai Chi group compared with various controls. Limitations Studies were heterogeneous and some trials were lacking in methodological rigor. Conclusions Tai Chi significantly improved sleep quality in both healthy adults and patients with chronic health conditions, which suggests that Tai Chi may be considered as an alternative behavioral therapy in the treatment of insomnia. High-quality, well-controlled randomized trials are needed to better inform clinical decisions. PMID:28845367

Lumbar Imaging with Reporting of Epidemiology (LIRE)- Protocol for a Pragmatic Cluster Randomized Trial

PubMed Central

Jarvik, Jeffrey G.; Comstock, Bryan A.; James, Kathryn T.; Avins, Andrew L.; Bresnahan, Brian W.; Deyo, Richard A.; Luetmer, Patrick H.; Friedly, Janna L.; Meier, Eric N.; Cherkin, Daniel C.; Gold, Laura S.; Rundell, Sean D.; Halabi, Safwan S.; Kallmes, David F.; Tan, Katherine W.; Turner, Judith A.; Kessler, Larry G.; Lavallee, Danielle C.; Stephens, Kari A.; Heagerty, Patrick J.

2015-01-01

Background Diagnostic imaging is often the first step in evaluating patients with back pain and likely functions as a “gateway” to a subsequent cascade of interventions. However, lumbar spine imaging frequently reveals incidental findings among normal, pain-free individuals suggesting that treatment of these “abnormalities” may not be warranted. Our prior work suggested that inserting the prevalence of imaging findings in patients without back pain into spine imaging reports may reduce subsequent interventions. We are now conducting a pragmatic cluster randomized clinical trial to test the hypothesis that inserting this prevalence data into lumbar spine imaging reports for studies ordered by primary care providers will reduce subsequent spine-related interventions. Methods/Design We are using a stepped wedge design that sequentially randomizes 100 primary care clinics at four health systems to receive either standard lumbar spine imaging reports, or reports containing prevalence data for common imaging findings in patients without back pain. We capture all outcomes passively through the electronic medical record. Our primary outcome is spine-related intervention intensity based on Relative Value Units (RVUs) during the following year. Secondary outcomes include subsequent prescriptions for opioid analgesics and cross-sectional lumbar spine re-imaging. Discussion If our study shows that adding prevalence data to spine imaging reports decreases subsequent back-related RVUs, this intervention could be easily generalized and applied to other kinds of testing, as well as other conditions where incidental findings may be common. Our study also serves as a model for cluster randomized trials that are minimal risk and highly pragmatic. PMID:26493088

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

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…

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

WWC Review of the Report "A Randomized Trial Examining the Effects of Aerobic Physical Activity on Attention-Deficit/Hyperactivity Disorder Symptoms in Young Children." What Works Clearinghouse Single Study Review

ERIC Educational Resources Information Center

What Works Clearinghouse, 2015

2015-01-01

For the 2014 study, "A Randomized Trial Examining the Effects of Aerobic Physical Activity on Attention-Deficit/Hyperactivity Disorder Symptoms in Young Children", researchers examined the effect of a daily before-school physical activity program on behavioral outcomes of students in grades K-2. The study sample included 202 students who…

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.

Reporting discrepancies between the ClinicalTrials.gov results database and peer-reviewed publications.

PubMed

Hartung, Daniel M; Zarin, Deborah A; Guise, Jeanne-Marie; McDonagh, Marian; Paynter, Robin; Helfand, Mark

2014-04-01

ClinicalTrials.gov requires reporting of result summaries for many drug and device trials. To evaluate the consistency of reporting of trials that are registered in the ClinicalTrials.gov results database and published in the literature. ClinicalTrials.gov results database and matched publications identified through ClinicalTrials.gov and a manual search of 2 electronic databases. 10% random sample of phase 3 or 4 trials with results in the ClinicalTrials.gov results database, completed before 1 January 2009, with 2 or more groups. One reviewer extracted data about trial design and results from the results database and matching publications. A subsample was independently verified. Of 110 trials with results, most were industry-sponsored, parallel-design drug studies. The most common inconsistency was the number of secondary outcome measures reported (80%). Sixteen trials (15%) reported the primary outcome description inconsistently, and 22 (20%) reported the primary outcome value inconsistently. Thirty-eight trials inconsistently reported the number of individuals with a serious adverse event (SAE); of these, 33 (87%) reported more SAEs in ClinicalTrials.gov. Among the 84 trials that reported SAEs in ClinicalTrials.gov, 11 publications did not mention SAEs, 5 reported them as zero or not occurring, and 21 reported a different number of SAEs. Among 29 trials that reported deaths in ClinicalTrials.gov, 28% differed from the matched publication. Small sample that included earliest results posted to the database. Reporting discrepancies between the ClinicalTrials.gov results database and matching publications are common. Which source contains the more accurate account of results is unclear, although ClinicalTrials.gov may provide a more comprehensive description of adverse events than the publication. Agency for Healthcare Research and Quality.

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.

Brief Strategic Family Therapy Versus Treatment as Usual: Results of a Multisite Randomized Trial for Substance Using Adolescents

PubMed Central

Robbins, Michael S.; Feaster, Daniel J.; Horigian, Viviana E.; Rohrbaugh, Michael; Shoham, Varda; Bachrach, Ken; Miller, Michael; Burlew, Kathleen A.; Hodgkins, Candy; Carrion, Ibis; Vandermark, Nancy; Schindler, Eric; Werstlein, Robert; Szapocznik, José

2012-01-01

Objective To determine the effectiveness of brief strategic family therapy (BSFT; an evidence-based family therapy) compared to treatment as usual (TAU) as provided in community-based adolescent outpatient drug abuse programs. Method A randomized effectiveness trial in the National Drug Abuse Treatment Clinical Trials Network compared BSFT to TAU with a multiethnic sample of adolescents (213 Hispanic, 148 White, and 110 Black) referred for drug abuse treatment at 8 community treatment agencies nationwide. Randomization encompassed both adolescents’ families (n = 480) and the agency therapists (n = 49) who provided either TAU or BSFT services. The primary outcome was adolescent drug use, assessed monthly via adolescent self-report and urinalysis for up to 1 year post randomization. Secondary outcomes included treatment engagement (≥2 sessions), retention (≥8 sessions), and participants’ reports of family functioning 4, 8, and 12 months following randomization. Results No overall differences between conditions were observed in the trajectories of self-reports of adolescent drug use. However, the median number of days of self-reported drug use was significantly higher, χ2(1) = 5.40, p < .02, in TAU (Mdn = 3.5, interquartile range [IQR] = 11) than BSFT (Mdn = 2, IQR = 9) at the final observation point. BSFT was significantly more effective than TAU in engaging, χ2(1) = 11.33, p < .001, and retaining, χ2(1) = 5.66, p < .02, family members in treatment and in improving parent reports of family functioning, χ2(2) = 9.10, p < .011. Conclusions We discuss challenges in treatment implementation in community settings and provide recommendations for further research. PMID:21967492

Re-starting smoking in the postpartum period after receiving a smoking cessation intervention: a systematic review.

PubMed

Jones, Matthew; Lewis, Sarah; Parrott, Steve; Wormall, Stephen; Coleman, Tim

2016-06-01

In pregnant smoking cessation trial participants, to estimate (1) among women abstinent at the end of pregnancy, the proportion who re-start smoking at time-points afterwards (primary analysis) and (2) among all trial participants, the proportion smoking at the end of pregnancy and at selected time-points during the postpartum period (secondary analysis). Trials identified from two Cochrane reviews plus searches of Medline and EMBASE. Twenty-seven trials were included. The included trials were randomized or quasi-randomized trials of within-pregnancy cessation interventions given to smokers who reported abstinence both at end of pregnancy and at one or more defined time-points after birth. Outcomes were validated biochemically and self-reported continuous abstinence from smoking and 7-day point prevalence abstinence. The primary random-effects meta-analysis used longitudinal data to estimate mean pooled proportions of re-starting smoking; a secondary analysis used cross-sectional data to estimate the mean proportions smoking at different postpartum time-points. Subgroup analyses were performed on biochemically validated abstinence. The pooled mean proportion re-starting at 6 months postpartum was 43% [95% confidence interval (CI) = 16-72%, I(2)  = 96.7%] (11 trials, 571 abstinent women). The pooled mean proportion smoking at the end of pregnancy was 87% (95% CI = 84-90%, I(2)  = 93.2%) and 94% (95% CI = 92-96%, I(2)  = 88%) at 6 months postpartum (23 trials, 9262 trial participants). Findings were similar when using biochemically validated abstinence. In clinical trials of smoking cessation interventions during pregnancy only 13% are abstinent at term. Of these, 43% re-start by 6 months postpartum. © 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

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.

Agreement in reporting between trial publications and current clinical trial registry in high impact journals: A methodological review.

PubMed

Kosa, Sarah Daisy; Mbuagbaw, Lawrence; Borg Debono, Victoria; Bhandari, Mohit; Dennis, Brittany B; Ene, Gabrielle; Leenus, Alvin; Shi, Daniel; Thabane, Michael; Valvasori, Sara; Vanniyasingam, Thuva; Ye, Chenglin; Yranon, Elgene; Zhang, Shiyuan; Thabane, Lehana

2018-02-01

The primary objective of this systematic survey was to examine the percentage of studies in which there was agreement in the reporting of the primary outcome between the currently updated version of the clinical trial registry and the published paper. We also investigated the factors associated with agreement in reporting of the primary outcome. We searched PubMed for all randomized control trials (RCT)s published in 2012-2015 in the top five general medicine journals (based on the 2014 impact factor). Two hundred abstracts (50 from each year) were randomly selected for data extraction. Agreement in reporting of 11 key study conduct items (e.g., sample size) and study characteristics (e.g., funding, number of sites) were extracted by two independent reviewers. Descriptive analyses were conducted to determine the proportion of studies on which there was agreement in reporting of key study conduct items. Generalized estimating equations were used to explore factors associated with agreement in reporting of the primary outcome. Of the 200 included studies, 87% had agreement in reporting of the primary outcome. After adjusting for other covariates, having greater than 50 sites was associated with an increased likelihood of agreement in reporting of the primary outcome (odds ratio=7.1, 95% confidence interval=1.39, 36.27, p=0.018). We identified substantive disagreement in reporting between publications and current clinical trial registry, which were associated with several study characteristics. Further measures are needed to improve reporting given the potential threats to the quality and integrity of scientific research. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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.

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 Randomized Crossover Trial Comparing Autotitrating and Continuous Positive Airway Pressure in Subjects With Symptoms of Aerophagia: Effects on Compliance and Subjective Symptoms

PubMed Central

Shirlaw, Teresa; Hanssen, Kevin; Duce, Brett; Hukins, Craig

2017-01-01

Study Objectives: To assess the benefit and tolerance of autotitrating positive airway pressure (APAP) versus continuous positive airway pressure (CPAP) in subjects who experience aerophagia. Methods: This is the report of a prospective, two-week, double-blinded, randomized crossover trial set in an Australian clinical sleep laboratory in a tertiary hospital. Fifty-six subjects who reported symptoms of aerophagia that they attributed to CPAP were recruited. Full face masks were used by 39 of the 56 subjects recruited. Subjects were randomly and blindly allocated to either CPAP at their treatment recommended pressure or APAP 6–20 cm H2O, in random order. Subjects spent two weeks on each therapy mode. Therapy usage hours, 95th centile pressure, maximum pressure, 95th centile leak, and residual apnea-hypopnea index (AHI) were reported at the end of each two-week treatment period. Functional Outcome of Sleepiness Questionnaire, Epworth Sleepiness Scale, and visual analog scale to measure symptoms of aerophagia were also completed at the end of each 2-week treatment arm. Results: The median pressure (P < .001) and 95th centile pressure (P < .001) were reduced with APAP but no differences in compliance (P = .120) and residual AHI were observed. APAP reduced the symptoms of bloating (P = .011), worst episode of bloating (P = .040), flatulence (P = .010), and belching (P = .001) compared to CPAP. There were no differences in Epworth Sleepiness Scale or Functional Outcome of Sleepiness Questionnaire outcomes between CPAP and APAP. Conclusions: APAP therapy reduces the symptoms of aerophagia while not affecting compliance when compared with CPAP therapy. Clinical Trial Registration: Australian and New Zealand Clinical Trials Registry at https://www.anzctr.org.au, trial number ACTRN12611001250921. Commentary: A commentary on this article appears in this issue on page 859. Citation: Shirlaw T, Hanssen K, Duce B, Hukins C. A randomized crossover trial comparing autotitrating and continuous positive airway pressure in subjects with symptoms of aerophagia: effects on compliance and subjective symptoms. J Clin Sleep Med. 2017;13(7):881–888. PMID:28558864

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.

Consequences of Frequent Hemodialysis: Comparison to Conventional Hemodialysis and Transplantation

PubMed Central

Stokes, John B.

2011-01-01

The average life expectancy of a person on hemodialysis is less than 3 years and hasn't changed in 20 years. The Hemodialysis (HEMO) trial, a randomized trial to determine whether increasing urea removal to the maximum practical degree through a 3-times-a-week schedule, showed no difference in mortality in the treatment and control groups. Investigators speculated that the increment in functional waste removal in the HEMO study was too small to produce improvements in mortality. To test this hypothesis, the NIDDK funded the Frequent Hemodialysis Network, a consortium of centers testing whether patients randomized to intensive dialysis would demonstrate improved (reduced) left ventricular LV mass and quality of life. The trial has two arms: the daily (in-center) and the home (nocturnal) arms. Each arm has patients randomized to conventional dialysis or 6 days (or nights) of dialysis. The results of the HEMO trial will be reported in the fall of 2010. PMID:21686215

Hyperforin plasma level as a marker of treatment adherence in the National Institutes of Health Hypericum Depression Trial.

PubMed

Vitiello, Benedetto; Shader, Richard I; Parker, Corette B; Ritz, Louise; Harlan, William; Greenblatt, David J; Gadde, Kishore M; Krishnan, K Ranga R; Davidson, Jonathan R T

2005-06-01

A previously reported clinical trial of Hypericum perforatum (St John's wort) in depression did not demonstrate efficacy. We assessed treatment adherence by measuring plasma hyperforin and evaluated the possible impact of adherence on study results. Outpatients with major depression (N = 340) were randomized to an 8-week trial of H. perforatum (900-1500 mg/d), sertraline (50-100 mg/d) as active comparator, or placebo. Plasma was available from 292 patients (86% of randomized). Samples from the placebo and H. perforatum groups were assayed for hyperforin, and samples from the sertraline group for sertraline/N-desmethyl-sertraline. Of the 104 patients randomized to placebo, 18 (17%) had detectable plasma hyperforin. Of the 97 patients randomized to H. perforatum, 17 (17%) had no detectable plasma hyperforin. All the assayed sertraline patients (N = 91) had plasma sertraline/N-desmethyl-sertraline. The clinical trial conclusions remained unchanged when only patients with plasma assay consistent with random assignment were included in the analyses. One of every 6 patients assigned to placebo had plasma hyperforin, and 1 of every 6 patients assigned to H. perforatum had no detectable plasma hyperforin. The finding underscores the difficulty of enforcing treatment adherence in clinical trials of preparations that are readily available in the community.

The Risk of Bias in Randomized Trials in General Dentistry Journals.

PubMed

Hinton, Stephanie; Beyari, Mohammed M; Madden, Kim; Lamfon, Hanadi A

2015-01-01

The use of a randomized controlled trial (RCT) research design is considered the gold standard for conducting evidence-based clinical research. In this present study, we aimed to assess the quality of RCTs in dentistry and create a general foundation for evidence-based dentistry on which to perform subsequent RCTs. We conducted a systematic assessment of bias of RCTs in seven general dentistry journals published between January 2011 and March 2012. We extracted study characteristics in duplicate and assessed each trial's quality using the Cochrane Risk of Bias tool. We compared risk of bias across studies graphically. Among 1,755 studies across seven journals, we identified 67 RCTs. Many included studies were conducted in Europe (39%), with an average sample size of 358 participants. These studies included 52% female participants and the maximum follow-up period was 13 years. Overall, we found a high percentage of unclear risk of bias among included RCTs, indicating poor quality of reporting within the included studies. An overall high proportion of trials with an "unclear risk of bias" suggests the need for better quality of reporting in dentistry. As such, key concepts in dental research and future trials should focus on high-quality reporting.

Parent-Child Interaction Therapy with Physically Abusive Parents: Efficacy for Reducing Future Abuse Reports

ERIC Educational Resources Information Center

Chaffin, Mark; Silovsky, Jane F.; Funderburk, Beverly; Valle, Linda Anne; Brestan, Elizabeth V.; Balachova, Tatiana; Jackson, Shelli; Lensgraf, Jay; Bonner, Barbara L.

2004-01-01

A randomized trial was conducted to test the efficacy and sufficiency of parent-child interaction therapy (PCIT) in preventing re-reports of physical abuse among abusive parents. Physically abusive parents (N=110) were randomly assigned to one of three intervention conditions: (a) PCIT, (b) PCIT plus individualized enhanced services, or (c) a…

The Consistency and Reporting of Quality-of-Life Outcomes in Trials of Immunosuppressive Agents in Kidney Transplantation: A Systematic Review and Meta-analysis.

PubMed

Howell, Martin; Wong, Germaine; Turner, Robin M; Tan, Ho Teck; Tong, Allison; Craig, Jonathan C; Howard, Kirsten

2016-05-01

Shared decision making regarding immunosuppression in kidney transplantation requires an understanding of effects on quality of life (QoL). Our aim was to review the frequency and reliability of QoL measures reported in randomized controlled trials of maintenance immunosuppression following kidney transplantation. Systematic literature review. Kidney transplant recipients enrolled in randomized trials of maintenance immunosuppression. Systematic search of the Cochrane Kidney and Transplant register, CENTRAL, MEDLINE, EMBASE, PsycINFO, and CINAHL databases to January 2014 identifying maintenance immunosuppression trials. An EQUATOR Network-endorsed checklist was used to assess QoL reporting and effect sizes estimated. Maintenance immunosuppression (comparative studies, dose adjustment, and agent withdrawal). Any quantitative patient-reported measure of physical, emotional, or social well-being. Of 2,272 reports, 41 (2%; involving 4,549 participants from 23 trials) included QoL outcomes using 22 instruments (8 generic, 2 disease specific, and 12 symptom specific). Reporting was incomplete for the majority with 1 (4%) addressing all 11 items of the checklist, 4 (17%) addressing clinical significance, and 15 (65%) reporting outcomes selectively. Almost all (n = 96 [95%]) effect size estimates for 101 QoL outcomes (18 trials; 3,919 participants) favored the interventions, with 37 (37%) statistically significant. In comparison, 30 (73%) clinical outcomes favored the intervention and 13 (31%) were significant. QoL outcomes are commonly secondary outcomes and may not be indexed or found using text word searches. Effect sizes were estimated from different QoL measures, populations, and interventions. The small number of trials limits the ability to identify statistically significant associations between effect size and study-/patient-related factors. QoL is infrequently reported in immunosuppression trials in kidney transplantation, appears subject to major biases, and thus may be unreliable for decision making. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy: study protocol for the ‘FC Prostate’ randomized controlled trial

PubMed Central

2013-01-01

Background Androgen deprivation therapy (ADT) is a cornerstone in the treatment of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted. The ‘Football Club (FC) Prostate’ study is a randomized trial comparing the effects of soccer training with standard treatment approaches on body composition, cardiovascular function, physical function parameters, glucose tolerance, bone health, and patient-reported outcomes in men undergoing ADT for prostate cancer. Methods/Design Using a single-center randomized controlled design, 80 men with histologically confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6 months or more at The Copenhagen University Hospital will be enrolled on this trial. After baseline assessments eligible participants will be randomly assigned to a soccer training group or a control group receiving usual care. The soccer intervention will consist of 12 weeks of training 2–3 times/week for 45–60 min after which the assessment protocol will be repeated. Soccer training will then continue bi-weekly for an additional 20 weeks at the end of which all measures will be repeated to allow for additional analyses of long-term effects. The primary endpoint is changes in lean body mass from baseline to 12 weeks assessed by dual X-ray absorptiometry scan. Secondary endpoints include changes of cardiovascular, metabolic, and physical function parameters, as well as markers of bone metabolism and patient-reported outcomes. Discussion The FC Prostate trial will assess the safety and efficacy of a novel soccer-training approach to cancer rehabilitation on a number of clinically important health outcomes in men with advanced prostate cancer during ADT. The results may pave the way for innovative, community-based interventions in the approach to treating prostate cancer. Trial registration ClinicalTrials.gov: NCT01711892 PMID:24330570

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.

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

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

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.

Outcomes of a Pilot Hand Hygiene Randomized Cluster Trial to Reduce Communicable Infections Among US Office-Based Employees

PubMed Central

DuBois, Cathy L.Z.; Grey, Scott F.; Kingsbury, Diana M.; Shakya, Sunita; Scofield, Jennifer; Slenkovich, Ken

2015-01-01

Objective: To determine the effectiveness of an office-based multimodal hand hygiene improvement intervention in reducing self-reported communicable infections and work-related absence. Methods: A randomized cluster trial including an electronic training video, hand sanitizer, and educational posters (n = 131, intervention; n = 193, control). Primary outcomes include (1) self-reported acute respiratory infections (ARIs)/influenza-like illness (ILI) and/or gastrointestinal (GI) infections during the prior 30 days; and (2) related lost work days. Incidence rate ratios calculated using generalized linear mixed models with a Poisson distribution, adjusted for confounders and random cluster effects. Results: A 31% relative reduction in self-reported combined ARI-ILI/GI infections (incidence rate ratio: 0.69; 95% confidence interval, 0.49 to 0.98). A 21% nonsignificant relative reduction in lost work days. Conclusions: An office-based multimodal hand hygiene improvement intervention demonstrated a substantive reduction in self-reported combined ARI-ILI/GI infections. PMID:25719534

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.

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.

Conflicting results between randomized trials and observational studies on the impact of proton pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy: systematic review.

PubMed

Melloni, Chiara; Washam, Jeffrey B; Jones, W Schuyler; Halim, Sharif A; Hasselblad, Victor; Mayer, Stephanie B; Heidenfelder, Brooke L; Dolor, Rowena J

2015-01-01

Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non-ST-segment-elevation myocardial infarction patients. We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 randomized controlled trials and 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class when compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic end points, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from randomized controlled trials evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole. Large, well-conducted observational studies of PPIs and randomized controlled trials of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in patients with unstable angina/non-ST-segment-elevation myocardial infarction treated with DAPT are warranted. © 2015 American Heart Association, Inc.

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.

Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment.

PubMed

Hróbjartsson, A; Gøtzsche, P C

2004-08-01

It is widely believed that placebo interventions induce powerful effects. We could not confirm this in a systematic review of 114 randomized trials that compared placebo-treated with untreated patients. To study whether a new sample of trials would reproduce our earlier findings, and to update the review. Systematic review of trials that were published since our last search (or not previously identified), and of all available trials. Data was available in 42 out of 52 new trials (3212 patients). The results were similar to our previous findings. The updated review summarizes data from 156 trials (11 737 patients). We found no statistically significant pooled effect in 38 trials with binary outcomes, relative risk 0.95 (95% confidence interval 0.89-1.01). The effect on continuous outcomes decreased with increasing sample size, and there was considerable variation in effect also between large trials; the effect estimates should therefore be interpreted cautiously. If this bias is disregarded, the pooled standardized mean difference in 118 trials with continuous outcomes was -0.24 (-0.31 to -0.17). For trials with patient-reported outcomes the effect was -0.30 (-0.38 to -0.21), but only -0.10 (-0.20 to 0.01) for trials with observer-reported outcomes. Of 10 clinical conditions investigated in three trials or more, placebo had a statistically significant pooled effect only on pain or phobia on continuous scales. We found no evidence of a generally large effect of placebo interventions. A possible small effect on patient-reported continuous outcomes, especially pain, could not be clearly distinguished from bias.

Protocol for the development of a CONSORT-equity guideline to improve reporting of health equity in randomized trials.

PubMed

Welch, Vivian; Jull, J; Petkovic, J; Armstrong, R; Boyer, Y; Cuervo, L G; Edwards, Sjl; Lydiatt, A; Gough, D; Grimshaw, J; Kristjansson, E; Mbuagbaw, L; McGowan, J; Moher, D; Pantoja, T; Petticrew, M; Pottie, K; Rader, T; Shea, B; Taljaard, M; Waters, E; Weijer, C; Wells, G A; White, H; Whitehead, M; Tugwell, P

2015-10-21

Health equity concerns the absence of avoidable and unfair differences in health. Randomized controlled trials (RCTs) can provide evidence about the impact of an intervention on health equity for specific disadvantaged populations or in general populations; this is important for equity-focused decision-making. Previous work has identified a lack of adequate reporting guidelines for assessing health equity in RCTs. The objective of this study is to develop guidelines to improve the reporting of health equity considerations in RCTs, as an extension of the Consolidated Standards of Reporting Trials (CONSORT). A six-phase study using integrated knowledge translation governed by a study executive and advisory board will assemble empirical evidence to inform the CONSORT-equity extension. To create the guideline, the following steps are proposed: (1) develop a conceptual framework for identifying "equity-relevant trials," (2) assess empirical evidence regarding reporting of equity-relevant trials, (3) consult with global methods and content experts on how to improve reporting of health equity in RCTs, (4) collect broad feedback and prioritize items needed to improve reporting of health equity in RCTs, (5) establish consensus on the CONSORT-equity extension: the guideline for equity-relevant trials, and (6) broadly disseminate and implement the CONSORT-equity extension. This work will be relevant to a broad range of RCTs addressing questions of effectiveness for strategies to improve practice and policy in the areas of social determinants of health, clinical care, health systems, public health, and international development, where health and/or access to health care is a primary outcome. The outcomes include a reporting guideline (CONSORT-equity extension) for equity-relevant RCTs and a knowledge translation strategy to broadly encourage its uptake and use by journal editors, authors, and funding agencies.

Randomized controlled trial of a cognitive-behavioral intervention for HIV-positive persons: an investigation of treatment effects on psychosocial adjustment.

PubMed

Carrico, Adam W; Chesney, Margaret A; Johnson, Mallory O; Morin, Stephen F; Neilands, Torsten B; Remien, Robert H; Rotheram-Borus, Mary Jane; Lennie Wong, F

2009-06-01

Questions remain regarding the clinical utility of psychological interventions for HIV-positive persons because randomized controlled trials have utilized stringent inclusion criteria and focused extensively on gay men. The present randomized controlled trial examined the efficacy of a 15-session, individually delivered cognitive-behavioral intervention (n = 467) compared to a wait-list control (n = 469) in a diverse sample of HIV-positive persons who reported HIV transmission risk behavior. Five intervention sessions that dealt with executing effective coping responses were delivered between baseline and the 5 months post-randomization. Additional assessments were completed through 25 months post-randomization. Despite previously documented reductions in HIV transmission risk, no intervention-related changes in psychosocial adjustment were observed across the 25-month investigation period. In addition, there were no intervention effects on psychosocial adjustment among individuals who presented with mild to moderate depressive symptoms. More intensive mental health interventions may be necessary to improve psychosocial adjustment among HIV-positive individuals.

The natural history of conducting and reporting clinical trials: interviews with trialists.

PubMed

Smyth, Rebecca M D; Jacoby, Ann; Altman, Douglas G; Gamble, Carrol; Williamson, Paula R

2015-01-26

To investigate the nature of the research process as a whole, factors that might influence the way in which research is carried out, and how researchers ultimately report their findings. Semi-structured qualitative telephone interviews with authors of trials, identified from two sources: trials published since 2002 included in Cochrane systematic reviews selected for the ORBIT project; and trial reports randomly sampled from 14,758 indexed on PubMed over the 12-month period from August 2007 to July 2008. A total of 268 trials were identified for inclusion, 183 published since 2002 and included in the Cochrane systematic reviews selected for the ORBIT project and 85 randomly selected published trials indexed on PubMed. The response rate from researchers in the former group was 21% (38/183) and in the latter group was 25% (21/85). Overall, 59 trialists were interviewed from the two different sources. A number of major but related themes emerged regarding the conduct and reporting of trials: establishment of the research question; identification of outcome variables; use of and adherence to the study protocol; conduct of the research; reporting and publishing of findings. Our results reveal that, although a substantial proportion of trialists identify outcome variables based on their clinical experience and knowing experts in the field, there can be insufficient reference to previous research in the planning of a new trial. We have revealed problems with trial recruitment: not reaching the target sample size, over-estimation of recruitment potential and recruiting clinicians not being in equipoise. We found a wide variation in the completeness of protocols, in terms of detailing study rationale, outlining the proposed methods, trial organisation and ethical considerations. Our results confirm that the conduct and reporting of some trials can be inadequate. Interviews with researchers identified aspects of clinical research that can be especially challenging: establishing appropriate and relevant outcome variables to measure, use of and adherence to the study protocol, recruiting of study participants and reporting and publishing the study findings. Our trialists considered the prestige and impact factors of academic journals to be the most important criteria for selecting those to which they would submit manuscripts.

Is ginger effective for the treatment of irritable bowel syndrome? A double blind randomized controlled pilot trial.

PubMed

van Tilburg, Miranda A L; Palsson, Olafur S; Ringel, Yehuda; Whitehead, William E

2014-02-01

Ginger is one of the most commonly used herbal medicines for irritable bowel syndrome (IBS) but no data exists about its effectiveness. Double blind randomized controlled trial. University of North Carolina, Chapel Hill, North Carolina, USA. Forty-five IBS patients were randomly assigned to three groups: placebo, 1g of ginger, and 2g of ginger daily for 28 days. The IBS severity scale (IBS-SS) was administered, as well as adequate relief of symptoms scale. A responder was defined as having at least 25% reduction in IBS-SS post-treatment. There were 57.1% responders to placebo, 46.7% to 1g and 33.3% to 2g of ginger. Adequate relief was reported by 53.3% on placebo and 53.3% in both ginger groups combined. Side effects were mild and reported by 35.7% in the placebo and 16.7% in the ginger groups. This double blind randomized controlled pilot study suggests ginger is well tolerated but did not perform better than placebo. Larger trials are needed before any definitive conclusions can be drawn. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nurse Family Partnership: Comparing Costs per Family in Randomized Trials Versus Scale-Up.

PubMed

Miller, Ted R; Hendrie, Delia

2015-12-01

The literature that addresses cost differences between randomized trials and full-scale replications is quite sparse. This paper examines how costs differed among three randomized trials and six statewide scale-ups of nurse family partnership (NFP) intensive home visitation to low income first-time mothers. A literature review provided data on pertinent trials. At our request, six well-established programs reported their total expenditures. We adjusted the costs to national prices based on mean hourly wages for registered nurses and then inflated them to 2010 dollars. A centralized data system provided utilization. Replications had fewer home visits per family than trials (25 vs. 31, p = .05), lower costs per client ($8860 vs. $12,398, p = .01), and lower costs per visit ($354 vs. $400, p = .30). Sample size limited the significance of these differences. In this type of labor intensive program, costs probably were lower in scale-up than in randomized trials. Key cost drivers were attrition and the stable caseload size possible in an ongoing program. Our estimates reveal a wide variation in cost per visit across six state programs, which suggests that those planning replications should not expect a simple rule to guide cost estimations for scale-ups. Nevertheless, NFP replications probably achieved some economies of scale.

Systematic review on the health effects of exposure to radiofrequency electromagnetic fields from mobile phone base stations.

PubMed

Röösli, Martin; Frei, Patrizia; Mohler, Evelyn; Hug, Kerstin

2010-12-01

to review and evaluate the recent literature on the health effects of exposure to mobile phone base station (MPBS) radiation. we performed a systematic review of randomized human trials conducted in laboratory settings and of epidemiological studies that investigated the health effects of MPBS radiation in the everyday environment. we included in the analysis 17 articles that met our basic quality criteria: 5 randomized human laboratory trials and 12 epidemiological studies. The majority of the papers (14) examined self-reported non-specific symptoms of ill-health. Most of the randomized trials did not detect any association between MPBS radiation and the development of acute symptoms during or shortly after exposure. The sporadically observed associations did not show a consistent pattern with regard to symptoms or types of exposure. We also found that the more sophisticated the exposure assessment, the less likely it was that an effect would be reported. Studies on health effects other than non-specific symptoms and studies on MPBS exposure in children were scarce. the evidence for a missing relationship between MPBS exposure up to 10 volts per metre and acute symptom development can be considered strong because it is based on randomized, blinded human laboratory trials. At present, there is insufficient data to draw firm conclusions about health effects from long-term low-level exposure typically occurring in the everyday environment.

Issues Relating to Selective Reporting When Including Non-Randomized Studies in Systematic Reviews on the Effects of Healthcare Interventions

ERIC Educational Resources Information Center

Norris, Susan L.; Moher, David; Reeves, Barnaby C.; Shea, Beverley; Loke, Yoon; Garner, Sarah; Anderson, Laurie; Tugwell, Peter; Wells, George

2013-01-01

Background: Selective outcome and analysis reporting (SOR and SAR) occur when only a subset of outcomes measured and analyzed in a study is fully reported, and are an important source of potential bias. Key methodological issues: We describe what is known about the prevalence and effects of SOR and SAR in both randomized controlled trials (RCTs)…

The reporting characteristics of bovine respiratory disease clinical intervention trials published prior to and following publication of the REFLECT statement.

PubMed

Totton, Sarah C; Cullen, Jonah N; Sargeant, Jan M; O'Connor, Annette M

2018-02-01

The goal of the REFLECT Statement (Reporting guidElines For randomized controLled trials in livEstoCk and food safeTy) (published in 2010) was to provide the veterinary research community with reporting guidelines tailored for randomized controlled trials for livestock and food safety. Our objective was to determine the prevalence of REFLECT Statement reporting of items 1-19 in controlled trials published in journals between 1970 and 2017 examining the comparative efficacy of FDA-registered antimicrobials against naturally acquired BRD (bovine respiratory disease) in weaned beef calves in Canada or the USA, and to compare the prevalence of reporting before and after 2010, when REFLECT was published. We divided REFLECT Statement, items 3, 5, 10, and 11 into subitems, because each dealt with multiple elements requiring separate assessment. As a result, 28 different items or subitems were evaluated independently. We searched MEDLINE ® and CABI (CAB Abstracts ® and Global Health ® ) (Web of Science™) in April 2017 and screened 2327 references. Two reviewers independently assessed the reporting of each item and subitem. Ninety-five references were eligible for the study. The reporting of the REFLECT items showed a point estimate for the prevalence ratio >1 (i.e. a higher proportion of studies published post-2010 reported this item compared to studies published pre-2010), apart from items 10.3, i.e., item 10, subitem 3 (who assigned study units to the interventions), 13 (the flow of study units through the study), 16 (number of study units in analysis), 18 (multiplicity), and 19 (adverse effects). Fifty-three (79%) of 67 studies published before 2010 and all 28 (100%) papers published after 2010 reported using a random allocation method in either the title, abstract, or methods (Prevalence ratio = 1.25; 95% CI (1.09,1.43)). However, 8 studies published prior to 2010 and 7 studies published post-2010 reported the term "systematic randomization" or variations of this term (which is not true randomization) to describe the allocation procedure. Fifty-five percent (37/67) of studies published pre-2010 reported blinding status (blinded/not blinded) of outcome assessors, compared to 24/28 (86%) of studies published post-2010 (Prevalence ratio = 1.5, 95% CI (1.19, 2.02)). The reporting of recommended items in journal articles in this body of work is generally improving; however, there is also evidence of confusion about what constitutes a random allocation procedure, and this suggests an educational need. As this study is observational, this precludes concluding that the publication of the REFLECT Statement was the cause of this trend. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

The Effects of Cognitive Therapy Versus ‘Treatment as Usual’ in Patients with Major Depressive Disorder

PubMed Central

Jakobsen, Janus Christian; Lindschou Hansen, Jane; Storebø, Ole Jakob; Simonsen, Erik; Gluud, Christian

2011-01-01

Background Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy may be an effective treatment option for major depressive disorder, but the effects have only had limited assessment in systematic reviews. Methods/Principal Findings Cochrane systematic review methodology, with meta-analyses and trial sequential analyses of randomized trials, are comparing the effects of cognitive therapy versus ‘treatment as usual’ for major depressive disorder. To be included the participants had to be older than 17 years with a primary diagnosis of major depressive disorder. Altogether, we included eight trials randomizing a total of 719 participants. All eight trials had high risk of bias. Four trials reported data on the 17-item Hamilton Rating Scale for Depression and four trials reported data on the Beck Depression Inventory. Meta-analysis on the data from the Hamilton Rating Scale for Depression showed that cognitive therapy compared with ‘treatment as usual’ significantly reduced depressive symptoms (mean difference −2.15 (95% confidence interval −3.70 to −0.60; P<0.007, no heterogeneity)). However, meta-analysis with both fixed-effect and random-effects model on the data from the Beck Depression Inventory (mean difference with both models −1.57 (95% CL −4.30 to 1.16; P = 0.26, I2 = 0) could not confirm the Hamilton Rating Scale for Depression results. Furthermore, trial sequential analysis on both the data from Hamilton Rating Scale for Depression and Becks Depression Inventory showed that insufficient data have been obtained. Discussion Cognitive therapy might not be an effective treatment for major depressive disorder compared with ‘treatment as usual’. The possible treatment effect measured on the Hamilton Rating Scale for Depression is relatively small. More randomized trials with low risk of bias, increased sample sizes, and broader more clinically relevant outcomes are needed. PMID:21829664

Mindfulness-based resilience training to reduce health risk, stress reactivity, and aggression among law enforcement officers: A feasibility and preliminary efficacy trial.

PubMed

Christopher, Michael S; Hunsinger, Matthew; Goerling, Lt Richard J; Bowen, Sarah; Rogers, Brant S; Gross, Cynthia R; Dapolonia, Eli; Pruessner, Jens C

2018-06-01

The primary objective of this study was to assess feasibility and gather preliminary outcome data on Mindfulness-Based Resilience Training (MBRT) for law enforcement officers. Participants (n = 61) were randomized to either an 8-week MBRT course or a no intervention control group. Self-report and physiological data were collected at baseline, post-training, and three months following intervention completion. Attendance, adherence, post-training participant feedback, and interventionist fidelity to protocol all demonstrated feasibility of MBRT for law enforcement officers. Compared to no intervention controls, MBRT participants experienced greater reductions in salivary cortisol, self-reported aggression, organizational stress, burnout, sleep disturbance, and reported increases in psychological flexibility and non-reactivity at post-training; however, group differences were not maintained at three-month follow-up. This initial randomized trial suggests MBRT is a feasible intervention. Outcome data suggest MBRT targets key physiological, psychological, and health risk factors in law enforcement officers, consistent with the potential to improve officer health and public safety. However, follow-up training or "booster" sessions may be needed to maintain training gains. A fully powered longitudinal randomized trial is warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

Incidental genetic findings in randomized clinical trials: recommendations from the Genomics and Randomized Trials Network (GARNET)

PubMed Central

2013-01-01

Recommendations and guidance on how to handle the return of genetic results to patients have offered limited insight into how to approach incidental genetic findings in the context of clinical trials. This paper provides the Genomics and Randomized Trials Network (GARNET) recommendations on incidental genetic findings in the context of clinical trials, and discusses the ethical and practical issues considered in formulating our recommendations. There are arguments in support of as well as against returning incidental genetic findings in clinical trials. For instance, reporting incidental findings in clinical trials may improve the investigator-participant relationship and the satisfaction of participation, but it may also blur the line between clinical care and research. The issues of whether and how to return incidental genetic findings, including the costs of doing so, should be considered when developing clinical trial protocols. Once decided, plans related to sharing individual results from the aim(s) of the trial, as well as incidental findings, should be discussed explicitly in the consent form. Institutional Review Boards (IRBs) and other study-specific governing bodies should be part of the decision as to if, when, and how to return incidental findings, including when plans in this regard are being reconsidered. PMID:23363732

Feasibility study from a randomized controlled trial of standard closure of a stoma site vs biological mesh reinforcement.

PubMed

2016-09-01

Hernia formation occurs at closed stoma sites in up to 30% of patients. The Reinforcement of Closure of Stoma Site (ROCSS) randomized controlled trial is evaluating whether placement of biological mesh during stoma closure safely reduces hernia rates compared with closure without mesh, without increasing surgical or wound complications. This paper aims to report recruitment, deliverability and safety from the internal feasibility study. A multicentre, patient and assessor blinded, randomized controlled trial, delivered through surgical trainee research networks. A 90-patient internal feasibility study assessed recruitment, randomization, deliverability and early (30 day) safety of the novel surgical technique (ClinicalTrials.gov registration number NCT02238964). The feasibility study recruited 90 patients from the 104 considered for entry (45 to mesh, 45 to no mesh). Seven of eight participating centres randomized patients within 30 days of opening. Overall, 41% of stomas were created for malignant disease and 73% were ileostomies. No mesh-specific complications occurred. Thirty-one postoperative adverse events were experienced by 31 patients, including surgical site infection (9%) and postoperative ileus (6%). One mesh was removed for re-access to the abdominal cavity, for reasons unrelated to the mesh. Independent review by the Data Monitoring and Ethics Committee of adverse event data by treatment allocation found no safety concerns. Multicentre randomization to this trial of biological mesh is feasible, with no early safety concerns. Progression to the full Phase III trial has continued. ROCSS shows that trainee research networks can efficiently develop and deliver complex interventional surgical trials. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Effect of Home Care Nursing on Patients Discharged From Hospital With Self-Reported Signs of Constipation: A Randomized Trial.

PubMed

Konradsen, Hanne; Rasmussen, Marie Louise Thiese; Noiesen, Eline; Trosborg, Ingelise

Constipation is a common health problem in relation to hospitalization. This randomized controlled trial aimed to investigate whether advice from a home care nurse after discharge had an effect on self-reported signs of constipation. A total of 59 patients were included in the study on the basis of their self-reported signs of constipation evaluated using the Constipation Assessment Scale. Advice from the home care nurses was given on the intake of fiber and liquid and mobilization related to scorings on the Constipation Risk Assessment Scale, the administration of laxatives, and referral to a physician when needed. Results showed a tendency toward the visits being effective, but a more complex intervention might be needed.

Current role of cryotherapy in retinopathy of prematurity: a report by the American Academy of Ophthalmology.

PubMed

Simpson, Jennifer L; Melia, Michele; Yang, Michael B; Buffenn, Angela N; Chiang, Michael F; Lambert, Scott R

2012-04-01

To evaluate the role of cryotherapy in the current treatment of retinopathy of prematurity (ROP). Literature searches of PubMed and the Cochrane Library were conducted on December 2, 2009, for articles published after 1984. The searches included all languages and retrieved 187 relevant citations. Thirteen articles were deemed relevant to the assessment question and were rated according to the strength of evidence. Four articles reported results from 2 large multicenter randomized clinical trials, and the remaining 9 articles reported results of 3 small randomized trials that directly compared cryotherapy and laser. Neither of the multicenter randomized clinical trials was a direct comparison of cryotherapy with laser. These studies were used to evaluate the comparative trials based on treatment criteria, study populations, and clinical results. Higher percentages of poor structural and functional outcomes generally were seen in eyes treated with cryotherapy compared with eyes undergoing laser treatment. Higher rates of systemic complications and myopia also were identified after treatment with cryotherapy. Despite a relative paucity of level I evidence directly comparing cryotherapy and laser treatment for threshold ROP, the literature suggests that neonatal facilities should gain access to laser technology and laser-trained ophthalmic staff to achieve better outcomes for treatment of the disease. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

“Entering a Clinical Trial: Is it Right For You?"-- A Randomized Study of The Clinical Trials Video and Its Impact on the Informed Consent Process

PubMed Central

Hoffner, Brianna; Bauer-Wu, Susan; Hitchcock-Bryan, Suzanne; Powell, Mark; Wolanski, Andrew; Joffe, Steven

2011-01-01

PURPOSE This randomized study was designed to assess the utility of an educational video in preparing cancer patients for decisions about clinical trial participation. The study assessed the effect of the video on patients’ understanding and perceptions of clinical trials, its impact on decision making and patient-provider communication, and patients’ satisfaction with the video. METHODS Ninety adults considering cancer clinical trials were randomized to receive (n=45) or not receive (n=45) the video. Using the validated Quality of Informed Consent (QuIC), respondents’ knowledge about clinical trial participation was assessed. All subjects completed additional questions about satisfaction with the video, decision making, and patient-provider communication. Data were analyzed using the Wilcoxon rank-sum test, regression model and descriptive statistics. RESULTS Although intent-to-treat analysis found no significant group differences in objective understanding between those randomized to view or not view the video, the majority of participants reported favorable experiences with regard to watching the video: 85% found the video was an important source of information about clinical trials; 81% felt better prepared to discuss the trial with their physician; 89% of those who watched the video with family indicated that it helped family better understand clinical trials; and 73% indicated it helped family accept their decision about participation. CONCLUSIONS Although the video did not measurably improve patients’ knowledge about clinical trials, it was an important source of information, helped educate families, and enhanced patient communication with their oncology providers. PMID:22009665

Urinary tract stone occurrence in the Women's Health Initiative (WHI) randomized clinical trial of calcium and vitamin D supplements.

PubMed

Wallace, Robert B; Wactawski-Wende, Jean; O'Sullivan, Mary Jo; Larson, Joseph C; Cochrane, Barbara; Gass, Margery; Masaki, Kamal

2011-07-01

The Women's Health Initiative (WHI) randomized clinical trial (RCT) of calcium plus vitamin D (CaD) supplements found a 17% excess in urinary tract stone incidence in the supplemented group. This study evaluated whether this risk is modified by participant characteristics. We examined the correlates of urinary tract stone occurrence in the CaD arm of the WHI trial. We analyzed an RCT involving 36,282 postmenopausal women aged 50-79 y from 40 WHI centers: 18,176 women received 500 mg calcium carbonate plus 200 IU vitamin D(3) twice daily (1000 mg and 400 IU daily, respectively), and 18,106 women received a matching placebo for an average of 7.0 y. The incidence of urinary tract stones was determined. The incidence of self-reported clinically diagnosed urinary tract stones was more common in the active CaD medication group than in the placebo group (hazard ratio: 1.17; 95% CI: 1.02, 1.34): 449 women in the CaD group and 381 women in the placebo group reported a stone during the trial. The rates of self-reported stones did not differ between various demographic, anthropomorphic, dietary, and other hypothesized risk factors according to randomization assignment. Neither the total calcium intake nor the use of calcium supplements at baseline was associated with the risk of stones. In sensitivity analyses that censored participants who were below 80% adherence, the findings were similar. Daily supplementation with CaD for 7 y was associated with an increase in the number of self-reported urinary tract stones. These findings have implications for CaD supplement use. This trial was registered with the WHI at clinicaltrials.gov as NCT00000611.

Urinary tract stone occurrence in the Women's Health Initiative (WHI) randomized clinical trial of calcium and vitamin D supplements123

PubMed Central

Wallace, Robert B; Wactawski-Wende, Jean; O'Sullivan, Mary Jo; Larson, Joseph C; Cochrane, Barbara; Gass, Margery; Masaki, Kamal

2011-01-01

Background: The Women's Health Initiative (WHI) randomized clinical trial (RCT) of calcium plus vitamin D (CaD) supplements found a 17% excess in urinary tract stone incidence in the supplemented group. This study evaluated whether this risk is modified by participant characteristics. Objective: We examined the correlates of urinary tract stone occurrence in the CaD arm of the WHI trial. Design: We analyzed an RCT involving 36,282 postmenopausal women aged 50–79 y from 40 WHI centers: 18,176 women received 500 mg calcium carbonate plus 200 IU vitamin D3 twice daily (1000 mg and 400 IU daily, respectively), and 18,106 women received a matching placebo for an average of 7.0 y. The incidence of urinary tract stones was determined. Results: The incidence of self-reported clinically diagnosed urinary tract stones was more common in the active CaD medication group than in the placebo group (hazard ratio: 1.17; 95% CI: 1.02, 1.34): 449 women in the CaD group and 381 women in the placebo group reported a stone during the trial. The rates of self-reported stones did not differ between various demographic, anthropomorphic, dietary, and other hypothesized risk factors according to randomization assignment. Neither the total calcium intake nor the use of calcium supplements at baseline was associated with the risk of stones. In sensitivity analyses that censored participants who were below 80% adherence, the findings were similar. Conclusions: Daily supplementation with CaD for 7 y was associated with an increase in the number of self-reported urinary tract stones. These findings have implications for CaD supplement use. This trial was registered with the WHI at clinicaltrials.gov as NCT00000611. PMID:21525191

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.

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.

Metamizole-Associated Adverse Events: A Systematic Review and Meta-Analysis

PubMed Central

Fässler, Margrit; Blozik, Eva; Linde, Klaus; Jüni, Peter; Reichenbach, Stephan; Scherer, Martin

2015-01-01

Background Metamizole is used to treat pain in many parts of the world. Information on the safety profile of metamizole is scarce; no conclusive summary of the literature exists. Objective To determine whether metamizole is clinically safe compared to placebo and other analgesics. Methods We searched CENTRAL, MEDLINE, EMBASE, CINAHL, and several clinical trial registries. We screened the reference lists of included trials and previous systematic reviews. We included randomized controlled trials that compared the effects of metamizole, administered to adults in any form and for any indication, to other analgesics or to placebo. Two authors extracted data regarding trial design and size, indications for pain medication, patient characteristics, treatment regimens, and methodological characteristics. Adverse events (AEs), serious adverse events (SAEs), and dropouts were assessed. We conducted separate meta-analyses for each metamizole comparator, using standard inverse-variance random effects meta-analysis to pool the estimates across trials, reported as risk ratios (RRs). We calculated the DerSimonian and Laird variance estimate T2 to measure heterogeneity between trials. The pre-specified primary end point was any AE during the trial period. Results Of the 696 potentially eligible trials, 79 trials including almost 4000 patients with short-term metamizole use of less than two weeks met our inclusion criteria. Fewer AEs were reported for metamizole compared to opioids, RR = 0.79 (confidence interval 0.79 to 0.96). We found no differences between metamizole and placebo, paracetamol and NSAIDs. Only a few SAEs were reported, with no difference between metamizole and other analgesics. No agranulocytosis or deaths were reported. Our results were limited by the mediocre overall quality of the reports. Conclusion For short-term use in the hospital setting, metamizole seems to be a safe choice when compared to other widely used analgesics. High-quality, adequately sized trials assessing the intermediate- and long-term safety of metamizole are needed. PMID:25875821

Design of the integrative medical group visits randomized control trial for underserved patients with chronic pain and depression.

PubMed

Gardiner, Paula; Lestoquoy, Anna Sophia; Gergen-Barnett, Katherine; Penti, Brian; White, Laura F; Saper, Robert; Fredman, Lisa; Stillman, Sarah; Lily Negash, N; Adelstein, Pamela; Brackup, Ivy; Farrell-Riley, Christine; Kabbara, Karim; Laird, Lance; Mitchell, Suzanne; Bickmore, Timothy; Shamekhi, Ameneh; Liebschutz, Jane M

2017-03-01

Given the public health crisis of opioid overprescribing for pain, there is a need for evidence-based non pharmacological treatment options that effectively reduce pain and depression. We aim to examine the effectiveness of the Integrative Medical Group Visits (IMGV) model in reducing chronic pain and depressive symptoms, as well as increasing pain self-management. This paper details the study design and implementation of an ongoing randomized controlled trial of the IMGV model as compared to primary care visits. The research aims to determine if the IMGV model is effective in achieving: a) a reduction in self-reported pain and depressive symptoms and 2) an improvement in the self-management of pain, through increasing pain self-efficacy and reducing use of self-reported pain medication. We intend to recruit 154 participants to be randomized in our intervention, the IMGV model (n=77) and to usual care (n=77). Usual care of chronic pain through pharmacological treatment has mixed evidence of efficacy and may not improve quality of life or functional status. We aim to conduct a randomized controlled trial to evaluate the effectiveness of the IMGV model as compared to usual care in reducing self-reported pain and depressive symptoms as well as increasing pain management skills. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Design and baseline characteristics of participants in a phase III randomized trial of celecoxib and selenium for colorectal adenoma prevention.

PubMed

Thompson, Patricia; Roe, Denise J; Fales, Liane; Buckmeier, Julie; Wang, Fang; Hamilton, Stanley R; Bhattacharyya, Achyut; Green, Sylvan; Hsu, Chiu-Hsieh; Chow, H-H Sherry; Ahnen, Dennis J; Boland, C Richard; Heigh, Russell I; Fay, David E; Martinez, Maria Elena; Jacobs, Elizabeth; Ashbeck, Erin L; Alberts, David S; Lance, Peter

2012-12-01

COX inhibitors reduce colorectal adenoma recurrence by up to 45% and selenium supplementation may prevent colorectal cancer. Following colonoscopic adenoma resection, 1,600 men and women, ages 40 to 80 years, were randomized to celecoxib (400 mg daily), a selective COX-2 inhibitor, and/or selenium (200 μg daily as selenized yeast), or double placebo. The trial was initiated in November 2001. The primary trial endpoint is adenoma recurrence in each intervention group compared with placebo, as determined by surveillance colonoscopy conducted three to five years after baseline. Randomization was stratified by use of low-dose aspirin (81 mg) and clinic site. Following reports of cardiovascular toxicity associated with COX-2 inhibitors, the celecoxib arm was discontinued in December 2004 when 824 participants had been randomized. Accrual continued with randomization to selenium alone or placebo. Randomization of the originally planned cohort (n = 1,621) was completed in November 2008. A further 200 patients with one or more advanced adenomas (denoting increased risk for colorectal cancer) were accrued to enhance statistical power for determining intervention efficacy in this higher-risk subgroup. Accrual of the total cohort (n = 1,824) was completed in January 2011. Baseline cohort characteristics include: mean age 62.9 years; 65% male; body mass index (BMI) 29.1 ± 5.1; 47% taking low-dose aspirin while on trial; 20% with three or more adenomas; and 38% with advanced adenomas. Intervention effects on adenoma recurrence will be determined, and their modification by genetic background and baseline selenium level. The effect of selenium supplementation on risk for type II diabetes will also be reported. ©2012 AACR

Design, Analysis, and Reporting of Crossover Trials for Inclusion in a Meta-Analysis.

PubMed

Li, Tianjing; Yu, Tsung; Hawkins, Barbara S; Dickersin, Kay

2015-01-01

To evaluate the characteristics of the design, analysis, and reporting of crossover trials for inclusion in a meta-analysis of treatment for primary open-angle glaucoma and to provide empirical evidence to inform the development of tools to assess the validity of the results from crossover trials and reporting guidelines. We searched MEDLINE, EMBASE, and Cochrane's CENTRAL register for randomized crossover trials for a systematic review and network meta-analysis we are conducting. Two individuals independently screened the search results for eligibility and abstracted data from each included report. We identified 83 crossover trials eligible for inclusion. Issues affecting the risk of bias in crossover trials, such as carryover, period effects and missing data, were often ignored. Some trials failed to accommodate the within-individual differences in the analysis. For a large proportion of the trials, the authors tabulated the results as if they arose from a parallel design. Precision estimates properly accounting for the paired nature of the design were often unavailable from the study reports; consequently, to include trial findings in a meta-analysis would require further manipulation and assumptions. The high proportion of poorly reported analyses and results has the potential to affect whether crossover data should or can be included in a meta-analysis. There is pressing need for reporting guidelines for crossover trials.

Neuropsychiatric safety with liraglutide 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials.

PubMed

O'Neil, Patrick M; Aroda, Vanita R; Astrup, Arne; Kushner, Robert; Lau, David C W; Wadden, Thomas A; Brett, Jason; Cancino, Ana-Paula; Wilding, John P H

2017-11-01

Liraglutide, a GLP-1 receptor agonist, regulates appetite via receptors in the brain. Because of concerns regarding the potential of centrally-acting anti-obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double-blind trials with liraglutide 3.0 mg were evaluated post hoc. Data from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 or ≥27 kg/m 2 with weight-related comorbidities were randomized to once-daily subcutaneous liraglutide 3.0 mg (n = 3384) or placebo (n = 1941), both with a 500 kcal/d deficit diet, plus exercise. Adverse events related to neuropsychiatric safety were collected in all trials. Additionally, in the phase 3a trials, validated mental-health questionnaires were prospectively and systematically administered. In the pooled analysis of 5325 randomized and exposed individuals, rates of depression (2.1 vs 2.1 events/100 person-years) and anxiety (1.9 vs 1.7 events/100 person-years) through adverse event reporting were similarly low in liraglutide and placebo groups. Nine (0.3%) individuals receiving liraglutide and 2 (0.1%) receiving placebo reported adverse events of suicidal ideation or behaviour. In phase 3a trials, mean baseline Patient Health Questionnaire-9 scores of 2.8 ± 3.0 vs 2.9 ± 3.1 for liraglutide vs placebo improved to 1.8 ± 2.7 vs 1.9 ± 2.7, respectively, at treatment end; 34/3291 individuals (1.0%) receiving liraglutide 3.0 mg vs 19/1843 (1.0%) receiving placebo reported suicidal ideation on the Columbia-Suicide Severity Rating Scale. Results of this exploratory pooled analysis provide no cause for concern regarding the neuropsychiatric safety of treatment with liraglutide 3.0 mg in patients similar to those included in the examined trials. Although there was a small numerical imbalance in suicidal ideation with liraglutide through adverse event reporting, no between-treatment imbalances in suicidal ideation/behaviour or depression were noted through prospective questionnaire assessments. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

An Evaluation of the Effectiveness of Recruitment Methods: The Staying Well after Depression Randomized Controlled Trial

PubMed Central

Krusche, Adele; Rudolf von Rohr, Isabelle; Muse, Kate; Duggan, Danielle; Crane, Catherine; Williams, J. Mark G.

2014-01-01

Background Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited and trials often fail to report sufficient details about the recruitment sources and resources utilised. Purpose We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression. Methods We describe eight recruitment methods utilised and two further sources not initiated by the research team and examine their efficacy in terms of (i) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial, (ii) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants, and (iii) comparison of sociodemographic characteristics of individuals recruited from different sources. Results Poster advertising, web-based advertising and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important. Limitations It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other populations, such as those currently unwell, or in other geographical locations. Recruitment source was unavailable for participants who could not be reached after the initial contact. Thus, it is possible that the efficiency of certain methods of recruitment was poorer than estimated. Efficacy and costs of other recruitment initiatives, such as providing travel expenses to the in-person eligibility assessment and making follow-up telephone calls to candidates who contacted the recruitment team but could not be screened promptly, were not analysed. Conclusions Website advertising resulted in the highest number of randomized participants and was the second cheapest method of recruiting. Future research should evaluate the effectiveness of recruitment strategies for other samples to contribute to a comprehensive base of knowledge for future RCTs. PMID:24686105

An evaluation of the effectiveness of recruitment methods: the staying well after depression randomized controlled trial.

PubMed

Krusche, Adele; Rudolf von Rohr, Isabelle; Muse, Kate; Duggan, Danielle; Crane, Catherine; Williams, J Mark G

2014-04-01

Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties in recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited, and trials often fail to report sufficient details about the recruitment sources and resources utilized. We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression. We describe eight recruitment methods utilized and two further sources not initiated by the research team and examine their efficacy in terms of (1) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial; (2) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants; and (3) comparison of sociodemographic characteristics of individuals recruited from different sources. Poster advertising, web-based advertising, and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters, and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important. It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other populations, such as those currently unwell, or in other geographical locations. Recruitment source was unavailable for participants who could not be reached after the initial contact. Thus, it is possible that the efficiency of certain methods of recruitment was poorer than estimated. Efficacy and costs of other recruitment initiatives, such as providing travel expenses to the in-person eligibility assessment and making follow-up telephone calls to candidates who contacted the recruitment team but could not be screened promptly, were not analysed. Website advertising resulted in the highest number of randomized participants and was the second cheapest method of recruiting. Future research should evaluate the effectiveness of recruitment strategies for other samples to contribute to a comprehensive base of knowledge for future RCTs.

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.

Omega-3 fatty acids (ῳ-3 fatty acids) in epilepsy: animal models and human clinical trials.

PubMed

DeGiorgio, Christopher M; Taha, Ameer Y

2016-10-01

There is growing interest in alternative and nutritional therapies for drug resistant epilepsy. ῳ-3 fatty acids such as fish or krill oil are widely available supplements used to lower triglycerides and enhance cardiovascular health. ῳ-3 fatty acids have been studied extensively in animal models of epilepsy. Yet, evidence from randomized controlled clinical trials in epilepsy is at an early stage. This report focuses on the key ῳ-3 fatty acids DHA and EPA, their incorporation into the lipid bilayer, modulation of ion channels, and mechanisms of action in reducing excitability within the central nervous system. This paper presents pre-clinical evidence from mouse, rat, and canine models, and reports the efficacy of n-3 fatty acids in randomized controlled clinical trials. An English language search of PubMed and Google scholar for the years 1981-2016 was performed for animal studies and human randomized controlled clinical trials. Expert commentary: Basic science and animal models provide a cogent rationale and substantial evidence for a role of ῳ-3 fatty acids in reducing seizures. Results in humans are limited. Recent Phase II RCT evidence suggests that low to moderate dose of ῳ-3 fatty acids reduce seizures; however, larger multicenter randomized trials are needed to confirm or refute the evidence. The safety, health effects, low cost and ease of use make ῳ-3 fatty acids an intriguing alternative therapy for drug resistant epilepsy. Though safety of profile is excellent, the human data is not yet sufficient to support efficacy in drug resistant epilepsy at this time.

Effect of magnesium added to local anesthetics for caudal anesthesia on postoperative pain in pediatric surgical patients: A systematic review and meta-analysis with Trial Sequential Analysis

PubMed Central

Mihara, Takahiro; Nakamura, Nobuhito; Ka, Koui; Goto, Takahisa

2018-01-01

Background Magnesium has been investigated as an adjuvant for neuraxial anesthesia, but the effect of caudal magnesium on postoperative pain is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of caudal magnesium. Methods We searched six databases, including trial registration sites. Randomized clinical trials reporting the effect of caudal magnesium on postoperative pain after general anesthesia were eligible. The risk ratio for use of rescue analgesics after surgery was combined using a random-effects model. We also assessed adverse events. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. Results Four randomized controlled trials (247 patients) evaluated the need for rescue analgesics. In all four trials, 50 mg of magnesium was administered with caudal ropivacaine. The results suggested that the need for rescue analgesia was reduced significantly by caudal magnesium administration (risk ratio 0.45; 95% confidence interval 0.24–0.86). There was considerable heterogeneity as indicated by an I2 value of 62.5%. The Trial Sequential Analysis-adjusted confidence interval was 0.04–5.55, indicating that further trials are required. The quality of evidence was very low. The rate of adverse events was comparable between treatment groups. Conclusion Caudal magnesium may reduce the need for rescue analgesia after surgery, but further randomized clinical trials with a low risk of bias and a low risk of random errors are necessary to assess the effect of caudal magnesium on postoperative pain and adverse events. Trial registration University Hospital Medical Information Network Clinical Trials Registry UMIN000025344. PMID:29293586

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.

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

Transfusion Indication Threshold Reduction (TITRe2) randomized controlled trial in cardiac surgery: statistical analysis plan.

PubMed

Pike, Katie; Nash, Rachel L; Murphy, Gavin J; Reeves, Barnaby C; Rogers, Chris A

2015-02-22

The Transfusion Indication Threshold Reduction (TITRe2) trial is the largest randomized controlled trial to date to compare red blood cell transfusion strategies following cardiac surgery. This update presents the statistical analysis plan, detailing how the study will be analyzed and presented. The statistical analysis plan has been written following recommendations from the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, prior to database lock and the final analysis of trial data. Outlined analyses are in line with the Consolidated Standards of Reporting Trials (CONSORT). The study aims to randomize 2000 patients from 17 UK centres. Patients are randomized to either a restrictive (transfuse if haemoglobin concentration <7.5 g/dl) or liberal (transfuse if haemoglobin concentration <9 g/dl) transfusion strategy. The primary outcome is a binary composite outcome of any serious infectious or ischaemic event in the first 3 months following randomization. The statistical analysis plan details how non-adherence with the intervention, withdrawals from the study, and the study population will be derived and dealt with in the analysis. The planned analyses of the trial primary and secondary outcome measures are described in detail, including approaches taken to deal with multiple testing, model assumptions not being met and missing data. Details of planned subgroup and sensitivity analyses and pre-specified ancillary analyses are given, along with potential issues that have been identified with such analyses and possible approaches to overcome such issues. ISRCTN70923932 .

Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial.

PubMed

Rog, David J; Nurmikko, Turo J; Young, Carolyn A

2007-09-01

Central neuropathic pain (CNP), pain initiated or caused by a primary lesion or dysfunction of the central nervous system, occurs in ~28% of patients with multiple sclerosis (MS). Delta(9)-Tetrahydrocannabinol/cannabidiol (THC/CBD), an endocannabinoid system modulator, has demonstrated efficacy for up to 4 weeks in randomized controlled trials in the treatment of CNP in patients with MS. The purpose of this extension was to establish long-term tolerability and effectiveness profiles for THC/CBD (Sativex (R), GW Pharmaceuticals plc, Salisbury, United Kingdom) oromucosal spray in CNP associated with MS. This uncontrolled, open-label trial was an indefinite-duration extension of a previously reported 5-week randomized study in patients with MS and CNP. In the initial trial, patients were randomized to placebo or THC/CBD. Patients were only required to maintain their existing analgesia in the randomized study. In the open-label trial they could vary their other analgesia as required. All patients (placebo and THC/CBD) who completed the randomized trial commenced the open-label follow-up on THC/CBD (27 mg/mL: 25 mg/mL). Patients titrated their dosage, maintaining their existing analgesia. The primary end point of the trial was the number, frequency, and type of adverse events (AEs) reported by patients. Secondary end points included changes from baseline in 11-point numerical rating scale (NRS-11) neuropathic pain score, hematology and clinical chemistry test results, vital signs, trial drug usage, and intoxication visual analogue scale scores. Sixty-six patients were enrolled in the randomized trial; 64 (97%) completed the randomized trial and 63 (95%) entered the open-label extension (race, white, 100%; sex, male, 14 [22%]; mean [SD] age, 49 [8.4] years [range, 27-71 years[). The mean (SD) duration of open-label treatment was 463 (378) days (median, 638 days; range, 3-917 days), with 34 (54%) patients completing >1 year of treatment with THC/CBD and 28 (44%) patients completing the open-label trial with a mean (SD) duration of treatment of 839 (42) days (median, 845 days; range, 701-917 days). Mean NRS-11 pain scores in the final week of the randomized trial were 3.8 in the treatment group and 5.0 in the placebo group. In the 28 (44%) patients who completed the 2-year follow up, the mean (SD) NRS-11 pain score in the final week of treatment was 2.9 (2.0) (range, 0-8.0). Fifty-eight (92%) patients experienced > or =1 treatment-related AE. These AEs were rated by the investigator as mild in 47 (75%) patients, moderate in 49 (78%), and severe in 32 (51%). The most commonly reported AEs were dizziness (27%), nausea (18 %), and feeling intoxicated (11%). Two treatment-related serious AEs (ventricular bigeminy and circulatory collapse) were judged to be treatment-related. Both serious AEs occurred in the same patient and resolved completely following a period of discontinuation. Eleven (17%) patients experienced oral discomfort, 4 persistently. Regular oral examinations revealed that 7 (11%) patients developed white buccal mucosal patches and 2 (3%) developed red buccal mucosal patches; all cases were deemed mild and resolved. Seventeen (25%) patients withdrew due to AEs. The mean number of sprays and patients experiencing intoxication remained stable throughout the follow-up trial. THC/CBD was effective, with no evidence of tolerance, in these select patients with CNP and MS who completed approximately 2 years of treatment (n = 28). Ninety-two percent of patients experienced an AE, the most common of which were dizziness and nausea. The majority of AEs were deemed to be of mild to moderate severity by the investigators.

Does ascorbic acid protect against contrast-induced acute kidney injury in patients undergoing coronary angiography: a systematic review with meta-analysis of randomized, controlled trials.

PubMed

Sadat, Umar; Usman, Ammara; Gillard, Jonathan H; Boyle, Jonathan R

2013-12-10

This study sought to perform a systematic review with meta-analysis of randomized controlled trials comparing the use of ascorbic acid with placebo or other treatment options for the treatment of contrast induced-acute kidney injury (CI-AKI) in patients undergoing coronary angiography. CI-AKI remains the most widely discussed and debated topic in cardiovascular medicine, with its incidence increasing due to an increasing number of contrast media-enhanced radiological procedures being performed. MEDLINE, Embase, and Cochrane central databases were searched from inception to May 2013, without language restrictions. For a study to be selected, it had to report the incidence of CI-AKI as an outcome measure. Studies were excluded if at least 1 study arm did not have ascorbic acid administered alone or with saline solution hydration. Data were extracted by 1 author, and random checks were made by another author. Nine randomized, controlled trials reported data on the incidence of CI-AKI in 1,536 patients who had completed the trial and were included in the final analysis. Patients receiving ascorbic acid had 33% less risk of CI-AKI compared with patients receiving placebo or an alternate pharmacological treatment (risk ratio by random-effects model: 0.672; 95% confidence interval, 0.466 to 0.969; p = 0.034). Ascorbic acid provides effective nephroprotection against CI-AKI and may form a part of effective prophylactic pharmacological regimens. Copyright © 2013 American College of Cardiology Foundation. 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).

Spouse READI (Resilience Education and Deployment Information): Randomized Clinical Trial Formerly Reintegration: The Role of Spouse Telephone BATTLEMIND Randomized Clinical Trial

DTIC Science & Technology

2015-05-01

Kroenke, K., Spitzer, R. L., Williams, J. B., Monahan, P. O., & Lowe, B. (2007). Anxiety disorders in primary care : Prevalence, impairment, comorbidity... Lingler , J., Sherwood, P., Crighton, M., Song, M. K., & Happ, M. B. (2008). Conceptual challenges in the study of caregiver care recipient relationships...rural areas (Hazle et al., 2012). However, community mental health and primary care providers report uncertainty about their ability to provide best

Spouse READI (Resilience Education and Deployment Information): Randomized Clinical Trial Formerly Reintegration: The Role of Spouse Telephone BATTLEMIND Randomized Clinical Trial

DTIC Science & Technology

2014-10-01

primary care : Prevalence, impairment, comorbidity, and detection. Annals of Internal Medicine, 146(5), 17-25. Kroenke, K., Spitzer, R.L., & Williams, J.B...in dependent use of health care services. Medical Care , 50(9), 821-8. Lingler , J., Sherwood, P., Crighton, M., Song, M.K., & Happ, M.B. (2008...et al., 2012). However, community mental health and primary care providers report uncertainty about their ability to provide best care for military

Ear Acupuncture for Post-Operative Pain Associated with Ambulatory Arthroscopic Knee Surgery: A Randomized Controlled Trial

DTIC Science & Technology

2014-01-14

E7(/(3+21(180%(5 ,QFOXGHDUHDFRGH 14 Jan 2014 Final Report Ear acupuncture for post-operative pain associated with ambulatory arthroscopic...DISTRIBUTION A. Approved for public release: distribution unlimited. The purpose of this study is to compare ear acupuncture plus standard therapy versus...3298 Ear Acupuncture for Post-operative Pa111 Assoc1ated With Ambulatory Arthroscopic Knee Surgery A Randomized Controlled Trial ’• V ’’ ’-’ I

Influence of therapist competence and quantity of cognitive behavioural therapy on suicidal behaviour and inpatient hospitalisation in a randomised controlled trial in borderline personality disorder: further analyses of treatment effects in the BOSCOT study.

PubMed

Norrie, John; Davidson, Kate; Tata, Philip; Gumley, Andrew

2013-09-01

We investigated the treatment effects reported from a high-quality randomized controlled trial of cognitive behavioural therapy (CBT) for 106 people with borderline personality disorder attending community-based clinics in the UK National Health Service - the BOSCOT trial. Specifically, we examined whether the amount of therapy and therapist competence had an impact on our primary outcome, the number of suicidal acts, using instrumental variables regression modelling. Randomized controlled trial. Participants from across three sites (London, Glasgow, and Ayrshire/Arran) were randomized equally to CBT for personality disorders (CBTpd) plus Treatment as Usual or to Treatment as Usual. Treatment as Usual varied between sites and individuals, but was consistent with routine treatment in the UK National Health Service at the time. CBTpd comprised an average 16 sessions (range 0-35) over 12 months. We used instrumental variable regression modelling to estimate the impact of quantity and quality of therapy received (recording activities and behaviours that took place after randomization) on number of suicidal acts and inpatient psychiatric hospitalization. A total of 101 participants provided full outcome data at 2 years post randomization. The previously reported intention-to-treat (ITT) results showed on average a reduction of 0.91 (95% confidence interval 0.15-1.67) suicidal acts over 2 years for those randomized to CBT. By incorporating the influence of quantity of therapy and therapist competence, we show that this estimate of the effect of CBTpd could be approximately two to three times greater for those receiving the right amount of therapy from a competent therapist. Trials should routinely control for and collect data on both quantity of therapy and therapist competence, which can be used, via instrumental variable regression modelling, to estimate treatment effects for optimal delivery of therapy. Such estimates complement rather than replace the ITT results, which are properly the principal analysis results from such trials. © 2013 The British Psychological Society.

Yoga vs. physical therapy vs. education for chronic low back pain in predominantly minority populations: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Chronic low back pain causes substantial morbidity and cost to society while disproportionately impacting low-income and minority adults. Several randomized controlled trials show yoga is an effective treatment. However, the comparative effectiveness of yoga and physical therapy, a common mainstream treatment for chronic low back pain, is unknown. Methods/Design This is a randomized controlled trial for 320 predominantly low-income minority adults with chronic low back pain, comparing yoga, physical therapy, and education. Inclusion criteria are adults 18–64 years old with non-specific low back pain lasting ≥12 weeks and a self-reported average pain intensity of ≥4 on a 0–10 scale. Recruitment takes place at Boston Medical Center, an urban academic safety-net hospital and seven federally qualified community health centers located in diverse neighborhoods. The 52-week study has an initial 12-week Treatment Phase where participants are randomized in a 2:2:1 ratio into i) a standardized weekly hatha yoga class supplemented by home practice; ii) a standardized evidence-based exercise therapy protocol adapted from the Treatment Based Classification method, individually delivered by a physical therapist and supplemented by home practice; and iii) education delivered through a self-care book. Co-primary outcome measures are 12-week pain intensity measured on an 11-point numerical rating scale and back-specific function measured using the modified Roland Morris Disability Questionnaire. In the subsequent 40-week Maintenance Phase, yoga participants are re-randomized in a 1:1 ratio to either structured maintenance yoga classes or home practice only. Physical therapy participants are similarly re-randomized to either five booster sessions or home practice only. Education participants continue to follow recommendations of educational materials. We will also assess cost effectiveness from the perspectives of the individual, insurers, and society using claims databases, electronic medical records, self-report cost data, and study records. Qualitative data from interviews will add subjective detail to complement quantitative data. Trial registration This trial is registered in ClinicalTrials.gov, with the ID number: NCT01343927. PMID:24568299

Oncology trial abstracts showed suboptimal improvement in reporting: a comparative before-and-after evaluation using CONSORT for Abstract guidelines.

PubMed

Ghimire, Saurav; Kyung, Eunjung; Lee, Heeyoung; Kim, Eunyoung

2014-06-01

The aims of this study were to evaluate the quality of randomized controlled trial (RCT) abstracts published in the field of oncology and identify characteristics associated with better reporting quality. All phase III trials published during 2005-2007 [before Consolidated Standards of Reporting Trials (CONSORT)] and 2010-2012 (after CONSORT) were searched electronically in MEDLINE/PubMed and retrieved for review using an 18-point overall quality score (OQS) for reporting based on the CONSORT for Abstract guidelines. Descriptive statistics followed by multivariate linear regression were used to identify features associated with improved reporting quality. The mean OQS was 8.2 (range: 5-13; 95% confidence interval (CI): 8.0, 8.3) and 9.9 (range: 5-18; 95% CI: 9.7, 10.2) in the pre- and post-CONSORT periods, respectively. The method for random sequence generation, allocation concealment, blinding details, and funding sources were missing in pre-CONSORT abstracts and insufficiently reported (<20%) in post-CONSORT abstracts. A high impact factor (P < 0.001) and the journal of publication (P < 0.001) were independent factors that were significantly associated with higher reporting quality on multivariate analysis. The reporting quality of RCT abstracts in oncology showed suboptimal improvement over time. Thus, stricter adherence to the CONSORT for Abstract guidelines is needed to improve the reporting quality of RCT abstracts published in oncology. Copyright © 2014 Elsevier Inc. All rights reserved.

Brief Report: Social Disability in Autism Spectrum Disorder--Results from Research Units on Pediatric Psychopharmacology (RUPP) Autism Network Trials

ERIC Educational Resources Information Center

Scahill, Lawrence; Hallett, Victoria; Aman, Michael G.; McDougle, Christopher J.; Arnold, L. Eugene; McCracken, James T.; Tierney, Elaine; Deng, Yanhong; Dziura, James; Vitiello, Benedetto

2013-01-01

There is growing interest in measuring social disability as a core element of autism spectrum disorders in medication trials. We conducted a secondary analysis on the Aberrant Behavior Checklist Social Withdrawal subscale using data from two federally-funded, multi-site, randomized trials with risperidone. Study 1 included 52 subjects assigned to…

N-acetyl cysteine add-on treatment for bipolar II disorder: a subgroup analysis of a randomized placebo-controlled trial.

PubMed

Magalhães, P V; Dean, O M; Bush, A I; Copolov, D L; Malhi, G S; Kohlmann, K; Jeavons, S; Schapkaitz, I; Anderson-Hunt, M; Berk, M

2011-03-01

The evidence base for the pharmacological treatment of bipolar II disorder is limited. In bipolar disorder, there is evidence for glutathione depletion and increased oxidative stress, as well as dysregulation of glutamate; N-acetyl cysteine (NAC) has effects on both of these systems. Add-on NAC has been shown to have a significant benefit on depressive symptoms in a randomized placebo-controlled trial. In this report, we explore the effects of this compound in a subset of patients with bipolar II disorder from that trial. Individuals were randomized to NAC or placebo in addition to treatment as usual, in a double-blind fashion. Mood and functional outcomes were assessed up to 24 weeks of treatment. Fourteen individuals were available for this report, seven in each group. Six people achieved full remission of both depressive and manic symptoms in the NAC group; this was true for only two people in the placebo group (χ(2)=4.67, p=0.031). Subgroup analyses in a small subsample of patients. Not all participants had elevated depression scores at baseline. Notwithstanding all the limitations that subgroup analysis of trials carry, this data could serve as a hypothesis-generating stimulus for further clinical trials of pharmacologic treatment for bipolar II depression. Copyright © 2010 Elsevier B.V. All rights reserved.

Androgen-deprivation therapy plus chemotherapy in metastatic hormone-sensitive prostate cancer. A systematic review and meta-analysis of randomized clinical trials.

PubMed

Ramos-Esquivel, Allan; Fernández, Cristina; Zeledón, Zenén

2016-08-01

To assess the efficacy and toxicity of androgen-deprivation therapy (ADT) plus chemotherapy in patients with hormone-sensitive metastatic prostate cancer. Randomized clinical trials were identified after systematic searching of databases and conference proceedings. A random-effect model was used to determine the pooled hazard ratio (HR) for the efficacy outcomes-overall survival (OS), biochemical progression-free survival (PFS), and clinical PFS, according to the inverse-variance method. Heterogeneity was measured using the Q and I(2) statistics. A narrative review was done to explore the major adverse drug reactions reported for each trial. After systematic searching, we included 6 trials (n = 2,675) in this meta-analysis. Estramustine-based chemotherapy plus ADT was not associated with improved OS (HR = 0.64; 95% CI: 0.22-1.89; P = 0.42). In contrast, docetaxel plus ADT was associated with improved OS (HR = 0.75; 95% CI: 0.61-0.91; P = 0.004) and clinical PFS (HR = 0.64; 95% CI: 0.57-0.72; P<0.00001). There was no significant heterogeneity detected among trials. Regarding adverse drug reactions grade 3 or higher, neutropenia was the most frequent side effect reported in a range from 12% to 32%. The addition of docetaxel-based chemotherapy to ADT improves OS and clinical PFS in hormone-sensitive metastatic prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Subacute effects of cervicothoracic spinal thrust/non-thrust in addition to shoulder manual therapy plus exercise intervention in individuals with subacromial impingement syndrome: a prospective, randomized controlled clinical trial pilot study.

PubMed

Wright, Alexis A; Donaldson, Megan; Wassinger, Craig A; Emerson-Kavchak, Alicia J

2017-09-01

To determine the subacute effects of cervicothoracic spinal thrust/non-thrust in addition to shoulder non-thrust plus exercise in patients with subacromial pathology. This was a randomized, single blinded controlled trial pilot study. This trial was registered at ClinicalTrials.gov (NCT01753271) and reported according to Consolidated Standards of Reporting Trials requirements. Patients were randomly assigned to either shoulder treatment plus cervicothoracic spinal thrust/non-thrust or shoulder treatment-only group. Primary outcomes were average pain intensity (Numeric Pain Rating Scale) and physical function (Shoulder Pain and Disability Index) at 2 weeks, 4 weeks, and patient discharge. 18 patients, mean age 43.1(15.8) years satisfied the eligibility criteria and were analyzed for follow-up data. Both groups showed statistically significant improvements in both pain and function at 2 weeks, 4 weeks, and discharge. The between-group differences for changes in pain or physical function were not significant at any time point. The addition of cervicothoracic spinal thrust/non-thrust to the shoulder treatment-only group did not significantly alter improvement in pain or function in patients with subacromial pathology. Both approaches appeared to provide an equally notable benefit. Both groups improved on all outcomes and met the criteria for clinical relevance for both pain and function. 2b.

Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be laid down on the quality of trials being conducted in order to provide justice in the name of EBP. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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.

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.

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

Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration

PubMed Central

Pitcher, Alex; Emberson, Jonathan; Lacro, Ronald V.; Sleeper, Lynn A.; Stylianou, Mario; Mahony, Lynn; Pearson, Gail D.; Groenink, Maarten; Mulder, Barbara J.; Zwinderman, Aeilko H.; De Backer, Julie; De Paepe, Anne M.; Arbustini, Eloisa; Erdem, Guliz; Jin, Xu Yu; Flather, Marcus D.; Mullen, Michael J.; Child, Anne H.; Forteza, Alberto; Evangelista, Arturo; Chiu, Hsin-Hui; Wu, Mei-Hwan; Sandor, George; Bhatt, Ami B.; Creager, Mark A.; Devereux, Richard B.; Loeys, Bart; Forfar, J. Colin; Neubauer, Stefan; Watkins, Hugh; Boileau, Catherine; Jondeau, Guillaume; Dietz, Harry C.; Baigent, Colin

2015-01-01

Rationale A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial. Design A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus β-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will be made available online (http://www.ctsu.ox.ac.uk/research/meta-trials). PMID:25965707

Surrogacy of progression-free survival (PFS) for overall survival (OS) in esophageal cancer trials with preoperative therapy: Literature-based meta-analysis.

PubMed

Kataoka, K; Nakamura, K; Mizusawa, J; Kato, K; Eba, J; Katayama, H; Shibata, T; Fukuda, H

2017-10-01

There have been no reports evaluating progression-free survival (PFS) as a surrogate endpoint in resectable esophageal cancer. This study was conducted to evaluate the trial level correlations between PFS and overall survival (OS) in resectable esophageal cancer with preoperative therapy and to explore the potential benefit of PFS as a surrogate endpoint for OS. A systematic literature search of randomized trials with preoperative chemotherapy or preoperative chemoradiotherapy for esophageal cancer reported from January 1990 to September 2014 was conducted using PubMed and the Cochrane Library. Weighted linear regression using sample size of each trial as a weight was used to estimate coefficient of determination (R 2 ) within PFS and OS. The primary analysis included trials in which the HR for both PFS and OS was reported. The sensitivity analysis included trials in which either HR or median survival time of PFS and OS was reported. In the sensitivity analysis, HR was estimated from the median survival time of PFS and OS, assuming exponential distribution. Of 614 articles, 10 trials were selected for the primary analysis and 15 for the sensitivity analysis. The primary analysis did not show a correlation between treatment effects on PFS and OS (R 2 0.283, 95% CI [0.00-0.90]). The sensitivity analysis did not show an association between PFS and OS (R 2 0.084, 95% CI [0.00-0.70]). Although the number of randomized controlled trials evaluating preoperative therapy for esophageal cancer is limited at the moment, PFS is not suitable for primary endpoint as a surrogate endpoint for OS. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

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.

A TAD better for myeloma therapy?

PubMed

Giralt, Sergio

2010-02-11

In this issue of Blood, Lokhorst and colleagues report on the results of HOVON-50, a phase 3 randomized trial designed to evaluate the effects of thalidomide during induction treatment and as maintenance in patients with multiple myeloma. There were 556 patients randomly assigned either to 3 cycles of VAD or to TAD. All patients were to receive high-dose melphalan with autologous stem cell support followed by maintenance with interferon for the VAD arm or thalidomide for the TAD arm.(1) This study together with other randomized and nonrandomized trials establish a definitive role for thalidomide as induction therapy in conjunction with dexamethasone, anthracyclines, and alkylating agents.

Clinical trials in dentistry in India: Analysis from trial registry.

PubMed

Gowri, S; Kannan, Sridharan

2017-01-01

Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy participants. From 2011, some of the postgraduate thesis trials had also been registered (2011-8; 2012-8; 2013-13; 2014-6). Inadequacy in reporting the method of randomization and allocation concealment was observed in 37/67 (55.2%) and 31/67 (46.2%) clinical trials respectively. A considerable number of postgraduate theses was also registered with CTRI in dentistry and majority of the clinical trials despite being completed are not yet published. The number of clinical trials in dentistry are low in India, and more focus should be placed by dental investigators regarding the reporting standards. Furthermore, researchers and trial sponsors should aim at publication of the research findings so that it is made publically available for use. A clear-cut need exists for an increase in both the quantity and quality of clinical trials in dentistry.

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.

Hydrazine Sulfate (PDQ®)—Patient Version

Cancer.gov

Hydrazine sulfate has shown no anticancer activity in randomized clinical trials. It was reported in some clinical trials to be helpful in treating poor appetite and weight loss due to cancer. Learn more about hydrazine sulfate as a treatment for people with cancer in this expert-reviewed summary.

Effect of addition of clopidogrel to aspirin on subdural hematoma: meta-analysis of randomized clinical trials.

PubMed

Bakheet, Majid F; Pearce, Lesly A; Hart, Robert G

2015-06-01

Clopidogrel combined with aspirin is routinely prescribed after coronary artery stenting, in patients with acute coronary syndromes, and recently to prevent stroke in patients with acute minor ischemic stroke and TIA. Subdural hematomas are an important complication of antithrombotic treatment, but the risk associated with clopidogrel plus aspirin has not been previously defined. To quantify the risk of subdural hematoma associated with dual antiplatelet therapy with clopidogrel plus aspirin. Randomized clinical trials comparing clopidogrel plus aspirin with aspirin alone were identified by searching the Cochrane Central Register of Controlled Trials from 1990 to 2014, and restricted to those with more than 7 days of treatment. Two reviewers independently extracted data about subdural hematomas. Of 24 randomized trials testing clopidogrel added to aspirin, results for subdural hematoma were available for 11 trials, of which eight did not identify any subdural hematomas. The three trials reporting subdural hematomas were double-blind and included patients with recent lacunar stroke, acute coronary syndromes or atrial fibrillation with a total of 23,136 patients (mean age 66 years) and reported 39 subdural hematomas during a mean follow-up 2.1 years per patient. Clopidogrel plus aspirin was associated with a significantly increased risk of subdural hematoma compared with aspirin alone (risk ratio 2.0, 95% CI 1.0, 3.8; P = 0.04; fixed effects model; I2 for heterogeneity of 0%, P = 0.51). The average absolute incidence of subdural hematoma averaged 1.1 (95% CI 0.7,1.6) per 1000 patient - years among those assigned clopidogrel plus aspirin in 11 randomized trials. The absolute rate of subdural hematoma during dual antiplatelet therapy is low, averaging 1.1 per 1000 patient-years. Chronic treatment with clopidogrel plus aspirin significantly increases the risk of subdural hematoma compared with aspirin alone. © 2014 World Stroke Organization.

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.

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.

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.

Practical issues regarding implementing a randomized clinical trial in a homeless population: strategies and lessons learned.

PubMed

Ojo-Fati, Olamide; Joseph, Anne M; Ig-Izevbekhai, Jed; Thomas, Janet L; Everson-Rose, Susan A; Pratt, Rebekah; Raymond, Nancy; Cooney, Ned L; Luo, Xianghua; Okuyemi, Kolawole S

2017-07-05

There is a critical need for objective data to guide effective health promotion and care for homeless populations. However, many investigators exclude homeless populations from clinical trials due to practical concerns about conducting research with this population. This report is based on our experience and lessons learned while conducting two large NIH-funded randomized controlled trials targeting smoking cessation among persons who are homeless. The current report also addresses challenges when conducting clinical trials among homeless populations and offers potential solutions. Homeless individuals face several challenges including the need to negotiate daily access to food, clothing, and shelter. Some of the critical issues investigators encounter include recruitment and retention obstacles; cognitive impairment, mental health and substance abuse disorders; transportation and scheduling challenges; issues pertaining to adequate study compensation; the need for safety protocols for study staff; and issues related to protecting the wellbeing of these potentially vulnerable adults. Anticipating realistic conditions in which to conduct studies with participants who are homeless will help investigators to design efficient protocols and may improve the feasibility of conducting clinical trials involving homeless populations and the quality of the data collected by the researchers. ClinicalTrials.gov, ID: NCT00786149 . Registered on 5 November 2008; ClinicalTrials.gov, ID: NCT01932996 . Registered on 20 November 2014.

A randomized, controlled trial of osteopathic manipulative treatment for acute low back pain in active duty military personnel

PubMed Central

Cruser, des Anges; Maurer, Douglas; Hensel, Kendi; Brown, Sarah K; White, Kathryn; Stoll, Scott T

2012-01-01

Objective Acute low back pain (ALBP) may limit mobility and impose functional limitations in active duty military personnel. Although some manual therapies have been reported effective for ALBP in military personnel, there have been no published randomized controlled trials (RCTs) of osteopathic manipulative treatment (OMT) in the military. Furthermore, current military ALBP guidelines do not specifically include OMT. Methods This RCT examined the efficacy of OMT in relieving ALBP and improving functioning in military personnel at Fort Lewis, Washington. Sixty-three male and female soldiers ages 18 to 35 were randomly assigned to a group receiving OMT plus usual care or a group receiving usual care only (UCO). Results The primary outcome measures were pain on the quadruple visual analog scale, and functioning on the Roland Morris Disability Questionnaire. Outcomes were measured immediately preceding each of four treatment sessions and at four weeks post-trial. Intention to treat analysis found significantly greater post-trial improvement in ‘Pain Now’ for OMT compared to UCO (P = 0·026). Furthermore, the OMT group reported less ‘Pain Now’ and ‘Pain Typical’ at all visits (P = 0·025 and P = 0·020 respectively). Osteopathic manipulative treatment subjects also tended to achieve a clinically meaningful improvement from baseline on ‘Pain at Best’ sooner than the UCO subjects. With similar baseline expectations, OMT subjects reported significantly greater satisfaction with treatment and overall self-reported improvement (P<0·01). Conclusion This study supports the effectiveness of OMT in reducing ALBP pain in active duty military personnel. PMID:23372389

Surgery for congenital choanal atresia.

PubMed

Cedin, Antonio C; Atallah, Alvaro N; Andriolo, Régis B; Cruz, Oswaldo L; Pignatari, Shirley N

2012-02-15

Congenital choanal atresia is a rare abnormality characterized by unilateral or bilateral lack of patency of the posterior end of the nasal cavity. With an incidence of 1:5000 to 1:8000 births, it is twice as prevalent in females as it is in males. Surgical procedures aim to provide adequate functional choanal patency and a low rate of restenosis, avoid harm to any structure in development, enable shorter surgery and hospitalization times, and minimize morbidity and mortality. To evaluate the effectiveness and safety of the available surgical techniques for the treatment of congenital choanal atresia in patients with unilateral and bilateral atresia. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the search was 31 January 2011. We planned to include parallel randomized or quasi-randomized controlled trials testing surgical approaches for the treatment of congenital atresia (irrespective of gender and age) that evaluated normal/adequate respiratory function (self reported or preserved nasal airway) and restenosis as the main primary outcomes. We did not consider reoperation and non-congenital atresia (e.g. traumatic, iatrogenic atresias) for inclusion. Three review authors independently assessed the titles and abstracts of the identified articles to determine potential relevance. For dichotomous and continuous variables, we planned to calculate risk ratios (relative risks; RR) and mean differences (MD) with 95% confidence intervals (CI), respectively. We planned to use the random-effects model since we were expecting substantial clinical and methodological heterogeneity. No randomized controlled trials were identified. From the 120 reports retrieved using our search strategy, 46 primary studies had the potential to be included since they had tested surgical approaches for choanal atresia. However, we excluded all of them during the final selection process because their study designs did not meet our inclusion criteria. There is no definitive evidence, based on randomized controlled trials, to demonstrate the potential advantages and disadvantages of any specific surgical technique for patients with choanal atresia. Specialists should unify their efforts in multicenter randomized controlled trials that test the effectiveness and safety of different surgical techniques in patients with choanal atresia.

The Efficacy of PCI's "Reading Program--Level One": A Report of a Randomized Experiment in Brevard Public Schools and Miami-Dade County Public Schools. Research Report

ERIC Educational Resources Information Center

Toby, Megan; Ma, Boya; Jaciw, Andrew; Cabalo, Jessica

2008-01-01

PCI Education sought scientifically based evidence on the effectiveness of the "PCI Reading Program--Level One" for students with severe disabilities. During the 2007-2008 academic year. Empirical Education conducted a randomized control trial (RCT) in two Florida districts, Brevard and Miami-Dade County Public Schools. For this…

Review of Three Recent Randomized Trials of School-Based Mentoring: Making Sense of Mixed Findings. Social Policy Report. Volume 24, Number 3

ERIC Educational Resources Information Center

Wheeler, Marc E.; Keller, Thomas E.; DuBois, David L.

2010-01-01

Between 2007 and 2009, reports were released on the results of three separate large-scale random assignment studies of the effectiveness of school-based mentoring programs for youth. The studies evaluated programs implemented by Big Brothers Big Sisters of America (BBBSA) affiliates (Herrera et al., 2007), Communities In Schools of San Antonio,…

WWC Review of the Report "Accommodations for English Language Learner Students: The Effect of Linguistic Modification of Math Test Item Sets"

ERIC Educational Resources Information Center

What Works Clearinghouse, 2012

2012-01-01

The research described in this report is a randomized controlled trial in which seventh- and eighth-grade students were randomly assigned to complete a set of 25 math questions delivered with either standard language or language that had undergone "linguistic modification" by the research team. The purpose of the study was to assess the…

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.

Test-treatment RCTs are susceptible to bias: a review of the methodological quality of randomized trials that evaluate diagnostic tests.

PubMed

Ferrante di Ruffano, Lavinia; Dinnes, Jacqueline; Sitch, Alice J; Hyde, Chris; Deeks, Jonathan J

2017-02-24

There is a growing recognition for the need to expand our evidence base for the clinical effectiveness of diagnostic tests. Many international bodies are calling for diagnostic randomized controlled trials to provide the most rigorous evidence of impact to patient health. Although these so-called test-treatment RCTs are very challenging to undertake due to their methodological complexity, they have not been subjected to a systematic appraisal of their methodological quality. The extent to which these trials may be producing biased results therefore remains unknown. We set out to address this issue by conducting a methodological review of published test-treatment trials to determine how often they implement adequate methods to limit bias and safeguard the validity of results. We ascertained all test-treatment RCTs published 2004-2007, indexed in CENTRAL, including RCTs which randomized patients to diagnostic tests and measured patient outcomes after treatment. Tests used for screening, monitoring or prognosis were excluded. We assessed adequacy of sequence generation, allocation concealment and intention-to-treat, appropriateness of primary analyses, blinding and reporting of power calculations, and extracted study characteristics including the primary outcome. One hundred three trials compared 105 control with 119 experimental interventions, and reported 150 primary outcomes. Randomization and allocation concealment were adequate in 57 and 37% of trials. Blinding was uncommon (patients 5%, clinicians 4%, outcome assessors 21%), as was an adequate intention-to-treat analysis (29%). Overall 101 of 103 trials (98%) were at risk of bias, as judged using standard Cochrane criteria. Test-treatment trials are particularly susceptible to attrition and inadequate primary analyses, lack of blinding and under-powering. These weaknesses pose much greater methodological and practical challenges to conducting reliable RCT evaluations of test-treatment strategies than standard treatment interventions. We suggest a cautious approach that first examines whether a test-treatment intervention can accommodate the methodological safeguards necessary to minimize bias, and highlight that test-treatment RCTs require different methods to ensure reliability than standard treatment trials. Please see the companion paper to this article: http://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-016-0286-0 .

The Effectiveness of Parent Training as a Treatment for Preschool Attention-Deficit/Hyperactivity Disorder: Study Protocol for a Randomized Controlled, Multicenter Trial of the New Forest Parenting Program in Everyday Clinical Practice

PubMed Central

Daley, David; Frydenberg, Morten; Rask, Charlotte U; Sonuga-Barke, Edmund; Thomsen, Per H

2016-01-01

Background Parent training is recommended as the first-line treatment for attention-deficit/hyperactivity disorder (ADHD) in preschool children. The New Forest Parenting Programme (NFPP) is an evidence-based parenting program developed specifically to target preschool ADHD. Objective The objective of this trial is to investigate whether the NFPP can be effectively delivered for children referred through official community pathways in everyday clinical practice. Methods A multicenter randomized controlled parallel arm trial design is employed. There are two treatment arms, NFPP and treatment as usual. NFPP consists of eight individually delivered parenting sessions, where the child attends during three of the sessions. Outcomes are examined at three time points (T1, T2, T3): T1 (baseline), T2 (week 12, post intervention), and T3 (6 month follow/up). 140 children between the ages of 3-7, with a clinical diagnosis of ADHD, informed by the Development and Well Being Assessment, and recruited from three child and adolescent psychiatry departments in Denmark will take part. Randomization is on a 1:1 basis, stratified for age and gender. Results The primary endpoint is change in ADHD symptoms as measured by the Preschool ADHD-Rating Scale (ADHD-RS) by T2. Secondary outcome measures include: effects on this measure at T3 and T2 and T3 measures of teacher reported Preschool ADHD-RS scores, parent and teacher rated scores on the Strength & Difficulties Questionnaire, direct observation of ADHD behaviors during Child’s Solo Play, observation of parent-child interaction, parent sense of competence, and family stress. Results will be reported using the standards set out in the Consolidated Standards of Reporting Trials Statement for Randomized Controlled Trials of nonpharmacological treatments. Conclusions The trial will provide evidence as to whether NFPP is a more effective treatment for preschool ADHD than the treatment usually offered in everyday clinical practice. Trial Registration ClinicalTrials.gov NCT01684644; https://clinicaltrials.gov/ct2/show/NCT01684644?term= NCT01684644&rank=1 (Archived by WebCite at http://www.webcitation/6eOOAe8Qe) PMID:27076496

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.

Benefit-Risk Summary of Nivolumab for Patients With Metastatic Squamous Cell Lung Cancer After Platinum-Based Chemotherapy: A Report From the US Food and Drug Administration.

PubMed

Kazandjian, Dickran; Khozin, Sean; Blumenthal, Gideon; Zhang, Lijun; Tang, Shenghui; Libeg, Meredith; Kluetz, Paul; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

2016-01-01

Metastatic squamous non-small-cell lung cancer (SQ NSCLC) is a serious and life-threatening malignant condition with unmet medical need. In late December 2014, the US Food and Drug Administration (FDA) obtained the data monitoring committee report of a planned interim analysis of a trial in second-line SQ NSCLC (CM017) that demonstrated an overall survival benefit for patients treated with nivolumab compared with docetaxel. In that trial, 272 patients with metastatic SQ NSCLC patients had been randomized to receive nivolumab (n = 135) or docetaxel (n = 137). Median overall survival was 9.2 months for patients randomized to nivolumab and 6.0 months for those randomized to docetaxel (hazard ratio, 0.59; 95% CI, 0.44-0.79; P < .001). The safety of nivolumab was evaluated in a single-arm trial of 117 patients in previously treated metastatic SQ NSCLC and was consistent with the safety profile in melanoma, with rare but serious immune-mediated adverse events managed with corticosteroids and dose interruption. The FDA granted nivolumab traditional approval on March 4, 2015, for treatment of metastatic SQ NSCLC with progression during or after platinum-based chemotherapy. The approval provides an important treatment option for these patients, affecting routine care and clinical trials.

Does Preoperative Radio(chemo)therapy Increase Anastomotic Leakage in Rectal Cancer Surgery? A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Qin, Changjiang; Ren, Xuequn; Xu, Kaiwu; Chen, Zhihui; He, Yulong; Song, Xinming

2014-01-01

Objective. Preoperative radio(chemo)therapy (pR(C)T) appears to increase postoperative complications of rectal cancer resection, but clinical trials have reported conflicting results. The objective of this meta-analysis was performed to assess the effects of pR(C)T on anastomotic leak after rectal cancer resection. Methods. PubMed, Embase, and the Cochrane Library were searched from January 1980 to January 2014. Randomized controlled trials included all original articles reporting anastomotic leak in patients with rectal cancer, among whom some received preoperative radiotherapy or chemoradiotherapy while others did not. The analysed end-points were the anastomotic leak. Result. Seven randomized controlled trials with 3375 patients were included in the meta-analysis. 1660 forming the group undergoing preoperative radiotherapy or chemoradiotherapy versus 1715 patients undergoing without preoperative radiotherapy or chemoradiotherapy. The meta-analyses found that pR(C)T was not an independent risk factor for anastomotic leakage (OR 1.02, 95% CI 0.80–1.30; P = 0.88). Subgroups analysis was performed and the result was not altered. Conclusions. Current evidence demonstrates that pR(C)T did not increase the risk of postoperative anastomotic leak after rectal cancer resection in patients. PMID:25477955

Review of Randomized Controlled Trials of Massage in Preterm Infants

PubMed Central

Niemi, Anna-Kaisa

2017-01-01

Preterm birth affects about 10% of infants born in the United States. Massage therapy is being used in some neonatal intensive care units for its potential beneficial effects on preterm infants. This article reviews published randomized controlled trials on the effects of massage in preterm infants. Most studies evaluating the effect of massage in weight gain in premature infants suggest a positive effect on weight gain. Increase in vagal tone has been reported in infants who receive massage and has been suggested as a possible mechanism for improved weight gain. More studies are needed on the underlying mechanisms of the effects of massage therapy on weight gain in preterm infants. While some trials suggest improvements in developmental scores, decreased stress behavior, positive effects on immune system, improved pain tolerance and earlier discharge from the hospital, the number of such studies is small and further evidence is needed. Further studies, including randomized controlled trials, are needed on the effects of massage in preterm infants. PMID:28368368

The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine.

PubMed

Vassy, Jason L; Lautenbach, Denise M; McLaughlin, Heather M; Kong, Sek Won; Christensen, Kurt D; Krier, Joel; Kohane, Isaac S; Feuerman, Lindsay Z; Blumenthal-Barby, Jennifer; Roberts, J Scott; Lehmann, Lisa Soleymani; Ho, Carolyn Y; Ubel, Peter A; MacRae, Calum A; Seidman, Christine E; Murray, Michael F; McGuire, Amy L; Rehm, Heidi L; Green, Robert C

2014-03-20

Whole genome sequencing (WGS) is already being used in certain clinical and research settings, but its impact on patient well-being, health-care utilization, and clinical decision-making remains largely unstudied. It is also unknown how best to communicate sequencing results to physicians and patients to improve health. We describe the design of the MedSeq Project: the first randomized trials of WGS in clinical care. This pair of randomized controlled trials compares WGS to standard of care in two clinical contexts: (a) disease-specific genomic medicine in a cardiomyopathy clinic and (b) general genomic medicine in primary care. We are recruiting 8 to 12 cardiologists, 8 to 12 primary care physicians, and approximately 200 of their patients. Patient participants in both the cardiology and primary care trials are randomly assigned to receive a family history assessment with or without WGS. Our laboratory delivers a genome report to physician participants that balances the needs to enhance understandability of genomic information and to convey its complexity. We provide an educational curriculum for physician participants and offer them a hotline to genetics professionals for guidance in interpreting and managing their patients' genome reports. Using varied data sources, including surveys, semi-structured interviews, and review of clinical data, we measure the attitudes, behaviors and outcomes of physician and patient participants at multiple time points before and after the disclosure of these results. The impact of emerging sequencing technologies on patient care is unclear. We have designed a process of interpreting WGS results and delivering them to physicians in a way that anticipates how we envision genomic medicine will evolve in the near future. That is, our WGS report provides clinically relevant information while communicating the complexity and uncertainty of WGS results to physicians and, through physicians, to their patients. This project will not only illuminate the impact of integrating genomic medicine into the clinical care of patients but also inform the design of future studies. ClinicalTrials.gov identifier NCT01736566.

Over the counter (OTC) artificial tear drops for dry eye syndrome

PubMed Central

Pucker, Andrew D; Ng, Sueko M; Nichols, Jason J

2016-01-01

Background Over the counter (OTC) artificial tears historically have been the first line of treatment for dry eye syndrome and dry eye-related conditions like contact lens discomfort, yet currently we know little regarding the overall efficacy of individual, commercially available artificial tears. This review provides a much needed meta-analytical look at all randomized and quasi-randomized clinical trials that have analyzed head-to-head comparisons of OTC artificial tears. Objectives To evaluate the effectiveness and toxicity of OTC artificial tear applications in the treatment of dry eye syndrome compared with another class of OTC artificial tears, no treatment, or placebo. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 4 December 2015. We searched reference lists of included trials for any additional trials not identified by the electronic searches. Selection criteria This review includes randomized controlled trials with adult participants who were diagnosed with dry eye, regardless of race and gender. We included trials in which the age of participants was not reported, and clinical trials comparing OTC artificial tears with another class of OTC artificial tears, placebo, or no treatment. This review did not consider head-to-head comparisons of artificial tears with another type of dry-eye therapy. Data collection and analysis We followed the standard methodological procedures expected by Cochrane. Two authors independently screened the search results, reviewed full-text copies for eligibility, examined risk of bias, and extracted data. We performed meta-analysis for trials that compared similar interventions and reported comparable outcomes with sufficient data. We summarized all other included trial results in the text. Main results We included 43 randomized controlled trials (3497 participants with dry eye). Due to the heterogeneity of study characteristics among the included trials with respect to types of diagnostic criteria, interventions, comparisons, and measurements taken, our ability to perform meta-analyses was limited. The review found that, in general, there was uncertainty whether different OTC artificial tears provide similar relief of signs and symptoms when compared with each other or placebo. Nevertheless, we found that 0.2% polyacrylic acid-based artificial tears were consistently more effective at treating dry eye symptoms than 1.4% polyvinyl alcohol-based artificial tears in two trials assessing this comparison (175 participants). All other included artificial tears produced contradictory between-group results or found no between-group differences. Our review also found that OTC artificial tears may be generally safe, but not without adverse events. Overall, we assessed the quality of evidence as low due to high risks of bias among included trials and poor reporting of outcome measures which were insufficient for quantitative analysis. Furthermore, we identified an additional 18 potentially eligible trials that were reported only in clinical trial registers with no associated results or publications. These trials reportedly enrolled 2079 total participants for whom no data are available. Such lack of reporting of trial results represents a high risk of publication bias. Authors’ conclusions OTC artificial tears may be safe and effective means for treating dry eye syndrome; the literature indicates that the majority of OTC artificial tears may have similar efficacies. This conclusion could be greatly skewed by the inconsistencies in study designs and inconsistencies in reporting trial results. Additional research is therefore needed before we can draw robust conclusions about the effectiveness of individual OTC artificial tear formulations. PMID:26905373

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.

Exploring reasons for the observed inconsistent trial reports on intra-articular injections with hyaluronic acid in the treatment of osteoarthritis: Meta-regression analyses of randomized trials.

PubMed

Johansen, Mette; Bahrt, Henriette; Altman, Roy D; Bartels, Else M; Juhl, Carsten B; Bliddal, Henning; Lund, Hans; Christensen, Robin

2016-08-01

The aim was to identify factors explaining inconsistent observations concerning the efficacy of intra-articular hyaluronic acid compared to intra-articular sham/control, or non-intervention control, in patients with symptomatic osteoarthritis, based on randomized clinical trials (RCTs). A systematic review and meta-regression analyses of available randomized trials were conducted. The outcome, pain, was assessed according to a pre-specified hierarchy of potentially available outcomes. Hedges׳s standardized mean difference [SMD (95% CI)] served as effect size. REstricted Maximum Likelihood (REML) mixed-effects models were used to combine study results, and heterogeneity was calculated and interpreted as Tau-squared and I-squared, respectively. Overall, 99 studies (14,804 patients) met the inclusion criteria: Of these, only 71 studies (72%), including 85 comparisons (11,216 patients), had adequate data available for inclusion in the primary meta-analysis. Overall, compared with placebo, intra-articular hyaluronic acid reduced pain with an effect size of -0.39 [-0.47 to -0.31; P < 0.001], combining very heterogeneous trial findings (I(2) = 73%). The three most important covariates in reducing heterogeneity were overall risk of bias, blinding of personnel and trial size, reducing heterogeneity with 26%, 26%, and 25%, respectively (Interaction: P ≤ 0.001). Adjusting for publication/selective outcome reporting bias (by imputing "null effects") in 24 of the comparisons with no data available reduced the combined estimate to -0.30 [-0.36 to -0.23; P < 0.001] still in favor of hyaluronic acid. Based on available trial data, intra-articular hyaluronic acid showed a better effect than intra-articular saline on pain reduction in osteoarthritis. Publication bias and the risk of selective outcome reporting suggest only small clinical effect compared to saline. Copyright © 2016 Elsevier Inc. All rights reserved.

Systematic review on the health effects of exposure to radiofrequency electromagnetic fields from mobile phone base stations

PubMed Central

Frei, Patrizia; Mohler, Evelyn; Hug, Kerstin

2010-01-01

Abstract Objective To review and evaluate the recent literature on the health effects of exposure to mobile phone base station (MPBS) radiation. Methods We performed a systematic review of randomized human trials conducted in laboratory settings and of epidemiological studies that investigated the health effects of MPBS radiation in the everyday environment. Findings We included in the analysis 17 articles that met our basic quality criteria: 5 randomized human laboratory trials and 12 epidemiological studies. The majority of the papers (14) examined self-reported non-specific symptoms of ill-health. Most of the randomized trials did not detect any association between MPBS radiation and the development of acute symptoms during or shortly after exposure. The sporadically observed associations did not show a consistent pattern with regard to symptoms or types of exposure. We also found that the more sophisticated the exposure assessment, the less likely it was that an effect would be reported. Studies on health effects other than non-specific symptoms and studies on MPBS exposure in children were scarce. Conclusion The evidence for a missing relationship between MPBS exposure up to 10 volts per metre and acute symptom development can be considered strong because it is based on randomized, blinded human laboratory trials. At present, there is insufficient data to draw firm conclusions about health effects from long-term low-level exposure typically occurring in the everyday environment. PMID:21124713

[Methodological controversies in chronic obstructive pulmonary disease therapeutic trials].

PubMed

Suissa, Samy

2009-03-01

Pharmacological treatment of chronic obstructive pulmonary disease (COPD) relies principally on long-acting bronchodilators. Inhaled corticosteroids (ICS) were introduced for COPD two decades ago, despite the fact that no randomized trial had yet assessed their efficacy for this indication. Since then, the numerous randomized trials and meta-analyses performed to justify their use in COPD have been contradictory and controversial. Moreover, observational studies have reported efficacy rates so exceptional that they are almost too good to be true. These studies contain important methodological flaws that produce the appearance of efficacy. The randomized trials infringe the fundamental principle of intention-to-treat analysis, an analysis necessary to prevent important biases. Two other complications are the interruption of treatment at the moment of randomization and the use of a run-in period; in both cases, the withdrawal of treatment can introduce bias. The observational studies reporting phenomenal reductions in mortality with ICS were distorted by "immortal time" bias. Finally, recent data suggest that the effect of ICS/bronchodilator combinations is due mainly to the effect of the long-acting bronchodilator. Given the absence of proof of the efficacy of inhaled corticosteroids in COPD and their associated risks, especially of ocular damage and pneumonia, and particularly among the elderly, as well as the high doses currently prescribed in COPD, it is difficult to recommend their use in this indication. They should be prescribed in COPD for at most a limited population of patients.

Avoidable waste related to inadequate methods and incomplete reporting of interventions: a systematic review of randomized trials performed in Sub-Saharan Africa.

PubMed

Ndounga Diakou, Lee Aymar; Ntoumi, Francine; Ravaud, Philippe; Boutron, Isabelle

2017-07-05

Randomized controlled trials (RCTs) are needed to improve health care in Sub-Saharan Africa (SSA). However, inadequate methods and incomplete reporting of interventions can prevent the transposition of research in practice which leads waste of research. The aim of this systematic review was to assess the avoidable waste in research related to inadequate methods and incomplete reporting of interventions in RCTs performed in SSA. We performed a methodological systematic review of RCTs performed in SSA and published between 1 January 2014 and 31 March 2015. We searched PubMed, the Cochrane library and the African Index Medicus to identify reports. We assessed the risk of bias using the Cochrane Risk of Bias tool, and for each risk of bias item, determined whether easy adjustments with no or minor cost could change the domain to low risk of bias. The reporting of interventions was assessed by using standardized checklists based on the Consolidated Standards for Reporting Trials, and core items of the Template for Intervention Description and Replication. Corresponding authors of reports with incomplete reporting of interventions were contacted to obtain additional information. Data were descriptively analyzed. Among 121 RCTs selected, 74 (61%) evaluated pharmacological treatments (PTs), including drugs and nutritional supplements; and 47 (39%) nonpharmacological treatments (NPTs) (40 participative interventions, 1 surgical procedure, 3 medical devices and 3 therapeutic strategies). Overall, the randomization sequence was adequately generated in 76 reports (62%) and the intervention allocation concealed in 48 (39%). The primary outcome was described as blinded in 46 reports (38%), and incomplete outcome data were adequately addressed in 78 (64%). Applying easy methodological adjustments with no or minor additional cost to trials with at least one domain at high risk of bias could have reduced the number of domains at high risk for 24 RCTs (19%). Interventions were completely reported for 73/121 (60%) RCTs: 51/74 (68%) of PTs and 22/47 (46%) of NPTs. Additional information was obtained from corresponding authors for 11/48 reports (22%). Inadequate methods and incomplete reporting of published SSA RCTs could be improved by easy and inexpensive methodological adjustments and adherence to reporting guidelines.

Efficacy of antimicrobial photodynamic therapy in the disinfection of acrylic denture surfaces: A systematic review.

PubMed

Varela Kellesarian, Sergio; Abduljabbar, Tariq; Vohra, Fahim; Malmstrom, Hans; Yunker, Michael; Varela Kellesarian, Tammy; Romanos, Georgios E; Javed, Fawad

2017-03-01

The aim of the present systematic review was to assess the efficacy of antimicrobial photodynamic therapy (aPDT) in the disinfection of acrylic denture surfaces. IN order to address the focused question: "Is aPDT more effective in decontaminating denture surfaces compared with traditional denture-disinfection techniques?" an electronic search without time or language restrictions was conducted up to November 2016 in indexed databases using different key words. The exclusion criteria included qualitative and/or quantitative reviews, case reports, case series, commentaries, letters to the editor, interviews, and updates. A total of 14 studies were included and processed for data extraction, out of which 1 study was a randomized clinical trial and 13 studies were performed in vitro. Results from 12 experimental studies reported that aPDT was effective in reducing bacteria and/or yeast cultured in single or multispecies biofilm growth on acrylic resin specimens. One experimental study reported selective microorganism reduction on acrylic resin after aPDT. One clinical randomized control trial reported that aPDT presented similar microorganism reduction compared with oral antifungal medication for the disinfection of denture surfaces. The role of aPDT in the disinfection of acrylic resin surfaces is unclear. From a clinical perspective further randomized control trials are needed to assess the efficacy of aPDT in the disinfection of acrylic resin surfaces. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel cognitive behaviour therapy for bipolar disorders (Think Effectively About Mood Swings or TEAMS): study protocol for a randomized controlled trial.

PubMed

Mansell, Warren; Tai, Sara; Clark, Alexandra; Akgonul, Savas; Dunn, Graham; Davies, Linda; Law, Heather; Morriss, Richard; Tinning, Neil; Morrison, Anthony P

2014-10-24

Existing psychological therapies for bipolar disorders have been found to have mixed results, with a consensus that they provide a significant, but modest, effect on clinical outcomes. Typically, these approaches have focused on promoting strategies to prevent future relapse. An alternative treatment approach, termed 'Think Effectively About Mood Swings' (TEAMS) addresses current symptoms, including subclinical hypomania, depression and anxiety, and promotes long-term recovery. Following the publication of a theoretical model, a range of research studies testing the model and a case series have demonstrated positive results. The current study reports the protocol of a feasibility randomized controlled trial to inform a future multi-centre trial. A target number of 84 patients with a diagnosis of bipolar I or II disorder, or bipolar disorder not-otherwise-specified are screened, allocated to a baseline assessment and randomized to either 16 sessions of TEAMS therapy plus treatment-as-usual (TAU) or TAU. Patients complete self-report inventories of depression, anxiety, recovery status and bipolar cognitions targeted by TEAMS. Assessments of diagnosis, bipolar symptoms, medication, access to services and quality of life are conducted by assessors blind to treatment condition at 3, 6, 12 and 18 months post-randomization. The main aim is to evaluate recruitment and retention of participants into both arms of the study, as well as adherence to therapy, to determine feasibility and acceptability. It is predicted that TEAMS plus TAU will reduce self-reported depression in comparison to TAU alone at six months post-randomization. The secondary hypotheses are that TEAMS will reduce the severity of hypomanic symptoms and anxiety, reduce bipolar cognitions, improve social functioning and promote recovery compared to TAU alone at post-treatment and follow-up. The study also incorporates semi-structured interviews about the experiences of previous treatment and the experience of TEAMS therapy that will be subject to qualitative analyses to inform future developments of the approach. The design will provide preliminary evidence of efficacy, feasibility, acceptability, uptake, attrition and barriers to treatment to design a definitive trial of this novel intervention compared to treatment as usual. This trial was registered with Current Controlled Trials (ISRCTN83928726) on registered 25 July 2014.

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.

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.

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

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.

Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials

PubMed Central

Zabetian, Azadeh; Ferket, Bart S.; Zhou, Jing; Testani, Jeffrey M.; Garg, Amit X.; Parikh, Chirag R.

2016-01-01

Observational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short–term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between–group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo–controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials. PMID:26712525

About the necessity to manage events coded with MedDRA prior to statistical analysis: proposal of a strategy with application to a randomized clinical trial, ANRS 099 ALIZE.

PubMed

Journot, Valérie; Tabuteau, Sophie; Collin, Fidéline; Molina, Jean-Michel; Chene, Geneviève; Rancinan, Corinne

2008-03-01

Since 2003, the Medical Dictionary for Regulatory Activities (MedDRA) is the regulatory standard for safety report in clinical trials in the European Community. Yet, we found no published example of a practical experience for a scientifically oriented statistical analysis of events coded with MedDRA. We took advantage of a randomized trial in HIV-infected patients with MedDRA-coded events to explain the difficulties encountered during the events analysis and the strategy developed to report events consistently with trial-specific objectives. MedDRA has a rich hierarchical structure, which allows the grouping of coded terms into 5 levels, the highest being "System Organ Class" (SOC). Each coded term may be related to several SOCs, among which one primary SOC is defined. We developed a new general 5-step strategy to select a SOC as trial primary SOC, consistently with trial-specific objectives for this analysis. We applied it to the ANRS 099 ALIZE trial, where all events were coded with MedDRA version 3.0. We compared the MedDRA and the ALIZE primary SOCs. In the ANRS 099 ALIZE trial, 355 patients were recruited, and 3,722 events were reported and documented, among which 35% had multiple SOCs (2 to 4). We applied the proposed 5-step strategy. Altogether, 23% of MedDRA primary SOCs were modified, mainly from MedDRA primary SOCs "Investigations" (69%) and "Ear and labyrinth disorders" (6%), for the ALIZE primary SOCs "Hepatobiliary disorders" (35%), "Musculoskeletal and connective tissue disorders" (21%), and "Gastrointestinal disorders" (15%). MedDRA largely enhanced in size and complexity with versioning and the development of Standardized MedDRA Queries. Yet, statisticians should not systematically rely on primary SOCs proposed by MedDRA to report events. A simple general 5-step strategy to re-classify events consistently with the trial-specific objectives might be useful in HIV trials as well as in other fields.

Zhen Gan Xi Feng Decoction, a Traditional Chinese Herbal Formula, for the Treatment of Essential Hypertension: A Systematic Review of Randomized Controlled Trials

PubMed Central

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. PMID:23573163

Effects of Electrical Stimulation in Spastic Muscles After Stroke: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Stein, Cinara; Fritsch, Carolina Gassen; Robinson, Caroline; Sbruzzi, Graciele; Plentz, Rodrigo Della Méa

2015-08-01

Neuromuscular electric stimulation (NMES) has been used to reduce spasticity and improve range of motion in patients with stroke. However, contradictory results have been reported by clinical trials. A systematic review of randomized clinical trials was conducted to assess the effect of treatment with NMES with or without association to another therapy on spastic muscles after stroke compared with placebo or another intervention. We searched the following electronic databases (from inception to February 2015): Medline (PubMed), EMBASE, Cochrane Central Register of Controlled Trials and Physiotherapy Evidence Database (PEDro). Two independent reviewers assessed the eligibility of studies based on predefined inclusion criteria (application of electric stimulation on the lower or upper extremities, regardless of NMES dosage, and comparison with a control group which was not exposed to electric stimulation), excluding studies with <3 days of intervention. The primary outcome extracted was spasticity, assessed by the Modified Ashworth Scale, and the secondary outcome extracted was range of motion, assessed by Goniometer. Of the total of 5066 titles, 29 randomized clinical trials were included with 940 subjects. NMES provided reductions in spasticity (-0.30 [95% confidence interval, -0.58 to -0.03], n=14 randomized clinical trials) and increase in range of motion when compared with control group (2.87 [95% confidence interval, 1.18-4.56], n=13 randomized clinical trials) after stroke. NMES combined with other intervention modalities can be considered as a treatment option that provides improvements in spasticity and range of motion in patients after stroke. URL: http://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42014008946. © 2015 American Heart Association, Inc.

A PARENT–ADOLESCENT INTERVENTION TO INCREASE SEXUAL RISK COMMUNICATION: RESULTS OF A RANDOMIZED CONTROLLED TRIAL

PubMed Central

Villarruel, Antonia M.; Cherry, Carol Loveland; Cabriales, Esther Gallegos; Ronis, David L.; Zhou, Yan

2009-01-01

This article reports results of a randomized controlled trial designed to test an intervention to increase parent–adolescent sexual risk communication among Mexican parents. Data were analyzed from parents (n = 791) randomly assigned to an HTV risk reduction or health promotion intervention. Measures were administered at pretest, posttest, and 6– and 12–month follow–ups. Generalized estimation equation (GEE) analysis indicates parents in the HIV risk reduction intervention reported significantly more general communication (p < .005), more sexual risk communication (p < .001) and more comfort with communication (p < .001) than parents in the control intervention. Behavioral, normative, and control beliefs significantly mediated the effect of the intervention on all communication outcomes. This study demonstrates the efficacy of an intervention to increase the quality and quantity of parent–adolescent communication related to general and sex–specific communication. PMID:18956979

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.

Effects of online cognitive treatment for problematic anger: a randomized controlled trial.

PubMed

Howie, Amanda J; Malouff, John M

2014-01-01

Problematic anger, which is common, has been associated with a wide range of negative interpersonal and intrapersonal consequences, including violent behaviour, relationship damage, health problems and low self-esteem. This article reports the results of the first randomized controlled trial of brief online cognitive treatment for anger. The sample included 75 adults who were randomly assigned to cognitive treatment or a waiting list control. The analyses with the 59 participants who completed the post-intervention assessment at four weeks after the beginning of the intervention showed that individuals who received the intervention reported significantly lower anger levels than the control group at post-assessment. The treatment group showed a substantial decrease in anger from pre to post. The results suggest that brief online cognitive treatment can be effective for reducing problematic anger in adults. These findings provide an initial support for the development of internet-based cognitive treatment for problematic anger.

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

Clinical Trials in Veterinary Medicine: A New Era Brings New Challenges.

PubMed

Oyama, M A; Ellenberg, S S; Shaw, P A

2017-07-01

Randomized clinical trials (RCTs) are among the most rigorous ways to determine the causal relationship between an intervention and important clinical outcome. Their use in veterinary medicine has become increasingly common, and as is often the case, with progress comes new challenges. Randomized clinical trials yield important answers, but results from these studies can be unhelpful or even misleading unless the study design and reporting are carried out with care. Herein, we offer some perspective on several emerging challenges associated with RCTs, including use of composite endpoints, the reporting of different forms of risk, analysis in the presence of missing data, and issues of reporting and safety assessment. These topics are explored in the context of previously reported veterinary internal medicine studies as well as through illustrative examples with hypothetical data sets. Moreover, many insights germane to RCTs in veterinary internal medicine can be drawn from the wealth of experience with RCTs in the human medical field. A better understanding of the issues presented here can help improve the design, interpretation, and reporting of veterinary RCTs. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Guidelines for the Reporting of Treatment Trials for Alcohol Use Disorders

PubMed Central

Witkiewitz, Katie; Finney, John W.; Harris, Alex H.S; Kivlahan, Daniel R.; Kranzler, Henry R.

2015-01-01

Background The primary goals in conducting clinical trials of treatments for alcohol use disorders (AUDs) is to identify efficacious treatments and determine which treatments are most efficacious for which patients. Accurate reporting of study design features and results is imperative to enable readers of research reports to evaluate to what extent a study has achieved these goals. Guidance on quality of clinical trial reporting has evolved substantially over the past two decades, primarily through the publication and widespread adoption of the Consolidated Standards of Reporting Trials (CONSORT) statement. However, there is room to improve the adoption of those standards in reporting the design and findings of treatment trials for AUD. Methods Narrative review of guidance on reporting quality in AUD treatment trials. Results Despite improvements in the reporting of results of treatment trials for AUD over the past two decades, many published reports provide insufficient information on design or methods. Conclusions The reporting of alcohol treatment trial design, analysis, and results requires improvement in four primary areas: (1) trial registration, (2) procedures for recruitment and retention, (3) procedures for randomization and intervention design considerations, and (4) statistical methods used to assess treatment efficacy. Improvements in these areas and the adoption of reporting standards by authors, reviewers, and editors are critical to an accurate assessment of the reliability and validity of treatment effects. Continued developments in this area are needed to move AUD treatment research forward via systematic reviews and meta-analyses that maximize the utility of completed studies. PMID:26259958

Recognizing and managing a deteriorating patient: a randomized controlled trial investigating the effectiveness of clinical simulation in improving clinical performance in undergraduate nursing students.

PubMed

Stayt, Louise Caroline; Merriman, Clair; Ricketts, Barry; Morton, Sean; Simpson, Trevor

2015-11-01

To report the results of a randomized controlled trial which explored the effectiveness of clinical simulation in improving the clinical performance of recognizing and managing an adult deteriorating patient in hospital. There is evidence that final year undergraduate nurses may lack knowledge, clinical skills and situation awareness required to manage a deteriorating patient competently. The effectiveness of clinical simulation as a strategy to teach the skills required to recognize and manage the early signs of deterioration needs to be evaluated. This study was a two centre phase II single, randomized, controlled trial with single blinded assessments. Data were collected in July 2013. Ninety-eight first year nursing students were randomized either into a control group, where they received a traditional lecture, or an intervention group where they received simulation. Participants completed a pre- and postintervention objective structured clinical examination. General Perceived Self Efficacy and Self-Reported Competency scores were measured before and after the intervention. Student satisfaction with teaching was also surveyed. The intervention group performed significantly better in the post-objective structured clinical examination. There was no significant difference in the postintervention General Perceived Self Efficacy and Self-Reported Competency scores between the control and intervention group. The intervention group was significantly more satisfied with their teaching method. Simulation-based education may be an effective educational strategy to teach nurses the skills to effectively recognize and manage a deteriorating patient. © 2015 John Wiley & Sons Ltd.

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview.

PubMed

Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

2017-07-01

Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo. An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect. Pharmacological active placebo control interventions are rarely used in randomized clinical trials, but they constitute a methodological tool which merits serious consideration. We suggest that active placebos are used more often in trials of drugs with noticeable side effects, especially in situations where the expected therapeutic effects are modest and the risk of bias due to unblinding is high. Copyright © 2017 Elsevier Inc. All rights reserved.

Weight management for overweight and obese men delivered through professional football clubs: a pilot randomized trial

PubMed Central

2013-01-01

Background The prevalence of male obesity is increasing, but men are less likely than women to attend existing weight management programmes. We have taken a novel approach to reducing perceived barriers to weight loss for men by using professional football (soccer) clubs to encourage participation in a weight management group programme, gender-sensitised in content and style of delivery. Football Fans in Training (FFIT) provides 12 weeks of weight loss, physical activity and healthy eating advice at top professional football clubs in Scotland. This pilot randomized trial explored the feasibility of using these clubs as a setting for a randomized controlled trial of 12 month weight loss following men’s participation in FFIT. Methods A two-arm pilot trial at two Scottish Premier League football clubs (one large, one smaller), with 103 men (aged 35–65, body mass index (BMI) ≥27 kg/m2) individually randomized to the intervention (n=51, received the pilot programme (p-FFIT) immediately) and waitlist comparison (n=52, received p-FFIT after four months) groups. Feasibility of recruitment, randomization, data collection and retention were assessed. Objective physical measurements (weight, waist circumference, blood pressure, body composition) and questionnaires (self-reported physical activity, diet, alcohol consumption, psychological outcomes) were obtained from both groups by fieldworkers trained to standard protocols at baseline and 12 weeks, and from the intervention group at 6 and 12 months. Qualitative methods elicited men’s experiences of participation in the pilot trial. Results Following a short recruitment period, the recruitment target was achieved at the large, but not smaller, club. Participants’ mean age was 47.1±8.4 years; mean BMI 34.5±5.0 kg/m2. Retention through the trial was good (>80% at 12 weeks and 6 months; >75% at 12 months), and 76% attended at least 80% of available programme delivery sessions. At 12 weeks, the intervention group lost significantly more weight than the comparison group (4.6% c.f. -0.6%, p<.001) and many maintained this to 12 months (intervention group baseline-12 month weight loss: 3.5%, p<.001). There were also improvements in self-reported physical activity and diet, many sustained long term. Conclusions The results demonstrated the feasibility of trial procedures and the potential of FFIT to engage men in sustained weight loss and positive lifestyle change. They supported the conduct of a fully-powered randomized controlled trial. PMID:24171842

Mentalization-based treatment in groups for adolescents with borderline personality disorder (BPD) or subthreshold BPD versus treatment as usual (M-GAB): study protocol for a randomized controlled trial.

PubMed

Beck, Emma; Bo, Sune; Gondan, Matthias; Poulsen, Stig; Pedersen, Liselotte; Pedersen, Jesper; Simonsen, Erik

2016-07-12

Evidence-based outpatient psychotherapeutic programs are first-line treatment of borderline personality disorder (BPD). Early and effective treatment of BPD is crucial to the prevention of its individual, psychosocial, and economic consequences. However, in spite of recent advantages in diagnosing adolescent BPD, there is a lack of cost-effective evidence-based treatment programs for adolescents. Mentalization-based treatment is an evidence-based program for BPD, originally developed for adults. We will investigate whether a specifically designed mentalization-based treatment in groups is an efficacious treatment for adolescents with BPD or subthreshold BPD compared to treatment as usual. The trial is a four-center, two-armed, parallel-group, assessor-blinded randomized clinical superiority trial. One hundred twelve patients aged 14 to 17 referred to Child and Adolescent Psychiatric Clinics in Region Zealand are randomized to 1 year of either mentalization-based treatment in groups or treatment as usual. Patients will be included if they meet at least four DSM-5 criteria for BPD. The primary outcome is self-reported borderline features at discharge. Secondary outcomes will include self-harm, depression, BPD criteria, externalizing and internalizing symptoms, and social functioning, together with parental reports on borderline features, externalizing and internalizing symptoms. Measures of attachment and mentalization will be included as mediational variables. Follow-up assessment will take place at 3 and 12 months after end of treatment. This is the first randomized controlled trial to test the efficacy of a group-based mentalization-based treatment for adolescents with BPD or subthreshold BPD. If the results confirm our hypothesis, this trial will add to the treatment options of cost-effective treatment of adolescent BPD. Clinicaltrials.gov NCT02068326 , February 19, 2014.

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.

Impact of the CONSORT Statement endorsement in the completeness of reporting of randomized clinical trials in restorative dentistry.

PubMed

Sarkis-Onofre, Rafael; Poletto-Neto, Victório; Cenci, Maximiliano Sérgio; Pereira-Cenci, Tatiana; Moher, David

2017-03-01

The aim of this study was to assess if journal endorsement of the CONSORT Statement is associated with improved completeness of reporting of randomized controlled trials (RCTs) in restorative dentistry. RCTs in restorative dentistry published in two journals that have (Journal of Dentistry and Clinical Oral Investigations) and have not (Operative Dentistry and Journal of Prosthetic Dentistry) endorsed the CONSORT Statement were selected. We compared the completeness of reporting between comparison groups (endorsers versus non-endorsers, before versus after endorsement) using a risk ratio (RR) with a 99% confidence interval for each outcome of CONSORT 2010. Also, the risk of bias of each study was evaluated. The electronic search retrieved a total of 3701 records. After the title and abstract evaluation, 169 full texts were screened and 79 RCTs identified. Considering CONSORT-endorsing journals before and after CONSORT endorsement, six items had effect estimates indicating a relatively higher proportion of completely reported RCTs published after CONSORT endorsement. Considering CONSORT-endorsing journals compared to non-endorsing journals, twelve items indicated a relatively higher proportion of completely reported RCTs published in CONSORT-endorsing journals. In both analyses the overall evidence did not present statistical significance. Although CONSORT endorsement has been linked with some improvement in the completeness of RCTs reports in the biomedical literature, this was not reflected in the present analysis confined to restorative dentistry. More innovative and involved approaches to enhancing reported may therefore be required. Inadequate reporting of randomized controlled trials can produce important consequences for all stakeholders including waste of resources and implication on healthcare decisions. A broad understandment of the use of reporting guidelines is necessary to lead to better results. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Theory-based interventions for contraception.

PubMed

Lopez, Laureen M; Tolley, Elizabeth E; Grimes, David A; Chen, Mario; Stockton, Laurie L

2013-08-07

The explicit use of theory in research helps expand the knowledge base. Theories and models have been used extensively in HIV-prevention research and in interventions for preventing sexually transmitted infections (STIs). The health behavior field uses many theories or models of change. However, educational interventions addressing contraception often have no stated theoretical base. Review randomized controlled trials (RCTs) that tested a theoretical approach to inform contraceptive choice; encourage contraceptive use; or promote adherence to, or continuation of, a contraceptive regimen. Through June 2013, we searched computerized databases for trials that tested a theory-based intervention for improving contraceptive use (MEDLINE, POPLINE, CENTRAL, PsycINFO, ClinicalTrials.gov, and ICTRP). Previous searches also included EMBASE. For the initial review, we wrote to investigators to find other trials. Trials tested a theory-based intervention for improving contraceptive use. We excluded trials focused on high-risk groups and preventing sexually transmitted infections or HIV. Interventions addressed the use of one or more contraceptive methods for contraception. The reports provided evidence that the intervention was based on a specific theory or model. The primary outcomes were pregnancy, contraceptive choice or use, and contraceptive adherence or continuation. The primary author evaluated abstracts for eligibility. Two authors extracted data from included studies. For the dichotomous outcomes, the Mantel-Haenszel odds ratio (OR) with 95% CI was calculated using a fixed-effect model. Cluster randomized trials used various methods of accounting for the clustering, such as multilevel modeling. Most reports did not provide information to calculate the effective sample size. Therefore, we presented the results as reported by the investigators. No meta-analysis was conducted due to differences in interventions and outcome measures. We included three new trials for a total of 17. Ten randomly assigned individuals and seven were cluster-randomized. Eight trials showed some intervention effect.Two of 12 trials with pregnancy or birth data showed some effect. A theory-based group was less likely than the comparison group to have a second birth (OR 0.41; 95% CI 0.17 to 1.00) or to report a pregnancy (OR 0.24 (95% CI 0.10 to 0.56); OR 0.27 (95% CI 0.11 to 0.66)). The theoretical bases were social cognitive theory (SCT) and another social cognition model.Of 12 trials with data on contraceptive use (non-condom), six showed some effect. A theory-based group was more likely to consistently use oral contraceptives (OR 1.41; 95% CI 1.06 to 1.87), hormonal contraceptives (reported relative risk (RR) 1.30; 95% CI 1.06 to 1.58) or dual methods (reported RR 1.36; 95% CI 1.01 to 1.85); to use an effective contraceptive method (reported effect size 1.76; OR 2.04 (95% CI 1.47 to 2.83)) or use more habitual contraception (reported P < 0.05); and were less likely to use ineffective contraception (OR 0.56; 95% CI 0.31 to 0.98). Theories and models included the Health Belief Model (HBM), SCT, SCT plus another theory, other social cognition, and motivational interviewing (MI).For condom use, a theory-based group had favorable results in 5 of 11 trials. The main differences were reporting more consistent condom use (reported RR 1.57; 95% CI 1.28 to 1.94) and more condom use during last sex (reported results: risk ratio 1.47 (95% CI 1.12 to 1.93); effect size 1.68; OR 2.12 (95% CI 1.24 to 3.56); OR 1.45 (95% CI 1.03 to 2.03)). The theories were SCT, SCT plus another theory, and HBM.Nearly all trials provided multiple sessions or contacts. SCT provided the basis for seven trials focused on adolescents, of which five reported some effectiveness. Two others based on other social cognition models had favorable results with adolescents. Of six trials including adult women, five provided individual sessions. Some effect was seen in two using MI and one using the HBM. Two based on the Transtheoretical Model did not show any effect. Eight trials provided evidence of high or moderate quality. Family planning researchers and practitioners could adapt the effective interventions, although most provided group sessions for adolescents. Three were conducted outside the USA. Clinics and low-resource settings need high-quality evidence on changing behavior. Thorough use of single theories would help in identifying what works, as would better reporting on research design and intervention implementation.

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

Rousseau, Cécile; Beauregard, Caroline; Daignault, Katherine; Petrakos, Harriet; Thombs, Brett D; Steele, Russell; Vasiliadis, Helen-Maria; Hechtman, Lily

2014-01-01

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. 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. 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. 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. ClinicalTrials.gov NCT01426451.

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.

Mobile access to virtual randomization for investigator-initiated trials.

PubMed

Deserno, Thomas M; Keszei, András P

2017-08-01

Background/aims Randomization is indispensable in clinical trials in order to provide unbiased treatment allocation and a valid statistical inference. Improper handling of allocation lists can be avoided using central systems, for example, human-based services. However, central systems are unaffordable for investigator-initiated trials and might be inaccessible from some places, where study subjects need allocations. We propose mobile access to virtual randomization, where the randomization lists are non-existent and the appropriate allocation is computed on demand. Methods The core of the system architecture is an electronic data capture system or a clinical trial management system, which is extended by an R interface connecting the R server using the Java R Interface. Mobile devices communicate via the representational state transfer web services. Furthermore, a simple web-based setup allows configuring the appropriate statistics by non-statisticians. Our comprehensive R script supports simple randomization, restricted randomization using a random allocation rule, block randomization, and stratified randomization for un-blinded, single-blinded, and double-blinded trials. For each trial, the electronic data capture system or the clinical trial management system stores the randomization parameters and the subject assignments. Results Apps are provided for iOS and Android and subjects are randomized using smartphones. After logging onto the system, the user selects the trial and the subject, and the allocation number and treatment arm are displayed instantaneously and stored in the core system. So far, 156 subjects have been allocated from mobile devices serving five investigator-initiated trials. Conclusion Transforming pre-printed allocation lists into virtual ones ensures the correct conduct of trials and guarantees a strictly sequential processing in all trial sites. Covering 88% of all randomization models that are used in recent trials, virtual randomization becomes available for investigator-initiated trials and potentially for large multi-center trials.

Reading and assessing reports of treatment studies in oncology.

PubMed

Simon, R

2000-04-01

Rapid advances in tumor biology, immunology, genomics, and technology give physicians great hopes for providing patients with better chances in the struggle against cancer. The pace of progress will be slowed, however, if we do not have clear answers regarding which treatments work and do not work. Such answers come from carefully designed, randomized, clinical trials. Such trials require infrastructure, commitment, cooperation, time, and money, and they provide little fame. They are, however, an invaluable contribution of the medical profession to their patients, to their next generation of colleagues, and to future patients. Randomized clinical trials that answer important medical questions definitively should be supported, participated in, and demanded by surgeons and oncologists.

Patient-reported outcomes, patient-reported information: from randomized controlled trials to the social web and beyond.

PubMed

Baldwin, Mike; Spong, Andrew; Doward, Lynda; Gnanasakthy, Ari

2011-01-01

Internet communication is developing. Social networking sites enable patients to publish and receive communications very easily. Many stakeholders, including patients, are using these media to find new ways to make sense of diseases, to find and discuss treatments, and to give support to patients and their caregivers. We argue for a new definition of patient-reported information (PRI), which differs from the usual patient-reported outcomes (PRO). These new emergent data from the social web have important implications for decision making, at both an individual and a population level. We discuss new emergent technologies that will help aggregate this information and discuss how this will be assessed alongside the use of PROs in randomized controlled trials and how these new emergent data will be one facet of changing the relationship between the various stakeholders in achieving better co-created health.

Urn models for response-adaptive randomized designs: a simulation study based on a non-adaptive randomized trial.

PubMed

Ghiglietti, Andrea; Scarale, Maria Giovanna; Miceli, Rosalba; Ieva, Francesca; Mariani, Luigi; Gavazzi, Cecilia; Paganoni, Anna Maria; Edefonti, Valeria

2018-03-22

Recently, response-adaptive designs have been proposed in randomized clinical trials to achieve ethical and/or cost advantages by using sequential accrual information collected during the trial to dynamically update the probabilities of treatment assignments. In this context, urn models-where the probability to assign patients to treatments is interpreted as the proportion of balls of different colors available in a virtual urn-have been used as response-adaptive randomization rules. We propose the use of Randomly Reinforced Urn (RRU) models in a simulation study based on a published randomized clinical trial on the efficacy of home enteral nutrition in cancer patients after major gastrointestinal surgery. We compare results with the RRU design with those previously published with the non-adaptive approach. We also provide a code written with the R software to implement the RRU design in practice. In detail, we simulate 10,000 trials based on the RRU model in three set-ups of different total sample sizes. We report information on the number of patients allocated to the inferior treatment and on the empirical power of the t-test for the treatment coefficient in the ANOVA model. We carry out a sensitivity analysis to assess the effect of different urn compositions. For each sample size, in approximately 75% of the simulation runs, the number of patients allocated to the inferior treatment by the RRU design is lower, as compared to the non-adaptive design. The empirical power of the t-test for the treatment effect is similar in the two designs.

Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials.

PubMed

Strand, Vibeke; Ahadieh, Sima; French, Jonathan; Geier, Jamie; Krishnaswami, Sriram; Menon, Sujatha; Checchio, Tina; Tensfeldt, Thomas G; Hoffman, Elaine; Riese, Richard; Boy, Mary; Gómez-Reino, Juan J

2015-12-15

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib modulates the signaling of cytokines that are integral to lymphocyte activation, proliferation, and function. Thus, tofacitinib therapy may result in suppression of multiple elements of the immune response. Serious infections have been reported in tofacitinib RA trials. However, limited head-to-head comparator data were available within the tofacitinib RA development program to directly compare rates of serious infections with tofacitinib relative to biologic agents, and specifically adalimumab (employed as an active control agent in two randomized controlled trials of tofacitinib). A systematic literature search of data from interventional randomized controlled trials and long-term extension studies with biologics in RA was carried out. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results of the review and meta-analysis. Incidence rates (unique patients with events/100 patient-years) for each therapy were estimated based on data from randomized controlled trials and long-term extension studies using a random-effects model. Relative and absolute risk comparisons versus placebo used Mantel-Haenszel methods. The search produced 657 hits. In total, 66 randomized controlled trials and 22 long-term extension studies met the selection criteria. Estimated incidence rates (95% confidence intervals [CIs]) for abatacept, rituximab, tocilizumab, and tumor necrosis factor inhibitors were 3.04 (2.49, 3.72), 3.72 (2.99, 4.62), 5.45 (4.26, 6.96), and 4.90 (4.41, 5.44), respectively. Incidence rates (95% CIs) for tofacitinib 5 and 10 mg twice daily (BID) in phase 3 trials were 3.02 (2.25, 4.05) and 3.00 (2.24, 4.02), respectively. Corresponding incidence rates in long-term extension studies were 2.50 (2.05, 3.04) and 3.19 (2.74, 3.72). The risk ratios (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 2.21 (0.60, 8.14) and 2.02 (0.56, 7.28), respectively. Risk differences (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 0.38% (-0.24%, 0.99%) and 0.40% (-0.22%, 1.02%), respectively. In interventional studies, the risk of serious infections with tofacitinib is comparable to published rates for biologic disease-modifying antirheumatic drugs in patients with moderate to severely active RA.

8-Way Randomized Controlled Trial of Doxylamine, Pyridoxine and Dicyclomine for Nausea and Vomiting during Pregnancy: Restoration of Unpublished Information.

PubMed

Zhang, Rujun; Persaud, Navindra

2017-01-01

We report information about an unpublished 1970s study ("8-way" Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of nausea and vomiting during pregnancy. We are publishing the trial's findings according to the restoring invisible and abandoned trials (RIAT) initiative because the trial was never published. Double blinded, multi-centred, randomized placebo-controlled study. 14 clinics in the United States. 2308 patients in the first 12 weeks of pregnancy with complaints of nausea or vomiting were enrolled. Each patient was randomized to one of eight arms: placebo, doxylamine/pyridoxine/dicylcomine, doxylamine/pyridoxine, dicylomine/pyridoxine, doxylamine, dicyclomine/pyridoxine, pyridoxine and dicyclomine. Each patient was instructed to take 2 tablets at bedtime and 1 additional tablet in the afternoon or morning if needed, for 7 nights. Reported outcomes included the number of hours of nausea reported by patients, the frequency of vomiting reported by patients and the overall efficacy of medication as judged by physicians. Data from 1599 (69% of those randomized) participants were analyzed. Based on the available summary data of physician evaluation of symptoms and ignoring missing data and data integrity issues, the proportion of participants who were "evaluated moderate or excellent" was greater in each of the seven active treatment groups when compared with placebo (57%): doxylamine/pyridoxine/dicylcomine (14% absolute difference versus placebo; 95% CI: 4 to 24), doxylamine/pyridoxine (21; 95% CI 11 to 30), dicylomine/pyridoxine (21; 95% CI 11 to 30), doxylamine (20; 95% CI 10 to 29), dicyclomine/pyridoxine (4; 95% CI -6 to 14), pyridoxine (9; 95% CI -1 to 19) and dicyclomine (4; 95% CI -6 to 14). Based on incomplete information, the most common adverse events were apparently drowsiness and fatigue. There is a high risk of bias in these previously unpublished results given the high attrition rate in a 7 day trial, the lack of prespecified outcomes or analyses, and the exclusion of some data because of questionable data integrity. The available information about this "8-way Bendectin" trial indicates it should not be used to support the efficacy of doxylamine, pyridoxine or dicyclomine for the treatment of nausea and vomiting during pregnancy because of a high risk of bias. Not registered.

A randomized trial of enhanced HIV risk-reduction and vaccine trial education interventions among HIV-negative, high-risk women who use noninjection drugs: the UNITY study.

PubMed

Koblin, Beryl A; Bonner, Sebastian; Hoover, Donald R; Xu, Guozhen; Lucy, Debbie; Fortin, Princess; Putnam, Sara; Latka, Mary H

2010-03-01

Limited data are available on interventions to reduce sexual risk behaviors and increase knowledge of HIV vaccine trial concepts in high-risk populations eligible to participate in HIV vaccine efficacy trials. The UNITY Study was a 2-arm randomized trial to determine the efficacy of enhanced HIV risk-reduction and vaccine trial education interventions to reduce the occurrence of unprotected vaginal sex acts and increase HIV vaccine trial knowledge among 311 HIV-negative noninjection drug using women. The enhanced vaccine education intervention using pictures along with application vignettes and enhanced risk-reduction counseling consisting of 3 one-on-one counseling sessions were compared with standard conditions. Follow-up visits at 1 week and 1, 6, and 12 months after randomization included HIV testing and assessment of outcomes. During follow-up, the percent of women reporting sexual risk behaviors declined significantly but did not differ significantly by study arm. Knowledge of HIV vaccine trial concepts significantly increased but did not significantly differ by study arm. Concepts about HIV vaccine trials not adequately addressed by either condition included those related to testing a vaccine for both efficacy and safety, guarantees about participation in future vaccine trials, assurances of safety, medical care, and assumptions about any protective effect of a test vaccine. Further research is needed to boost educational efforts and strengthen risk-reduction counseling among high-risk noninjection drug using women.

Recruitment strategies in two Reproductive Medicine Network infertility trials

PubMed Central

Usadi, Rebecca S.; Diamond, Michael P.; Legro, Richard S.; Schlaff, William D.; Hansen, Karl R.; Casson, Peter; Christman, Gregory; Bates, G. Wright; Baker, Valerie; Seungdamrong, Aimee; Rosen, Mitchell P.; Lucidi, Scott; Thomas, Tracey; Huang, Hao; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping; Alvero, Ruben

2016-01-01

Background Recruitment of individuals into clinical trials is a critical step in completing studies. Reports examining the effectiveness of different recruitment strategies, and specifically in infertile couples, are limited. Methods We investigated recruitment methods used in two NIH sponsored trials, Pregnancy in Polycystic Ovary Syndrome (PPCOS II) and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), and examined which strategies yielded the greatest number of participants completing the trials. Results 3683 couples were eligible for screening. 1650 participants were randomized and 1339 completed the trials. 750 women were randomized in PPCOS II; 212 of the participants who completed the trial were referred by physicians. Participants recruited from radio ads (84/750) and the internet (81/750) resulted in similar rates of trial completion in PPCOS II. 900 participants were randomized in AMIGOS. 440 participants who completed the trial were referred to the study by physicians. The next most successful method in AMIGOS was use of the internet, achieving 78 completed participants. Radio ads proved the most successful strategy in both trials for participants who earned <$50,000 annually. Radio ads were most successful in enrolling white patients in PPCOS II and black patients in AMIGOS. Seven ancillary Clinical Research Scientist Training (CREST) sites enrolled 324 of the participants who completed the trials. Conclusions Physician referral was the most successful recruitment strategy. Radio ads and the internet were the next most successful strategies, particularly for women of limited income. Ancillary clinical sites were important for overall recruitment. PMID:26386293

Recruitment strategies in two reproductive medicine network infertility trials.

PubMed

Usadi, Rebecca S; Diamond, Michael P; Legro, Richard S; Schlaff, William D; Hansen, Karl R; Casson, Peter; Christman, Gregory; Wright Bates, G; Baker, Valerie; Seungdamrong, Aimee; Rosen, Mitchell P; Lucidi, Scott; Thomas, Tracey; Huang, Hao; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping; Alvero, Ruben

2015-11-01

Recruitment of individuals into clinical trials is a critical step in completing studies. Reports examining the effectiveness of different recruitment strategies, and specifically in infertile couples, are limited. We investigated recruitment methods used in two NIH sponsored trials, Pregnancy in Polycystic Ovary Syndrome (PPCOS II) and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), and examined which strategies yielded the greatest number of participants completing the trials. 3683 couples were eligible for screening. 1650 participants were randomized and 1339 completed the trials. 750 women were randomized in PPCOS II; 212 of the participants who completed the trial were referred by physicians. Participants recruited from radio ads (84/750) and the internet (81/750) resulted in similar rates of trial completion in PPCOS II. 900 participants were randomized in AMIGOS. 440 participants who completed the trial were referred to the study by physicians. The next most successful method in AMIGOS was the use of the internet, achieving 78 completed participants. Radio ads proved the most successful strategy in both trials for participants who earned <$50,000 annually. Radio ads were most successful in enrolling white patients in PPCOS II and black patients in AMIGOS. Seven ancillary Clinical Research Scientist Training (CREST) sites enrolled 324 of the participants who completed the trials. Physician referral was the most successful recruitment strategy. Radio ads and the internet were the next most successful strategies, particularly for women of limited income. Ancillary clinical sites were important for overall recruitment. Copyright © 2015 Elsevier Inc. All rights reserved.

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).

A randomised controlled trial of a probiotic 'functional food' in the management of irritable bowel syndrome.

PubMed

Roberts, Lesley M; McCahon, Deborah; Holder, Roger; Wilson, Sue; Hobbs, F D Richard

2013-03-07

Irritable Bowel Syndrome (IBS) is a common condition characterised by pain, distension and altered bowel habit. Evidence suggests functional foods containing probiotics improve gastrointestinal transit, however, data are limited by short follow-up periods and evaluation in selected populations. A multi-centre, randomized, double blind, controlled trial to evaluate the effect of a probiotic vs non-probiotic dairy product on symptoms in IBS with a constipation element (IBS-Constipation or IBS-Mixed profile). Set in 13 general practices within central England. Individuals meeting the ROME III criteria for IBS, aged 18-65 completed a pre-study diary. Eligible individuals were randomized to consume dairy 'yoghurt' products which either did or did not contain active probiotics twice daily and to complete a daily diary. Primary outcome was subjective global assessment of symptom relief at week 4. Other outcomes comprised, IBS symptom scores, pain, bloating and flatulence levels, stool frequency, stool consistency, ease of bowel movement and quality of life. 179 were randomized (91 active, 88 placebo). 76 (43 active, 33 placebo) completed the study. No significant between group differences existed at 4 weeks (57% active vs 53% placebo, reported adequate relief (p = 0.71)). By week 8, 46% active vs 68% placebo reported adequate relief (p = 0.03). This was sustained at week 12. Significant improvements were reported for most outcomes in all trial participants but improvement did not differ by group. This trial does not provide evidence for effectiveness of a probiotic in IBS, in variance with a body of published literature and review conclusions. Differential drop out may however cloud interpretation of data. UK TRIAL REGISTRATION: ISRCTN78863629.

The effect of cactus pear (Opuntia ficus-indica) on body weight and cardiovascular risk factors: a systematic review and meta-analysis of randomized clinical trials.

PubMed

Onakpoya, Igho J; O'Sullivan, Jack; Heneghan, Carl J

2015-05-01

Hundreds of dietary supplements are currently marketed as weight loss supplements. However, the advertised health claims of effectiveness for most of these have not been proven. The aim of this study was to critically appraise and evaluate the evidence for effectiveness of cactus pear, Opuntia ficus-indica (OFI), using data from published randomized clinical trials. We conducted electronic searches in Medline, Embase, Amed, Cinahl, and the Cochrane Library. No restrictions on age, time, or language were imposed. The risk for bias in the studies included was assessed using the Cochrane Collaboration criteria. Two reviewers independently determined the eligibility of included studies, assessed reporting quality, and extracted data. We identified seven eligible studies, of which five were included. The studies varied in design and reporting quality. Meta-analysis revealed a nonsignificant difference in body weight between OFI and controls (mean difference = -0.83 kg; 95% confidence interval, -2.49 to 0.83; I(2) = 93%). Significant reductions in body mass index, percentage body fat, systolic and diastolic blood pressures, and total cholesterol were observed. Adverse events included gastric intolerance and flu symptoms. The evidence from randomized clinical trials does not indicate that supplementation with OFI generates statistically significant effects on body weight. Consumption of OFI can cause significant reductions in percentage body fat, blood pressure, and total cholesterol. Few clinical trials evaluating the effects of OFI have been published. They vary in design and methodology, and are characterized by inconsistent quality of reporting. Further clinical trials evaluating the effects of OFI on body composition and metabolic parameters are warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

Computer-Based Driving in Dementia Decision Tool With Mail Support: Cluster Randomized Controlled Trial.

PubMed

Rapoport, Mark J; Zucchero Sarracini, Carla; Kiss, Alex; Lee, Linda; Byszewski, Anna; Seitz, Dallas P; Vrkljan, Brenda; Molnar, Frank; Herrmann, Nathan; Tang-Wai, David F; Frank, Christopher; Henry, Blair; Pimlott, Nicholas; Masellis, Mario; Naglie, Gary

2018-05-25

Physicians often find significant challenges in assessing automobile driving in persons with mild cognitive impairment and mild dementia and deciding when to report to transportation administrators. Care must be taken to balance the safety of patients and other road users with potential negative effects of issuing such reports. The aim of this study was to assess whether a computer-based Driving in Dementia Decision Tool (DD-DT) increased appropriate reporting of patients with mild dementia or mild cognitive impairment to transportation administrators. The study used a parallel-group cluster nonblinded randomized controlled trial design to test a multifaceted knowledge translation intervention. The intervention included a computer-based decision support system activated by the physician-user, which provides a recommendation about whether to report patients with mild dementia or mild cognitive impairment to transportation administrators, based on an algorithm derived from earlier work. The intervention also included a mailed educational package and Web-based specialized reporting forms. Specialists and family physicians with expertise in dementia or care of the elderly were stratified by sex and randomized to either use the DD-DT or a control version of the tool that required identical data input as the intervention group, but instead generated a generic reminder about the reporting legislation in Ontario, Canada. The trial ran from September 9, 2014 to January 29, 2016, and the primary outcome was the number of reports made to the transportation administrators concordant with the algorithm. A total of 69 participating physicians were randomized, and 36 of these used the DD-DT; 20 of the 35 randomized to the intervention group used DD-DT with 114 patients, and 16 of the 34 randomized to the control group used it with 103 patients. The proportion of all assessed patients reported to the transportation administrators concordant with recommendation did not differ between the intervention and the control groups (50% vs 49%; Z=-0.19, P=.85). Two variables predicted algorithm-based reporting-caregiver concern (odds ratio [OR]=5.8, 95% CI 2.5-13.6, P<.001) and abnormal clock drawing (OR 6.1, 95% CI 3.1-11.8, P<.001). On the basis of this quantitative analysis, in-office abnormal clock drawing and expressions of concern about driving from caregivers substantially influenced physicians to report patients with mild dementia or mild cognitive impairment to transportation administrators, but the DD-DT tool itself did not increase such reports among these expert physicians. ClinicalTrials.gov NCT02036099; https://clinicaltrials.gov/ct2/show/NCT02036099 (Archived by WebCite at http://www.webcitation.org/6zGMF1ky8). ©Mark J Rapoport, Carla Zucchero Sarracini, Alex Kiss, Linda Lee, Anna Byszewski, Dallas P Seitz, Brenda Vrkljan, Frank Molnar, Nathan Herrmann, David F Tang-Wai, Christopher Frank, Blair Henry, Nicholas Pimlott, Mario Masellis, Gary Naglie. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 25.05.2018.

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

A systematic review identifies shortcomings in the reporting of crossover trials in chronic painful conditions.

PubMed

Straube, Sebastian; Werny, Benedikt; Friede, Tim

2015-12-01

To investigate the reporting of study features of interest in abstracts and full texts of journal publications of crossover trials in chronic painful conditions. Systematic review based on a MEDLINE (PubMed) search (January 1990-August 2014). Ninety-eight publications on crossover studies with 3,513 study participants were eligible for inclusion. Double-blind status and randomized allocation to treatment groups are commonly reported in both abstracts and full texts (90 of 98 publications and 82 of 98 publications, respectively). Adverse events are reported in both abstract and full text in 49 of 98 publications and in the full text only in 44 of 98. A breakdown of results by treatment period is provided only in 23 of 98 publications, and if so, is reported only in the full text, never in the abstract. There is a time trend for the reporting of randomization in abstracts; it is more likely to be reported in recent studies (P = 0.0094). No time trends are detected in the reporting of double-blind status (P = 0.1087) and adverse events (P = 0.6084). The reporting of adverse events in the abstract and the reporting of results specified by crossover period in the full texts of journal publications on crossover pain trials should be improved. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

A Meta-Analysis of Depressive Symptom Outcomes in Randomized, Controlled Trials for PTSD.

PubMed

Ronconi, Julia McDougal; Shiner, Brian; Watts, Bradley V

2015-07-01

Posttraumatic stress disorder (PTSD) often co-occurs with depression. Current PTSD practice guidelines lack specific guidance for clinicians regarding the treatment of depressive symptoms. We conducted a meta-analysis of all randomized, placebo-controlled trials for PTSD therapies focusing on depression outcomes to inform clinicians about effective treatment options for depressive symptoms associated with PTSD. We searched literature databases for randomized, controlled clinical trials of any treatment for PTSD published between 1980 and 2013. We selected articles in which all subjects were adults with a diagnosis of PTSD based on the Diagnostic and Statistical Manual of Mental Disorders criteria, and valid PTSD and depressive symptom measures were reported. The sample consisted of 116 treatment comparisons drawn from 93 manuscripts. Evidence-based PTSD treatments are effective for comorbid depressive symptoms. Existing PTSD treatments work as well for comorbid depressive symptoms as they do for PTSD symptoms.

The positive deviance/hearth approach to reducing child malnutrition: systematic review.

PubMed

Bisits Bullen, Piroska A

2011-11-01

The Positive Deviance/Hearth approach aims to rehabilitate malnourished children using practices from mothers in the community who have well-nourished children despite living in poverty. This study assesses its effectiveness in a range of settings. Systematic review of peer reviewed intervention trials and grey literature evaluation reports of child malnutrition programs using the Positive Deviance/Hearth approach. Ten peer reviewed studies and 14 grey literature reports met the inclusion criteria. These described results for 17 unique Positive Deviance/Hearth programs in 12 countries. Nine programs used a pre- and post-test design without a control, which limited the conclusions that could be drawn. Eight used more robust designs such as non-randomized trials, non-randomized cross-sectional sibling studies and randomized controlled trials (RCTs). Of the eight programs that reported nutritional outcomes, five reported some type of positive result in terms of nutritional status - although the improvement was not always as large as predicted, or across the entire target population. Both the two RCTs demonstrated improvements in carer feeding practices. Qualitative results unanimously reported high levels of satisfaction from participants and recipient communities. Overall this study shows mixed results in terms of program effectiveness, although some Positive Deviance/Hearth programs have clearly been successful in particular settings. Sibling studies suggest that the Positive Deviance/Hearth approach may have a role in preventing malnutrition, not just rehabilitation. Further research is needed using more robust study designs and larger sample sizes. Issues related to community participation and consistency in reporting results need to be addressed. © 2011 Blackwell Publishing Ltd.

Hyperbaric Side Effects in a Traumatic Brain Injury Randomized Clinical Trial

DTIC Science & Technology

2012-01-01

aHrQ) evidence report/technology assessment, Number 85, “Hyperbaric oxygen therapy for brain injury, cerebral palsy , and stroke” [1]. the report...Carson S, Ash JS, Russman BS, Stavri PZ, Krages KP, et al. Hyperbaric oxygen therapy for brain injury, cerebral palsy , and stroke. Rockville, MD...clini- cal trial to compare the the effect of hyperbaric to normobaric hyperoxia on cerebral metabolism, intracranial pressure, and oxygen toxicity in

Brief Report: Randomized Test of the Efficacy of Picture Exchange Communication System on Highly Generalized Picture Exchanges in Children with ASD

ERIC Educational Resources Information Center

Yoder, Paul J.; Lieberman, Rebecca G.

2010-01-01

A randomized control trial comparing two social-communication interventions in young children with autism examined far-transfer of the use of picture exchange to communicate. Thirty-six children were randomly assigned to one of two treatment conditions, one of which was the Picture Exchange Communication System (PECS). All children had access to…

Quality of reporting of randomized clinical trials in implant dentistry. A systematic review on critical aspects in design, outcome assessment and clinical relevance.

PubMed

Cairo, Francesco; Sanz, Ignacio; Matesanz, Paula; Nieri, Michele; Pagliaro, Umberto

2012-02-01

The aim of this systematic review (SR) was to assess the quality of reporting randomized clinical trials (RCTs) in the field of implant dentistry, its evolution over time and the possible relations between quality items and reported outcomes. RCTs in implant dentistry were retrieved through electronic and hand searches. Risk of bias in individual studies was assessed focusing on study design, outcome assessment and clinical relevance. Associations between quality items and year of publication of RCTs or reporting of statistically significant outcomes were tested. Among the 495 originally screened manuscripts published from 1989 to April 2011, 276 RCTs were assessed in this SR; 59% of them were published between 2006 and 2011. RCTs were mainly parallel (65%), with a single centre (83%) and a superiority design (88%). Trials in implant dentistry showed several methodological flaws: only 37% showed a random sequence generation at low risk of bias, 75% did not provide information on allocation concealment, only 12% performed a correct sample size calculation, the examiner was blind solely in 42% of studies where blinding was feasible. In addition, only 21% of RCTs declared operator experience and 31% reported patient-related outcomes. Many quality items improved over time. Allocation concealment at high risk of bias (p = 0.0125), no information on drop-out (p = 0.0318) and lack of CONSORT adherence (p = 0.0333) were associated with statistically significant reported outcomes. The overall quality of reporting of RCTs in implant dentistry is poor and only partially improved in the last years. Caution is suggested when interpreting these RCTs since risk of bias was associated with higher chance of reporting of statistically significant results. © 2012 John Wiley & Sons A/S.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of rehabilitation interventions for osteoarthritis.

PubMed

Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L

2015-05-01

A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Second thoughts on the final rule: An analysis of baseline participant characteristics reports on ClinicalTrials.gov.

PubMed

Cahan, Amos; Anand, Vibha

2017-01-01

ClinicalTrials.gov is valuable for aggregate-level analysis of trials. The recently published final rule aims to improve reporting of trial results. We aimed to assess variability in ClinicalTirals.gov records reporting participants' baseline measures. The September 2015 edition of the database for Aggregate Analysis of ClinicalTrials.gov (AACT), was used in this study. To date, AACT contains 186,941 trials of which 16,660 trials reporting baseline (participant) measures were analyzed. We also analyzed a subset of 13,818 Highly Likely Applicable Clinical Trials (HLACT), for which reporting of results is likely mandatory and compared a random sample of 30 trial records to their journal articles. We report counts for each mandatory baseline measure and variability reporting in their formats. The AACT dataset contains 8,161 baseline measures with 1206 unique measurement units. However, of these 6,940 (85%) variables appear only once in the dataset. Age and Gender are reported using many different formats (178 and 49 respectively). "Age" as the variable name is reported in 60 different formats. HLACT subset reports measures using 3,931 variables. The most frequent Age format (i.e. mean (years) ± sd) is found in only 45% of trials. Overall only 4 baseline measures (Region of Enrollment, Age, Number of Participants, and Gender) are reported by > 10% of trials. Discrepancies are found in both the types and formats of ClinicalTrials.gov records and their corresponding journal articles. On average, journal articles include twice the number of baseline measures (13.6±7.1 (sd) vs. 6.6±7.6) when compared to the ClinicalTrials.gov records that report any results. We found marked variability in baseline measures reporting. This is not addressed by the final rule. To support secondary use of ClinicalTrials.gov, a uniform format for baseline measures reporting is warranted.

Endometrial Scratch Injury Induces Higher Pregnancy Rate for Women With Unexplained Infertility Undergoing IUI With Ovarian Stimulation: A Randomized Controlled Trial.

PubMed

Maged, Ahmed M; Al-Inany, Hesham; Salama, Khaled M; Souidan, Ibrahim I; Abo Ragab, Hesham M; Elnassery, Noura

2016-02-01

To explore the impact of endometrial scratch injury (ESI) on intrauterine insemination (IUI) success. One hundred and fifty four infertile women received 100 mg of oral clomiphene citrate for 5 days starting on day 3 of the menstrual cycle. Patients were randomized to 2 equal groups: Group C received IUI without ESI and group S had ESI. Successful pregnancy was confirmed by ultrasound. 13, 21, and 10 women got pregnant after the first, second, and third IUI trials, respectively, with 28.6% cumulative pregnancy rate (PR). The cumulative PR was significantly higher in group S (39%) compared to group C (18.2%). The PR in group S was significantly higher compared to that in group C at the second and third trials. The PR was significantly higher in group S at the second trial compared to that reported in the same group at the first trial but nonsignificantly higher compared to that reported during the third trial, while in group C, the difference was nonsignificant. Eight pregnant women had first trimester abortion with 18.2% total abortion rate with nonsignificant difference between studied groups. The ESI significantly improves the outcome of IUI in women with unexplained infertility especially when conducted 1 month prior to IUI. © The Author(s) 2015.

Reporting guidelines for primary research: Saying what you did.

PubMed

O'Connor, Annette

2010-12-01

Reporting guidelines aim to facilitate publication of a full and accurate description of research conducted. The motivations for a full and accurate description of research is to enable reproduction of the study, assessment of bias, extraction of data from the study, and to fulfill an ethical obligation to maximize the utility of research findings. Many reporting guidelines exist and most are based on a specific study design such as randomized controlled trials (CONSORT statement) and observational studies (STROBE statement). The REFLECT statement focuses on randomized control trials in livestock and food safety studies. The REFLECT statement has increased emphasis on conveying information about animal housing, group level allocation and challenge studies. Guidelines can be used by authors, reviewers and editors to provide readers with a full and accurate description of the work conducted. Copyright © 2010 Elsevier B.V. All rights reserved.

Comparison of Data on Serious Adverse Events and Mortality in ClinicalTrials.gov, Corresponding Journal Articles, and FDA Medical Reviews: Cross-Sectional Analysis.

PubMed

Pradhan, Richeek; Singh, Sonal

2018-04-11

Inconsistencies in data on serious adverse events (SAEs) and mortality in ClinicalTrials.gov and corresponding journal articles pose a challenge to research transparency. The objective of this study was to compare data on SAEs and mortality from clinical trials reported in ClinicalTrials.gov and corresponding journal articles with US Food and Drug Administration (FDA) medical reviews. We conducted a cross-sectional study of a randomly selected sample of new molecular entities approved during the study period 1 January 2013 to 31 December 2015. We extracted data on SAEs and mortality from 15 pivotal trials from ClinicalTrials.gov and corresponding journal articles (the two index resources), and FDA medical reviews (reference standard). We estimated the magnitude of deviations in rates of SAEs and mortality between the index resources and the reference standard. We found deviations in rates of SAEs (30% in ClinicalTrials.gov and 30% in corresponding journal articles) and mortality (72% in ClinicalTrials.gov and 53% in corresponding journal articles) when compared with the reference standard. The intra-class correlation coefficient between the three resources was 0.99 (95% confidence interval [CI] 0.98-0.99) for SAE rates and 0.99 (95% CI 0.97-0.99) for mortality rates. There are differences in data on rates of SAEs and mortality in randomized clinical trials in both ClinicalTrials.gov and journal articles compared with FDA reviews. Further efforts should focus on decreasing existing discrepancies to enhance the transparency and reproducibility of data reporting in clinical trials.

8-Way Randomized Controlled Trial of Doxylamine, Pyridoxine and Dicyclomine for Nausea and Vomiting during Pregnancy: Restoration of Unpublished Information

PubMed Central

Zhang, Rujun; Persaud, Navindra

2017-01-01

Objectives We report information about an unpublished 1970s study (“8-way” Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of nausea and vomiting during pregnancy. We are publishing the trial's findings according to the restoring invisible and abandoned trials (RIAT) initiative because the trial was never published. Design Double blinded, multi-centred, randomized placebo-controlled study. Setting 14 clinics in the United States. Participants 2308 patients in the first 12 weeks of pregnancy with complaints of nausea or vomiting were enrolled. Interventions Each patient was randomized to one of eight arms: placebo, doxylamine/pyridoxine/dicylcomine, doxylamine/pyridoxine, dicylomine/pyridoxine, doxylamine, dicyclomine/pyridoxine, pyridoxine and dicyclomine. Each patient was instructed to take 2 tablets at bedtime and 1 additional tablet in the afternoon or morning if needed, for 7 nights. Outcomes Reported outcomes included the number of hours of nausea reported by patients, the frequency of vomiting reported by patients and the overall efficacy of medication as judged by physicians. Results Data from 1599 (69% of those randomized) participants were analyzed. Based on the available summary data of physician evaluation of symptoms and ignoring missing data and data integrity issues, the proportion of participants who were “evaluated moderate or excellent” was greater in each of the seven active treatment groups when compared with placebo (57%): doxylamine/pyridoxine/dicylcomine (14% absolute difference versus placebo; 95% CI: 4 to 24), doxylamine/pyridoxine (21; 95% CI 11 to 30), dicylomine/pyridoxine (21; 95% CI 11 to 30), doxylamine (20; 95% CI 10 to 29), dicyclomine/pyridoxine (4; 95% CI -6 to 14), pyridoxine (9; 95% CI -1 to 19) and dicyclomine (4; 95% CI -6 to 14). Based on incomplete information, the most common adverse events were apparently drowsiness and fatigue. There is a high risk of bias in these previously unpublished results given the high attrition rate in a 7 day trial, the lack of prespecified outcomes or analyses, and the exclusion of some data because of questionable data integrity. Conclusion The available information about this “8-way Bendectin” trial indicates it should not be used to support the efficacy of doxylamine, pyridoxine or dicyclomine for the treatment of nausea and vomiting during pregnancy because of a high risk of bias. Trial registration Not registered. PMID:28052111

Corticosteroids as adjuvant therapy for ocular toxoplasmosis.

PubMed

Jasper, Smitha; Vedula, Satyanarayana S; John, Sheeja S; Horo, Saban; Sepah, Yasir J; Nguyen, Quan Dong

2017-01-26

Ocular infection caused by Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea, and consequently lead to complications such as glaucoma, cataract, and posterior synechiae. The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids to anti-parasitic therapy versus anti-parasitic therapy alone for ocular toxoplasmosis. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register (2016; Issue 11)), MEDLINE Ovid, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE Ovid Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS (January 1982 to December 2016)), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), 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 7 December 2016. We had planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with acute ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, different doses or times of initiation of corticosteroids. Two authors independently screened titles and abstracts retrieved through the electronic searches. We retrieved full-text reports of studies categorized as 'unsure' or 'include' after we reviewed the abstracts. Two authors independently reviewed each full-text report for eligibility. Discrepancies were resolved through discussion. We identified no completed or ongoing trial that was eligible for this Cochrane review. Although research has identified a wide variation in practice regarding the use of corticosteroids, our review did not identify any evidence from randomized controlled trials for or against the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether the use of corticosteroids as an adjunctive agent is more effective than the use of anti-parasitic therapy alone; if so, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and what would be the best dose and duration of steroid use.

Corticosteroids as adjuvant therapy for ocular toxoplasmosis

PubMed Central

Jasper, Smitha; Vedula, Satyanarayana S; John, Sheeja S; Horo, Saban; Sepah, Yasir J; Nguyen, Quan Dong

2017-01-01

Background Ocular infection caused by Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea, and consequently lead to complications such as glaucoma, cataract, and posterior synechiae. Objectives The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids to anti-parasitic therapy versus anti-parasitic therapy alone for ocular toxoplasmosis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register (2016; Issue 11)), MEDLINE Ovid, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE Ovid Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS (January 1982 to December 2016)), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), 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 7 December 2016. Selection criteria We had planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with acute ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, different doses or times of initiation of corticosteroids. Data collection and analysis Two authors independently screened titles and abstracts retrieved through the electronic searches. We retrieved full-text reports of studies categorized as ’unsure’ or ’include’ after we reviewed the abstracts. Two authors independently reviewed each full-text report for eligibility. Discrepancies were resolved through discussion. Main results We identified no completed or ongoing trial that was eligible for this Cochrane review. Authors’ conclusions Although research has identified a wide variation in practice regarding the use of corticosteroids, our review did not identify any evidence from randomized controlled trials for or against the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether the use of corticosteroids as an adjunctive agent is more effective than the use of anti-parasitic therapy alone; if so, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and what would be the best dose and duration of steroid use. PMID:28125765

A Short-Term, Multicenter, Placebo-Controlled, Randomized Withdrawal Study of a Metabotropic Glutamate 2/3 Receptor Agonist Using an Electronic Patient-Reported Outcome Device in Patients With Schizophrenia

PubMed Central

Stauffer, Virginia L.; Baygani, Simin K.; Kinon, Bruce J.; Krikke-Workel, Judith O.

2014-01-01

Abstract This 6-week, multicenter, randomized withdrawal, placebo-controlled trial sought to determine whether symptoms of physical dependence occur after abrupt cessation of pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate 2/3 receptor agonist, in patients with schizophrenia. Eligible outpatients, 18 to 65 years old who required a modification or initiation of antipsychotic medication received 4 weeks of pomaglumetad methionil during open-label treatment and then were randomized, double-blind, to continue pomaglumetad methionil or receive placebo for 2 weeks. The primary outcome compared results of the 3-day moving mean of the total score on the Discontinuation Symptom Checklist-Modified Rickels for pomaglumetad methionil-treated patients with those on placebo during the randomized withdrawal phase. An electronic patient-reported outcome (ePRO) device was used daily to record these results. During the withdrawal phase, 103 patients were randomized, and 98 patients completed the trial. There was no statistically significant evidence of withdrawal symptoms associated with placebo compared with pomaglumetad methionil continuation as measured by Discontinuation Symptom Checklist-Modified Rickels (P = 0.170). The results are supported by secondary analyses with the clinician-rated, Clinical Institute Withdrawal Assessment of Alcohol Scale Revised, which showed no statistically significant differences between treatment groups. Using the ePRO device, 82.5% of the patients achieved 75% to 100% of compliance. No discontinuations due to worsening of schizophrenia, serious adverse events, deaths, or seizures were reported during either phase of the study. These findings suggest that there is no evidence of withdrawal symptoms associated with the abrupt discontinuation of pomaglumetad methionil and that an ePRO device can be successfully used in a multicenter schizophrenia trial. PMID:25006819

Biochemical verification of the self-reported smoking status of screened male smokers of the Dutch-Belgian randomized controlled lung cancer screening trial.

PubMed

van der Aalst, Carlijn M; de Koning, Harry J

2016-04-01

Smoking is the main cause of lung cancer, so data linked to smoking behaviour are important in lung cancer screening trials. However, self-reporting data concerning smoking behaviour are mainly used. The aim of this study was to biochemically determine the validity and reliability of self-reported smoking status among smokers at high risk for developing lung cancer participating in the Dutch-Belgian lung cancer screening (NELSON) trial. For this sub study, a random sample of 475 men was selected who were scheduled for the fourth screening round in the NELSON trial. They were asked to complete a short questionnaire to verify the smoking behaviour for the previous seven days and a blood sample was collected to measure the cotinine level. The validity (sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV)) and reliability (Kappa) of the self-reported smoking status compared to the cotinine level (as golden standard) were determined. Both a completed questionnaire as well as a cotinine level were available for 199 (41.9%) participants. Based on these data, Se and Sp were respectively 98% (95%-Confidence Interval (CI): 91-99) and 98% (95%-CI: 93-100). PPV and NPV were 98% and 96% and Kappa was 0.96. In conclusion, the validity of the self-reported smoking status turned out to be reliable amongst men at high risk for developing lung cancer who participate in the NELSON lung cancer screening trial. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

Active versus passive adverse event reporting after pediatric chiropractic manual therapy: study protocol for a cluster randomized controlled trial.

PubMed

Pohlman, Katherine A; Carroll, Linda; Tsuyuki, Ross T; Hartling, Lisa; Vohra, Sunita

2017-12-01

Patient safety performance can be assessed with several systems, including passive and active surveillance. Passive surveillance systems provide opportunity for health care personnel to confidentially and voluntarily report incidents, including adverse events, occurring in their work environment. Active surveillance systems systematically monitor patient encounters to seek detailed information about adverse events that occur in work environments; unlike passive surveillance, active surveillance allows for collection of both numerator (number of adverse events) and denominator (number of patients seen) data. Chiropractic manual therapy is commonly used in both adults and children, yet few studies have been done to evaluate the safety of chiropractic manual therapy for children. In an attempt to evaluate this, this study will compare adverse event reporting in passive versus active surveillance systems after chiropractic manual therapy in the pediatric population. This cluster randomized controlled trial aims to enroll 70 physicians of chiropractic (unit of randomization) to either passive or active surveillance system to report adverse events that occur after treatment for 60 consecutive pediatric (13 years of age and younger) patient visits (unit of analysis). A modified enrollment process with a two-phase consent procedure will be implemented to maintain provider blinding and minimize dropouts. The first phase of consent is for the provider to confirm their interest in a trial investigating the safety of chiropractic manual therapy. The second phase ensures that they understand the specific requirements for the group to which they were randomized. Percentages, incidence estimates, and 95% confidence intervals will be used to describe the count of reported adverse events in each group. The primary outcome will be the number and quality of the adverse event reports in the active versus the passive surveillance group. With 80% power and 5% one-sided significance level, the sample size was calculated to be 35 providers in each group, which includes an 11% lost to follow-up of chiropractors and 20% of patient visits. This study will be the first direct comparison of adverse event reporting using passive versus active surveillance. It is also the largest prospective evaluation of adverse events reported after chiropractic manual therapy in children, identified as a major gap in the academic literature. ClinicalTrials.gov, ID: NCT02268331 . Registered on 10 October 2014.

Carnitine for fatigue in multiple sclerosis.

PubMed

Tejani, Aaron M; Wasdell, Michael; Spiwak, Rae; Rowell, Greg; Nathwani, Shabita

2010-02-17

Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose. A literature search was performed using Cochrane MS Group Trials Register (21 May 2009), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2009, issue 2, MEDLINE (PubMed) (1966-21 May 2009), EMBASE (1974-21 May 2009). Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied. Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults with a clinical diagnosis of fatigue associated with multiple sclerosis were included. Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer however this was not necessary. The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up. The search identified one randomized cross-over trial. In this study patients were exposed to both acetyl L-carnitine (ALCAR(tm)) 2 grams daily and amantadine 200 mg daily in adult patients with relapsing-remitting and secondary progressive MS. The effects of carnitine on fatigue are not clear based on the one included crossover RCT. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55. Mortality, serious adverse events, total adverse events, and quality of life were not reported. There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators.

Warm-needle moxibustion for spasticity after stroke: A systematic review of randomized controlled trials.

PubMed

Yang, Liu; Tan, Jing-Yu; Ma, Haili; Zhao, Hongjia; Lai, Jinghui; Chen, Jin-Xiu; Suen, Lorna K P

2018-03-22

Spasticity is a common post-stroke complication, and it results in substantial deterioration in the quality of life of patients. Although potential positive effects of warm-needle moxibustion on spasticity after stroke have been observed, evidence on its definitive effect remains uncertain. This study aimed to summarize clinical evidence pertaining to therapeutic effects and safety of warm-needle moxibustion for treating spasticity after stroke. Randomized controlled trials were reviewed systematically on the basis of the Cochrane Handbook for Systematic Reviews of Interventions. The report follows the PRISMA statement. Ten electronic databases (PubMed, CENTRAL, EMBASE, AMED, CINAHL, Web of Science, CBM, CNKI, WanFang, and VIP) were explored, and articles were retrieved manually from two Chinese journals (The Journal of Traditional Chinese Medicine and Zhong Guo Zhen Jiu) through retrospective search. Randomized controlled trials with warm-needle moxibustion as treatment intervention for patients with limb spasm after stroke were included in this review. The risk of bias assessment tool was utilized in accordance with Cochrane Handbook 5.1.0. All included studies reported spasm effect as primary outcome. Effect size was estimated using relative risk, standardized mean difference, or mean difference with a corresponding 95% confidence interval. Review Manager 5.3 was utilized for meta-analysis. Twelve randomized controlled trials with certain methodological flaws and risk of bias were included, and they involved a total of 878 participants. Warm-needle moxibustion was found to be superior to electroacupuncture or acupuncture in reducing spasm and in promoting motor function and daily living activities. Pooled results for spasm effect and motor function were significant when warm-needle moxibustion was compared with electroacupuncture or acupuncture. A comparison of daily living activities indicated significant differences between warm-needle moxibustion and electroacupuncture. However, no difference was observed between warm-needle moxibustion and acupuncture. Warm-needle moxibustion may be a promising intervention to reduce limb spasm as well as improve motor function and daily living activities for stroke patients with spasticity. However, evidence was not conclusive. Rigorously designed randomized controlled trials with sample sizes larger than that in the included trials should be conducted for verification. Copyright © 2018 Elsevier Ltd. All rights reserved.

A randomized control trial evaluating fluorescent ink versus dark ink tattoos for breast radiotherapy

PubMed Central

Kirby, Anna M; Lee, Steven F; Bartlett, Freddie; Titmarsh, Kumud; Donovan, Ellen; Griffin, Clare L; Gothard, Lone; Locke, Imogen; McNair, Helen A

2016-01-01

Objective: The purpose of this UK study was to evaluate interfraction reproducibility and body image score when using ultraviolet (UV) tattoos (not visible in ambient lighting) for external references during breast/chest wall radiotherapy and compare with conventional dark ink. Methods: In this non-blinded, single-centre, parallel group, randomized control trial, patients were allocated to receive either conventional dark ink or UV ink tattoos using computer-generated random blocks. Participant assignment was not masked. Systematic (∑) and random (σ) setup errors were determined using electronic portal images. Body image questionnaires were completed at pre-treatment, 1 month and 6 months to determine the impact of tattoo type on body image. The primary end point was to determine that UV tattoo random error (σsetup) was no less accurate than with conventional dark ink tattoos, i.e. <2.8 mm. Results: 46 patients were randomized to receive conventional dark or UV ink tattoos. 45 patients completed treatment (UV: n = 23, dark: n = 22). σsetup for the UV tattoo group was <2.8 mm in the u and v directions (p = 0.001 and p = 0.009, respectively). A larger proportion of patients reported improvement in body image score in the UV tattoo group compared with the dark ink group at 1 month [56% (13/23) vs 14% (3/22), respectively] and 6 months [52% (11/21) vs 38% (8/21), respectively]. Conclusion: UV tattoos were associated with interfraction setup reproducibility comparable with conventional dark ink. Patients reported a more favourable change in body image score up to 6 months following treatment. Advances in knowledge: This study is the first to evaluate UV tattoo external references in a randomized control trial. PMID:27710100

A randomized control trial evaluating fluorescent ink versus dark ink tattoos for breast radiotherapy.

PubMed

Landeg, Steven J; Kirby, Anna M; Lee, Steven F; Bartlett, Freddie; Titmarsh, Kumud; Donovan, Ellen; Griffin, Clare L; Gothard, Lone; Locke, Imogen; McNair, Helen A

2016-12-01

The purpose of this UK study was to evaluate interfraction reproducibility and body image score when using ultraviolet (UV) tattoos (not visible in ambient lighting) for external references during breast/chest wall radiotherapy and compare with conventional dark ink. In this non-blinded, single-centre, parallel group, randomized control trial, patients were allocated to receive either conventional dark ink or UV ink tattoos using computer-generated random blocks. Participant assignment was not masked. Systematic (∑) and random (σ) setup errors were determined using electronic portal images. Body image questionnaires were completed at pre-treatment, 1 month and 6 months to determine the impact of tattoo type on body image. The primary end point was to determine that UV tattoo random error (σ setup ) was no less accurate than with conventional dark ink tattoos, i.e. <2.8 mm. 46 patients were randomized to receive conventional dark or UV ink tattoos. 45 patients completed treatment (UV: n = 23, dark: n = 22). σ setup for the UV tattoo group was <2.8 mm in the u and v directions (p = 0.001 and p = 0.009, respectively). A larger proportion of patients reported improvement in body image score in the UV tattoo group compared with the dark ink group at 1 month [56% (13/23) vs 14% (3/22), respectively] and 6 months [52% (11/21) vs 38% (8/21), respectively]. UV tattoos were associated with interfraction setup reproducibility comparable with conventional dark ink. Patients reported a more favourable change in body image score up to 6 months following treatment. Advances in knowledge: This study is the first to evaluate UV tattoo external references in a randomized control trial.

Investigator-reported efficacy of azelaic acid foam 15% in patients with papulopustular rosacea: secondary efficacy outcomes from a randomized, controlled, double-blind, phase 3 trial.

PubMed

Solomon, James A; Tyring, Stephen; Staedtler, Gerald; Sand, Meike; Nkulikiyinka, Richard; Shakery, Kaweh

2016-09-01

Papulopustular rosacea (PPR) is characterized by centrofacial papules and pustules commonly associated with erythema. To compare investigator-reported efficacy outcomes for azelaic acid (AzA) foam 15% versus vehicle foam in PPR, a randomized, vehicle-controlled, double-blind phase 3 clinical trial was conducted at 48 US sites. Participants received AzA foam or vehicle foam for 12 weeks. Secondary efficacy outcomes included change in inflammatory lesion count (ILC), therapeutic response rate according to investigator global assessment (IGA), and change in erythema rating. This study was comprised of 961 participants with PPR. The results support the therapeutic superiority of AzA foam over vehicle foam.

Early Behavioral Intervention Is Associated with Normalized Brain Activity in Young Children with Autism

ERIC Educational Resources Information Center

Dawson, Geraldine; Jones, Emily J. H.; Merkle, Kristen; Venema, Kaitlin; Lowy, Rachel; Faja, Susan; Kamara, Dana; Murias, Michael; Greenson, Jessica; Winter, Jamie; Smith, Milani; Rogers, Sally J.; Webb, Sara J.

2012-01-01

Objective: A previously published randomized clinical trial indicated that a developmental behavioral intervention, the Early Start Denver Model (ESDM), resulted in gains in IQ, language, and adaptive behavior of children with autism spectrum disorder. This report describes a secondary outcome measurement from this trial, EEG activity. Method:…

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…

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

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.

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.

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

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

Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials123

PubMed Central

Juraschek, Stephen P; Guallar, Eliseo; Appel, Lawrence J

2012-01-01

Background: In observational studies, increased vitamin C intake, vitamin C supplementation, and higher blood concentrations of vitamin C are associated with lower blood pressure (BP). However, evidence for blood pressure–lowering effects of vitamin C in clinical trials is inconsistent. Objective: The objective was to conduct a systematic review and meta-analysis of clinical trials that examined the effects of vitamin C supplementation on BP. Design: We searched Medline, EMBASE, and Central databases from 1966 to 2011. Prespecified inclusion criteria were as follows: 1) use of a randomized controlled trial design; 2) trial reported effects on systolic BP (SBP) or diastolic BP (DBP) or both; 3) trial used oral vitamin C and concurrent control groups; and 4) trial had a minimum duration of 2 wk. BP effects were pooled by random-effects models, with trials weighted by inverse variance. Results: Twenty-nine trials met eligibility criteria for the primary analysis. The median dose was 500 mg/d, the median duration was 8 wk, and trial sizes ranged from 10 to 120 participants. The pooled changes in SBP and DBP were −3.84 mm Hg (95% CI: −5.29, −2.38 mm Hg; P < 0.01) and −1.48 mm Hg (95% CI: −2.86, −0.10 mm Hg; P = 0.04), respectively. In trials in hypertensive participants, corresponding reductions in SBP and DBP were −4.85 mm Hg (P < 0.01) and −1.67 mm Hg (P = 0.17). After the inclusion of 9 trials with imputed BP effects, BP effects were attenuated but remained significant. Conclusions: In short-term trials, vitamin C supplementation reduced SBP and DBP. Long-term trials on the effects of vitamin C supplementation on BP and clinical events are needed. PMID:22492364

MIDAS (Modafinil in Debilitating Fatigue After Stroke): A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.

PubMed

Bivard, Andrew; Lillicrap, Thomas; Krishnamurthy, Venkatesh; Holliday, Elizabeth; Attia, John; Pagram, Heather; Nilsson, Michael; Parsons, Mark; Levi, Christopher R

2017-05-01

This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent in alleviating post-stroke fatigue ≥3 months after stroke. We hypothesized that 200 mg of modafinil daily for 6 weeks would result in reduced symptoms of fatigue compared with placebo. This single-center phase 2 trial used a randomized, double-blind, placebo-controlled, crossover design. The key inclusion criterion was a multidimensional fatigue inventory score of ≥60. Patients were randomized to either modafinil or placebo for 6 weeks of therapy, then after a 1 week washout period swapped treatment arms for a second 6 weeks of therapy. The primary outcome was the multidimensional fatigue inventory; secondary outcomes included the Montreal cognitive assessment, the Depression, Anxiety, and Stress Scale (DASS), and the Stroke-Specific Quality of Life (SSQoL) scale. The multidimensional fatigue inventory is a self-administered questionnaire with a range of 0 to 100. Treatment efficacy was assessed using linear regression by estimating within-person, baseline-adjusted differences in mean outcomes after therapy. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000350527). A total of 232 stroke survivors were screened and 36 were randomized. Participants receiving modafinil reported a significant decrease in fatigue (multidimensional fatigue inventory, -7.38; 95% CI, -21.76 to -2.99; P <0.001) and improved quality of life (SSQoL, 11.81; 95% CI, 2.31 to 21.31; P =0.0148) compared with placebo. Montreal cognitive assessment and DASS were not significantly improved with modafinil therapy during the study period ( P >0.05). Stroke survivors with nonresolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368268. Unique identifier: ACTRN12615000350527. © 2017 The Authors.

Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials.

PubMed

Mahr, Alfred; Golmard, Clara; Pham, Emilie; Iordache, Laura; Deville, Laure; Faure, Pierre

2017-07-01

Scarce studies analyzing adverse event (AE) data from randomized placebo-controlled clinical trials (RPCCTs) of selected illnesses suggested that a substantial proportion of collected AEs are unrelated to the drug taken. This study analyzed the nonspecific AEs occurring with active-drug exposure in RPCCTs for a large range of medical conditions. Randomized placebo-controlled clinical trials published in five prominent medical journals during 2006-2012 were searched. Only trials that evaluated orally or parenterally administered active drugs versus placebo in a head-to-head setting were selected. For AEs reported from ≥10 RPCCTs, Pearson's correlation coefficients (r) were calculated to determine the relationship between AE rates in placebo and active-drug recipients. Random-effects meta-analyses were used to compute proportions of nonspecific AEs, which were truncated at a maximum of 100%, in active-drug recipients. We included 231 trials addressing various medical domains or healthy participants. For the 88 analyzed AE variables, AE rates for placebo and active-drug recipients were in general strongly correlated (r > 0.50) or very strongly correlated (r > 0.80). The pooled proportions of nonspecific AEs for the active-drug recipients were 96.8% (95%CI: 95.5-98.1) for any AEs, 100% (97.9-100) for serious AEs, and 77.7% (72.7-83.2) for drug-related AEs. Results were similar for individual medical domains and healthy participants. The pooled proportion of nonspecificity of 82 system organ class and individual AE types ranged from 38% to 100%. The large proportion of nonspecific AEs reported in active-drug recipients of RPCCTs, including serious and drug-related AEs, highlights the limitations of clinical trial data to determine the tolerability of drugs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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.

Yoga vs. physical therapy vs. education for chronic low back pain in predominantly minority populations: study protocol for a randomized controlled trial.

PubMed

Saper, Robert B; Sherman, Karen J; Delitto, Anthony; Herman, Patricia M; Stevans, Joel; Paris, Ruth; Keosaian, Julia E; Cerrada, Christian J; Lemaster, Chelsey M; Faulkner, Carol; Breuer, Maya; Weinberg, Janice

2014-02-26

Chronic low back pain causes substantial morbidity and cost to society while disproportionately impacting low-income and minority adults. Several randomized controlled trials show yoga is an effective treatment. However, the comparative effectiveness of yoga and physical therapy, a common mainstream treatment for chronic low back pain, is unknown. This is a randomized controlled trial for 320 predominantly low-income minority adults with chronic low back pain, comparing yoga, physical therapy, and education. Inclusion criteria are adults 18-64 years old with non-specific low back pain lasting ≥ 12 weeks and a self-reported average pain intensity of ≥ 4 on a 0-10 scale. Recruitment takes place at Boston Medical Center, an urban academic safety-net hospital and seven federally qualified community health centers located in diverse neighborhoods. The 52-week study has an initial 12-week Treatment Phase where participants are randomized in a 2:2:1 ratio into i) a standardized weekly hatha yoga class supplemented by home practice; ii) a standardized evidence-based exercise therapy protocol adapted from the Treatment Based Classification method, individually delivered by a physical therapist and supplemented by home practice; and iii) education delivered through a self-care book. Co-primary outcome measures are 12-week pain intensity measured on an 11-point numerical rating scale and back-specific function measured using the modified Roland Morris Disability Questionnaire. In the subsequent 40-week Maintenance Phase, yoga participants are re-randomized in a 1:1 ratio to either structured maintenance yoga classes or home practice only. Physical therapy participants are similarly re-randomized to either five booster sessions or home practice only. Education participants continue to follow recommendations of educational materials. We will also assess cost effectiveness from the perspectives of the individual, insurers, and society using claims databases, electronic medical records, self-report cost data, and study records. Qualitative data from interviews will add subjective detail to complement quantitative data. This trial is registered in ClinicalTrials.gov, with the ID number: NCT01343927.

Ethanol for preventing preterm birth in threatened preterm labor.

PubMed

Haas, David M; Morgan, Amanda M; Deans, Samantha J; Schubert, Frank P

2015-11-05

Preterm birth is the leading cause of death and disability in newborns worldwide. A wide variety of tocolytic agents have been utilized to delay birth for women in preterm labor. One of the earliest tocolytics utilized for this purpose was ethanol infusion, although this is not generally used in current practice due to safety concerns for both the mother and her baby. To determine the efficacy of ethanol in stopping preterm labor, preventing preterm birth, and the impact of ethanol on neonatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies. We included randomized and quasi-randomized studies. Cluster-randomized trials and cross-over design trials were not eligible for inclusion. We only included studies published in abstract form if there was enough information on methods and relevant outcomes. Trials were included if they compared ethanol infusion to stop preterm labor versus placebo/control or versus other tocolytic drugs. At least two review authors independently assessed studies for inclusion and risk of bias. At least two review authors independently extracted data. Data were checked for accuracy. Twelve trials involving 1586 women met inclusion criteria for this review. One trial did not report on the outcomes of interest in this review.Risk of bias of included studies: The included studies generally were of low quality based on inadequate reporting of methodology. Only three trials had low risk of bias for random sequence generation and one had low risk of bias for allocation concealment and participant blinding. Most studies were either high risk of bias or uncertain in these key areas. Comparison 1: Ethanol versus placebo/control (two trials, 77 women) Compared to controls receiving pain medications and dextrose solution, ethanol did not improve any of the primary outcomes: birth < 48 hours after trial entry (one trial, 35 women; risk ratio (RR) 0.93, 95% confidence interval (CI) 0.43 to 2.00), or neonatal mortality (one trial, 35 women; RR 1.06, 95% CI 0.31 to 3.58). Serious maternal adverse events and perinatal mortality were not reported by either of the two trials in this comparison. Maternal adverse events (overall) were not reported but one trial (42 women) reported that there were no maternal adverse events that required stopping or changing drug) in either group. One trial did report delay until delivery but this outcome was reported as a median with no mention of the standard deviation (median 19 days in ethanol group versus "less than 1" day in the glucose/water group). There were no differences in any secondary outcomes reported: preterm birth < 34 weeks or < 37 weeks; serious infant outcome; fetal alcohol syndrome/fetal alcohol spectrum disorder; or small-for-gestational age. Comparison 2: Ethanol versus other tocolytic (betamimetics) (nine trials, 1438 women) Compared to betamimetics (the only tocolytic used as a comparator in these studies), ethanol was associated with no clear difference in the rate of birth < 48 hours after trial entry (two trials, 130 women; average RR 1.12, 95% CI 0.53 to 2.37, Tau² = 0.19, I² = 59%), similar rates of perinatal mortality (six trials, 698 women; RR1.20, 95% CI 0.78 to 1.84), higher rates of neonatal mortality (eight trials, 1238 women; RR 1.43, 95% CI 1.02 to 2.02), higher rates of preterm birth < 34 weeks (two trials, 599 women; RR 1.56, 95% CI 1.11 to 2.19), higher rates of neonatal respiratory distress syndrome (three trials, 823 women; RR 1.76, 95% CI 1.33 to 2.33), and higher rates of low birthweight babies < 2500 g (five trials, 834 women; RR 1.30, 95% CI 1.09 to 1.54). These outcomes are likely all related to the lower incidence of preterm birth seen with other tocolytics, which for all these comparisons were betamimetics. Serious maternal adverse events were not reported in any of the nine trial reports. However, ethanol had a trend towards a lower rate of maternal adverse events requiring stopping or changing the drug (three trials, 214 women; RR 0.25, 95% CI 0.06 to 0.97). There were no differences in other secondary outcomes of preterm birth < 37 weeks, number of days delivery was delayed, or overall maternal adverse events.Planned sensitivity analysis, excluding quasi-randomized trials did not substantially change the results of the primary outcome analyses with the exception of neonatal mortality which no longer showed a clear difference between the ethanol and other tocolytic groups (3 trials, 330 women; RR 1.49, 95% CI 0.82 to 2.72). This review is based on evidence from twelve studies which were mostly low quality. There is no evidence that to suggest that ethanol is an effective tocolytic compared to placebo. There is some evidence that ethanol may be better tolerated than other tocolytics (in this case betamimetics), but this result is based on few studies and small sample size and therefore should be interpreted with caution. Ethanol appears to be inferior to betamimetics for preventing preterm birth in threatened preterm labor.Ethanol is generally no longer used in current practice due to safety concerns for the mother and her baby. There is no need for new studies to evaluate the use of ethanol for preventing preterm birth in threatened preterm labour. However, it would be useful for long-term follow-up studies on the babies born to mothers from the existing studies in order to assess the risk of long-term neurodevelopmental status.

Designing a valid randomized pragmatic primary care implementation trial: the my own health report (MOHR) project.

PubMed

Krist, Alex H; Glenn, Beth A; Glasgow, Russell E; Balasubramanian, Bijal A; Chambers, David A; Fernandez, Maria E; Heurtin-Roberts, Suzanne; Kessler, Rodger; Ory, Marcia G; Phillips, Siobhan M; Ritzwoller, Debra P; Roby, Dylan H; Rodriguez, Hector P; Sabo, Roy T; Sheinfeld Gorin, Sherri N; Stange, Kurt C

2013-06-25

There is a pressing need for greater attention to patient-centered health behavior and psychosocial issues in primary care, and for practical tools, study designs and results of clinical and policy relevance. Our goal is to design a scientifically rigorous and valid pragmatic trial to test whether primary care practices can systematically implement the collection of patient-reported information and provide patients needed advice, goal setting, and counseling in response. This manuscript reports on the iterative design of the My Own Health Report (MOHR) study, a cluster randomized delayed intervention trial. Nine pairs of diverse primary care practices will be randomized to early or delayed intervention four months later. The intervention consists of fielding the MOHR assessment--addresses 10 domains of health behaviors and psychosocial issues--and subsequent provision of needed counseling and support for patients presenting for wellness or chronic care. As a pragmatic participatory trial, stakeholder groups including practice partners and patients have been engaged throughout the study design to account for local resources and characteristics. Participatory tasks include identifying MOHR assessment content, refining the study design, providing input on outcomes measures, and designing the implementation workflow. Study outcomes include the intervention reach (percent of patients offered and completing the MOHR assessment), effectiveness (patients reporting being asked about topics, setting change goals, and receiving assistance in early versus delayed intervention practices), contextual factors influencing outcomes, and intervention costs. The MOHR study shows how a participatory design can be used to promote the consistent collection and use of patient-reported health behavior and psychosocial assessments in a broad range of primary care settings. While pragmatic in nature, the study design will allow valid comparisons to answer the posed research question, and findings will be broadly generalizable to a range of primary care settings. Per the pragmatic explanatory continuum indicator summary (PRECIS) framework, the study design is substantially more pragmatic than other published trials. The methods and findings should be of interest to researchers, practitioners, and policy makers attempting to make healthcare more patient-centered and relevant. Clinicaltrials.gov: NCT01825746.

Accounting for center in the Early External Cephalic Version trials: an empirical comparison of statistical methods to adjust for center in a multicenter trial with binary outcomes.

PubMed

Reitsma, Angela; Chu, Rong; Thorpe, Julia; McDonald, Sarah; Thabane, Lehana; Hutton, Eileen

2014-09-26

Clustering of outcomes at centers involved in multicenter trials is a type of center effect. The Consolidated Standards of Reporting Trials Statement recommends that multicenter randomized controlled trials (RCTs) should account for center effects in their analysis, however most do not. The Early External Cephalic Version (EECV) trials published in 2003 and 2011 stratified by center at randomization, but did not account for center in the analyses, and due to the nature of the intervention and number of centers, may have been prone to center effects. Using data from the EECV trials, we undertook an empirical study to compare various statistical approaches to account for center effect while estimating the impact of external cephalic version timing (early or delayed) on the outcomes of cesarean section, preterm birth, and non-cephalic presentation at the time of birth. The data from the EECV pilot trial and the EECV2 trial were merged into one dataset. Fisher's exact method was used to test the overall effect of external cephalic version timing unadjusted for center effects. Seven statistical models that accounted for center effects were applied to the data. The models included: i) the Mantel-Haenszel test, ii) logistic regression with fixed center effect and fixed treatment effect, iii) center-size weighted and iv) un-weighted logistic regression with fixed center effect and fixed treatment-by-center interaction, iv) logistic regression with random center effect and fixed treatment effect, v) logistic regression with random center effect and random treatment-by-center interaction, and vi) generalized estimating equations. For each of the three outcomes of interest approaches to account for center effect did not alter the overall findings of the trial. The results were similar for the majority of the methods used to adjust for center, illustrating the robustness of the findings. Despite literature that suggests center effect can change the estimate of effect in multicenter trials, this empirical study does not show a difference in the outcomes of the EECV trials when accounting for center effect. The EECV2 trial was registered on 30 July 30 2005 with Current Controlled Trials: ISRCTN 56498577.

Design of a cluster-randomized minority recruitment trial: RECRUIT.

PubMed

Tilley, Barbara C; Mainous, Arch G; Smith, Daniel W; McKee, M Diane; Amorrortu, Rossybelle P; Alvidrez, Jennifer; Diaz, Vanessa; Ford, Marvella E; Fernandez, Maria E; Hauser, Robert A; Singer, Carlos; Landa, Veronica; Trevino, Aron; DeSantis, Stacia M; Zhang, Yefei; Daniels, Elvan; Tabor, Derrick; Vernon, Sally W

2017-06-01

Racial/ethnic minority groups remain underrepresented in clinical trials. Many strategies to increase minority recruitment focus on minority communities and emphasize common diseases such as hypertension. Scant literature focuses on minority recruitment to trials of less common conditions, often conducted in specialty clinics and dependent on physician referrals. We identified trust/mistrust of specialist physician investigators and institutions conducting medical research and consequent participant reluctance to participate in clinical trials as key-shared barriers across racial/ethnic groups. We developed a trust-based continuous quality improvement intervention to build trust between specialist physician investigators and community minority-serving physicians and ultimately potential trial participants. To avoid the inherent biases of non-randomized studies, we evaluated the intervention in the national Randomized Recruitment Intervention Trial (RECRUIT). This report presents the design of RECRUIT. Specialty clinic follow-up continues through April 2017. We hypothesized that specialist physician investigators and coordinators trained in the trust-based continuous quality improvement intervention would enroll a greater proportion of minority participants in their specialty clinics than specialist physician investigators in control specialty clinics. Specialty clinic was the unit of randomization. Using continuous quality improvement, the specialist physician investigators and coordinators tailored recruitment approaches to their specialty clinic characteristics and populations. Primary analyses were adjusted for clustering by specialty clinic within parent trial and matching covariates. RECRUIT was implemented in four multi-site clinical trials (parent trials) supported by three National Institutes of Health institutes and included 50 associated specialty clinics from these parent trials. Using current data, we have 88% power or greater to detect a 0.15 or greater difference from the currently observed control proportion adjusting for clustering. We detected no differences in baseline matching criteria between intervention and control specialty clinics (all p values > 0.17). RECRUIT was the first multi-site randomized control trial to examine the effectiveness of a trust-based continuous quality improvement intervention to increase minority recruitment into clinical trials. RECRUIT's innovations included its focus on building trust between specialist investigators and minority-serving physicians, the use of continuous quality improvement to tailor the intervention to each specialty clinic's specific racial/ethnic populations and barriers to minority recruitment, and the use of specialty clinics from more than one parent multi-site trial to increase generalizability. The effectiveness of the RECRUIT intervention will be determined after the completion of trial data collection and planned analyses.

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.

Serious adverse events in randomized psychosocial treatment studies: Safety or Arbitrary Edicts?

PubMed Central

Petry, Nancy M.; Roll, John M.; Rounsaville, Bruce J.; Ball, Samuel A.; Stitzer, Maxine; Peirce, Jessica M.; Blaine, Jack; Kirby, Kimberly C.; McCarty, Dennis; Carroll, Kathleen M.

2009-01-01

Human subjects protection policies developed for pharmaceutical trials are now being widely applied to psychosocial intervention studies. This study examined occurrences of serious adverse events (SAEs) reported in multicenter psychosocial trials of the National Institute on Drug Abuse Clinical Trials Network. Substance abusing participants (N=1,687) were randomized to standard care or standard care plus either contingency management or motivational enhancement. Twelve percent of participants experienced one or more SAEs during the 27,198 person-weeks of follow-up. Of the 260 SAEs recorded, none were judged by the Data Safety Monitoring Board to be study related, and there were no significant differences between experimental and control conditions in SAE incidence rates. These data underscore the need to reconsider the rationale behind, and appropriate methods for, monitoring safety during psychosocial therapy trials. PMID:19045975

Extracorporeal shock wave treatment for chronic plantar fasciitis (heel pain).

PubMed

Ho, C

2007-01-01

(1) Electrohydraulic, electromagnetic, or piezoelectric devices are used to translate energy into acoustic waves during extracorporeal shock wave treatment (ESWT) for chronic plantar fasciitis (or heel pain). These waves may help to accelerate the healing process via an unknown mechanism. (2) ESWT, which is performed as an outpatient procedure, is intended to alleviate the pain due to chronic plantar fasciitis. (3) Results from randomized controlled trials have been conflicting. Six trials reported data that favour ESWT over placebo or conservative treatment for efficacy outcomes, while three trials showed no significant difference between the ESWT group and the placebo group. (4) The lack of convergent findings from randomized trials of ESWT for chronic plantar fasciitis suggests uncertainty about its effectiveness. The evidence reviewed in this bulletin does not support the use of this technology for this condition.

Executive summary of the joint position paper on renal denervation of the Cardiovascular and Interventional Radiological Society of Europe and the European Society of Hypertension.

PubMed

Moss, Jonathan G; Belli, Anna-Maria; Coca, Antonio; Lee, Michael; Mancia, Giuseppe; Peregrin, Jan H; Redon, Josep; Reekers, Jim A; Tsioufis, Costas; Vorwerk, Dierk; Schmieder, Roland E

2016-12-01

Renal denervation (RDN) was reported as a novel exciting treatment for resistant hypertension in 2009. An initial randomized trial supported its efficacy and the technique gained rapid acceptance across the globe. However, a subsequent large blinded, sham arm randomized trial conducted in the USA (to gain Food and Drug Administration approval) failed to achieve its primary efficacy end point in reducing office blood pressure at 6 months. Published in 2014 this trial received both widespread praise and criticism. RDN has effectively stopped out with clinical trials pending further evidence. This joint consensus document representing the European Society of Hypertension and the Cardiovascular and Radiological Society of Europe attempts to distill the current evidence and provide future direction and guidance.

Randomization in clinical trials in orthodontics: its significance in research design and methods to achieve it.

PubMed

Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2011-12-01

Randomization is a key step in reducing selection bias during the treatment allocation phase in randomized clinical trials. The process of randomization follows specific steps, which include generation of the randomization list, allocation concealment, and implementation of randomization. The phenomenon in the dental and orthodontic literature of characterizing treatment allocation as random is frequent; however, often the randomization procedures followed are not appropriate. Randomization methods assign, at random, treatment to the trial arms without foreknowledge of allocation by either the participants or the investigators thus reducing selection bias. Randomization entails generation of random allocation, allocation concealment, and the actual methodology of implementing treatment allocation randomly and unpredictably. Most popular randomization methods include some form of restricted and/or stratified randomization. This article introduces the reasons, which make randomization an integral part of solid clinical trial methodology, and presents the main randomization schemes applicable to clinical trials in orthodontics.

Comparison of Registered and Reported Outcomes in Randomized Clinical Trials Published in Anesthesiology Journals.

PubMed

Jones, Philip M; Chow, Jeffrey T Y; Arango, Miguel F; Fridfinnson, Jason A; Gai, Nan; Lam, Kevin; Turkstra, Timothy P

2017-10-01

Randomized clinical trials (RCTs) provide high-quality evidence for clinical decision-making. Trial registration is one of the many tools used to improve the reporting of RCTs by reducing publication bias and selective outcome reporting bias. The purpose of our study is to examine whether RCTs published in the top 6 general anesthesiology journals were adequately registered and whether the reported primary and secondary outcomes corresponded to the originally registered outcomes. Following a prespecified protocol, an electronic database was used to systematically screen and extract data from RCTs published in the top 6 general anesthesiology journals by impact factor (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anesthesia, and European Journal of Anaesthesiology) during the years 2007, 2010, 2013, and 2015. A manual search of each journal's Table of Contents was performed (in duplicate) to identify eligible RCTs. An adequately registered trial was defined as being registered in a publicly available trials registry before the first patient being enrolled with an unambiguously defined primary outcome. For adequately registered trials, the outcomes registered in the trial registry were compared with the outcomes reported in the article, with outcome discrepancies documented and analyzed by the type of discrepancy. During the 4 years studied, there were 860 RCTs identified, with 102 RCTs determined to be adequately registered (12%). The proportion of adequately registered trials increased over time, with 38% of RCTs being adequately registered in 2015. The most common reason in 2015 for inadequate registration was registering the RCT after the first patient had already been enrolled. Among adequately registered trials, 92% had at least 1 primary or secondary outcome discrepancy. In 2015, 42% of RCTs had at least 1 primary outcome discrepancy, while 90% of RCTs had at least 1 secondary outcome discrepancy. Despite trial registration being an accepted best practice, RCTs published in anesthesiology journals have a high rate of inadequate registration. While mandating trial registration has increased the proportion of adequately registered trials over time, there is still an unacceptably high proportion of inadequately registered RCTs. Among adequately registered trials, there are high rates of discrepancies between registered and reported outcomes, suggesting a need to compare a published RCT with its trial registry entry to be able to fully assess the quality of the study. If clinicians base their decisions on evidence distorted by primary outcome switching, patient care could be negatively affected.

Influence of therapist competence and quantity of cognitive behavioural therapy on suicidal behaviour and inpatient hospitalisation in a randomised controlled trial in borderline personality disorder: Further analyses of treatment effects in the BOSCOT study

PubMed Central

Norrie, John; Davidson, Kate; Tata, Philip; Gumley, Andrew

2013-01-01

Objectives We investigated the treatment effects reported from a high-quality randomized controlled trial of cognitive behavioural therapy (CBT) for 106 people with borderline personality disorder attending community-based clinics in the UK National Health Service – the BOSCOT trial. Specifically, we examined whether the amount of therapy and therapist competence had an impact on our primary outcome, the number of suicidal acts†, using instrumental variables regression modelling. Design Randomized controlled trial. Participants from across three sites (London, Glasgow, and Ayrshire/Arran) were randomized equally to CBT for personality disorders (CBTpd) plus Treatment as Usual or to Treatment as Usual. Treatment as Usual varied between sites and individuals, but was consistent with routine treatment in the UK National Health Service at the time. CBTpd comprised an average 16 sessions (range 0–35) over 12 months. Method We used instrumental variable regression modelling to estimate the impact of quantity and quality of therapy received (recording activities and behaviours that took place after randomization) on number of suicidal acts and inpatient psychiatric hospitalization. Results A total of 101 participants provided full outcome data at 2 years post randomization. The previously reported intention-to-treat (ITT) results showed on average a reduction of 0.91 (95% confidence interval 0.15–1.67) suicidal acts over 2 years for those randomized to CBT. By incorporating the influence of quantity of therapy and therapist competence, we show that this estimate of the effect of CBTpd could be approximately two to three times greater for those receiving the right amount of therapy from a competent therapist. Conclusions Trials should routinely control for and collect data on both quantity of therapy and therapist competence, which can be used, via instrumental variable regression modelling, to estimate treatment effects for optimal delivery of therapy. Such estimates complement rather than replace the ITT results, which are properly the principal analysis results from such trials. Practitioner points Assessing the impact of the quantity and quality of therapy (competence of therapists) is complex. More competent therapists, trained in CBTpd, may significantly reduce the number of suicidal act in patients with borderline personality disorder. PMID:23420622

The multimedia computer for office-based patient education: a systematic review.

PubMed

Wofford, James L; Smith, Edward D; Miller, David P

2005-11-01

Use of the multimedia computer for education is widespread in schools and businesses, and yet computer-assisted patient education is rare. In order to explore the potential use of computer-assisted patient education in the office setting, we performed a systematic review of randomized controlled trials (search date April 2004 using MEDLINE and Cochrane databases). Of the 26 trials identified, outcome measures included clinical indicators (12/26, 46.1%), knowledge retention (12/26, 46.1%), health attitudes (15/26, 57.7%), level of shared decision-making (5/26, 19.2%), health services utilization (4/26, 17.6%), and costs (5/26, 19.2%), respectively. Four trials targeted patients with breast cancer, but the clinical issues were otherwise diverse. Reporting of the testing of randomization (76.9%) and appropriate analysis of main effect variables (70.6%) were more common than reporting of a reliable randomization process (35.3%), blinding of outcomes assessment (17.6%), or sample size definition (29.4%). We concluded that the potential for improving the efficiency of the office through computer-assisted patient education has been demonstrated, but better proof of the impact on clinical outcomes is warranted before this strategy is accepted in the office setting.

Randomized controlled trials and neuro-oncology: should alternative designs be considered?

PubMed

Mansouri, Alireza; Shin, Samuel; Cooper, Benjamin; Srivastava, Archita; Bhandari, Mohit; Kondziolka, Douglas

2015-09-01

Deficiencies in design and reporting of randomized controlled trials (RCTs) hinders interpretability and critical appraisal. The reporting quality of recent RCTs in neuro-oncology was analyzed to assess adequacy of design and reporting. The MEDLINE and EMBASE databases were searched to identify non-surgical RCTs (years 2005-2014, inclusive). The CONSORT and Jadad scales were used to assess the quality of design/reporting. Studies published in 2005-2010 were compared as a cohort against studies published in 2011-2014, in terms of general characteristics and reporting quality. A PRECIS-based scale was used to designate studies on the pragmatic-explanatory continuum. Spearman's test was used to assess correlations. Regression analysis was used to assess associations. Overall 68 RCTs were identified. Studies were often chemotherapy-based (n = 41 studies) focusing upon high grade gliomas (46 %) and metastases (41 %) as the top pathologies. Multi-center trials (71 %) were frequent. The overall median CONSORT and Jadad scores were 34.5 (maximum 44) and 2 (maximum 5), respectively; these scores were similar in radiation and chemotherapy-based trials. Major areas of deficiency pertained to allocation concealment, implementation of methods, and blinding whereby less than 20 % of articles fulfilled all criteria. Description of intervention, random sequence generation, and the details regarding recruitment were also deficient; less than 50 % of studies fulfilled all criteria. Description of sample size calculations and blinding improved in later published cohorts. Journal impact factor was significantly associated with higher quality (p = 0.04). Large academic consortia, multi-center designs, ITT analysis, collaboration with biostatisticians, larger sample sizes, and studies with pragmatic objectives were more likely to achieve positive primary outcomes on univariate analysis; none of these variables were significant on multivariate analysis. Deficiencies in the quality of design/reporting of RCTs in neuro-oncology persist. Quality improvement is necessary. Consideration of alternative strategies should be considered.

The role of ECT in posttraumatic stress disorder: A systematic review.

PubMed

Youssef, Nagy A; McCall, W Vaughn; Andrade, Chittaranjan

2017-02-01

Posttraumatic stress disorder (PTSD) is associated with a high burden of disability and mortality and frequently is treatment resistant. There is little to offer patients who are not responding to standard interventions. Thus, the objective of this report is to systematically review human data on whether electroconvulsive therapy (ECT) is effective in PTSD. We performed a systematic literature review from 1958 through August 2016 for clinical studies and case reports published in English examining the efficacy of ECT in improving PTSD symptoms. The literature search generated 3 retrospective studies, 1 prospective uncontrolled clinical trial, and 5 case reports. It is not clear, given the small sample size and lack of a large randomized trial, whether favorable outcomes were attributed to improvement in depression (as opposed to core PTSD symptoms). Current efficacy data do not separate conclusively the effects of ECT on PTSD symptoms from those on depression. Randomized controlled trials are necessary to examine the use of ECT in medication-refractory PTSD patients with and without comorbid depression. Subsequent studies may address response in PTSD subtypes, and the use of novel techniques, such as memory reactivation, before ECT.

Gameplay as a Source of Intrinsic Motivation in a Randomized Controlled Trial of Auditory Training for Tinnitus

PubMed Central

Hoare, Derek J.; Van Labeke, Nicolas; McCormack, Abby; Sereda, Magdalena; Smith, Sandra; Taher, Hala Al; Kowalkowski, Victoria L.; Sharples, Mike; Hall, Deborah A.

2014-01-01

Background Previous studies of frequency discrimination training (FDT) for tinnitus used repetitive task-based training programmes relying on extrinsic factors to motivate participation. Studies reported limited improvement in tinnitus symptoms. Purpose To evaluate FDT exploiting intrinsic motivations by integrating training with computer-gameplay. Methods Sixty participants were randomly assigned to train on either a conventional task-based training, or one of two interactive game-based training platforms over six weeks. Outcomes included assessment of motivation, tinnitus handicap, and performance on tests of attention. Results Participants reported greater intrinsic motivation to train on the interactive game-based platforms, yet compliance of all three groups was similar (∼70%) and changes in self-reported tinnitus severity were not significant. There was no difference between groups in terms of change in tinnitus severity or performance on measures of attention. Conclusion FDT can be integrated within an intrinsically motivating game. Whilst this may improve participant experience, in this instance it did not translate to additional compliance or therapeutic benefit. Trial Registration ClinicalTrials.gov NCT02095262 PMID:25215617

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.

Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trials.

PubMed

Ezekowitz, Justin A; McAlister, Finlay A

2009-02-01

Aldosterone blockade has been used to treat acute myocardial infarction (MI) and chronic heart failure. The aim of this study is to summarize the evidence on the efficacy of spironolactone (SP), eplerenone (EP), or canrenoate (CAN) in patients with left ventricular dysfunction. A search of multiple electronic databases until June 2008 was supplemented by hand searches of reference lists of included studies and review articles, meeting abstracts, FDA reports, and contact with study authors and drug manufacturers. Studies were eligible for inclusion if they included patients with left ventricular systolic or diastolic dysfunction, treatment with SP, EP, or CAN vs. control, and reported clinical outcomes. Nineteen randomized controlled trials (four in acute MI and 15 in heart failure, n = 10 807 patients) were included -- 14 of SP, three of EP, and three of CAN. Analysis was performed using relative risks (RRs) with 95% confidence intervals (CIs) and a random effects model with statistical heterogeneity assessed by I(2). Aldosterone blockade reduced all-cause mortality by 20% (RR 0.80, 95% CI 0.74-0.87). All-cause mortality was reduced in both heart failure (RR = 0.75, 95% CI 0.67-0.84) and post-MI (RR 0.85, 95% CI 0.76-0.95) patients. Only nine trials reported hospitalizations, and the RR reduction was 23% (RR 0.77, 95% CI 0.68-0.87), although 98% of the outcomes came from two trials. Ejection fraction (EF) improved in the seven heart failure trials, which assessed this outcome (weighted mean difference 3.1%, 95% CI 1.6-4.5). We demonstrated a 20% reduction in all-cause mortality with the use of aldosterone blockade in a clinically heterogeneous group of clinical trial participants with heart failure and post-MI. In addition, we found a 3.1% improvement in EF. Further study in those with less severe symptoms or preserved systolic function is warranted.

A benefit-finding intervention for family caregivers of persons with Alzheimer disease: study protocol of a randomized controlled trial

PubMed Central

2012-01-01

Background Caregivers of relatives with Alzheimer’s disease are highly stressed and at risk for physical and psychiatric conditions. Interventions are usually focused on providing caregivers with knowledge of dementia, skills, and/or support, to help them cope with the stress. This model, though true to a certain extent, ignores how caregiver stress is construed in the first place. Besides burden, caregivers also report rewards, uplifts, and gains, such as a sense of purpose and personal growth. Finding benefits through positive reappraisal may offset the effect of caregiving on caregiver outcomes. Design Two randomized controlled trials are planned. They are essentially the same except that Trial 1 is a cluster trial (that is, randomization based on groups of participants) whereas in Trial 2, randomization is based on individuals. Participants are randomized into three groups - benefit finding, psychoeducation, and simplified psychoeducation. Participants in each group receive a total of approximately 12 hours of training either in group or individually at home. Booster sessions are provided at around 14 months after the initial treatment. The primary outcomes are caregiver stress (subjective burden, role overload, and cortisol), perceived benefits, subjective health, psychological well-being, and depression. The secondary outcomes are caregiver coping, and behavioral problems and functional impairment of the care-recipient. Outcome measures are obtained at baseline, post-treatment (2 months), and 6, 12, 18 and 30 months. Discussion The emphasis on benefits, rather than losses and difficulties, provides a new dimension to the way interventions for caregivers can be conceptualized and delivered. By focusing on the positive, caregivers may be empowered to sustain caregiving efforts in the long term despite the day-to-day challenges. The two parallel trials will provide an assessment of whether the effectiveness of the intervention depends on the mode of delivery. Trial registration Chinese Clinical Trial Registry (http://www.chictr.org/en/) identifier number ChiCTR-TRC-10000881. PMID:22747914

Design paper: the DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of aerobic versus non-aerobic versus relaxation training for patients with light to moderate depression.

PubMed

Krogh, Jesper; Petersen, Lone; Timmermann, Michael; Saltin, Bengt; Nordentoft, Merete

2007-01-01

In western countries, the yearly incidence of depression is estimated to be 3-5% and the lifetime prevalence is 17%. In patient populations with chronic diseases the point prevalence may be 20%. Depression is associated with increased risk for various conditions such as osteoporoses, cardiovascular diseases, and dementia. WHO stated in 2000 that depression was the fourth leading cause of disease burden in terms of disability. In 2000 the cost of depression in the US was estimated to 83 billion dollars. A predominance of trials suggests that physical exercise has a positive effect on depressive symptoms. However, a meta-analysis from 2001 stated: "The effectiveness of exercise in reducing symptoms of depression cannot be determined because of a lack of good quality research on clinical populations with adequate follow-up." The major objective for this randomized trial is to compare the effect of non-aerobic, aerobic, and relaxation training on depressive symptoms using the blindly assessed Hamilton depression scale (HAM-D(17)) as primary outcome. The secondary outcome is the effect of the intervention on working status (i.e., lost days from work, employed/unemployed) and the tertiary outcomes consist of biological responses. The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are recruited through general practitioners and psychiatrist and randomized to three different interventions: 1) non-aerobic, -- progressive resistance training, 2) aerobic training, -- cardio respiratory fitness, and 3) relaxation training with minimal impact on strength or cardio respiratory fitness. Training for all three groups takes place twice a week for 4 months. Evaluation of patients' symptoms takes place four and 12 months after inclusion. The trial is designed to include 45 patients in each group. Statistical analysis will be done as intention to treat (all randomized patients). Results from the DEMO trial will be reported according to the CONSORT guidelines in 2008-2009.

High flow nasal cannula oxygen versus noninvasive ventilation in adult acute respiratory failure: a systematic review of randomized-controlled trials.

PubMed

Beng Leong, Lim; Wei Ming, Ng; Wei Feng, Lee

2018-06-19

We reviewed the use of noninvasive ventilation (NIV) versus high flow nasal cannula (HFNC) oxygen in adult acute respiratory failure (ARF). We searched major databases and included randomized trials comparing at least NIV with HFNC or NIV+HFNC with NIV in ARF. Primary outcomes included intubation/re-intubation rates. Secondary outcomes were ICU mortality and morbidities. Five trials were included; three compared HFNC with NIV, one compared HFNC, NIV and oxygen whereas one compared HFNC+NIV with NIV. Patients had hypoxaemic ARF (PaO2/FiO2≤300 mmHg). Heterogeneity prevented result pooling. Three and two studies had superiority and noninferiority design, respectively. Patients were postcardiothoracic surgery, mixed medical/surgical patients and those with pneumonia. Two trials were conducted after extubation, two before intubation and one during intubation. Three trials reported intubation/re-intubation rates as the primary outcomes. The other two trials reported the lowest peripheral capillary oxygen saturation readings during bronchoscopy or intubation. In the former three trials, the odds ratio for intubation/re-intubation rates between HFNC versus the NIV group ranged from 0.80 (95% confidence interval: 0.54-1.19) to 1.65 (95% confidence interval: 0.96-2.84). In the latter two trials, only one reported a difference in the lowest peripheral capillary oxygen saturation between NIV+HFNC versus the NIV group during intubation [100% (interquartile range: 95-100) vs. 96% (interquartile range: 92-99); P=0.029]. The secondary outcomes included differences in ICU mortality and patient tolerability, favouring HFNC, were conflicting, but highlighted future research directions. These include patients with hypercapneic ARF, more severe hypoxaemia (PaO2/FiO2≤200 mmHg), a superiority design, an oxygen arm and patient-centred outcomes.

Implantable cardioverter defibrillators for primary prevention in patients with nonischemic cardiomyopathy: A systematic review and meta-analysis.

PubMed

Akel, Tamer; Lafferty, James

2017-06-01

Implantable cardioverter defibrillators (ICDs) have proved their favorable outcomes on survival in selected patients with cardiomyopathy. Although previous meta-analyses have shown benefit for their use in primary prevention, the evidence remains less robust for patients with nonischemic cardiomyopathy (NICM) in comparison to patients with coronary artery disease (CAD). To evaluate the effect of ICD therapy on reducing all-cause mortality and sudden cardiac death (SCD) in patients with NICM. PubMed (1993-2016), the Cochrane Central Register of Controlled Trials (2000-2016), reference lists of relevant articles, and previous meta-analyses. Search terms included defibrillator, heart failure, cardiomyopathy, randomized controlled trials, and clinical trials. Eligible trials were randomized controlled trials with at least an arm of ICD, an arm of medical therapy and enrolled some patients with NICM. The primary endpoint in the trials should include all-cause mortality or mortality from SCD. Hazard ratios (HRs) for all-cause mortality and mortality from SCD were either extracted or calculated along with their standard errors. Of the 1047 abstracts retained by the initial screen, eight randomized controlled trials were identified. Five of these trials reported relevant data regarding patients with NICM and were subsequently included in this meta-analysis. Pooled analysis of HRs suggested a statistically significant reduction in all-cause mortality among a total of 2573 patients randomized to ICD vs medical therapy (HR 0.80; 95% CI, 0.67-0.96; P=.02). Pooled analysis of HRs for mortality from SCD was also statistically significant (n=1677) (HR 0.51; 95% CI, 0.34-0.76; P=.001). ICD implantation is beneficial in terms of all-cause mortality and mortality from SCD in certain subgroups of patients with NICM. © 2017 John Wiley & Sons Ltd.

Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials.

PubMed

Coca, Steven G; Zabetian, Azadeh; Ferket, Bart S; Zhou, Jing; Testani, Jeffrey M; Garg, Amit X; Parikh, Chirag R

2016-08-01

Observational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short-term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between-group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo-controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials. Copyright © 2016 by the American Society of Nephrology.

Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation.

PubMed

Hart, Robert G; Pearce, Lesly A; Aguilar, Maria I

2007-06-19

Atrial fibrillation is a strong independent risk factor for stroke. To characterize the efficacy and safety of antithrombotic agents for stroke prevention in patients who have atrial fibrillation, adding 13 recent randomized trials to a previous meta-analysis. Randomized trials identified by using the Cochrane Stroke Group search strategy, 1966 to March 2007, unrestricted by language. All published randomized trials with a mean follow-up of 3 months or longer that tested antithrombotic agents in patients who have nonvalvular atrial fibrillation. Two coauthors independently extracted information regarding interventions; participants; and occurrences of ischemic and hemorrhagic stroke, major extracranial bleeding, and death. Twenty-nine trials included 28,044 participants (mean age, 71 years; mean follow-up, 1.5 years). Compared with the control, adjusted-dose warfarin (6 trials, 2900 participants) and antiplatelet agents (8 trials, 4876 participants) reduced stroke by 64% (95% CI, 49% to 74%) and 22% (CI, 6% to 35%), respectively. Adjusted-dose warfarin was substantially more efficacious than antiplatelet therapy (relative risk reduction, 39% [CI, 22% to 52%]) (12 trials, 12 963 participants). Other randomized comparisons were inconclusive. Absolute increases in major extracranial hemorrhage were small (< or =0.3% per year) on the basis of meta-analysis. Methodological features and quality varied substantially and often were incompletely reported. Adjusted-dose warfarin and antiplatelet agents reduce stroke by approximately 60% and by approximately 20%, respectively, in patients who have atrial fibrillation. Warfarin is substantially more efficacious (by approximately 40%) than antiplatelet therapy. Absolute increases in major extracranial hemorrhage associated with antithrombotic therapy in participants from the trials included in this meta-analysis were less than the absolute reductions in stroke. Judicious use of antithrombotic therapy importantly reduces stroke for most patients who have atrial fibrillation.

Hospital recruitment for a pragmatic cluster-randomized clinical trial: Lessons learned from the COMPASS study.

PubMed

Johnson, Anna M; Jones, Sara B; Duncan, Pamela W; Bushnell, Cheryl D; Coleman, Sylvia W; Mettam, Laurie H; Kucharska-Newton, Anna M; Sissine, Mysha E; Rosamond, Wayne D

2018-01-26

Pragmatic randomized clinical trials are essential to determine the effectiveness of interventions in "real-world" clinical practice. These trials frequently use a cluster-randomized methodology, with randomization at the site level. Despite policymakers' increased interest in supporting pragmatic randomized clinical trials, no studies to date have reported on the unique recruitment challenges faced by cluster-randomized pragmatic trials. We investigated key challenges and successful strategies for hospital recruitment in the Comprehensive Post-Acute Stroke Services (COMPASS) study. The COMPASS study is designed to compare the effectiveness of the COMPASS model versus usual care in improving functional outcomes, reducing the numbers of hospital readmissions, and reducing caregiver strain for patients discharged home after stroke or transient ischemic attack. This model integrates early supported discharge planning with transitional care management, including nurse-led follow-up phone calls after 2, 30, and 60 days and an in-person clinic visit at 7-14 days involving a functional assessment and neurological examination. We present descriptive statistics of the characteristics of successfully recruited hospitals compared with all eligible hospitals, reasons for non-participation, and effective recruitment strategies. We successfully recruited 41 (43%) of 95 eligible North Carolina hospitals. Leading, non-exclusive reasons for non-participation included: insufficient staff or financial resources (n = 33, 61%), lack of health system support (n = 16, 30%), and lack of support of individual decision-makers (n = 11, 20%). Successful recruitment strategies included: building and nurturing relationships, engaging team members and community partners with a diverse skill mix, identifying gatekeepers, finding mutually beneficial solutions, having a central institutional review board, sharing published pilot data, and integrating contracts and review board administrators. Although we incorporated strategies based on the best available evidence at the outset of the study, hospital recruitment required three times as much time and considerably more staff than anticipated. To reach our goal, we tailored strategies to individuals, hospitals, and health systems. Successful recruitment of a sufficient number and representative mix of hospitals requires considerable preparation, planning, and flexibility. Strategies presented here may assist future trial organizers in implementing cluster-randomized pragmatic trials. Clinicaltrials.gov, NCT02588664 . Registered on 23 October 2015.

Randomized clinical trials presented at the World Congress of Endourology: how is the quality of reporting?

PubMed

Autorino, Riccardo; Borges, Claudio; White, Michael A; Altunrende, Fatih; Perdoná, Sisto; Haber, Georges-Pascal; De Sio, Marco; Khanna, Rakesh; Stein, Robert J; Kaouk, Jihad H

2010-12-01

To assess the quality of reporting of randomized controlled trials (RCTs) presented in abstract form at the annual World Congress of Endourology (WCE) and evaluate their course of subsequent publication. All RCTs presented in abstract form at the 2004, 2005, and 2006 WCE annual meetings were identified for review. Quality of reporting was assessed by applying a standardized 14-item evaluation tool based on the Consolidated Standards for the Reporting of Trials (CONSORT) statement. The subsequent publication rate for the corresponding studies by scanning Medline was also evaluated. Appropriate statistical analysis was performed. A total of 94 RCTs (3.5% of 2669) were identified for review: 21 in 2004, 36 in 2005, and 37 in 2006. Overall, 45 (47.3% of the total) were subsequently published as a full length indexed manuscript with a mean time to publication of 16.4 ± 13.2 months. Approximately 61 (60%) identified the study design as RCT in the abstract title. None reported the method of randomization. In studies that reported blinding (seven, 11% of 62), five were double blinded and two single blinded. Adverse events were reported in 38% of cases. Only 10% of the abstracts complied fully with more than 10 items according to our CONSORT-based checklist, whereas the majority of them failed to comply with most of the CONSORT requirements. Although representing a small portion of the overall number of abstracts, there has been a steady increase of presentation of RCTs at the WCE over the assessed 3-year period. Most of the time they are recognized as RCTs in the abstract title. When applying the CONSORT criteria, necessary information to assess their methodologic quality is incomplete in some cases.

Evolution of Randomized Trials in Advanced/Metastatic Soft Tissue Sarcoma: End Point Selection, Surrogacy, and Quality of Reporting.

PubMed

Zer, Alona; Prince, Rebecca M; Amir, Eitan; Abdul Razak, Albiruni

2016-05-01

Randomized controlled trials (RCTs) in soft tissue sarcoma (STS) have used varying end points. The surrogacy of intermediate end points, such as progression-free survival (PFS), response rate (RR), and 3-month and 6-month PFS (3moPFS and 6moPFS) with overall survival (OS), remains unknown. The quality of efficacy and toxicity reporting in these studies is also uncertain. A systematic review of systemic therapy RCTs in STS was performed. Surrogacy between intermediate end points and OS was explored using weighted linear regression for the hazard ratio for OS with the hazard ratio for PFS or the odds ratio for RR, 3moPFS, and 6moPFS. The quality of reporting for efficacy and toxicity was also evaluated. Fifty-two RCTs published between 1974 and 2014, comprising 9,762 patients, met the inclusion criteria. There were significant correlations between PFS and OS (R = 0.61) and between RR and OS (R = 0.51). Conversely, there were nonsignificant correlations between 3moPFS and 6moPFS with OS. A reduction in the use of RR as the primary end point was observed over time, favoring time-based events (P for trend = .02). In 14% of RCTs, the primary end point was not met, but the study was reported as being positive. Toxicity was comprehensively reported in 47% of RCTs, whereas 14% inadequately reported toxicity. In advanced STS, PFS and RR seem to be appropriate surrogates for OS. There is poor correlation between OS and both 3moPFS and 6moPFS. As such, caution is urged with the use of these as primary end points in randomized STS trials. The quality of toxicity reporting and interpretation of results is suboptimal. © 2016 by American Society of Clinical Oncology.

Mandibular single-implant overdentures: a review with surgical and prosthodontic perspectives of a novel approach.

PubMed

Alsabeeha, Nabeel; Payne, Alan G T; De Silva, Rohana K; Swain, Michael V

2009-04-01

To review the literature on mandibular single-implant overdentures (opposing complete maxillary dentures), and present surgical and prosthodontic perspectives of a novel approach for this treatment option. An electronic search through the databases of Pubmed, Embase and Medline using the linked key words 'mandibular single implant overdentures' was performed. The search was limited to English language articles published up to August 2008. Hand searches through articles retrieved from the electronic search, peer-reviewed journals and recent conference proceedings were also conducted. A limited number of reports were identified on mandibular single-implant overdentures (opposing maxillary complete dentures). They comprised of case-series reports, short-term prospective trials and current randomized-controlled clinical trials. Different loading protocols with different implant systems have been used, but always with regular diameter implants. Specific anatomical and vascular dangers of the mandibular midline symphysis are identified including a novel surgical approach using a currently available short, wide diameter tapered implant. In addition, the prosthodontic rationale for using a larger attachment system (incorporating a platform switch) for mandibular single-implant overdentures is described. The review reveals that there is a lack of published randomized clinical trials using mandibular single-implant overdentures, opposing maxillary complete dentures. Without the evidence from randomized clinical trials, routine use of this novel approach cannot be recommended, compared with using regular diameter implants and matching attachment systems.

Preclinical neuroprotective actions of xenon and possible implications for human therapeutics: a narrative review.

PubMed

Maze, Mervyn

2016-02-01

The purpose of this report is to facilitate an understanding of the possible application of xenon for neuroprotection in critical care settings. This narrative review appraises the literature assessing the efficacy and safety of xenon in preclinical models of acute ongoing neurologic injury. Databases of the published literature (MEDLINE® and EMBASE™) were appraised for peer-reviewed manuscripts addressing the use of xenon in both preclinical models and disease states of acute ongoing neurologic injury. For randomized clinical trials not yet reported, the investigators' declarations in the National Institutes of Health clinical trials website were considered. While not a primary focus of this review, to date, xenon cannot be distinguished as superior for surgical anesthesia over existing alternatives in adults. Nevertheless, studies in a variety of preclinical disease models from multiple laboratories have consistently shown xenon's neuroprotective properties. These properties are enhanced in settings where xenon is combined with hypothermia. Small randomized clinical trials are underway to explore xenon's efficacy and safety in clinical settings of acute neurologic injury where hypothermia is the current standard of care. According to the evidence to date, the neuroprotective efficacy of xenon in preclinical models and its safety in clinical anesthesia set the stage for the launch of randomized clinical trials to determine whether these encouraging neuroprotective findings can be translated into clinical utility.

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