Intention-to-treat analysis and accounting for missing data in orthopaedic randomized clinical trials.

PubMed

Herman, Amir; Botser, Itamar Busheri; Tenenbaum, Shay; Chechick, Ahron

2009-09-01

The intention-to-treat principle implies that all patients who are randomized in a clinical trial should be analyzed according to their original allocation. This means that patients crossing over to another treatment group and patients lost to follow-up should be included in the analysis as a part of their original group. This principle is important for preserving the randomization scheme, which is the basis for correct inference in any randomized trial. In this study, we examined the use of the intention-to-treat principle in recently published orthopaedic clinical trials. We surveyed eight leading orthopaedic journals for randomized clinical trials published between January 2005 and August 2008. We determined whether the intention-to-treat principle was implemented and, if so, how it was used in each trial. Specifically, we ascertained which methods were used to account for missing data. Our search yielded 274 randomized clinical trials, and the intention-to-treat principle was used in ninety-six (35%) of them. There were significant differences among the journals with regard to the use of the intention-to-treat principle. The relative number of trials in which the principle was used increased each year. The authors adhered to the strict definition of the intention-to-treat principle in forty-five of the ninety-six studies in which it was claimed that this principle had been used. In forty-four randomized trials, patients who had been lost to follow-up were excluded from the final analysis; this practice was most notable in studies of surgical interventions. The most popular method of adjusting for missing data was the "last observation carried forward" technique. In most of the randomized clinical trials published in the orthopaedic literature, the investigators did not adhere to the stringent use of the intention-to-treat principle, with the most conspicuous problem being a lack of accounting for patients lost to follow-up. This omission might introduce bias to orthopaedic randomized clinical trials and their analysis.

A Bayesian comparative effectiveness trial in action: developing a platform for multisite study adaptive randomization.

PubMed

Brown, Alexandra R; Gajewski, Byron J; Aaronson, Lauren S; Mudaranthakam, Dinesh Pal; Hunt, Suzanne L; Berry, Scott M; Quintana, Melanie; Pasnoor, Mamatha; Dimachkie, Mazen M; Jawdat, Omar; Herbelin, Laura; Barohn, Richard J

2016-08-31

In the last few decades, the number of trials using Bayesian methods has grown rapidly. Publications prior to 1990 included only three clinical trials that used Bayesian methods, but that number quickly jumped to 19 in the 1990s and to 99 from 2000 to 2012. While this literature provides many examples of Bayesian Adaptive Designs (BAD), none of the papers that are available walks the reader through the detailed process of conducting a BAD. This paper fills that gap by describing the BAD process used for one comparative effectiveness trial (Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations) that can be generalized for use by others. A BAD was chosen with efficiency in mind. Response-adaptive randomization allows the potential for substantially smaller sample sizes, and can provide faster conclusions about which treatment or treatments are most effective. An Internet-based electronic data capture tool, which features a randomization module, facilitated data capture across study sites and an in-house computation software program was developed to implement the response-adaptive randomization. A process for adapting randomization with minimal interruption to study sites was developed. A new randomization table can be generated quickly and can be seamlessly integrated in the data capture tool with minimal interruption to study sites. This manuscript is the first to detail the technical process used to evaluate a multisite comparative effectiveness trial using adaptive randomization. An important opportunity for the application of Bayesian trials is in comparative effectiveness trials. The specific case study presented in this paper can be used as a model for conducting future clinical trials using a combination of statistical software and a web-based application. ClinicalTrials.gov Identifier: NCT02260388 , registered on 6 October 2014.

Methodological quality of randomized trials published in the Journal of the American Podiatric Medical Association, 1999-2013.

PubMed

Landorf, Karl B; Menz, Hylton B; Armstrong, David G; Herbert, Robert D

2015-07-01

Randomized trials must be of high methodological quality to yield credible, actionable findings. The main aim of this project was to evaluate whether there has been an improvement in the methodological quality of randomized trials published in the Journal of the American Podiatric Medical Association (JAPMA). Randomized trials published in JAPMA during a 15-year period (January 1999 to December 2013) were evaluated. The methodological quality of randomized trials was evaluated using the PEDro scale (scores range from 0 to 10, with 0 being lowest quality). Linear regression was used to assess changes in methodological quality over time. A total of 1,143 articles were published in JAPMA between January 1999 and December 2013. Of these, 44 articles were reports of randomized trials. Although the number of randomized trials published each year increased, there was only minimal improvement in their methodological quality (mean rate of improvement = 0.01 points per year). The methodological quality of the trials studied was typically moderate, with a mean ± SD PEDro score of 5.1 ± 1.5. Although there were a few high-quality randomized trials published in the journal, most (84.1%) scored between 3 and 6. Although there has been an increase in the number of randomized trials published in JAPMA, there is substantial opportunity for improvement in the methodological quality of trials published in the journal. Researchers seeking to publish reports of randomized trials should seek to meet current best-practice standards in the conduct and reporting of their trials.

A Randomized Controlled Trial of the Group-Based Modified Story Memory Technique in TBI

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0726 TITLE: A Randomized Controlled Trial of the Group -Based Modified Story Memory Technique in TBI PRINCIPAL...2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Randomized Controlled Trial of the Group -Based Modified Story Memory Technique in TBI 5b. GRANT...forthcoming, The current study addresses this need through a double blind, placebo- controlled , randomized clinical trial (RCT) of a group

Osteoporosis therapies: evidence from health-care databases and observational population studies.

PubMed

Silverman, Stuart L

2010-11-01

Osteoporosis is a well-recognized disease with severe consequences if left untreated. Randomized controlled trials are the most rigorous method for determining the efficacy and safety of therapies. Nevertheless, randomized controlled trials underrepresent the real-world patient population and are costly in both time and money. Modern technology has enabled researchers to use information gathered from large health-care or medical-claims databases to assess the practical utilization of available therapies in appropriate patients. Observational database studies lack randomization but, if carefully designed and successfully completed, can provide valuable information that complements results obtained from randomized controlled trials and extends our knowledge to real-world clinical patients. Randomized controlled trials comparing fracture outcomes among osteoporosis therapies are difficult to perform. In this regard, large observational database studies could be useful in identifying clinically important differences among therapeutic options. Database studies can also provide important information with regard to osteoporosis prevalence, health economics, and compliance and persistence with treatment. This article describes the strengths and limitations of both randomized controlled trials and observational database studies, discusses considerations for observational study design, and reviews a wealth of information generated by database studies in the field of osteoporosis.

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all.

PubMed

Papageorgiou, Spyridon N; Antonoglou, Georgios N; Sándor, George K; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date.

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all

PubMed Central

Antonoglou, Georgios N.; Sándor, George K.; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date. PMID:28777820

From randomized controlled trials to observational studies.

PubMed

Silverman, Stuart L

2009-02-01

Randomized controlled trials are considered the gold standard in the hierarchy of research designs for evaluating the efficacy and safety of a treatment intervention. However, their results can have limited applicability to patients in clinical settings. Observational studies using large health care databases can complement findings from randomized controlled trials by assessing treatment effectiveness in patients encountered in day-to-day clinical practice. Results from these designs can expand upon outcomes of randomized controlled trials because of the use of larger and more diverse patient populations with common comorbidities and longer follow-up periods. Furthermore, well-designed observational studies can identify clinically important differences among therapeutic options and provide data on long-term drug effectiveness and safety.

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

Comparison of evidence on harms of medical interventions in randomized and nonrandomized studies

PubMed Central

Papanikolaou, Panagiotis N.; Christidi, Georgia D.; Ioannidis, John P.A.

2006-01-01

Background Information on major harms of medical interventions comes primarily from epidemiologic studies performed after licensing and marketing. Comparison with data from large-scale randomized trials is occasionally feasible. We compared evidence from randomized trials with that from epidemiologic studies to determine whether they give different estimates of risk for important harms of medical interventions. Methods We targeted well-defined, specific harms of various medical interventions for which data were already available from large-scale randomized trials (> 4000 subjects). Nonrandomized studies involving at least 4000 subjects addressing these same harms were retrieved through a search of MEDLINE. We compared the relative risks and absolute risk differences for specific harms in the randomized and nonrandomized studies. Results Eligible nonrandomized studies were found for 15 harms for which data were available from randomized trials addressing the same harms. Comparisons of relative risks between the study types were feasible for 13 of the 15 topics, and of absolute risk differences for 8 topics. The estimated increase in relative risk differed more than 2-fold between the randomized and nonrandomized studies for 7 (54%) of the 13 topics; the estimated increase in absolute risk differed more than 2-fold for 5 (62%) of the 8 topics. There was no clear predilection for randomized or nonrandomized studies to estimate greater relative risks, but usually (75% [6/8]) the randomized trials estimated larger absolute excess risks of harm than the nonrandomized studies did. Interpretation Nonrandomized studies are often conservative in estimating absolute risks of harms. It would be useful to compare and scrutinize the evidence on harms obtained from both randomized and nonrandomized studies. PMID:16505459

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.

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.

A Randomized Trial of Telephone Psychotherapy and Pharmacotherapy for Depression: Continuation and Durability of Effects

ERIC Educational Resources Information Center

Ludman, Evette J.; Simon, Gregory E.; Tutty, Steve; Von Korff, Michael

2007-01-01

Randomized trial evidence and expert guidelines are mixed regarding the value of combined pharmacotherapy and psychotherapy as initial treatment for depression. This study describes long-term results of a randomized trial (N = 393) evaluating telephone-based cognitive-behavioral therapy (CBT) plus care management for primary care patients…

Assessing the Generalizability of Randomized Trial Results to Target Populations

PubMed Central

Stuart, Elizabeth A.; Bradshaw, Catherine P.; Leaf, Philip J.

2014-01-01

Recent years have seen increasing interest in and attention to evidence-based practices, where the “evidence” generally comes from well-conducted randomized trials. However, while those trials yield accurate estimates of the effect of the intervention for the participants in the trial (known as “internal validity”), they do not always yield relevant information about the effects in a particular target population (known as “external validity”). This may be due to a lack of specification of a target population when designing the trial, difficulties recruiting a sample that is representative of a pre-specified target population, or to interest in considering a target population somewhat different from the population directly targeted by the trial. This paper first provides an overview of existing design and analysis methods for assessing and enhancing the ability of a randomized trial to estimate treatment effects in a target population. It then provides a case study using one particular method, which weights the subjects in a randomized trial to match the population on a set of observed characteristics. The case study uses data from a randomized trial of School-wide Positive Behavioral Interventions and Supports (PBIS); our interest is in generalizing the results to the state of Maryland. In the case of PBIS, after weighting, estimated effects in the target population were similar to those observed in the randomized trial. The paper illustrates that statistical methods can be used to assess and enhance the external validity of randomized trials, making the results more applicable to policy and clinical questions. However, there are also many open research questions; future research should focus on questions of treatment effect heterogeneity and further developing these methods for enhancing external validity. Researchers should think carefully about the external validity of randomized trials and be cautious about extrapolating results to specific populations unless they are confident of the similarity between the trial sample and that target population. PMID:25307417

Assessing the generalizability of randomized trial results to target populations.

PubMed

Stuart, Elizabeth A; Bradshaw, Catherine P; Leaf, Philip J

2015-04-01

Recent years have seen increasing interest in and attention to evidence-based practices, where the "evidence" generally comes from well-conducted randomized trials. However, while those trials yield accurate estimates of the effect of the intervention for the participants in the trial (known as "internal validity"), they do not always yield relevant information about the effects in a particular target population (known as "external validity"). This may be due to a lack of specification of a target population when designing the trial, difficulties recruiting a sample that is representative of a prespecified target population, or to interest in considering a target population somewhat different from the population directly targeted by the trial. This paper first provides an overview of existing design and analysis methods for assessing and enhancing the ability of a randomized trial to estimate treatment effects in a target population. It then provides a case study using one particular method, which weights the subjects in a randomized trial to match the population on a set of observed characteristics. The case study uses data from a randomized trial of school-wide positive behavioral interventions and supports (PBIS); our interest is in generalizing the results to the state of Maryland. In the case of PBIS, after weighting, estimated effects in the target population were similar to those observed in the randomized trial. The paper illustrates that statistical methods can be used to assess and enhance the external validity of randomized trials, making the results more applicable to policy and clinical questions. However, there are also many open research questions; future research should focus on questions of treatment effect heterogeneity and further developing these methods for enhancing external validity. Researchers should think carefully about the external validity of randomized trials and be cautious about extrapolating results to specific populations unless they are confident of the similarity between the trial sample and that target population.

Knowledge translation interventions for critically ill patients: a systematic review*.

PubMed

Sinuff, Tasnim; Muscedere, John; Adhikari, Neill K J; Stelfox, Henry T; Dodek, Peter; Heyland, Daren K; Rubenfeld, Gordon D; Cook, Deborah J; Pinto, Ruxandra; Manoharan, Venika; Currie, Jan; Cahill, Naomi; Friedrich, Jan O; Amaral, Andre; Piquette, Dominique; Scales, Damon C; Dhanani, Sonny; Garland, Allan

2013-11-01

We systematically reviewed ICU-based knowledge translation studies to assess the impact of knowledge translation interventions on processes and outcomes of care. We searched electronic databases (to July, 2010) without language restrictions and hand-searched reference lists of relevant studies and reviews. Two reviewers independently identified randomized controlled trials and observational studies comparing any ICU-based knowledge translation intervention (e.g., protocols, guidelines, and audit and feedback) to management without a knowledge translation intervention. We focused on clinical topics that were addressed in greater than or equal to five studies. Pairs of reviewers abstracted data on the clinical topic, knowledge translation intervention(s), process of care measures, and patient outcomes. For each individual or combination of knowledge translation intervention(s) addressed in greater than or equal to three studies, we summarized each study using median risk ratio for dichotomous and standardized mean difference for continuous process measures. We used random-effects models. Anticipating a small number of randomized controlled trials, our primary meta-analyses included randomized controlled trials and observational studies. In separate sensitivity analyses, we excluded randomized controlled trials and collapsed protocols, guidelines, and bundles into one category of intervention. We conducted meta-analyses for clinical outcomes (ICU and hospital mortality, ventilator-associated pneumonia, duration of mechanical ventilation, and ICU length of stay) related to interventions that were associated with improvements in processes of care. From 11,742 publications, we included 119 investigations (seven randomized controlled trials, 112 observational studies) on nine clinical topics. Interventions that included protocols with or without education improved continuous process measures (seven observational studies and one randomized controlled trial; standardized mean difference [95% CI]: 0.26 [0.1, 0.42]; p = 0.001 and four observational studies and one randomized controlled trial; 0.83 [0.37, 1.29]; p = 0.0004, respectively). Heterogeneity among studies within topics ranged from low to extreme. The exclusion of randomized controlled trials did not change our results. Single-intervention and lower-quality studies had higher standardized mean differences compared to multiple-intervention and higher-quality studies (p = 0.013 and 0.016, respectively). There were no associated improvements in clinical outcomes. Knowledge translation interventions in the ICU that include protocols with or without education are associated with the greatest improvements in processes of critical care.

An analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia.

PubMed

Montgomery, John H; Byerly, Matthew; Carmody, Thomas; Li, Baitao; Miller, Daniel R; Varghese, Femina; Holland, Rhiannon

2004-12-01

The effect of funding source on the outcome of randomized controlled trials has been investigated in several medical disciplines; however, psychiatry has been largely excluded from such analyses. In this article, randomized controlled trials of second generation antipsychotics in schizophrenia are reviewed and analyzed with respect to funding source (industry vs. non-industry funding). A literature search was conducted for randomized, double-blind trials in which at least one of the tested treatments was a second generation antipsychotic. In each study, design quality and study outcome were assessed quantitatively according to rating scales. Mean quality and outcome scores were compared in the industry-funded studies and non-industry-funded studies. An analysis of the primary author's affiliation with industry was similarly performed. Results of industry-funded studies significantly favored second generation over first generation antipsychotics when compared to non-industry-funded studies. Non-industry-funded studies showed a trend toward higher quality than industry-funded studies; however, the difference between the two was not significant. Also, within the industry-funded studies, outcomes of trials involving first authors employed by industry sponsors demonstrated a trend toward second generation over first generation antipsychotics to a greater degree than did trials involving first authors employed outside the industry (p=0.05). While the retrospective design of the study limits the strength of the findings, the data suggest that industry bias may occur in randomized controlled trials in schizophrenia. There appears to be several sources by which bias may enter clinical research, including trial design, control of data analysis and multiplicity/redundancy of trials.

[Methodological quality evaluation of randomized controlled trials for traditional Chinese medicines for treatment of sub-health].

PubMed

Zhao, Jun; Liao, Xing; Zhao, Hui; Li, Zhi-Geng; Wang, Nan-Yue; Wang, Li-Min

2016-11-01

To evaluate the methodological quality of the randomized controlled trials(RCTs) for traditional Chinese medicines for treatment of sub-health, in order to provide a scientific basis for the improvement of clinical trials and systematic review. Such databases as CNKI, CBM, VIP, Wanfang, EMbase, Medline, Clinical Trials, Web of Science and Cochrane Library were searched for RCTS for traditional Chinese medicines for treatment of sub-health between the time of establishment and February 29, 2016. Cochrane Handbook 5.1 was used to screen literatures and extract data, and CONSORT statement and CONSORT for traditional Chinese medicine statement were adopted as the basis for quality evaluation. Among the 72 RCTs included in this study, 67 (93.05%) trials described the inter-group baseline data comparability, 39(54.17%) trials described the unified diagnostic criteria, 28(38.89%) trials described the unified standards of efficacy, 4 (5.55%) trials mentioned the multi-center study, 19(26.38%) trials disclosed the random distribution method, 6(8.33%) trials used the random distribution concealment, 15(20.83%) trials adopted the method of blindness, 3(4.17%) study reported the sample size estimation in details, 5 (6.94%) trials showed a sample size of more than two hundred, 19(26.38%) trials reported the number of withdrawal, defluxion cases and those lost to follow-up, but only 2 trials adopted the ITT analysis,10(13.89%) trials reported the follow-up results, none of the trial reported the test registration and the test protocol, 48(66.7%) trials reported all of the indicators of expected outcomes, 26(36.11%) trials reported the adverse reactions and adverse events, and 4(5.56%) trials reported patient compliance. The overall quality of these randomized controlled trials for traditional Chinese medicines for treatment of sub-health is low, with methodological defects in different degrees. Therefore, it is still necessary to emphasize the correct application of principles such as blindness, randomization and control in RCTs, while requiring reporting in accordance with international standards. Copyright© by the Chinese Pharmaceutical Association.

A Systematic Review of Surgical Randomized Controlled Trials: Part 2. Funding Source, Conflict of Interest, and Sample Size in Plastic Surgery.

PubMed

Voineskos, Sophocles H; Coroneos, Christopher J; Ziolkowski, Natalia I; Kaur, Manraj N; Banfield, Laura; Meade, Maureen O; Chung, Kevin C; Thoma, Achilleas; Bhandari, Mohit

2016-02-01

The authors examined industry support, conflict of interest, and sample size in plastic surgery randomized controlled trials that compared surgical interventions. They hypothesized that industry-funded trials demonstrate statistically significant outcomes more often, and randomized controlled trials with small sample sizes report statistically significant results more frequently. An electronic search identified randomized controlled trials published between 2000 and 2013. Independent reviewers assessed manuscripts and performed data extraction. Funding source, conflict of interest, primary outcome direction, and sample size were examined. Chi-squared and independent-samples t tests were used in the analysis. The search identified 173 randomized controlled trials, of which 100 (58 percent) did not acknowledge funding status. A relationship between funding source and trial outcome direction was not observed. Both funding status and conflict of interest reporting improved over time. Only 24 percent (six of 25) of industry-funded randomized controlled trials reported authors to have independent control of data and manuscript contents. The mean number of patients randomized was 73 per trial (median, 43, minimum, 3, maximum, 936). Small trials were not found to be positive more often than large trials (p = 0.87). Randomized controlled trials with small sample size were common; however, this provides great opportunity for the field to engage in further collaboration and produce larger, more definitive trials. Reporting of trial funding and conflict of interest is historically poor, but it greatly improved over the study period. Underreporting at author and journal levels remains a limitation when assessing the relationship between funding source and trial outcomes. Improved reporting and manuscript control should be goals that both authors and journals can actively achieve.

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.

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.

A Data Management System Integrating Web-based Training and Randomized Trials: Requirements, Experiences and Recommendations.

PubMed

Muroff, Jordana; Amodeo, Maryann; Larson, Mary Jo; Carey, Margaret; Loftin, Ralph D

2011-01-01

This article describes a data management system (DMS) developed to support a large-scale randomized study of an innovative web-course that was designed to improve substance abuse counselors' knowledge and skills in applying a substance abuse treatment method (i.e., cognitive behavioral therapy; CBT). The randomized trial compared the performance of web-course-trained participants (intervention group) and printed-manual-trained participants (comparison group) to determine the effectiveness of the web-course in teaching CBT skills. A single DMS was needed to support all aspects of the study: web-course delivery and management, as well as randomized trial management. The authors briefly reviewed several other systems that were described as built either to handle randomized trials or to deliver and evaluate web-based training. However it was clear that these systems fell short of meeting our needs for simultaneous, coordinated management of the web-course and the randomized trial. New England Research Institute's (NERI) proprietary Advanced Data Entry and Protocol Tracking (ADEPT) system was coupled with the web-programmed course and customized for our purposes. This article highlights the requirements for a DMS that operates at the intersection of web-based course management systems and randomized clinical trial systems, and the extent to which the coupled, customized ADEPT satisfied those requirements. Recommendations are included for institutions and individuals considering conducting randomized trials and web-based training programs, and seeking a DMS that can meet similar requirements.

Methodological reporting quality of randomized controlled trials: A survey of seven core journals of orthopaedics from Mainland China over 5 years following the CONSORT statement.

PubMed

Zhang, J; Chen, X; Zhu, Q; Cui, J; Cao, L; Su, J

2016-11-01

In recent years, the number of randomized controlled trials (RCTs) in the field of orthopaedics is increasing in Mainland China. However, randomized controlled trials (RCTs) are inclined to bias if they lack methodological quality. Therefore, we performed a survey of RCT to assess: (1) What about the quality of RCTs in the field of orthopedics in Mainland China? (2) Whether there is difference between the core journals of the Chinese department of orthopedics and Orthopaedics Traumatology Surgery & Research (OTSR). This research aimed to evaluate the methodological reporting quality according to the CONSORT statement of randomized controlled trials (RCTs) in seven key orthopaedic journals published in Mainland China over 5 years from 2010 to 2014. All of the articles were hand researched on Chongqing VIP database between 2010 and 2014. Studies were considered eligible if the words "random", "randomly", "randomization", "randomized" were employed to describe the allocation way. Trials including animals, cadavers, trials published as abstracts and case report, trials dealing with subgroups analysis, or trials without the outcomes were excluded. In addition, eight articles selected from Orthopaedics Traumatology Surgery & Research (OTSR) between 2010 and 2014 were included in this study for comparison. The identified RCTs are analyzed using a modified version of the Consolidated Standards of Reporting Trials (CONSORT), including the sample size calculation, allocation sequence generation, allocation concealment, blinding and handling of dropouts. A total of 222 RCTs were identified in seven core orthopaedic journals. No trials reported adequate sample size calculation, 74 (33.4%) reported adequate allocation generation, 8 (3.7%) trials reported adequate allocation concealment, 18 (8.1%) trials reported adequate blinding and 16 (7.2%) trials reported handling of dropouts. In OTSR, 1 (12.5%) trial reported adequate sample size calculation, 4 (50.0%) reported adequate allocation generation, 1 (12.5%) trials reported adequate allocation concealment, 2 (25.0%) trials reported adequate blinding and 5 (62.5%) trials reported handling of dropouts. There were statistical differences as for sample size calculation and handling of dropouts between papers from Mainland China and OTSR (P<0.05). The findings of this study show that the methodological reporting quality of RCTs in seven core orthopaedic journals from the Mainland China is far from satisfaction and it needs to further improve to keep up with the standards of the CONSORT statement. Level III case control. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Timing and Characteristics of Cumulative Evidence Available on Novel Therapeutic Agents Receiving Food and Drug Administration Accelerated Approval.

PubMed

Naci, Huseyin; Wouters, Olivier J; Gupta, Radhika; Ioannidis, John P A

2017-06-01

Policy Points: Randomized trials-the gold standard of evaluating effectiveness-constitute a small minority of existing evidence on agents given accelerated approval. One-third of randomized trials are in therapeutic areas outside of FDA approval and less than half evaluate the therapeutic benefits of these agents but use them instead as common backbone treatments. Agents receiving accelerated approval are often tested concurrently in several therapeutic areas. For most agents, no substantial time lag is apparent between the average start dates of randomized trials evaluating their effectiveness and those using them as part of background therapies. There appears to be a tendency for therapeutic agents receiving accelerated approval to quickly become an integral component of standard treatment, despite potential shortcomings in their evidence base. Therapeutic agents treating serious conditions are eligible for Food and Drug Administration (FDA) accelerated approval. The clinical evidence accrued on agents receiving accelerated approval has not been systematically evaluated. Our objective was to assess the timing and characteristics of available studies. We first identified clinical studies of novel therapeutic agents receiving accelerated approval. We then (1) categorized those studies as randomized or nonrandomized, (2) explored whether they evaluated the FDA-approved indications, and (3) documented the available treatment comparisons. We also meta-analyzed the difference in start times between randomized studies that (1) did or did not evaluate approved indications and (2) were or were not designed to evaluate the agent's effectiveness. In total, 37 novel therapeutic agents received accelerated approval between 2000 and 2013. Our search of ClinicalTrials.gov identified 7,757 studies, which included 1,258,315 participants. Only one-third of identified studies were randomized controlled trials. Of 1,631 randomized trials with advanced recruitment status, 906 were conducted in therapeutic areas for which agents received initial accelerated approval, 202 were in supplemental indications, and 523 were outside approved indications. Only 411 out of 906 (45.4%) trials were designed to test the effectiveness of agents that received accelerated approval ("evaluation" trials); others used these agents as common background treatment in both arms ("background" trials). There was no detectable lag between average start times of trials conducted within and outside initially approved indications. Evaluation trials started on average 1.52 years (95% CI: 0.87 to 2.17) earlier than background trials. Cumulative evidence on agents with accelerated approvals has major limitations. Most clinical studies including these agents are small and nonrandomized, and about a third are conducted in unapproved areas, typically concurrently with those conducted in approved areas. Most randomized trials including these therapeutic agents are not designed to directly evaluate their clinical benefits but to incorporate them as standard treatment. © 2017 Milbank Memorial Fund.

[Realization of design regarding experimental research in the clinical real-world research].

PubMed

He, Q; Shi, J P

2018-04-10

Real world study (RWS), a further verification and supplement for explanatory randomized controlled trial to evaluate the effectiveness of intervention measures in real clinical environment, has increasingly become the focus in the field of research on medical and health care services. However, some people mistakenly equate real world study with observational research, and argue that intervention and randomization cannot be carried out in real world study. In fact, both observational and experimental design are the basic designs in real world study, while the latter usually refers to pragmatic randomized controlled trial and registry-based randomized controlled trial. Other nonrandomized controlled and adaptive designs can also be adopted in the RWS.

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.

Efficacy of Parent-Child Interaction Therapy with Chinese ADHD Children: Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Ng, Gene S. H.; Choi, S. Y.

2017-01-01

Purpose: This study aimed to evaluate the efficacy of Parent-Child Interaction Therapy (PCIT) in Chinese children with attention-deficit/hyperactivity disorder (ADHD) or ADHD features. Methods: This study adopted a randomized controlled trial design without blinding. Participants were randomized into either the intervention group (n = 32) and…

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.

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

Finite-sample corrected generalized estimating equation of population average treatment effects in stepped wedge cluster randomized trials.

PubMed

Scott, JoAnna M; deCamp, Allan; Juraska, Michal; Fay, Michael P; Gilbert, Peter B

2017-04-01

Stepped wedge designs are increasingly commonplace and advantageous for cluster randomized trials when it is both unethical to assign placebo, and it is logistically difficult to allocate an intervention simultaneously to many clusters. We study marginal mean models fit with generalized estimating equations for assessing treatment effectiveness in stepped wedge cluster randomized trials. This approach has advantages over the more commonly used mixed models that (1) the population-average parameters have an important interpretation for public health applications and (2) they avoid untestable assumptions on latent variable distributions and avoid parametric assumptions about error distributions, therefore, providing more robust evidence on treatment effects. However, cluster randomized trials typically have a small number of clusters, rendering the standard generalized estimating equation sandwich variance estimator biased and highly variable and hence yielding incorrect inferences. We study the usual asymptotic generalized estimating equation inferences (i.e., using sandwich variance estimators and asymptotic normality) and four small-sample corrections to generalized estimating equation for stepped wedge cluster randomized trials and for parallel cluster randomized trials as a comparison. We show by simulation that the small-sample corrections provide improvement, with one correction appearing to provide at least nominal coverage even with only 10 clusters per group. These results demonstrate the viability of the marginal mean approach for both stepped wedge and parallel cluster randomized trials. We also study the comparative performance of the corrected methods for stepped wedge and parallel designs, and describe how the methods can accommodate interval censoring of individual failure times and incorporate semiparametric efficient estimators.

Micro-Randomized Trials: An Experimental Design for Developing Just-in-Time Adaptive Interventions

PubMed Central

Klasnja, Predrag; Hekler, Eric B.; Shiffman, Saul; Boruvka, Audrey; Almirall, Daniel; Tewari, Ambuj; Murphy, Susan A.

2015-01-01

Objective This paper presents an experimental design, the micro-randomized trial, developed to support optimization of just-in-time adaptive interventions (JITAIs). JITAIs are mHealth technologies that aim to deliver the right intervention components at the right times and locations to optimally support individuals’ health behaviors. Micro-randomized trials offer a way to optimize such interventions by enabling modeling of causal effects and time-varying effect moderation for individual intervention components within a JITAI. Methods The paper describes the micro-randomized trial design, enumerates research questions that this experimental design can help answer, and provides an overview of the data analyses that can be used to assess the causal effects of studied intervention components and investigate time-varying moderation of those effects. Results Micro-randomized trials enable causal modeling of proximal effects of the randomized intervention components and assessment of time-varying moderation of those effects. Conclusions Micro-randomized trials can help researchers understand whether their interventions are having intended effects, when and for whom they are effective, and what factors moderate the interventions’ effects, enabling creation of more effective JITAIs. PMID:26651463

Delivering successful randomized controlled trials in surgery: Methods to optimize collaboration and study design.

PubMed

Blencowe, Natalie S; Cook, Jonathan A; Pinkney, Thomas; Rogers, Chris; Reeves, Barnaby C; Blazeby, Jane M

2017-04-01

Randomized controlled trials in surgery are notoriously difficult to design and conduct due to numerous methodological and cultural challenges. Over the last 5 years, several UK-based surgical trial-related initiatives have been funded to address these issues. These include the development of Surgical Trials Centers and Surgical Specialty Leads (individual surgeons responsible for championing randomized controlled trials in their specialist fields), both funded by the Royal College of Surgeons of England; networks of research-active surgeons in training; and investment in methodological research relating to surgical randomized controlled trials (to address issues such as recruitment, blinding, and the selection and standardization of interventions). This article discusses these initiatives more in detail and provides exemplar cases to illustrate how the methodological challenges have been tackled. The initiatives have surpassed expectations, resulting in a renaissance in surgical research throughout the United Kingdom, such that the number of patients entering surgical randomized controlled trials has doubled.

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

Population-Level Cost-Effectiveness of Implementing Evidence-Based Practices into Routine Care

PubMed Central

Fortney, John C; Pyne, Jeffrey M; Burgess, James F

2014-01-01

Objective The objective of this research was to apply a new methodology (population-level cost-effectiveness analysis) to determine the value of implementing an evidence-based practice in routine care. Data Sources/Study Setting Data are from sequentially conducted studies: a randomized controlled trial and an implementation trial of collaborative care for depression. Both trials were conducted in the same practice setting and population (primary care patients prescribed antidepressants). Study Design The study combined results from a randomized controlled trial and a pre-post-quasi-experimental implementation trial. Data Collection/Extraction Methods The randomized controlled trial collected quality-adjusted life years (QALYs) from survey and medication possession ratios (MPRs) from administrative data. The implementation trial collected MPRs and intervention costs from administrative data and implementation costs from survey. Principal Findings In the randomized controlled trial, MPRs were significantly correlated with QALYs (p = .03). In the implementation trial, patients at implementation sites had significantly higher MPRs (p = .01) than patients at control sites, and by extrapolation higher QALYs (0.00188). Total costs (implementation, intervention) were nonsignificantly higher ($63.76) at implementation sites. The incremental population-level cost-effectiveness ratio was $33,905.92/QALY (bootstrap interquartile range −$45,343.10/QALY to $99,260.90/QALY). Conclusions The methodology was feasible to operationalize and gave reasonable estimates of implementation value. PMID:25328029

The Prevention Program for Externalizing Problem Behavior (PEP) Improves Child Behavior by Reducing Negative Parenting: Analysis of Mediating Processes in a Randomized Controlled Trial

ERIC Educational Resources Information Center

Hanisch, Charlotte; Hautmann, Christopher; Plück, Julia; Eichelberger, Ilka; Döpfner, Manfred

2014-01-01

Background: Our indicated Prevention program for preschool children with Externalizing Problem behavior (PEP) demonstrated improved parenting and child problem behavior in a randomized controlled efficacy trial and in a study with an effectiveness design. The aim of the present analysis of data from the randomized controlled trial was to identify…

Impact and Costs of Incentives to Reduce Attrition in Online Trials: Two Randomized Controlled Trials

PubMed Central

Murray, Elizabeth; Kalaitzaki, Eleftheria; White, Ian R; McCambridge, Jim; Thompson, Simon G; Wallace, Paul; Godfrey, Christine

2011-01-01

Background Attrition from follow-up is a major methodological challenge in randomized trials. Incentives are known to improve response rates in cross-sectional postal and online surveys, yet few studies have investigated whether they can reduce attrition from follow-up in online trials, which are particularly vulnerable to low follow-up rates. Objectives Our objective was to determine the impact of incentives on follow-up rates in an online trial. Methods Two randomized controlled trials were embedded in a large online trial of a Web-based intervention to reduce alcohol consumption (the Down Your Drink randomized controlled trial, DYD-RCT). Participants were those in the DYD pilot trial eligible for 3-month follow-up (study 1) and those eligible for 12-month follow-up in the DYD main trial (study 2). Participants in both studies were randomly allocated to receive an offer of an incentive or to receive no offer of an incentive. In study 1, participants in the incentive arm were randomly offered a £5 Amazon.co.uk gift voucher, a £5 charity donation to Cancer Research UK, or entry in a prize draw for £250. In study 2, participants in the incentive arm were offered a £10 Amazon.co.uk gift voucher. The primary outcome was the proportion of participants who completed follow-up questionnaires in the incentive arm(s) compared with the no incentive arm. Results In study 1 (n = 1226), there was no significant difference in response rates between those participants offered an incentive (175/615, 29%) and those with no offer (162/611, 27%) (difference = 2%, 95% confidence interval [CI] –3% to 7%). There was no significant difference in response rates among the three different incentives offered. In study 2 (n = 2591), response rates were 9% higher in the group offered an incentive (476/1296, 37%) than in the group not offered an incentive (364/1295, 28%) (difference = 9%, 95% CI 5% to 12%, P < .001). The incremental cost per extra successful follow-up in the incentive arm was £110 in study 1 and £52 in study 2. Conclusion Whereas an offer of a £10 Amazon.co.uk gift voucher can increase follow-up rates in online trials, an offer of a lower incentive may not. The marginal costs involved require careful consideration. Trial registration ISRCTN31070347; http://www.controlled-trials.com/ISRCTN31070347 (Archived by WebCite at http://www.webcitation.org/5wgr5pl3s) PMID:21371988

A case study of SMART attributes: a qualitative assessment of generalizability, retention rate, and trial quality.

PubMed

Moodie, Erica E M; Karran, James C; Shortreed, Susan M

2016-05-14

Personalizing medical care is becoming increasingly popular, particularly mental health care. There is growing interest in formalizing medical decision making based on evolving patient symptoms in an evidence-based manner. To determine optimal sequencing of treatments, the sequences themselves must be studied; this may be accomplished by using a sequential multiple assignment randomized trial (SMART). It has been hypothesized that SMART studies may improve participant retention and generalizability. We examine the hypotheses that SMART studies are more generalizable and have better retention than traditional randomized clinical trials via a case study of a SMART study of antipsychotic medications. We considered the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study, comparing the trial participant characteristics and overall retention to those of comparable trials found via a review of all related trials conducted from 2000 onwards. A MEDLINE search returned 6435 results for primary screening; ultimately, 48 distinct trials were retained for analysis. The study population in CATIE was similar to, although perhaps less symptomatic than, the study populations of traditional randomized clinical trials (RCTs), suggesting no large gains in generalizability despite the pragmatic nature of the trial. However, CATIE did see good month-by-month retention. SMARTs offer the possibility of studying treatment sequences in a way that a series of traditional RCTs cannot. SMARTs may offer improved retention; however, this case study did not find evidence to suggest greater generalizability using this trial design. ClinicalTrials.gov NCT00014001 . Registered on 6 April 2001.

[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.

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

Testing a Violence-Prevention Intervention for Incarcerated Women Using a Randomized Control Trial

ERIC Educational Resources Information Center

Kubiak, Sheryl Pimlott; Kim, Woo Jong; Fedock, Gina; Bybee, Deborah

2015-01-01

Objective: Beyond Violence (BV), a new prevention program for women with assaultive offenses, demonstrated feasibility in previous studies. This study's purpose is to assess the efficacy of BV using a randomized control trial. Method: Eligible women were randomly assigned to treatment as usual (TAU) and the experimental condition (BV). Measures of…

Does Fidelity of Implementation Account for Changes in Teacher-Child Interactions in a Randomized Controlled Trial of Banking Time?

ERIC Educational Resources Information Center

LoCasale-Crouch, Jennifer; Williford, Amanda; Whittaker, Jessica; DeCoster, Jamie; Alamos, Pilar

2018-01-01

This study examined fidelity of implementation in a randomized trial of Banking Time, a classroom-based intervention intended to improve children's behavior, specifically for those at risk for developing externalizing behavior problems, through improving the quality of teacher-child interactions. The study sample comes from a randomized controlled…

Effects of live sax music on various physiological parameters, pain level, and mood level in cancer patients: a randomized controlled trial.

PubMed

Burrai, Francesco; Micheluzzi, Valentina; Bugani, Valentina

2014-01-01

Few randomized controlled trial studies have focused on the effect of music in cancer patients, and there are no randomized controlled trials on the effects of live music with saxophone in cancer patients. To determine the effects of live saxophone music on various physiological parameters, pain level, and mood level. A randomized controlled trial study. 52 cancer patients were randomized to a control group (n = 26), an experimental group (n = 26) whose members received 30 minutes of live music therapy with saxophone. Systolic and diastolic blood pressure, pulse rate, glycemia, oxygen saturation, pain level, and mood level were measured before and after the live music performance. There was a statistical difference between the groups for oxygen saturation (0.003) and mood level (0.001). Live music performed with a saxophone could be introduced in oncology care to improve the oxygen saturation and mood in cancer patients.

A comparative study of restricted randomization procedures for multiarm trials with equal or unequal treatment allocation ratios.

PubMed

Ryeznik, Yevgen; Sverdlov, Oleksandr

2018-06-04

Randomization designs for multiarm clinical trials are increasingly used in practice, especially in phase II dose-ranging studies. Many new methods have been proposed in the literature; however, there is lack of systematic, head-to-head comparison of the competing designs. In this paper, we systematically investigate statistical properties of various restricted randomization procedures for multiarm trials with fixed and possibly unequal allocation ratios. The design operating characteristics include measures of allocation balance, randomness of treatment assignments, variations in the allocation ratio, and statistical characteristics such as type I error rate and power. The results from the current paper should help clinical investigators select an appropriate randomization procedure for their clinical trial. We also provide a web-based R shiny application that can be used to reproduce all results in this paper and run simulations under additional user-defined experimental scenarios. Copyright © 2018 John Wiley & Sons, Ltd.

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.

Adaptive Designs for Randomized Trials in Public Health

PubMed Central

Brown, C. Hendricks; Have, Thomas R. Ten; Jo, Booil; Dagne, Getachew; Wyman, Peter A.; Muthén, Bengt; Gibbons, Robert D.

2009-01-01

In this article, we present a discussion of two general ways in which the traditional randomized trial can be modified or adapted in response to the data being collected. We use the term adaptive design to refer to a trial in which characteristics of the study itself, such as the proportion assigned to active intervention versus control, change during the trial in response to data being collected. The term adaptive sequence of trials refers to a decision-making process that fundamentally informs the conceptualization and conduct of each new trial with the results of previous trials. Our discussion below investigates the utility of these two types of adaptations for public health evaluations. Examples are provided to illustrate how adaptation can be used in practice. From these case studies, we discuss whether such evaluations can or should be analyzed as if they were formal randomized trials, and we discuss practical as well as ethical issues arising in the conduct of these new-generation trials. PMID:19296774

Assessment of the Reporting Quality of Placebo-controlled Randomized Trials on the Treatment of Type 2 Diabetes With Traditional Chinese Medicine in Mainland China: A PRISMA-Compliant Systematic Review.

PubMed

Zhao, Xiyan; Zhen, Zhong; Guo, Jing; Zhao, Tianyu; Ye, Ru; Guo, Yu; Chen, Hongdong; Lian, Fengmei; Tong, Xiaolin

2016-01-01

Placebo-controlled randomized trials are often used to evaluate the absolute effect of new treatments and are considered gold standard for clinical trials. No studies, however, have yet been conducted evaluating the reporting quality of placebo-controlled randomized trials. The current study aims to assess the reporting quality of placebo-controlled randomized trials on treatment of diabetes with Traditional Chinese Medicine (TCM) in Mainland China and to provide recommendations for improvements.China National Knowledge Infrastructure database, Wanfang database, China Biology Medicine database, and VIP database were searched for placebo-controlled randomized trials on treatment of diabetes with TCM. Review, animal experiment, and randomized controlled trials without placebo control were excluded. According to Consolidated Standards of Reporting Trials (CONSORT) 2010 checklists items, each item was given a yes or no depending on whether it was reported or not.A total of 68 articles were included. The reporting percentage in each article ranged from 24.3% to 73%, and 30.9% articles reported more than 50% of the items. Seven of the 37 items were reported more than 90% of the items, whereas 7 items were not mentioned at all. The average reporting for "title and abstract," "introduction," "methods," "results," "discussion," and "other information" was 43.4%, 78.7%, 40.1%, 49.9%, 71.1%, and 17.2%, respectively. The percentage of each section had increased after 2010. In addition, the reporting of multiple study centers, funding, placebo species, informed consent forms, and ethical approvals were 14.7%, 50%, 36.85%, 33.8%, and 4.4%, respectively.Although a scoring system was created according to the CONSORT 2010 checklist, it was not designed as an assessment tool. According to CONSORT 2010, the reporting quality of placebo-controlled randomized trials on the treatment of diabetes with TCM improved after 2010. Future improvements, however, are still needed, particularly in methods sections.

Preference in Random Assignment: Implications for the Interpretation of Randomized Trials

PubMed Central

Gold, Paul B.; Hargreaves, William A.; Aronson, Elliot; Bickman, Leonard; Barreira, Paul J.; Jones, Danson R.; Rodican, Charles F.; Fisher, William H.

2009-01-01

Random assignment to a preferred experimental condition can increase service engagement and enhance outcomes, while assignment to a less-preferred condition can discourage service receipt and limit outcome attainment. We examined randomized trials for one prominent psychiatric rehabilitation intervention, supported employment, to gauge how often assignment preference might have complicated the interpretation of findings. Condition descriptions, and greater early attrition from services-as-usual comparison conditions, suggest that many study enrollees favored assignment to new rapid-job-placement supported employment, but no study took this possibility into account. Reviews of trials in other service fields are needed to determine whether this design problem is widespread. PMID:19434489

Evaluating the Flipped Classroom: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Wozny, Nathan; Balser, Cary; Ives, Drew

2018-01-01

Despite recent interest in flipped classrooms, rigorous research evaluating their effectiveness is sparse. In this study, the authors implement a randomized controlled trial to evaluate the effect of a flipped classroom technique relative to a traditional lecture in an introductory undergraduate econometrics course. Random assignment enables the…

A Randomized Clinical Trial of Cognitive-Behavioral Treatment for PTSD in Women

DTIC Science & Technology

2004-10-01

This study is a randomized clinical trial comparing two types of individual psychotherapy for treating PTSD in 384 female veterans and active duty...Exposure therapy will be more effective than Present Centered Therapy for the treatment of PTSD in female veterans and active duty personnel. The study has entered the randomized phase. There are no conclusions to date.

Understanding Statistical Power in Cluster Randomized Trials: Challenges Posed by Differences in Notation and Terminology

ERIC Educational Resources Information Center

Spybrook, Jessaca; Hedges, Larry; Borenstein, Michael

2014-01-01

Research designs in which clusters are the unit of randomization are quite common in the social sciences. Given the multilevel nature of these studies, the power analyses for these studies are more complex than in a simple individually randomized trial. Tools are now available to help researchers conduct power analyses for cluster randomized…

Weighted re-randomization tests for minimization with unbalanced allocation.

PubMed

Han, Baoguang; Yu, Menggang; McEntegart, Damian

2013-01-01

Re-randomization test has been considered as a robust alternative to the traditional population model-based methods for analyzing randomized clinical trials. This is especially so when the clinical trials are randomized according to minimization, which is a popular covariate-adaptive randomization method for ensuring balance among prognostic factors. Among various re-randomization tests, fixed-entry-order re-randomization is advocated as an effective strategy when a temporal trend is suspected. Yet when the minimization is applied to trials with unequal allocation, fixed-entry-order re-randomization test is biased and thus compromised in power. We find that the bias is due to non-uniform re-allocation probabilities incurred by the re-randomization in this case. We therefore propose a weighted fixed-entry-order re-randomization test to overcome the bias. The performance of the new test was investigated in simulation studies that mimic the settings of a real clinical trial. The weighted re-randomization test was found to work well in the scenarios investigated including the presence of a strong temporal trend. Copyright © 2013 John Wiley & Sons, Ltd.

Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series.

PubMed

Martínez-Lavín, Manuel; Amezcua-Guerra, Luis

2017-10-01

This article critically reviews HPV vaccine serious adverse events described in pre-licensure randomized trials and in post-marketing case series. HPV vaccine randomized trials were identified in PubMed. Safety data were extracted. Post-marketing case series describing HPV immunization adverse events were reviewed. Most HPV vaccine randomized trials did not use inert placebo in the control group. Two of the largest randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study. Compared to 2871 women receiving aluminum placebo, the group of 2881 women injected with the bivalent HPV vaccine had more deaths on follow-up (14 vs. 3, p = 0.012). Compared to 7078 girls injected with the 4-valent HPV vaccine, 7071 girls receiving the 9-valent dose had more serious systemic adverse events (3.3 vs. 2.6%, p = 0.01). For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 79–653) [DOSAGE ERROR CORRECTED] . The number needed to vaccinate is 1757 (95% CI, 131 to infinity). Practically, none of the serious adverse events occurring in any arm of both studies were judged to be vaccine-related. Pre-clinical trials, post-marketing case series, and the global drug adverse reaction database (VigiBase) describe similar post-HPV immunization symptom clusters. Two of the largest randomized HPV vaccine trials unveiled more severe adverse events in the tested HPV vaccine arm of the study. Nine-valent HPV vaccine has a worrisome number needed to vaccinate/number needed to harm quotient. Pre-clinical trials and post-marketing case series describe similar post-HPV immunization symptoms.

POLICY IMPLICATIONS OF ADJUSTING RANDOMIZED TRIAL DATA FOR ECONOMIC EVALUATIONS: A DEMONSTRATION FROM THE ASCUS-LSIL TRIAGE STUDY

PubMed Central

Campos, Nicole G.; Castle, Philip E.; Schiffman, Mark; Kim, Jane J.

2013-01-01

Background Although the randomized controlled trial (RCT) is widely considered the most reliable method for evaluation of health care interventions, challenges to both internal and external validity exist. Thus, the efficacy of an intervention in a trial setting does not necessarily represent the real-world performance that decision makers seek to inform comparative effectiveness studies and economic evaluations. Methods Using data from the ASCUS-LSIL Triage Study (ALTS), we performed a simplified economic evaluation of age-based management strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3) among women who were referred to the study with low-grade squamous intraepithelial lesions (LSIL). We used data from the trial itself to adjust for 1) potential lead time bias and random error that led to variation in the observed prevalence of CIN3 by study arm, and 2) potential ascertainment bias among providers in the most aggressive management arm. Results We found that using unadjusted RCT data may result in counterintuitive cost-effectiveness results when random error and/or bias are present. Following adjustment, the rank order of management strategies changed for two of the three age groups we considered. Conclusion Decision analysts need to examine study design, available trial data and cost-effectiveness results closely in order to detect evidence of potential bias. Adjustment for random error and bias in RCTs may yield different policy conclusions relative to unadjusted trial data. PMID:22147881

Bayesian network meta-analysis for cluster randomized trials with binary outcomes.

PubMed

Uhlmann, Lorenz; Jensen, Katrin; Kieser, Meinhard

2017-06-01

Network meta-analysis is becoming a common approach to combine direct and indirect comparisons of several treatment arms. In recent research, there have been various developments and extensions of the standard methodology. Simultaneously, cluster randomized trials are experiencing an increased popularity, especially in the field of health services research, where, for example, medical practices are the units of randomization but the outcome is measured at the patient level. Combination of the results of cluster randomized trials is challenging. In this tutorial, we examine and compare different approaches for the incorporation of cluster randomized trials in a (network) meta-analysis. Furthermore, we provide practical insight on the implementation of the models. In simulation studies, it is shown that some of the examined approaches lead to unsatisfying results. However, there are alternatives which are suitable to combine cluster randomized trials in a network meta-analysis as they are unbiased and reach accurate coverage rates. In conclusion, the methodology can be extended in such a way that an adequate inclusion of the results obtained in cluster randomized trials becomes feasible. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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.

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.

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.

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.

Recruiting participants with peripheral arterial disease for clinical trials: experience from the Study to Improve Leg Circulation (SILC).

PubMed

McDermott, Mary M; Domanchuk, Kathryn; Dyer, Alan; Ades, Philip; Kibbe, Melina; Criqui, Michael H

2009-03-01

To describe the success of diverse recruitment methods in a randomized controlled clinical trial of exercise in persons with peripheral arterial disease (PAD). An analysis of recruitment sources conducted for the 746 men and women completing a baseline visit for the study to improve leg circulation (SILC), a randomized controlled trial of exercise for patients with PAD. For each recruitment source, we determined the number of randomized participants, the rate of randomization among those completing a baseline visit, and cost per randomized participant. Of the 746 individuals who completed a baseline visit, 156 were eligible and randomized. The most frequent sources of randomized participants were newspaper advertising (n = 67), mailed recruitment letters to patients with PAD identified at the study medical center (n = 25), and radio advertising (n = 18). Costs per randomized participant were $2750 for television advertising, $2167 for Life Line Screening, $2369 for newspaper advertising, $3931 for mailed postcards to older community dwelling men and women, and $5691 for radio advertising. Among those completing a baseline visit, randomization rates ranged from 10% for those identified from radio advertising to 32% for those identified from the Chicago Veterans Administration and 33% for those identified from posted flyers. Most participants in a randomized controlled trial of exercise were recruited from newspaper advertising and mailed recruitment letters to patients with known PAD. The highest randomization rates after a baseline visit occurred among participants identified from posted flyers and mailed recruitment letters to PAD patients.

Using instrumental variables to disentangle treatment and placebo effects in blinded and unblinded randomized clinical trials influenced by unmeasured confounders

NASA Astrophysics Data System (ADS)

Chaibub Neto, Elias

2016-11-01

Clinical trials traditionally employ blinding as a design mechanism to reduce the influence of placebo effects. In practice, however, it can be difficult or impossible to blind study participants and unblinded trials are common in medical research. Here we show how instrumental variables can be used to quantify and disentangle treatment and placebo effects in randomized clinical trials comparing control and active treatments in the presence of confounders. The key idea is to use randomization to separately manipulate treatment assignment and psychological encouragement conversations/interactions that increase the participants’ desire for improved symptoms. The proposed approach is able to improve the estimation of treatment effects in blinded studies and, most importantly, opens the doors to account for placebo effects in unblinded trials.

A Randomized Prospective Trial Comparing Paravertebral Block and General Anesthesia for Operative Treatment of Breast Cancer

DTIC Science & Technology

2001-10-01

block the anesthetic of choice for operative treatment of breast cancer. To test this hypothesis we proposed a prospective randomized clinical trial ...coordinators. Months 4-6. Status: Complete The study’s existing part-time Clinical Trial Coordinator, Mr. John Arbo, was enlisted full-time in June...of full-time Clinical Trial Coordinator for Mount Sinai. ■ Poster presentation by Mount Sinai staff of study goals and methods at a Department of

Effectiveness of De Qi during acupuncture for the treatment of tinnitus: study protocol for a randomized controlled trial.

PubMed

Xie, Hui; Li, Xinrong; Lai, Jiaqin; Zhou, Yanan; Wang, Caiying; Liang, Jiao

2014-10-15

Acupuncture has been used in China to treat tinnitus for a long time. There is debate as to whether or not De Qi is a key factor in achieving the efficacy of acupuncture. However, there is no sufficient evidence obtained from randomized controlled trials to confirm the role of De Qi in the treatment of acupuncture for tinnitus. This study aims to identify the effect of De Qi for patients who receive acupuncture to alleviate tinnitus by a prospective, double-blind, randomized, sham-controlled trial. This study compares two acupuncture groups (with or without manipulation) in 292 patients with a history of subjective tinnitus. The trial will be conducted in the Teaching Hospital of Chengdu University of Traditional Chinese Medicine. In the study, the patients will be randomly assigned into two groups according to a computer-generated randomization list and assessed prior to treatment. Then, they will receive 5 daily sessions of 30 minutes each time for 4 consecutive weeks and undergo a 12-week follow-up phase. The administration of acupuncture follows the guidelines for clinical research on acupuncture (WHO Regional Publication, Western Pacific Series Number 15, 1995), and is performed double-blind by physicians well-trained in acupuncture. The measures of outcome include the subjective symptoms scores and quantitative sensations of De Qi evaluated by Visual Analog Scales (VAS) and the Chinese version of the 'modified' Massachusetts General Hospital Acupuncture Sensation Scale (C-MMASS). Furthermore, adverse events are recorded and analyzed. If any subjects are withdrawn from the trial, intention-to-treat analysis (ITT) and per-protocol (PP) analysis will be performed. The key features of this trial include the randomization procedures, large sample and the standardized protocol to evaluate De Qi qualitatively and quantitatively in the treatment of acupuncture for tinnitus. The trial will be the first study with a high evidence level in China to assess the efficacy of De Qi in the treatment of tinnitus in a randomized, double-blind, sham-controlled manner. Chinese Clinical Trial Registry: ChiCTR-TRC-14004720 (6 May 2014).

Efficacy and safety of acupuncture for chronic dizziness: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Dizziness is one of the most challenging symptoms in medicine. No medication for dizziness in current use has well-established curative or prophylactic value or is suitable for long-term palliative use. Unconventional remedies, such as acupuncture, should be considered and scientifically evaluated. However, there has been relatively little evidence in randomized controlled clinical trials on acupuncture to treat chronic dizziness. The aim of our study is to evaluate the efficacy and safety of acupuncture in patients with dizziness. Methods/Design This trial is a randomized, single-blind, controlled study. A total of 80 participants will be randomly assigned to two treatment groups receiving acupuncture and sham acupuncture treatment, respectively, for 4 weeks. The primary outcome measures are the Dizziness Handicap Inventory (DHI) and the Vertigo Symptom Scale (VSS). Treatment will be conducted over a period of 4 weeks, at a frequency of two sessions per week. The assessment is at baseline (before treatment initiation), 4 weeks after the first acupuncture session, and 8 weeks after the first acupuncture session. Discussion The results from this study will provide clinical evidence on the efficacy and safety of acupuncture in patients with chronic dizziness. Trial registration International Standard Randomized Controlled Trial Number Register: ISRCTN52695239 PMID:24330810

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.

Reporting of participant flow diagrams in published reports of randomized trials.

PubMed

Hopewell, Sally; Hirst, Allison; Collins, Gary S; Mallett, Sue; Yu, Ly-Mee; Altman, Douglas G

2011-12-05

Reporting of the flow of participants through each stage of a randomized trial is essential to assess the generalisability and validity of its results. We assessed the type and completeness of information reported in CONSORT (Consolidated Standards of Reporting Trials) flow diagrams published in current reports of randomized trials. A cross sectional review of all primary reports of randomized trials which included a CONSORT flow diagram indexed in PubMed core clinical journals (2009). We assessed the proportion of parallel group trial publications reporting specific items recommended by CONSORT for inclusion in a flow diagram. Of 469 primary reports of randomized trials, 263 (56%) included a CONSORT flow diagram of which 89% (237/263) were published in a CONSORT endorsing journal. Reports published in CONSORT endorsing journals were more likely to include a flow diagram (62%; 237/380 versus 29%; 26/89). Ninety percent (236/263) of reports which included a flow diagram had a parallel group design, of which 49% (116/236) evaluated drug interventions, 58% (137/236) were multicentre, and 79% (187/236) compared two study groups, with a median sample size of 213 participants. Eighty-one percent (191/236) reported the overall number of participants assessed for eligibility, 71% (168/236) the number excluded prior to randomization and 98% (231/236) the overall number randomized. Reasons for exclusion prior to randomization were more poorly reported. Ninety-four percent (223/236) reported the number of participants allocated to each arm of the trial. However, only 40% (95/236) reported the number who actually received the allocated intervention, 67% (158/236) the number lost to follow up in each arm of the trial, 61% (145/236) whether participants discontinued the intervention during the trial and 54% (128/236) the number included in the main analysis. Over half of published reports of randomized trials included a diagram showing the flow of participants through the trial. However, information was often missing from published flow diagrams, even in articles published in CONSORT endorsing journals. If important information is not reported it can be difficult and sometimes impossible to know if the conclusions of that trial are justified by the data presented.

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.

Randomized Controlled Trials Evaluating Effect of Television Advertising on Food Intake in Children: Why Such a Sensitive Topic is Lacking Top-Level Evidence?

PubMed

Gregori, Dario; Ballali, Simonetta; Vecchio, Maria Gabriella; Sciré, Antonella Silvia; Foltran, Francesca; Berchialla, Paola

2014-01-01

The aim of this study was to perform a systematic review of evidence coming from randomized controlled trials (RCT) aimed at assessing the effect of television advertising on food intake in children from 4 to 12 years old. Randomized controlled trials were searched in PubMed database and included if they assessed the effect of direct exposure to television food advertising over the actual energy intake of children. Seven studies out of 2166 fulfilled the inclusion criteria. The association between television advertising and energy intake is based on a very limited set of randomized researches lacking a solid ground of first-level evidence.

Relaxation Therapy and Anxiety, Self-Esteem, and Emotional Regulation among Adults with Intellectual Disabilities: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Bouvet, Cyrille; Coulet, Aurélie

2016-01-01

This pilot study is a randomized controlled trial on the effects of relaxation on anxiety, self-esteem, and emotional regulation in adults with intellectual disabilities (ID) working in a center of supported employment in France. We studied 30 adults with mild or moderate ID who were split at random into a relaxation group (RG, 15 subjects), who…

The role of randomized cluster crossover trials for comparative effectiveness testing in anesthesia: design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial.

PubMed

Spence, Jessica; Belley-Côté, Emilie; Lee, Shun Fu; Bangdiwala, Shrikant; Whitlock, Richard; LeManach, Yannick; Syed, Summer; Lamy, Andre; Jacobsohn, Eric; MacIsaac, Sarah; Devereaux, P J; Connolly, Stuart

2018-07-01

Increasingly, clinicians and researchers recognize that studies of interventions need to evaluate not only their therapeutic efficacy (i.e., the effect on an outcome in ideal, controlled settings) but also their real-world effectiveness in broad, unselected patient groups. Effectiveness trials inform clinical practice by comparing variations in therapeutic approaches that fall within the standard of care. In this article, we discuss the need for studies of comparative effectiveness in anesthesia and the limitations of individual patient randomized-controlled trials in determining comparative effectiveness. We introduce the concept of randomized cluster crossover trials as a means of answering questions of comparative effectiveness in anesthesia, using the design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial (Clinicaltrials.gov identifier NCT03053869).

Randomized clinical trials in dentistry: Risks of bias, risks of random errors, reporting quality, and methodologic quality over the years 1955–2013

PubMed Central

Armijo-Olivo, Susan; Cummings, Greta G.; Amin, Maryam; Flores-Mir, Carlos

2017-01-01

Objectives To examine the risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions and the development of these aspects over time. Methods We included 540 randomized clinical trials from 64 selected systematic reviews. We extracted, in duplicate, details from each of the selected randomized clinical trials with respect to publication and trial characteristics, reporting and methodologic characteristics, and Cochrane risk of bias domains. We analyzed data using logistic regression and Chi-square statistics. Results Sequence generation was assessed to be inadequate (at unclear or high risk of bias) in 68% (n = 367) of the trials, while allocation concealment was inadequate in the majority of trials (n = 464; 85.9%). Blinding of participants and blinding of the outcome assessment were judged to be inadequate in 28.5% (n = 154) and 40.5% (n = 219) of the trials, respectively. A sample size calculation before the initiation of the study was not performed/reported in 79.1% (n = 427) of the trials, while the sample size was assessed as adequate in only 17.6% (n = 95) of the trials. Two thirds of the trials were not described as double blinded (n = 358; 66.3%), while the method of blinding was appropriate in 53% (n = 286) of the trials. We identified a significant decrease over time (1955–2013) in the proportion of trials assessed as having inadequately addressed methodological quality items (P < 0.05) in 30 out of the 40 quality criteria, or as being inadequate (at high or unclear risk of bias) in five domains of the Cochrane risk of bias tool: sequence generation, allocation concealment, incomplete outcome data, other sources of bias, and overall risk of bias. Conclusions The risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions have improved over time; however, further efforts that contribute to the development of more stringent methodology and detailed reporting of trials are still needed. PMID:29272315

Randomized clinical trials in dentistry: Risks of bias, risks of random errors, reporting quality, and methodologic quality over the years 1955-2013.

PubMed

Saltaji, Humam; Armijo-Olivo, Susan; Cummings, Greta G; Amin, Maryam; Flores-Mir, Carlos

2017-01-01

To examine the risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions and the development of these aspects over time. We included 540 randomized clinical trials from 64 selected systematic reviews. We extracted, in duplicate, details from each of the selected randomized clinical trials with respect to publication and trial characteristics, reporting and methodologic characteristics, and Cochrane risk of bias domains. We analyzed data using logistic regression and Chi-square statistics. Sequence generation was assessed to be inadequate (at unclear or high risk of bias) in 68% (n = 367) of the trials, while allocation concealment was inadequate in the majority of trials (n = 464; 85.9%). Blinding of participants and blinding of the outcome assessment were judged to be inadequate in 28.5% (n = 154) and 40.5% (n = 219) of the trials, respectively. A sample size calculation before the initiation of the study was not performed/reported in 79.1% (n = 427) of the trials, while the sample size was assessed as adequate in only 17.6% (n = 95) of the trials. Two thirds of the trials were not described as double blinded (n = 358; 66.3%), while the method of blinding was appropriate in 53% (n = 286) of the trials. We identified a significant decrease over time (1955-2013) in the proportion of trials assessed as having inadequately addressed methodological quality items (P < 0.05) in 30 out of the 40 quality criteria, or as being inadequate (at high or unclear risk of bias) in five domains of the Cochrane risk of bias tool: sequence generation, allocation concealment, incomplete outcome data, other sources of bias, and overall risk of bias. The risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions have improved over time; however, further efforts that contribute to the development of more stringent methodology and detailed reporting of trials are still needed.

From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology

PubMed Central

Raghav, Kanwal Pratap Singh; Mahajan, Sminil; Yao, James C.; Hobbs, Brian P.; Berry, Donald A.; Pentz, Rebecca D.; Tam, Alda; Hong, Waun K.; Ellis, Lee M.; Abbruzzese, James; Overman, Michael J.

2015-01-01

Purpose The decision by journals to append protocols to published reports of randomized trials was a landmark event in clinical trial reporting. However, limited information is available on how this initiative effected transparency and selective reporting of clinical trial data. Methods We analyzed 74 oncology-based randomized trials published in Journal of Clinical Oncology, the New England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of reporting, we compared published reports with their respective appended protocols with regard to primary end points, nonprimary end points, unplanned end points, and unplanned analyses. Results A total of 86 primary end points were reported in 74 randomized trials; nine trials had greater than one primary end point. Nine trials (12.2%) had some discrepancy between their planned and published primary end points. A total of 579 nonprimary end points (median, seven per trial) were planned, of which 373 (64.4%; median, five per trial) were reported. A significant positive correlation was found between the number of planned and nonreported nonprimary end points (Spearman r = 0.66; P < .001). Twenty-eight studies (37.8%) reported a total of 65 unplanned end points; 52 (80.0%) of which were not identified as unplanned. Thirty-one (41.9%) and 19 (25.7%) of 74 trials reported a total of 52 unplanned analyses involving primary end points and 33 unplanned analyses involving nonprimary end points, respectively. Studies reported positive unplanned end points and unplanned analyses more frequently than negative outcomes in abstracts (unplanned end points odds ratio, 6.8; P = .002; unplanned analyses odd ratio, 8.4; P = .007). Conclusion Despite public and reviewer access to protocols, selective outcome reporting persists and is a major concern in the reporting of randomized clinical trials. To foster credible evidence-based medicine, additional initiatives are needed to minimize selective reporting. PMID:26304898

Study design and "evidence" in patient-oriented research.

PubMed

Concato, John

2013-06-01

Individual studies in patient-oriented research, whether described as "comparative effectiveness" or using other terms, are based on underlying methodological designs. A simple taxonomy of study designs includes randomized controlled trials on the one hand, and observational studies (such as case series, cohort studies, and case-control studies) on the other. A rigid hierarchy of these design types is a fairly recent phenomenon, promoted as a tenet of "evidence-based medicine," with randomized controlled trials receiving gold-standard status in terms of producing valid results. Although randomized trials have many strengths, and contribute substantially to the evidence base in clinical care, making presumptions about the quality of a study based solely on category of research design is unscientific. Both the limitations of randomized trials as well as the strengths of observational studies tend to be overlooked when a priori assumptions are made. This essay presents an argument in support of a more balanced approach to evaluating evidence, and discusses representative examples from the general medical as well as pulmonary and critical care literature. The simultaneous consideration of validity (whether results are correct "internally") and generalizability (how well results apply to "external" populations) is warranted in assessing whether a study's results are accurate for patients likely to receive the intervention-examining the intersection of clinical and methodological issues in what can be called a medicine-based evidence approach. Examination of cause-effect associations in patient-oriented research should recognize both the strengths and limitations of randomized trials as well as observational studies.

Some practical problems in implementing randomization.

PubMed

Downs, Matt; Tucker, Kathryn; Christ-Schmidt, Heidi; Wittes, Janet

2010-06-01

While often theoretically simple, implementing randomization to treatment in a masked, but confirmable, fashion can prove difficult in practice. At least three categories of problems occur in randomization: (1) bad judgment in the choice of method, (2) design and programming errors in implementing the method, and (3) human error during the conduct of the trial. This article focuses on these latter two types of errors, dealing operationally with what can go wrong after trial designers have selected the allocation method. We offer several case studies and corresponding recommendations for lessening the frequency of problems in allocating treatment or for mitigating the consequences of errors. Recommendations include: (1) reviewing the randomization schedule before starting a trial, (2) being especially cautious of systems that use on-demand random number generators, (3) drafting unambiguous randomization specifications, (4) performing thorough testing before entering a randomization system into production, (5) maintaining a dataset that captures the values investigators used to randomize participants, thereby allowing the process of treatment allocation to be reproduced and verified, (6) resisting the urge to correct errors that occur in individual treatment assignments, (7) preventing inadvertent unmasking to treatment assignments in kit allocations, and (8) checking a sample of study drug kits to allow detection of errors in drug packaging and labeling. Although we performed a literature search of documented randomization errors, the examples that we provide and the resultant recommendations are based largely on our own experience in industry-sponsored clinical trials. We do not know how representative our experience is or how common errors of the type we have seen occur. Our experience underscores the importance of verifying the integrity of the treatment allocation process before and during a trial. Clinical Trials 2010; 7: 235-245. http://ctj.sagepub.com.

A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design.

PubMed

Goswami, Neela D; Tsalik, Ephraim L; Naggie, Susanna; Miller, William C; Horton, John R; Pfeiffer, Christopher D; Hicks, Charles B

2014-01-22

The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US population, insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases. Debate exists about whether pharmaceutical companies undertake more market-driven research practices to promote therapeutics, or instead conduct more rigorous trials than their non-industry counterparts because of increased resources and scrutiny. The ClinicalTrials.gov registry, which allows investigators to fulfill a federal mandate for public trial registration, provides an opportunity for critical evaluation of study designs for industry-sponsored trials, independent of publication status. As part of a large public policy effort, the Clinical Trials Transformation Initiative (CTTI) recently transformed the ClinicalTrials.gov registry into a searchable dataset to facilitate research on clinical trials themselves. We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials, registered with ClinicalTrials.gov from 1 October 2007 to 27 September 2010, to study the relationship of study sponsorship with randomized study design. The likelihood of using randomization given industry (versus non-industry) sponsorship was reported with prevalence ratios (PR). PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee, enrollment size, study phase, number of study sites, inclusion of foreign study sites, exclusion of persons older than age 65, and disease condition. The crude PR was 1.17 (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82, 1.56). There was a trend toward mild effect measure modification by study phase, but this was not statistically significant. In stratified tabular analysis the adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI 0.50, 2.22) among phase 4 trials. No significant relationship was found between industry sponsorship and use of randomization in trial design in this cross-sectional study. Prospective studies evaluating other aspects of trial design may shed further light on the relationship between industry sponsorship and appropriate trial methodology.

A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design

PubMed Central

2014-01-01

Background The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US population, insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases. Debate exists about whether pharmaceutical companies undertake more market-driven research practices to promote therapeutics, or instead conduct more rigorous trials than their non-industry counterparts because of increased resources and scrutiny. The ClinicalTrials.gov registry, which allows investigators to fulfill a federal mandate for public trial registration, provides an opportunity for critical evaluation of study designs for industry-sponsored trials, independent of publication status. As part of a large public policy effort, the Clinical Trials Transformation Initiative (CTTI) recently transformed the ClinicalTrials.gov registry into a searchable dataset to facilitate research on clinical trials themselves. Methods We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials, registered with ClinicalTrials.gov from 1 October 2007 to 27 September 2010, to study the relationship of study sponsorship with randomized study design. The likelihood of using randomization given industry (versus non-industry) sponsorship was reported with prevalence ratios (PR). PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee, enrollment size, study phase, number of study sites, inclusion of foreign study sites, exclusion of persons older than age 65, and disease condition. Results The crude PR was 1.17 (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82, 1.56). There was a trend toward mild effect measure modification by study phase, but this was not statistically significant. In stratified tabular analysis the adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI 0.50, 2.22) among phase 4 trials. Conclusions No significant relationship was found between industry sponsorship and use of randomization in trial design in this cross-sectional study. Prospective studies evaluating other aspects of trial design may shed further light on the relationship between industry sponsorship and appropriate trial methodology. PMID:24450313

Intraclass Correlations for Three-Level Multi-Site Cluster-Randomized Trials of Science Achievement

ERIC Educational Resources Information Center

Westine, Carl D.

2015-01-01

A cluster-randomized trial (CRT) relies on random assignment of intact clusters to treatment conditions, such as classrooms or schools (Raudenbush & Bryk, 2002). One specific type of CRT, a multi-site CRT (MSCRT), is commonly employed in educational research and evaluation studies (Spybrook & Raudenbush, 2009; Spybrook, 2014; Bloom,…

A Data Management System Integrating Web-Based Training and Randomized Trials

ERIC Educational Resources Information Center

Muroff, Jordana; Amodeo, Maryann; Larson, Mary Jo; Carey, Margaret; Loftin, Ralph D.

2011-01-01

This article describes a data management system (DMS) developed to support a large-scale randomized study of an innovative web-course that was designed to improve substance abuse counselors' knowledge and skills in applying a substance abuse treatment method (i.e., cognitive behavioral therapy; CBT). The randomized trial compared the performance…

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…

After-School Multifamily Groups: A Randomized Controlled Trial Involving Low-Income, Urban, Latino Children

ERIC Educational Resources Information Center

McDonald, Lynn; Moberg, D. Paul; Brown, Roger; Rodriguez-Espiricueta, Ismael; Flores, Nydia I.; Burke, Melissa P.; Coover, Gail

2006-01-01

This randomized controlled trial evaluated a culturally representative parent engagement strategy with Latino parents of elementary school children. Ten urban schools serving low-income children from mixed cultural backgrounds participated in a large study. Classrooms were randomly assigned either either to an after-school, multifamily support…

The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.

PubMed

Eichhorn, Eric J; Bristow, Michael R

2001-01-01

Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of beta-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of beta-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction.

The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial

PubMed Central

Eichhorn, Eric J; Bristow, Michael R

2001-01-01

Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of β-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of β-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction. PMID:11806769

Electronic prompts significantly increase response rates to postal questionnaires: a randomized trial within a randomized trial and meta-analysis.

PubMed

Clark, Laura; Ronaldson, Sarah; Dyson, Lisa; Hewitt, Catherine; Torgerson, David; Adamson, Joy

2015-12-01

To assess the effectiveness of sending electronic prompts to randomized controlled trial participants to return study questionnaires. A "trial within a trial" embedded within a study determining the effectiveness of chronic obstructive pulmonary disease (DOC) screening on smoking cessation. Those participants taking part in DOC who provided a mobile phone number and/or an electronic mail address were randomized to either receive an electronic prompt or no electronic prompt to return a study questionnaire. The results were combined with two previous studies in a meta-analysis. A total of 437 participants were randomized: 226 to the electronic prompt group and 211 to the control group. A total of 285 (65.2%) participants returned the follow-up questionnaire: 157 (69.5%) in the electronic prompt group and 128 (60.7%) in the control group [difference 8.8%; 95% confidence interval (CI): -0.11%, 17.7%; P = 0.05]. The mean time to response was 23 days in the electronic prompt group and 33 days in the control group (hazard ratio = 1.27; 95% CI: 1.105, 1.47). The meta-analysis of all three studies showed an increase in response rate of 7.1% (95% CI: 0.8%, 13.3%). The use of electronic prompts increased response rates and reduces the time to response. Copyright © 2015 Elsevier Inc. 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.

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 .

Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial.

PubMed

Fröbert, Ole; Götberg, Matthias; Angerås, Oskar; Jonasson, Lena; Erlinge, David; Engstrøm, Thomas; Persson, Jonas; Jensen, Svend E; Omerovic, Elmir; James, Stefan K; Lagerqvist, Bo; Nilsson, Johan; Kåregren, Amra; Moer, Rasmus; Yang, Cao; Agus, David B; Erglis, Andrejs; Jensen, Lisette O; Jakobsen, Lars; Christiansen, Evald H; Pernow, John

2017-07-01

Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI. The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all-cause death, a new AMI, or stent thrombosis at 1 year. The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Rationale of a novel study design for the BIOFLOW V study, a prospective, randomized multicenter study to assess the safety and efficacy of the Orsiro sirolimus-eluting coronary stent system using a Bayesian approach.

PubMed

Doros, Gheorghe; Massaro, Joseph M; Kandzari, David E; Waksman, Ron; Koolen, Jacques J; Cutlip, Donald E; Mauri, Laura

2017-11-01

Traditional study design submitted to the Food and Drug Administration to test newer drug-eluting stents (DES) for marketing approval is the prospective randomized controlled trial. However, several DES have extensive clinical data from trials conducted outside the United States that have led to utilization of a novel design using the Bayesian approach. This design was proposed for testing DES with bioresorbable polymer compared with DES most commonly in use today that use durable polymers for drug elution. This prospective, multicenter, randomized, controlled trial is designed to assess the safety and efficacy of the Orsiro bioresorbable polymer sirolimus-eluting stent (BP SES). Up to 1,334 subjects with up to 3 de novo or restenotic coronary artery lesions who qualify for percutaneous coronary intervention with stenting will be randomized 2:1 to the BP SES versus the Xience durable polymer everolimus-eluting stent (DP EES). Data from this trial will be combined with data from 2 similarly designed trials that also randomize subjects to BP SES and DP EES (BIOFLOW II, N=452 and BIOFLOW IV, N=579) by using a Bayesian approach. The primary end point is target lesion failure at 12 months post index procedure, defined as cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization, and the primary analysis is a test of noninferiority of the BP SES versus DP EES on the primary end point according to a noninferiority delta of 3.85%. Secondary end points include stent thrombosis and the individual components of target lesion failure. Subjects will be followed for 5 years after randomization. The BIOFLOW V trial offers an opportunity to assess clinical outcomes in patients treated with coronary revascularization using the Orsiro BP SES relative to a commonly used DP EES. The use of a Bayesian analysis combines a large randomized cohort of patients 2 two smaller contributing randomized trials to augment the efficiency of the comparison. Copyright © 2017 Elsevier Inc. All rights reserved.

[Randomized, controlled clinical trials with observational follow-up investigations for evaluating efficacy of antihyperglycaemic treatment. I. Main results of the studies].

PubMed

Jermendy, György

2018-04-01

The effect of antihyperglycaemic (antidiabetic) treatment on the late diabetic complications is one of the most important research areas in clinical diabetology. The relationship between glycaemic control and late micro- and macrovascular complications was highlighted by the results of the DCCT (Diabetes Control and Complications Trial) with type 1 and by the UKPDS (United Kingdom Prospective Diabetes Study) with type 2 diabetic patients. In these studies, observational follow-up investigations were also performed after the close-out of the randomized phase of the trial. In addition to these landmark studies, other randomized, controlled efficacy trials were also performed with observational follow-up investigations resulting in the development of the concept of metabolic memory or metabolic legacy. In this article, the main results of the studies are summarized. Orv Hetil. 2018; 159(15): 575-582.

Brief Treatments for Cannabis Dependence: Findings From a Randomized Multisite Trial

ERIC Educational Resources Information Center

Babor, Thomas F.

2004-01-01

This study evaluated the efficacy of 2 brief interventions for cannabis-dependent adults. A multisite randomized controlled trial compared cannabis use outcomes across 3 study conditions: (a) 2 sessions of motivational enhancement therapy (MET); (b) 9 sessions of multicomponent therapy that included MET, cognitive-behavioral therapy, and case…

“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

The Efficacy of Parent-Child Interaction Therapy with Chinese Families: Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Sin, Tammy C. S.; Choi, Siu-yan

2015-01-01

Objective: This study aimed to examine the efficacy of the Parent-Child Interaction Therapy (PCIT) in Hong Kong Chinese families, using randomized controlled trial design. Methods: The participants included 111 Hong Kong Chinese parents with children aged 2--7 years old, who were randomized into the intervention group (n = 54) and control group (n…

Interventions to Improve Medication Adherence among Older Adults: Meta-Analysis of Adherence Outcomes among Randomized Controlled Trials

ERIC Educational Resources Information Center

Conn, Vicki S.; Hafdahl, Adam R.; Cooper, Pamela S.; Ruppar, Todd M.; Mehr, David R.; Russell, Cynthia L.

2009-01-01

Purpose: This study investigated the effectiveness of interventions to improve medication adherence (MA) in older adults. Design and Methods: Meta-analysis was used to synthesize results of 33 published and unpublished randomized controlled trials. Random-effects models were used to estimate overall mean effect sizes (ESs) for MA, knowledge,…

Randomized Controlled Trial of the Resilience and Coping Intervention (RCI) with Undergraduate University Students

ERIC Educational Resources Information Center

Houston, J. Brian; First, Jennifer; Spialek, Matthew L.; Sorenson, Mary E.; Mills-Sandoval, Toby; Lockett, McKenzie; First, Nathan L.; Nitiéma, Pascal; Allen, Sandra F.; Pfefferbaum, Betty

2017-01-01

Objective: The purpose of this pilot study was to evaluate the Resilience and Coping Intervention (RCI) with college students. Participants: College students (aged 18-23) from a large Midwest US university who volunteered for a randomized controlled trial during the 2015 spring semester. Methods: College students were randomly assigned to an…

Evaluating the Collaborative Strategic Reading Intervention: An Overview of Randomized Controlled Trial Options

ERIC Educational Resources Information Center

Hitchcock, John H.; Kurki, Anja; Wilkins, Chuck; Dimino, Joseph; Gersten, Russell

2009-01-01

When attempting to determine if an intervention has a causal impact, the "gold standard" of program evaluation is the randomized controlled trial (RCT). In education studies random assignment is rarely feasible at the student level, making RCTs harder to conduct. School-level assignment is more common but this often requires considerable resources…

Effect of Educational Package on Lifestyle of Primiparous Mothers during Postpartum Period: A Randomized Controlled Clinical Trial

ERIC Educational Resources Information Center

Khodabandeh, Farzaneh; Mirghafourvand, Mojgan; KamaliFard, Mahin; Mohammad-Alizadeh-Charandabi, Sakineh; Asghari Jafarabadi, Mohammad

2017-01-01

A healthy lifestyle is important for mothers during the postpartum period. This study was conducted to determine the effects of a lifestyle educational package in primiparous women. This randomized clinical trial was conducted on 220 mothers assigned to two groups using block randomization. In the intervention group, the mothers received…

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…

Effects of Check and Connect on Attendance, Behavior, and Academics: A Randomized Effectiveness Trial

ERIC Educational Resources Information Center

Maynard, Brandy R.; Kjellstrand, Elizabeth K.; Thompson, Aaron M.

2014-01-01

Objectives: This study examined the effects of Check & Connect (C&C) on the attendance, behavior, and academic outcomes of at-risk youth in a field-based effectiveness trial. Method: A multisite randomized block design was used, wherein 260 primarily Hispanic (89%) and economically disadvantaged (74%) students were randomized to treatment…

Establishing Evidence-Based Indications for Proton Therapy: An Overview of Current Clinical Trials

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

Mishra, Mark V., E-mail: mmishra@umm.edu; Aggarwal, Sameer; Bentzen, Soren M.

Purpose: To review and assess ongoing proton beam therapy (PBT) clinical trials and to identify major gaps. Methods and Materials: Active PBT clinical trials were identified from (clinicaltrials.gov) and the World Health Organization International Clinical Trials Platform Registry. Data on clinical trial disease site, age group, projected patient enrollment, expected start and end dates, study type, and funding source were extracted. Results: A total of 122 active PBT clinical trials were identified, with target enrollment of >42,000 patients worldwide. Ninety-six trials (79%), with a median planned sample size of 68, were classified as interventional studies. Observational studies accounted for 21% ofmore » trials but 71% (n=29,852) of planned patient enrollment. The most common PBT clinical trials focus on gastrointestinal tract tumors (21%, n=26), tumors of the central nervous system (15%, n=18), and prostate cancer (12%, n=15). Five active studies (lung, esophagus, head and neck, prostate, breast) will randomize patients between protons and photons, and 3 will randomize patients between protons and carbon ion therapy. Conclusions: The PBT clinical trial portfolio is expanding rapidly. Although the majority of ongoing studies are interventional, the majority of patients will be accrued to observational studies. Future efforts should focus on strategies to encourage optimal patient enrollment and retention, with an emphasis on randomized, controlled trials, which will require support from third-party payers. Results of ongoing PBT studies should be evaluated in terms of comparative effectiveness, as well as incremental effectiveness and value offered by PBT in comparison with conventional radiation modalities.« less

Person mobility in the design and analysis of cluster-randomized cohort prevention trials.

PubMed

Vuchinich, Sam; Flay, Brian R; Aber, Lawrence; Bickman, Leonard

2012-06-01

Person mobility is an inescapable fact of life for most cluster-randomized (e.g., schools, hospitals, clinic, cities, state) cohort prevention trials. Mobility rates are an important substantive consideration in estimating the effects of an intervention. In cluster-randomized trials, mobility rates are often correlated with ethnicity, poverty and other variables associated with disparity. This raises the possibility that estimated intervention effects may generalize to only the least mobile segments of a population and, thus, create a threat to external validity. Such mobility can also create threats to the internal validity of conclusions from randomized trials. Researchers must decide how to deal with persons who leave study clusters during a trial (dropouts), persons and clusters that do not comply with an assigned intervention, and persons who enter clusters during a trial (late entrants), in addition to the persons who remain for the duration of a trial (stayers). Statistical techniques alone cannot solve the key issues of internal and external validity raised by the phenomenon of person mobility. This commentary presents a systematic, Campbellian-type analysis of person mobility in cluster-randomized cohort prevention trials. It describes four approaches for dealing with dropouts, late entrants and stayers with respect to data collection, analysis and generalizability. The questions at issue are: 1) From whom should data be collected at each wave of data collection? 2) Which cases should be included in the analyses of an intervention effect? and 3) To what populations can trial results be generalized? The conclusions lead to recommendations for the design and analysis of future cluster-randomized cohort prevention trials.

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.

Perceptions of Massage Therapists Participating in a Randomized Controlled Trial

PubMed Central

Perlman, Adam; Dreusicke, Mark; Keever, Teresa; Ali, Ather

2015-01-01

Background Clinical practice and randomized trials often have disparate aims, despite involving similar interventions. Attitudes and expectancies of practitioners influence patient outcomes, and there is growing emphasis on optimizing provider–patient relationships. In this study, we evaluated the experiences of licensed massage therapists involved in a randomized controlled clinical trial using qualitative methodology. Methods Seven massage therapists who were interventionists in a randomized controlled trial participated in structured interviews approximately 30 minutes in length. Interviews focused on their experiences and perceptions regarding aspects of the clinical trial, as well as recommendations for future trials. Transcribed interviews were analyzed for emergent topics and themes using standard qualitative methods. Results Six themes emerged. Therapists discussed 1) promoting the profession of massage therapy through research, 2) mixed views on using standardized protocols, 3) challenges of sham interventions, 4) participant response to the sham intervention, 5) views on scheduling and compensation, and 6) unanticipated benefits of participating in research. Conclusions Therapists largely appreciated the opportunity to promote massage through research. They demonstrated insight and understanding of the rationale for a clinical trial adhering to a standardized protocol. Evaluating the experiences and ideas of complementary and alternative medicine practitioners provides valuable insight that is relevant for the implementation and design of randomized trials. PMID:26388961

Random Versus Blocked Practice to Enhance Mental Representation in Golf Putting.

PubMed

Fazeli, Davoud; Taheri, HamidReza; Saberi Kakhki, Alireza

2017-06-01

The purpose of this study was to investigate changes in mental representation from either random or blocked practice when engaged in golf putting. Thirty participants were randomly assigned to random practice, blocked practice, and no-practice groups. First, we measured novice golfers' initial mental representation levels and required them to perform 18 putting trials as a pre-test. We then asked random and blocked groups to practice in accordance with their group assignment for six consecutive days (10 blocks each day, 18 trials each). A week after the last practice session, we re-measured all participants' final mental representation levels and required them to perform 18 putting trials to evaluate learning retention through practice. While those engaged in the random practice method putted more poorly during acquisition (i.e., practice) than those in blocked practice, the random practice group experienced more accurate retention during the final putting trials, and they showed a more structured mental representation than those in blocked practice, one that was more similar to that of skilled golfers. These results support the acquisition of a rich mental representation through random versus blocked practice.

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

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.

Informed Consent to Study Purpose in Randomized Clinical Trials of Antibiotics, 1991 Through 2011.

PubMed

Doshi, Peter; Hur, Peter; Jones, Mark; Albarmawi, Husam; Jefferson, Tom; Morgan, Daniel J; Spears, Patricia A; Powers, John H

2017-10-01

Potential research participants may assume that randomized trials comparing new interventions with older interventions always hypothesize greater efficacy for the new intervention, as in superiority trials. However, antibiotic trials frequently use "noninferiority" hypotheses allowing a degree of inferior efficacy deemed "clinically acceptable" compared with an older effective drug, in exchange for nonefficacy benefits (eg, decreased adverse effects). Considering these different benefit-harm trade-offs, proper informed consent necessitates supplying different information on the purposes of superiority and noninferiority trials. To determine the degree to which the study purpose is explained to potential participants in randomized clinical trials of antibiotics and the degree to which study protocols justify their selection of noninferiority hypotheses and amount of "clinically acceptable" inferiority. Cross-sectional analysis of study protocols, statistical analysis plans (SAPs), and informed consent forms (ICFs) from clinical study reports submitted to the European Medicines Agency. The ICFs were read by both methodologists and patient investigators. Protocols and SAPs were used as the reference standard to determine prespecified primary hypothesis and record rationale for selection of noninferiority hypotheses and noninferiority margins. This information was cross-referenced against ICFs to determine whether ICFs explained the study purpose. We obtained trial documents from 78 randomized trials with prespecified efficacy hypotheses (6 superiority, 72 noninferiority) for 17 antibiotics conducted between 1991 and 2011 that enrolled 39 407 patients. Fifty were included in the ICF analysis. All ICFs contained sections describing study purpose; however, none consistently conveyed study hypothesis to both methodologists and patient investigators. Methodologists found that 1 of 50 conveyed a study purpose. Patient investigators found that 11 of 50 conveyed a study purpose, 7 accurately and 4 inaccurately compared with the reference standard. Seventy-one of 72 noninferiority trial protocols or SAPs provided no rationale for selection of noninferiority hypothesis. None provided a clinical rationale for the chosen amount of decreased efficacy. Patients were not accurately informed of study purpose, which raises questions regarding the ethics of informed consent in antibiotic trials. Noninferiority and superiority trials entail different benefit-harm trade-offs that must be conveyed for ethical informed consent.

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.

Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid (TPOP): study protocol for a randomized controlled trial.

PubMed

Matsuoka, Yutaka; Nishi, Daisuke; Yonemoto, Naohiro; Hamazaki, Kei; Matsumura, Kenta; Noguchi, Hiroko; Hashimoto, Kenji; Hamazaki, Tomohito

2013-01-05

Preclinical and clinical studies suggest that supplementation with omega-3 fatty acids after trauma might reduce subsequent posttraumatic stress disorder (PTSD). To date, we have shown in an open trial that PTSD symptoms in critically injured patients can be reduced by taking omega-3 fatty acids, hypothesized to stimulate hippocampal neurogenesis. The primary aim of the present randomized controlled trial is to examine the efficacy of omega-3 fatty acid supplementation in the secondary prevention of PTSD following accidental injury, as compared with placebo. This paper describes the rationale and protocol of this trial. The Tachikawa Project for Prevention of Posttraumatic Stress Disorder with Polyunsaturated Fatty Acid (TPOP) is a double-blinded, parallel group, randomized controlled trial to assess whether omega-3 fatty acid supplementation can prevent PTSD symptoms among accident-injured patients consecutively admitted to an intensive care unit. We plan to recruit accident-injured patients and follow them prospectively for 12 weeks. Enrolled patients will be randomized to either the omega-3 fatty acid supplement group (1,470 mg docosahexaenoic acid and 147 mg eicosapentaenoic acid daily) or placebo group. Primary outcome is score on the Clinician-Administered PTSD Scale (CAPS). We will need to randomize 140 injured patients to have 90% power to detect a 10-point difference in mean CAPS scores with omega-3 fatty acid supplementation compared with placebo. Secondary measures are diagnosis of PTSD and major depressive disorder, depressive symptoms, physiologic response in the experiment using script-driven imagery and acoustic stimulation, serum brain-derived neurotrophic factor, health-related quality of life, resilience, and aggression. Analyses will be by intent to treat. The trial was initiated on December 13 2008, with 104 subjects randomized by November 30 2012. This study promises to be the first trial to provide a novel prevention strategy for PTSD among traumatized people. ClinicalTrials.gov Identifier NCT00671099.

Orthodontic treatment in periodontitis‐susceptible subjects: a systematic literature review

PubMed Central

Lindsten, Rune; Slotte, Christer; Bjerklin, Krister

2016-01-01

Abstract The aim is to evaluate the literature for clinical scientific data on possible effects of orthodontic treatment on periodontal status in periodontitis‐susceptible subjects. A systematic literature review was performed on studies in English using PubMed, MEDLINE, and Cochrane Library central databases (1965‐2014). By manually searching reference lists of selected studies, we identified additional articles; then we searched these publications: Journal of Periodontology, Periodontology 2000, Journal of Clinical Periodontology, American Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontist, International Journal of Periodontics & Restorative Dentistry, and European Journal of Orthodontics. Search terms included randomized clinical trials, controlled clinical trials, prospective and retrospective clinical studies, case series >5 patients, periodontitis, orthodontics, alveolar bone loss, tooth migration, tooth movement, orthodontic extrusion, and orthodontic intrusion. Only studies on orthodontic treatment in periodontally compromised dentitions were included. One randomized controlled clinical trial, one controlled clinical trial, and 12 clinical studies were included. No evidence currently exists from controlled studies and randomized controlled clinical trials, which shows that orthodontic treatment improves or aggravates the status of periodontally compromised dentitions. PMID:29744163

Reporting of participant flow diagrams in published reports of randomized trials

PubMed Central

2011-01-01

Background Reporting of the flow of participants through each stage of a randomized trial is essential to assess the generalisability and validity of its results. We assessed the type and completeness of information reported in CONSORT (Consolidated Standards of Reporting Trials) flow diagrams published in current reports of randomized trials. Methods A cross sectional review of all primary reports of randomized trials which included a CONSORT flow diagram indexed in PubMed core clinical journals (2009). We assessed the proportion of parallel group trial publications reporting specific items recommended by CONSORT for inclusion in a flow diagram. Results Of 469 primary reports of randomized trials, 263 (56%) included a CONSORT flow diagram of which 89% (237/263) were published in a CONSORT endorsing journal. Reports published in CONSORT endorsing journals were more likely to include a flow diagram (62%; 237/380 versus 29%; 26/89). Ninety percent (236/263) of reports which included a flow diagram had a parallel group design, of which 49% (116/236) evaluated drug interventions, 58% (137/236) were multicentre, and 79% (187/236) compared two study groups, with a median sample size of 213 participants. Eighty-one percent (191/236) reported the overall number of participants assessed for eligibility, 71% (168/236) the number excluded prior to randomization and 98% (231/236) the overall number randomized. Reasons for exclusion prior to randomization were more poorly reported. Ninety-four percent (223/236) reported the number of participants allocated to each arm of the trial. However, only 40% (95/236) reported the number who actually received the allocated intervention, 67% (158/236) the number lost to follow up in each arm of the trial, 61% (145/236) whether participants discontinued the intervention during the trial and 54% (128/236) the number included in the main analysis. Conclusions Over half of published reports of randomized trials included a diagram showing the flow of participants through the trial. However, information was often missing from published flow diagrams, even in articles published in CONSORT endorsing journals. If important information is not reported it can be difficult and sometimes impossible to know if the conclusions of that trial are justified by the data presented. PMID:22141446

Latent Subgroup Analysis of a Randomized Clinical Trial Through a Semiparametric Accelerated Failure Time Mixture Model

PubMed Central

Altstein, L.; Li, G.

2012-01-01

Summary This paper studies a semiparametric accelerated failure time mixture model for estimation of a biological treatment effect on a latent subgroup of interest with a time-to-event outcome in randomized clinical trials. Latency is induced because membership is observable in one arm of the trial and unidentified in the other. This method is useful in randomized clinical trials with all-or-none noncompliance when patients in the control arm have no access to active treatment and in, for example, oncology trials when a biopsy used to identify the latent subgroup is performed only on subjects randomized to active treatment. We derive a computational method to estimate model parameters by iterating between an expectation step and a weighted Buckley-James optimization step. The bootstrap method is used for variance estimation, and the performance of our method is corroborated in simulation. We illustrate our method through an analysis of a multicenter selective lymphadenectomy trial for melanoma. PMID:23383608

A Mixed-Methods, Randomized, Controlled Feasibility Trial to Inform the Design of a Phase III Trial to Test the Effect of the Handheld Fan on Physical Activity and Carer Anxiety in Patients With Refractory Breathlessness.

PubMed

Johnson, Miriam J; Booth, Sara; Currow, David C; Lam, Lawrence T; Phillips, Jane L

2016-05-01

The handheld fan is an inexpensive and safe way to provide facial airflow, which may reduce the sensation of chronic refractory breathlessness, a frequently encountered symptom. To test the feasibility of developing an adequately powered, multicenter, multinational randomized controlled trial comparing the efficacy of a handheld fan and exercise advice with advice alone in increasing activity in people with chronic refractory breathlessness from a variety of medical conditions, measuring recruitment rates; data quality; and potential primary outcome measures. This was a Phase II, multisite, international, parallel, nonblinded, mixed-methods randomized controlled trial. Participants were centrally randomized to fan or control. All received breathlessness self-management/exercise advice and were followed up weekly for four weeks. Participants/carers were invited to participate in a semistructured interview at the study's conclusion. Ninety-seven people were screened, 49 randomized (mean age 68 years; 49% men), and 43 completed the study. Site recruitment varied from 0.25 to 3.3/month and screening:randomization from 1.1:1 to 8.5:1. There were few missing data except for the Chronic Obstructive Pulmonary Disease Self-Efficacy Scale (two-thirds of data missing). No harms were observed. Three interview themes included 1) a fan is a helpful self-management strategy, 2) a fan aids recovery, and 3) a symptom control trial was welcome. A definitive, multisite trial to study the use of the handheld fan as part of self-management of chronic refractory breathlessness is feasible. Participants found the fan useful. However, the value of information for changing practice or policy is unlikely to justify the expense of such a trial, given perceived benefits, the minimal costs, and an absence of harms demonstrated in this study. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Recruiting Participants for Randomized Controlled Trials

ERIC Educational Resources Information Center

Gallagher, H. Alix; Roschelle, Jeremy; Feng, Mingyu

2014-01-01

The objective of this study was to look across strategies used in a wide range of studies to build a framework for researchers to use in conceptualizing the recruitment process. This paper harvests lessons learned across 19 randomized controlled trials in K-12 school settings conducted by a leading research organization to identify strategies that…

A Randomized Trial of Two Promising Computer-Based Interventions for Students with Attention Difficulties

ERIC Educational Resources Information Center

Rabiner, David L.; Murray, Desiree W.; Skinner, Ann T; Malone, Patrick S.

2010-01-01

Few studies have examined whether attention can be improved with training, even though attention difficulties adversely affect academic achievement. The present study was a randomized-controlled trial evaluating the impact of Computerized Attention Training (CAT) and Computer Assisted Instruction (CAI) on attention and academic performance in 77…

Acupuncture for Children with Autism Spectrum Disorders: A Systematic Review of Randomized Clinical Trials

ERIC Educational Resources Information Center

Lee, Myeong Soo; Choi, Tae-Young; Shin, Byung-Cheul; Ernst, Edzard

2012-01-01

This study aimed to assess the effectiveness of acupuncture as a treatment for autism spectrum disorders (ASD). We searched the literature using 15 databases. Eleven randomized clinical trials (RCTs) met our inclusion criteria. Most had significant methodological weaknesses. The studies' statistical and clinical heterogeneity prevented us from…

Fit 5 Kids TV reduction program for Latino preschoolers: A cluster randomized controlled trial

USDA-ARS?s Scientific Manuscript database

Reducing Latino preschoolers' TV viewing is needed to reduce their risk of obesity and other chronic diseases. This study's objective was to evaluate the Fit 5 Kids (F5K) TV reduction program's impact on Latino preschooler's TV viewing. The study design was a cluster randomized controlled trial (RCT...

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…

Explanatory Versus Pragmatic Trials: An Essential Concept in Study Design and Interpretation.

PubMed

Merali, Zamir; Wilson, Jefferson R

2017-11-01

Randomized clinical trials often represent the highest level of clinical evidence available to evaluate the efficacy of an intervention in clinical medicine. Although the process of randomization serves to maximize internal validity, the external validity, or generalizability, of such studies depends on several factors determined at the design phase of the trial including eligibility criteria, study setting, and outcomes of interest. In general, explanatory trials are optimized to demonstrate the efficacy of an intervention in a highly selected patient group; however, findings from these studies may not be generalizable to the larger clinical problem. In contrast, pragmatic trials attempt to understand the real-world benefit of an intervention by incorporating design elements that allow for greater generalizability and clinical applicability of study results. In this article we describe the explanatory-pragmatic continuum for clinical trials in greater detail. Further, a well-accepted tool for grading trials on this continuum is described, and applied, to 2 recently published trials pertaining to the surgical management of lumbar degenerative spondylolisthesis.

Efficient design of clinical trials and epidemiological research: is it possible?

PubMed

Lauer, Michael S; Gordon, David; Wei, Gina; Pearson, Gail

2017-08-01

Randomized clinical trials and large-scale, cohort studies continue to have a critical role in generating evidence in cardiovascular medicine; however, the increasing concern is that ballooning costs threaten the clinical trial enterprise. In this Perspectives article, we discuss the changing landscape of clinical research, and clinical trials in particular, focusing on reasons for the increasing costs and inefficiencies. These reasons include excessively complex design, overly restrictive inclusion and exclusion criteria, burdensome regulations, excessive source-data verification, and concerns about the effect of clinical research conduct on workflow. Thought leaders have called on the clinical research community to consider alternative, transformative business models, including those models that focus on simplicity and leveraging of digital resources. We present some examples of innovative approaches by which some investigators have successfully conducted large-scale, clinical trials at relatively low cost. These examples include randomized registry trials, cluster-randomized trials, adaptive trials, and trials that are fully embedded within digital clinical care or administrative platforms.

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.

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design

PubMed Central

2011-01-01

Background Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. Discussion patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011). Trial Registration Trial listed in ClinicalTrials.gov as NCT00166257 and sponsored by AGA Medical, Plymouth, MN, USA PMID:21356042

Randomized controlled trials in mild cognitive impairment

PubMed Central

Thomas, Ronald G.; Aisen, Paul S.; Mohs, Richard C.; Carrillo, Maria C.; Albert, Marilyn S.

2017-01-01

Objective: To examine the variability in performance among placebo groups in randomized controlled trials for mild cognitive impairment (MCI). Methods: Placebo group data were obtained from 2 National Institute on Aging (NIA) MCI randomized controlled trials, the Alzheimer's Disease Cooperative Study (ADCS) MCI trial and the Alzheimer's Disease Neuroimaging Initiative (ADNI), which is a simulated clinical trial, in addition to industry-sponsored clinical trials involving rivastigmine, galantamine, rofecoxib, and donepezil. The data were collated for common measurement instruments. The performance of the placebo participants from these studies was tracked on the Alzheimer's Disease Assessment Scale–cognitive subscale, Mini-Mental State Examination, and Clinical Dementia Rating–sum of boxes, and for progression on these measures to prespecified clinical study endpoints. APOE status, where available, was also analyzed for its effects. Results: The progression to clinical endpoints varied a great deal among the trials. The expected performances were seen for the participants in the 2 NIA trials, ADCS and ADNI, with generally worsening of performance over time; however, the industry-sponsored trials largely showed stable or improved performance in their placebo participants. APOE4 carrier status influenced results in an expected fashion on the study outcomes, including rates of progression and cognitive subscales. Conclusions: In spite of apparently similar criteria for MCI being adopted by the 7 studies, the implementation of the criteria varied a great deal. Several explanations including instruments used to characterize participants and variability among study populations contributed to the findings. PMID:28381516

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.

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…

A Randomized Controlled Trial of Two Syntactic Treatment Procedures with Cantonese-Speaking, School-Age Children with Language Disorders

ERIC Educational Resources Information Center

To, Carol K. S.; Lui, Hoi Ming; Li, Xin Xin; Lam, Gary Y. H

2015-01-01

Purpose: In this study, we aimed to evaluate the efficacy of sentence-combining (SC) and narrative-based (NAR) intervention approaches to syntax intervention using a randomized-controlled-trial design. Method: Fifty-two Cantonese-speaking, school-age children with language impairment were assigned randomly to either the SC or the NAR treatment…

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.

Randomization in clinical trials: stratification or minimization? The HERMES free simulation software.

PubMed

Fron Chabouis, Hélène; Chabouis, Francis; Gillaizeau, Florence; Durieux, Pierre; Chatellier, Gilles; Ruse, N Dorin; Attal, Jean-Pierre

2014-01-01

Operative clinical trials are often small and open-label. Randomization is therefore very important. Stratification and minimization are two randomization options in such trials. The first aim of this study was to compare stratification and minimization in terms of predictability and balance in order to help investigators choose the most appropriate allocation method. Our second aim was to evaluate the influence of various parameters on the performance of these techniques. The created software generated patients according to chosen trial parameters (e.g., number of important prognostic factors, number of operators or centers, etc.) and computed predictability and balance indicators for several stratification and minimization methods over a given number of simulations. Block size and proportion of random allocations could be chosen. A reference trial was chosen (50 patients, 1 prognostic factor, and 2 operators) and eight other trials derived from this reference trial were modeled. Predictability and balance indicators were calculated from 10,000 simulations per trial. Minimization performed better with complex trials (e.g., smaller sample size, increasing number of prognostic factors, and operators); stratification imbalance increased when the number of strata increased. An inverse correlation between imbalance and predictability was observed. A compromise between predictability and imbalance still has to be found by the investigator but our software (HERMES) gives concrete reasons for choosing between stratification and minimization; it can be downloaded free of charge. This software will help investigators choose the appropriate randomization method in future two-arm trials.

Effects of zinc supplementation on subscales of anorexia in children: A randomized controlled trial.

PubMed

Khademian, Majid; Farhangpajouh, Neda; Shahsanaee, Armindokht; Bahreynian, Maryam; Mirshamsi, Mehran; Kelishadi, Roya

2014-01-01

This study aims to assess the effects of zinc supplementation on improving the appetite and its subscales in children. This study was conducted in 2013 in Isfahan, Iran. It had two phases. At the first step, after validation of the Child Eating Behaviour Questionaire (CEBQ), it was completed for 300 preschool children, who were randomly selected. The second phase was conducted as a randomized controlled trial. Eighty of these children were randomly selected, and were randomly assigned to two groups of equal number receiving zinc (10 mg/day) or placebo for 12 weeks. Overall 77 children completed the trial (39 in the case and 3 in the control group).The results showed that zinc supplement can improve calorie intake in children by affecting some CEBQ subscales like Emotional over Eating and Food Responsible. Zinc supplementation had positive impact in promoting the calorie intake and some subscales of anorexia.

Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen M; Alothman, Adel; Balkhy, Hanan H; Al-Dawood, Abdulaziz; AlJohani, Sameera; Al Harbi, Shmeylan; Kojan, Suleiman; Al Jeraisy, Majed; Deeb, Ahmad M; Assiri, Abdullah M; Al-Hameed, Fahad; AlSaedi, Asim; Mandourah, Yasser; Almekhlafi, Ghaleb A; Sherbeeni, Nisreen Murad; Elzein, Fatehi Elnour; Memon, Javed; Taha, Yusri; Almotairi, Abdullah; Maghrabi, Khalid A; Qushmaq, Ismael; Al Bshabshe, Ali; Kharaba, Ayman; Shalhoub, Sarah; Jose, Jesna; Fowler, Robert A; Hayden, Frederick G; Hussein, Mohamed A

2018-01-30

It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

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

Biases in Estimating Treatment Effects Due to Attrition in Randomized Controlled Trials and Cluster Randomized Controlled Trials: A Simulation Study

ERIC Educational Resources Information Center

Dong, Nianbo; Lipsey, Mark W.

2011-01-01

Attrition occurs when study participants who were assigned to the treatment and control conditions do not provide outcome data and thus do not contribute to the estimation of the treatment effects. It is very common in experimental studies in education as illustrated, for instance, in a meta-analysis studying "the effects of attrition on baseline…

Methodological quality of randomized controlled trials of spinal manipulation and mobilization in tension-type headache, migraine, and cervicogenic headache.

PubMed

Fernández-de-las-Peñas, César; Alonso-Blanco, Cristina; San-Roman, Jesús; Miangolarra-Page, Juan C

2006-03-01

Literature review of quality of clinical trials. To determine the methodological quality of published randomized controlled trials that used spinal manipulation and/or mobilization to treat patients with tension-type headache (TTH), cervicogenic headache (CeH), and migraine (M) in the last decade. TTH, CeH, and M are the most prevalent types of headaches seen in adults. Individuals who have headaches frequently use physical therapy, manual therapy, or chiropractic care. Randomized controlled trials are considered an optimal method with which to assess the efficacy of any intervention. Computerized literature searches were performed in MEDLINE, EMBASE, COCHRANE, AMED, MANTIS, CINHAL, and PEDro databases. Randomized controlled trials in which spinal manipulation and/or mobilization had been used for TTH, CeH, and M published in a peer-reviewed journal as full text, and with at least 1 clinically relevant outcome measure (ie, headache intensity, duration, or frequency) were reviewed. The methodological quality of the studies was assessed independently by 2 reviewers using a set of predefined criteria. Only 8 studies met all the inclusion criteria. One clinical trial evaluated spinal manipulation and mobilization together, and the remaining 7 assessed spinal manipulative therapy. No controlled trials analyzing exclusively the effects of spinal mobilization were found. Methodological scores ranged from 35 to 56 points out of a theoretical maximum of 100 points, indicating an overall poor methodology of the studies. Only 2 studies obtained a high-quality score (greater than 50 points). No significant differences in quality scores were found based on the type of headache investigated. Methodological quality was not associated with the year of publication (before 2000, or later) nor with the results (positive, neutral, negative) reported in the studies. The most common flaws were a small sample size, the absence of a placebo control group, lack of blinded patients, and no description of the manipulative procedure. There are few published randomized controlled trials analyzing the effectiveness of spinal manipulation and/or mobilization for TTH, CeH, and M in the last decade. In addition, the methodological quality of these papers is typically low. Clearly, there is a need for high-quality randomized controlled trials assessing the effectiveness of these interventions in these headache disorders.

Value of information analysis optimizing future trial design from a pilot study on catheter securement devices.

PubMed

Tuffaha, Haitham W; Reynolds, Heather; Gordon, Louisa G; Rickard, Claire M; Scuffham, Paul A

2014-12-01

Value of information analysis has been proposed as an alternative to the standard hypothesis testing approach, which is based on type I and type II errors, in determining sample sizes for randomized clinical trials. However, in addition to sample size calculation, value of information analysis can optimize other aspects of research design such as possible comparator arms and alternative follow-up times, by considering trial designs that maximize the expected net benefit of research, which is the difference between the expected cost of the trial and the expected value of additional information. To apply value of information methods to the results of a pilot study on catheter securement devices to determine the optimal design of a future larger clinical trial. An economic evaluation was performed using data from a multi-arm randomized controlled pilot study comparing the efficacy of four types of catheter securement devices: standard polyurethane, tissue adhesive, bordered polyurethane and sutureless securement device. Probabilistic Monte Carlo simulation was used to characterize uncertainty surrounding the study results and to calculate the expected value of additional information. To guide the optimal future trial design, the expected costs and benefits of the alternative trial designs were estimated and compared. Analysis of the value of further information indicated that a randomized controlled trial on catheter securement devices is potentially worthwhile. Among the possible designs for the future trial, a four-arm study with 220 patients/arm would provide the highest expected net benefit corresponding to 130% return-on-investment. The initially considered design of 388 patients/arm, based on hypothesis testing calculations, would provide lower net benefit with return-on-investment of 79%. Cost-effectiveness and value of information analyses were based on the data from a single pilot trial which might affect the accuracy of our uncertainty estimation. Another limitation was that different follow-up durations for the larger trial were not evaluated. The value of information approach allows efficient trial design by maximizing the expected net benefit of additional research. This approach should be considered early in the design of randomized clinical trials. © The Author(s) 2014.

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

PubMed

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

2018-06-07

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

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.

Effect of Cosmos caudatus (Ulam raja) supplementation in patients with type 2 diabetes: Study protocol for a randomized controlled trial.

PubMed

Cheng, Shi-Hui; Ismail, Amin; Anthony, Joseph; Ng, Ooi Chuan; Hamid, Azizah Abdul; Yusof, Barakatun-Nisak Mohd

2016-02-27

Type 2 diabetes mellitus is a major health threat worldwide. Cosmos caudatus is one of the medicinal plants used to treat type 2 diabetes. Therefore, this study aims to determine the effectiveness and safety of C. caudatus in patients with type 2 diabetes. Metabolomic approach will be carried out to compare the metabolite profiles between C. Caudatus treated diabetic patients and diabetic controls. This is a single-center, randomized, controlled, two-arm parallel design clinical trial that will be carried out in a tertiary hospital in Malaysia. In this study, 100 patients diagnosed with type 2 diabetes will be enrolled. Diabetic patients who meet the eligibility criteria will be randomly allocated to two groups, which are diabetic C. caudatus treated(U) group and diabetic control (C) group. Primary and secondary outcomes will be measured at baseline, 4, 8, and 12 weeks. The serum and urine metabolome of both groups will be examined using proton NMR spectroscopy. The study will be the first randomized controlled trial to assess whether C. caudatus can confer beneficial effect in patients with type 2 diabetes. The results of this trial will provide clinical evidence on the effectiveness and safety of C. caudatus in patients with type 2 diabetes. ClinicalTrials.gov identifier: NCT02322268.

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.

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.

Implementing collaborative primary care for depression and posttraumatic stress disorder: design and sample for a randomized trial in the U.S. military health system.

PubMed

Engel, Charles C; Bray, Robert M; Jaycox, Lisa H; Freed, Michael C; Zatzick, Doug; Lane, Marian E; Brambilla, Donald; Rae Olmsted, Kristine; Vandermaas-Peeler, Russ; Litz, Brett; Tanielian, Terri; Belsher, Bradley E; Evatt, Daniel P; Novak, Laura A; Unützer, Jürgen; Katon, Wayne J

2014-11-01

War-related trauma, posttraumatic stress disorder (PTSD), depression and suicide are common in US military members. Often, those affected do not seek treatment due to stigma and barriers to care. When care is sought, it often fails to meet quality standards. A randomized trial is assessing whether collaborative primary care improves quality and outcomes of PTSD and depression care in the US military health system. The aim of this study is to describe the design and sample for a randomized effectiveness trial of collaborative care for PTSD and depression in military members attending primary care. The STEPS-UP Trial (STepped Enhancement of PTSD Services Using Primary Care) is a 6 installation (18 clinic) randomized effectiveness trial in the US military health system. Study rationale, design, enrollment and sample characteristics are summarized. Military members attending primary care with suspected PTSD, depression or both were referred to care management and recruited for the trial (2592), and 1041 gave permission to contact for research participation. Of those, 666 (64%) met eligibility criteria, completed baseline assessments, and were randomized to 12 months of usual collaborative primary care versus STEPS-UP collaborative care. Implementation was locally managed for usual collaborative care and centrally managed for STEPS-UP. Research reassessments occurred at 3-, 6-, and 12-months. Baseline characteristics were similar across the two intervention groups. STEPS-UP will be the first large scale randomized effectiveness trial completed in the US military health system, assessing how an implementation model affects collaborative care impact on mental health outcomes. It promises lessons for health system change. Copyright © 2014 Elsevier Inc. All rights reserved.

Increasing response rates to follow-up questionnaires in health intervention research: Randomized controlled trial of a gift card prize incentive.

PubMed

Morgan, Amy J; Rapee, Ronald M; Bayer, Jordana K

2017-08-01

Background/aims Achieving a high response rate to follow-up questionnaires in randomized controlled trials of interventions is important for study validity. Few studies have tested the value of incentives in increasing response rates to online questionnaires in clinical trials of health interventions. This study evaluated the effect of a gift card prize-draw incentive on response rates to follow-up questionnaires within a trial of an online health intervention. Method The study was embedded in a host randomized controlled trial of an online parenting program for child anxiety. A total of 433 participants were randomly allocated to one of two groups: (1) being informed that they would enter a gift card prize-draw if they completed the final study questionnaire (24-week follow-up) and (2) not informed about the prize-draw. All participants had a 1 in 20 chance of winning an AUD50 gift card after they completed the online questionnaire. Results The odds of the informed group completing the follow-up questionnaire were significantly higher than the uninformed group, (79.6% vs 68.5%, odds ratio = 1.79, 95% confidence interval = 1.15-2.79). This response rate increase of 11.1% (95% confidence interval = 2.8-19.1) occurred in both intervention and control groups in the host randomized controlled trial. The incentive was also effective in increasing questionnaire commencement (84.6% vs 75.9%, odds ratio = 1.74, 95% confidence interval = 1.07-2.84) and reducing the delay in completing the questionnaire (19.9 vs 22.6 days, hazard ratio = 1.34, 95% confidence interval = 1.07-1.67). Conclusion This study adds to evidence for the effectiveness of incentives to increase response rates to follow-up questionnaires in health intervention trials.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol.

PubMed

Sandilands, Euan A; Cameron, Sharon; Paterson, Frances; Donaldson, Sam; Briody, Lesley; Crowe, Jane; Donnelly, Julie; Thompson, Adrian; Johnston, Neil R; Mackenzie, Ivor; Uren, Neal; Goddard, Jane; Webb, David J; Megson, Ian L; Bateman, Nicholas; Eddleston, Michael

2012-02-03

Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.

Experiences of being a control group: lessons from a UK-based randomized controlled trial of group singing as a health promotion initiative for older people.

PubMed

Skingley, Ann; Bungay, Hilary; Clift, Stephen; Warden, June

2014-12-01

Existing randomized controlled trials within the health field suggest that the concept of randomization is not always well understood and that feelings of disappointment may occur when participants are not placed in their preferred arm. This may affect a study's rigour and ethical integrity if not addressed. We aimed to test whether these issues apply to a healthy volunteer sample within a health promotion trial of singing for older people. Written comments from control group participants at two points during the trial were analysed, together with individual semi-structured interviews with a small sample (n = 11) of this group. We found that motivation to participate in the trial was largely due to the appeal of singing and disappointment resulted from allocation to the control group. Understanding of randomization was generally good and feelings of disappointment lessened over time and with a post-research opportunity to sing. Findings suggest that measures should be put in place to minimize the potential negative impacts of randomized controlled trials in health promotion research. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

Sleep-Disordered Breathing in Chronic SCI: A Randomized Controlled Trial of Treatment Impact on Cognition, Quality of Life, and Cardiovascular Disease

DTIC Science & Technology

2014-10-01

SCI. In this prospective randomized controlled trial, we will objectively measure sleep disordered breathing ( SDB ) in chronic SCI patients using...portable sleep studies, and systematically evaluate the association between SDB , cognitive performance, mood, pain, and CV measures. We will randomize...randomized shortly. 15. SUBJECT TERMS SDB , SCI, PAP, CV 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a

Revisiting sample size: are big trials the answer?

PubMed

Lurati Buse, Giovanna A L; Botto, Fernando; Devereaux, P J

2012-07-18

The superiority of the evidence generated in randomized controlled trials over observational data is not only conditional to randomization. Randomized controlled trials require proper design and implementation to provide a reliable effect estimate. Adequate random sequence generation, allocation implementation, analyses based on the intention-to-treat principle, and sufficient power are crucial to the quality of a randomized controlled trial. Power, or the probability of the trial to detect a difference when a real difference between treatments exists, strongly depends on sample size. The quality of orthopaedic randomized controlled trials is frequently threatened by a limited sample size. This paper reviews basic concepts and pitfalls in sample-size estimation and focuses on the importance of large trials in the generation of valid evidence.

Update to the study protocol, including statistical analysis plan for a randomized clinical trial comparing comprehensive cardiac rehabilitation after heart valve surgery with control: the CopenHeartVR trial.

PubMed

Sibilitz, Kirstine Laerum; Berg, Selina Kikkenborg; Hansen, Tina Birgitte; Risom, Signe Stelling; Rasmussen, Trine Bernholdt; Hassager, Christian; Køber, Lars; Gluud, Christian; Thygesen, Lau Caspar; Lindschou, Jane; Schmid, Jean Paul; Taylor, Rod S; Zwisler, Ann-Dorthe

2015-02-05

Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising because of an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post-surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesize that a comprehensive cardiac rehabilitation program can improve physical capacity and self-assessed mental health and reduce hospitalization and healthcare costs after heart valve surgery. This randomized clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients 1:1 to an intervention or a control group, using central randomization, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise and a psycho-educational intervention comprising five consultations. The primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. The secondary outcome is self-assessed mental health measured by the standardized questionnaire Short Form-36. Long-term healthcare utilization and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design will be used to evaluate qualitative and quantitative findings, encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. This randomized clinical trial will contribute with evidence of whether cardiac rehabilitation should be provided after heart valve surgery. The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015). Trial registered 16 March 2012; ClinicalTrials.gov ( NCT01558765 ).

Why Randomized Trials Are Challenging within Adventure Therapy Research: Lessons Learned in Norway

ERIC Educational Resources Information Center

Gabrielsen, Leiv Einar; Fernee, Carina Ribe; Aasen, Gunnar Oland; Eskedal, Leif Torvald

2016-01-01

There are few high-quality studies using randomized controlled trials (RCTs) in the adventure and wilderness therapy literature. Thus, a unison call is heard for more such studies to be carried out. This article presents a Norwegian wilderness therapy research project that planned to incorporate this "gold standard" that is regarded as…

Lesson Study to Scale up Research-Based Knowledge: A Randomized, Controlled Trial of Fractions Learning

ERIC Educational Resources Information Center

Lewis, Catherine; Perry, Rebecca

2017-01-01

An understanding of fractions eludes many U.S. students, and research-based knowledge about fraction, such as the utility of linear representations, has not broadly influenced instruction. This randomized trial of lesson study supported by mathematical resources assigned 39 educator teams across the United States to locally managed lesson study…

A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma

USDA-ARS?s Scientific Manuscript database

Background: Evidence from observational studies suggests that inadequate folate status enhances colorectal carcinogenesis, but results from some randomized trials do not support this hypothesis. Objective: To assess the effect of folic acid supplementation on recurrent colorectal adenoma, we conduc...

Randomized Trial of the Effect of Four Second-Generation Antipsychotics and One First-Generation Antipsychotic on Cigarette Smoking, Alcohol, and Drug Use in Chronic Schizophrenia.

PubMed

Mohamed, Somaia; Rosenheck, Robert A; Lin, Haiqun; Swartz, Marvin; McEvoy, Joseph; Stroup, Scott

2015-07-01

No large-scale randomized trial has compared the effect of different second-generation antipsychotic drugs and any first-generation drug on alcohol, drug and nicotine use in patients with schizophrenia. The Clinical Antipsychotic Trial of Intervention Effectiveness study randomly assigned 1432 patients formally diagnosed with schizophrenia to four second-generation antipsychotic drugs (olanzapine, risperidone quetiapine, and ziprasidone) and one first-generation antipsychotic (perphenazine) and followed them for up to 18 months. Secondary outcome data documented cigarettes smoked in the past week and alcohol and drug use severity ratings. At baseline, 61% of patients smoked, 35% used alcohol, and 23% used illicit drugs. Although there were significant effects of time showing reduction in substance use over the 18 months (all p < 0.0001), this study found no evidence that any antipsychotic was robustly superior to any other in a secondary analysis of data on substance use outcomes from a large 18-month randomized schizophrenia trial.

How informative are open-label studies for youth with bipolar disorder? A meta-analysis comparing open-label versus randomized, placebo-controlled clinical trials.

PubMed

Biederman, Joseph; Petty, Carter R; Woodworth, K Yvonne; Lomedico, Alexandra; O'Connor, Katherine B; Wozniak, Janet; Faraone, Stephen V

2012-03-01

To examine the informativeness of open-label trials toward predicting results in subsequent randomized, placebo-controlled clinical trials of psychopharmacologic treatments for pediatric bipolar disorder. We searched journal articles through PubMed at the National Library of Medicine using bipolar disorder, mania, pharmacotherapy, treatment and clinical trial as keywords. This search was supplemented with scientific presentations at national and international scientific meetings and submitted manuscripts from our group. Selection criteria included (1) enrollment of children diagnosed with DSM-IV bipolar disorder; (2) prospective assessment of at least 3 weeks; (3) monotherapy of a pharmacologic treatment for bipolar disorder; (4) use of a randomized placebo-controlled design or an open-label design for the same therapeutic compound; and (5) repeated use of the Young Mania Rating Scale (YMRS) as an outcome. The following information and data were extracted from 14 studies: study design, name of medication, class of medication, dose of medication, sample size, age, sex, trial length, and YMRS mean and standard deviation baseline and follow-up scores. For both study designs, the pooled effect size was statistically significant (open-label studies, z = 8.88, P < .001; randomized placebo-controlled studies, z = 13.75, P < .001), indicating a reduction in the YMRS from baseline to endpoint in both study designs. In a meta-analysis regression, study design was not a significant predictor of mean change in the YMRS. We found similarities in the treatment effects between open-label and randomized placebo-controlled studies in youth with bipolar disorder indicating that open-label studies are useful predictors of the potential safety and efficacy of a given compound in the treatment of pediatric bipolar disorder. © Copyright 2012 Physicians Postgraduate Press, Inc.

Prevention of nosocomial infections in critically ill patients with lactoferrin (PREVAIL study): study protocol for a randomized controlled trial.

PubMed

Muscedere, John; Maslove, David; Boyd, John Gordon; O'Callaghan, Nicole; Lamontagne, Francois; Reynolds, Steven; Albert, Martin; Hall, Rick; McGolrick, Danielle; Jiang, Xuran; Day, Andrew G

2016-09-29

Nosocomial infections remain an important source of morbidity, mortality, and increased health care costs in hospitalized patients. This is particularly problematic in intensive care units (ICUs) because of increased patient vulnerability due to the underlying severity of illness and increased susceptibility from utilization of invasive therapeutic and monitoring devices. Lactoferrin (LF) and the products of its breakdown have multiple biological effects, which make its utilization of interest for the prevention of nosocomial infections in the critically ill. This is a phase II randomized, multicenter, double-blinded trial to determine the effect of LF on antibiotic-free days in mechanically ventilated, critically ill, adult patients in the ICU. Eligible, consenting patients will be randomized to receive either LF or placebo. The treating clinician will remain blinded to allocation during the study; blinding will be maintained by using opaque syringes and containers. The primary outcome will be antibiotic-free days, defined as the number of days alive and free of antibiotics 28 days after randomization. Secondary outcomes will include: antibiotic utilization, adjudicated diagnosis of nosocomial infection (longer than 72 h of admission to ICU), hospital and ICU length of stay, change in organ function after randomization, hospital and 90-day mortality, incidence of tracheal colonization, changes in gastrointestinal permeability, and immune function. Outcomes to inform the conduct of a larger definitive trial will also be evaluated, including feasibility as determined by recruitment rates and protocol adherence. The results from this study are expected to provide insight into a potential novel therapeutic use for LF in critically ill adult patients. Further, analysis of study outcomes will inform a future, large-scale phase III randomized controlled trial powered on clinically important outcomes related to the use of LF. The trial was registered at www.ClinicalTrials.gov on 18 November 2013. NCT01996579 .

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.

Divalproex Sodium for the Treatment of PTSD and Conduct Disordered Youth: A Pilot Randomized Controlled Clinical Trial

ERIC Educational Resources Information Center

Steiner, Hans; Saxena, Kirti S.; Carrion, Victor; Khanzode, Leena A.; Silverman, Melissa; Chang, Kiki

2007-01-01

We examined the efficacy of divalproex sodium (DVP) for the treatment of PTSD in conduct disorder, utilizing a previous study in which 71 youth were enrolled in a randomized controlled clinical trial. Twelve had PTSD. Subjects (all males, mean age 16, SD 1.0) were randomized into high and low dose conditions. Clinical Global Impression (CGI)…

Developing a Reporting Guideline for Social and Psychological Intervention Trials

PubMed Central

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

2013-01-01

Understanding randomized controlled trials of complex social and psychological interventions requires a detailed description of the interventions tested and the methods used to evaluate them. However, randomized controlled trial reports often omit, or inadequately report, this information. Incomplete and inaccurate reporting hinders the optimal use of research, wastes resources, and fails to meet ethical obligations to research participants and consumers. We explain how reporting guidelines have improved the quality of reports in medicine, and describe the ongoing development of a new reporting guideline for randomized controlled trials: an extension of the Consolidated Standards of Reporting Trials for social and psychological interventions. We invite readers to participate in the project by visiting our Web site, to help us reach the best-informed consensus on these guidelines (http://tinyurl.com/consort-study). PMID:23947317

Statistical analysis plan for the Pneumatic CompREssion for PreVENting Venous Thromboembolism (PREVENT) trial: a study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen; Al-Hameed, Fahad; Burns, Karen E A; Mehta, Sangeeta; Alsolamy, Sami; Almaani, Mohammed; Mandourah, Yasser; Almekhlafi, Ghaleb A; Al Bshabshe, Ali; Finfer, Simon; Alshahrani, Mohammed; Khalid, Imran; Mehta, Yatin; Gaur, Atul; Hawa, Hassan; Buscher, Hergen; Arshad, Zia; Lababidi, Hani; Al Aithan, Abdulsalam; Jose, Jesna; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Al-Dawood, Abdulaziz

2018-03-15

The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is "incident" proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. ClinicalTrials.gov , ID: NCT02040103 . Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506 . Registered on 30 October 2013.

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.

Large-scale randomized clinical trials of bioactives and nutrients in relation to human health and disease prevention - Lessons from the VITAL and COSMOS trials.

PubMed

Rautiainen, Susanne; Sesso, Howard D; Manson, JoAnn E

2017-12-29

Several bioactive compounds and nutrients in foods have physiological properties that are beneficial for human health. While nutrients typically have clear definitions with established levels of recommended intakes, bioactive compounds often lack such a definition. Although a food-based approach is often the optimal approach to ensure adequate intake of bioactives and nutrients, these components are also often produced as dietary supplements. However, many of these supplements are not sufficiently studied and have an unclear role in chronic disease prevention. Randomized trials are considered the gold standard of study designs, but have not been fully applied to understand the effects of bioactives and nutrients. We review the specific role of large-scale trials to test whether bioactives and nutrients have an effect on health outcomes through several crucial components of trial design, including selection of intervention, recruitment, compliance, outcome selection, and interpretation and generalizability of study findings. We will discuss these components in the context of two randomized clinical trials, the VITamin D and OmegA-3 TriaL (VITAL) and the COcoa Supplement and Multivitamin Outcomes Study (COSMOS). We will mainly focus on dietary supplements of bioactives and nutrients while also emphasizing the need for translation and integration with food-based trials that are of vital importance within nutritional research. Copyright © 2017. Published by Elsevier Ltd.

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.

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

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

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.

Cumulative Evidence of Randomized Controlled and Observational Studies on Catheter-Related Infection Risk of Central Venous Catheter Insertion Site in ICU Patients: A Pairwise and Network Meta-Analysis.

PubMed

Arvaniti, Kostoula; Lathyris, Dimitrios; Blot, Stijn; Apostolidou-Kiouti, Fani; Koulenti, Despoina; Haidich, Anna-Bettina

2017-04-01

Selection of central venous catheter insertion site in ICU patients could help reduce catheter-related infections. Although subclavian was considered the most appropriate site, its preferential use in ICU patients is not generalized and questioned by contradicted meta-analysis results. In addition, conflicting data exist on alternative site selection whenever subclavian is contraindicated. To compare catheter-related bloodstream infection and colonization risk between the three sites (subclavian, internal jugular, and femoral) in adult ICU patients. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled trials, CINAHL, and ClinicalTrials.gov. Eligible studies were randomized controlled trials and observational ones. Extracted data were analyzed by pairwise and network meta-analysis. Twenty studies were included; 11 were observational, seven were randomized controlled trials for other outcomes, and two were randomized controlled trials for sites. We evaluated 18,554 central venous catheters: 9,331 from observational studies, 5,482 from randomized controlled trials for other outcomes, and 3,741 from randomized controlled trials for sites. Colonization risk was higher for internal jugular (relative risk, 2.25 [95% CI, 1.84-2.75]; I = 0%) and femoral (relative risk, 2.92 [95% CI, 2.11-4.04]; I = 24%), compared with subclavian. Catheter-related bloodstream infection risk was comparable for internal jugular and subclavian, higher for femoral than subclavian (relative risk, 2.44 [95% CI, 1.25-4.75]; I = 61%), and lower for internal jugular than femoral (relative risk, 0.55 [95% CI, 0.34-0.89]; I = 61%). When observational studies that did not control for baseline characteristics were excluded, catheter-related bloodstream infection risk was comparable between the sites. In ICU patients, internal jugular and subclavian may, similarly, decrease catheter-related bloodstream infection risk, when compared with femoral. Subclavian could be suggested as the most appropriate site, whenever colonization risk is considered and not, otherwise, contraindicated. Current evidence on catheter-related bloodstream infection femoral risk, compared with the other sites, is inconclusive.

Comparing cluster-level dynamic treatment regimens using sequential, multiple assignment, randomized trials: Regression estimation and sample size considerations.

PubMed

NeCamp, Timothy; Kilbourne, Amy; Almirall, Daniel

2017-08-01

Cluster-level dynamic treatment regimens can be used to guide sequential treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level dynamic treatment regimen, the treatment is potentially adapted and re-adapted over time based on changes in the cluster that could be impacted by prior intervention, including aggregate measures of the individuals or patients that compose it. Cluster-randomized sequential multiple assignment randomized trials can be used to answer multiple open questions preventing scientists from developing high-quality cluster-level dynamic treatment regimens. In a cluster-randomized sequential multiple assignment randomized trial, sequential randomizations occur at the cluster level and outcomes are observed at the individual level. This manuscript makes two contributions to the design and analysis of cluster-randomized sequential multiple assignment randomized trials. First, a weighted least squares regression approach is proposed for comparing the mean of a patient-level outcome between the cluster-level dynamic treatment regimens embedded in a sequential multiple assignment randomized trial. The regression approach facilitates the use of baseline covariates which is often critical in the analysis of cluster-level trials. Second, sample size calculators are derived for two common cluster-randomized sequential multiple assignment randomized trial designs for use when the primary aim is a between-dynamic treatment regimen comparison of the mean of a continuous patient-level outcome. The methods are motivated by the Adaptive Implementation of Effective Programs Trial which is, to our knowledge, the first-ever cluster-randomized sequential multiple assignment randomized trial in psychiatry.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol

PubMed Central

2012-01-01

Background Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. Methods/Design We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Discussion Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Trial registration Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18. PMID:22305183

Opinions of researchers based in the UK on recruiting subjects from developing countries into randomized controlled trials.

PubMed

Newton, Sam K; Appiah-Poku, John

2007-12-01

Explaining technical terms in consent forms prior to seeking informed consent to recruit into trials can be challenging in developing countries, and more so when the studies are randomized controlled trials. This study was carried out to examine the opinions of researchers on ways of dealing with these challenges in developing countries. Recorded in-depth interviews with 12 lecturers and five doctoral students, who had carried out research in developing countries, at a leading school of public health in the United Kingdom. A purposive, snowballing approach was used to identify interviewees. Researchers were divided on the feasibility of explaining technical trials in illiterate populations; the majority of them held the view that local analogies could be used to explain these technical terms. Others were of the opinion that this could not be done since it was too difficult to explain technical trials, such as randomized controlled trials, even to people in developed countries. Researchers acknowledged the difficulty in explaining randomized controlled trials but it was also their perception that this was an important part of the ethics of the work of scientific research involving human subjects. These difficulties notwithstanding, efforts should be made to ensure that subjects have sufficient understanding to consent, taking into account the fact that peculiar situations in developing countries might compound this difficulty.

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.

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial.

PubMed

Bucur, Roxana C; Reid, Lauren S; Hamilton, Celeste J; Cummings, Steven R; Jamal, Sophie A

2013-09-08

Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. This will be an open-label randomized, controlled trial conducted at Women's College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the 'multiple comparisons with the best' approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures. ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742.

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.

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.

Nonpharmacological treatments for patients with Parkinson's disease.

PubMed

Bloem, Bastiaan R; de Vries, Nienke M; Ebersbach, Georg

2015-09-15

Since 2013, a number of studies have enhanced the literature and have guided clinicians on viable treatment interventions outside of pharmacotherapy and surgery. Thirty-three randomized controlled trials and one large observational study on exercise and physiotherapy were published in this period. Four randomized controlled trials focused on dance interventions, eight on treatment of cognition and behavior, two on occupational therapy, and two on speech and language therapy (the latter two specifically addressed dysphagia). Three randomized controlled trials focused on multidisciplinary care models, one study on telemedicine, and four studies on alternative interventions, including music therapy and mindfulness. These studies attest to the marked interest in these therapeutic approaches and the increasing evidence base that places nonpharmacological treatments firmly within the integrated repertoire of treatment options in Parkinson's disease. © 2015 International Parkinson and Movement Disorder Society.

A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics.

PubMed

Jones, L A T; Lammertse, D P; Charlifue, S B; Kirshblum, S C; Apple, D F; Ragnarsson, K T; Poonian, D; Betz, R R; Knoller, N; Heary, R F; Choudhri, T F; Jenkins, A L; Falci, S P; Snyder, D A

2010-11-01

Post hoc analysis from a randomized controlled cellular therapy trial in acute, complete spinal cord injury (SCI). Description and quantitative review of study logistics, referral patterns, current practice patterns and subject demographics. Subjects were recruited to one of six international study centers. Data are presented from 1816 patients pre-screened, 75 participants screened and 50 randomized. Of the 1816 patients pre-screened, 53.7% did not meet initial study criteria, primarily due to an injury outside the time window (14 days) or failure to meet neurological criteria (complete SCI between C5 motor/C4 sensory and T11). MRIs were obtained on 339 patients; 51.0% were ineligible based on imaging criteria. Of the 75 participants enrolled, 25 failed screening (SF), leaving 50 randomized. The primary reason for SF was based on the neurological exam (51.9%), followed by failure to meet MRI criteria (22.2%). Of the 50 randomized subjects, there were no significant differences in demographics in the active versus control arms. In those participants for whom data was available, 93.8% (45 of 48) of randomized participants received steroids before study entry, whereas 94.0% (47 of 50) had spine surgery before study enrollment. The 'funnel effect' (large numbers of potentially eligible participants with a small number enrolled) impacts all trials, but was particularly challenging in this trial due to eligibility criteria and logistics. Data collected may provide information on current practice patterns and the issues encountered and addressed may facilitate design of future trials.

A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial: the ProtecT prostate cancer trial.

PubMed

Donovan, Jenny L; Young, Grace J; Walsh, Eleanor I; Metcalfe, Chris; Lane, J Athene; Martin, Richard M; Tazewell, Marta K; Davis, Michael; Peters, Tim J; Turner, Emma L; Mills, Nicola; Khazragui, Hanan; Khera, Tarnjit K; Neal, David E; Hamdy, Freddie C

2018-04-01

Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability is often neglected. Design features built into the Prostate testing for cancer and Treatment (ProtecT) RCT of treatments for localized prostate cancer (PCa) provided insights into its generalizability. Population-based cluster randomization created a prospective study of prostate-specific antigen (PSA) testing and a comprehensive-cohort study including groups choosing treatment or excluded from the RCT, as well as those randomized. Baseline information assessed selection and response during RCT conduct. The prospective study (82,430 PSA-tested men) represented healthy men likely to respond to a screening invitation. The extended comprehensive cohort comprised 1,643 randomized, 997 choosing treatment, and 557 excluded with advanced cancer/comorbidities. Men choosing treatment were very similar to randomized men except for having more professional/managerial occupations. Excluded men were similar to the randomized socio-demographically but different clinically, representing less healthy men with more advanced PCa. The design features of the ProtecT RCT provided data to assess the representativeness of the prospective cohort and generalizability of the findings of the RCT. Greater attention to collecting data at the design stage of pragmatic trials would better support later judgments by clinicians/policy-makers about the generalizability of RCT findings in clinical practice. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Rational and design of a stepped-wedge cluster randomized trial evaluating quality improvement initiative for reducing cardiovascular events among patients with acute coronary syndromes in resource-constrained hospitals in China.

PubMed

Li, Shenshen; Wu, Yangfeng; Du, Xin; Li, Xian; Patel, Anushka; Peterson, Eric D; Turnbull, Fiona; Lo, Serigne; Billot, Laurent; Laba, Tracey; Gao, Runlin

2015-03-01

Acute coronary syndromes (ACSs) are a major cause of morbidity and mortality, yet effective ACS treatments are frequently underused in clinical practice. Randomized trials including the CPACS-2 study suggest that quality improvement initiatives can increase the use of effective treatments, but whether such programs can impact hard clinical outcomes has never been demonstrated in a well-powered randomized controlled trial. The CPACS-3 study is a stepped-wedge cluster-randomized trial conducted in 104 remote level 2 hospitals without PCI facilities in China. All hospitalized ACS patients will be recruited consecutively over a 30-month period to an anticipated total study population of more than 25,000 patients. After a 6-month baseline period, hospitals will be randomized to 1 of 4 groups, and a 6-component quality improvement intervention will be implemented sequentially in each group every 6months. These components include the following: establishment of a quality improvement team, implementation of a clinical pathway, training of physicians and nurses, hospital performance audit and feedback, online technical support, and patient education. All patients will be followed up for 6months postdischarge. The primary outcome will be the incidence of in-hospital major adverse cardiovascular events comprising all-cause mortality, myocardial infarction or reinfarction, and nonfatal stroke. The CPACS-3 study will be the first large randomized trial with sufficient power to assess the effects of a multifaceted quality of care improvement initiative on hard clinical outcomes, in patients with ACS. Copyright © 2014 Elsevier Inc. All rights reserved.

Strategies to retain participants in a long-term HIV prevention randomized controlled trial: Lessons from the MINTS-II study

PubMed Central

Horvath, Keith J.; Nygaard, Kate; Danilenko, Gene P.; Goknur, Sinan; Oakes, J. Michael; Rosser, B.R. Simon

2012-01-01

Achieving satisfactory retention in online HIV prevention trials typically have proved difficult, particularly over extended timeframes. The overall aim of this study was to assess factors associated with retention in the Men’s INTernet Study II (MINTS-II), a randomized controlled trial of a sexual risk reduction intervention for men who have sex with men. Participants were recruited via e-mails and banner advertisements in December, 2007 to participate in the MINTS-II Sexpulse intervention and followed over a 12-month period. Retention across the treatment and control arms was 85.2% at 12 months. Factors associated with higher retention included: randomization to the control arm, previous participation in a study by the research team, e-mail and telephone reminders to complete a survey once it was available to take, and fewer e-mail contacts between surveys. The results provide evidence that achieving satisfactory retention is possible in online HIV prevention trials, and suggest best practices for maximizing retention. PMID:21538084

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

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.

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…

A General Framework for Power Analysis to Detect the Moderator Effects in Two- and Three-Level Cluster Randomized Trials

ERIC Educational Resources Information Center

Dong, Nianbo; Spybrook, Jessaca; Kelcey, Ben

2016-01-01

The purpose of this study is to propose a general framework for power analyses to detect the moderator effects in two- and three-level cluster randomized trials (CRTs). The study specifically aims to: (1) develop the statistical formulations for calculating statistical power, minimum detectable effect size (MDES) and its confidence interval to…

The Impact of Curriculum-Based Professional Development on Science Instruction: Results from a Cluster-Randomized Trial

ERIC Educational Resources Information Center

Taylor, Joseph; Kowalski, Susan; Getty, Stephen; Wilson, Christopher; Carlson, Janet

2011-01-01

This research is part of a larger, IES-funded study titled: "Measuring the Efficacy and Student Achievement of Research-based Instructional Materials in High School Multidisciplinary Science" (Award # R305K060142). The larger study seeks to use a cluster-randomized trial design, with schools as the unit of assignment, to make causal…

Effects of the Caregiver Interaction Profile Training on Caregiver-Child Interactions in Dutch Child Care Centers: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Helmerhorst, Katrien O.; Riksen-Walraven, J. Marianne; Fukkink, Ruben G.; Tavecchio, Louis W. C.; Gevers Deynoot-Schaub, Mirjam J. J. M.

2017-01-01

Background: Previous studies underscore the need to improve caregiver-child interactions in early child care centers. Objective: In this study we used a randomized controlled trial to examine whether a 5-week video feedback training can improve six key interactive skills of caregivers in early child care centers: Sensitive responsiveness, respect…

Teaching Medical Ethics in Graduate and Undergraduate Medical Education: A Systematic Review of Effectiveness.

PubMed

de la Garza, Santiago; Phuoc, Vania; Throneberry, Steven; Blumenthal-Barby, Jennifer; McCullough, Laurence; Coverdale, John

2017-08-01

One objective was to identify and review studies on teaching medical ethics to psychiatry residents. In order to gain insights from other disciplines that have published research in this area, a second objective was to identify and review studies on teaching medical ethics to residents across all other specialties of training and on teaching medical students. PubMed, EMBASE, and PsycINFO were searched for controlled trials on teaching medical ethics with quantitative outcomes. Search terms included ethics, bioethics, medical ethics, medical students, residents/registrars, teaching, education, outcomes, and controlled trials. Nine studies were found that met inclusion criteria, including five randomized controlled trails and four controlled non-randomized trials. Subjects included medical students (5 studies), surgical residents (2 studies), internal medicine house officers (1 study), and family medicine preceptors and their medical students (1 study). Teaching methods, course content, and outcome measures varied considerably across studies. Common methodological issues included a lack of concealment of allocation, a lack of blinding, and generally low numbers of subjects as learners. One randomized controlled trial which taught surgical residents using a standardized patient was judged to be especially methodologically rigorous. None of the trials incorporated psychiatry residents. Ethics educators should undertake additional rigorously controlled trials in order to secure a strong evidence base for the design of medical ethics curricula. Psychiatry ethics educators can also benefit from the findings of trials in other disciplines and in undergraduate medical education.

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.

App-based serious gaming for training of chest tube insertion: study protocol for a randomized controlled trial.

PubMed

Friedrich, Mirco; Bergdolt, Christian; Haubruck, Patrick; Bruckner, Thomas; Kowalewski, Karl-Friedrich; Müller-Stich, Beat Peter; Tanner, Michael C; Nickel, Felix

2017-02-06

Chest tube insertion is a standard intervention for management of various injuries of the thorax. Quick and accurate execution facilitates efficient therapy without further complications. Here, we propose a new training concept comprised of e-learning elements as well as continuous rating using an objective structured assessment of technical skills (OSATS) tool. The study protocol is presented for a randomized trial to evaluate e-learning with app-based serious gaming for chest drain insertion. The proposed randomized trial will be carried out at the Department of Orthopedics and Traumatology at Heidelberg University in the context of regular curricular teaching for medical students (n = 90, 3rd to 6th year). The intervention group will use e-learning with the serious gaming app Touch Surgery (TM) for chest drain insertion, whereas the control group uses serious gaming for an unrelated procedure. Primary endpoint is operative performance of chest drain insertion in a porcine cadaveric model according to OSATS. The randomized trial will help determine the value of e-learning with the serious gaming app Touch Surgery (TM) for chest drain insertion by using the OSATS score. The study will improve surgical training for trauma situations. Trial Registration Number, DRKS00009994 . Registered on 27 May 2016.

Confidence intervals for a difference between lognormal means in cluster randomization trials.

PubMed

Poirier, Julia; Zou, G Y; Koval, John

2017-04-01

Cluster randomization trials, in which intact social units are randomized to different interventions, have become popular in the last 25 years. Outcomes from these trials in many cases are positively skewed, following approximately lognormal distributions. When inference is focused on the difference between treatment arm arithmetic means, existent confidence interval procedures either make restricting assumptions or are complex to implement. We approach this problem by assuming log-transformed outcomes from each treatment arm follow a one-way random effects model. The treatment arm means are functions of multiple parameters for which separate confidence intervals are readily available, suggesting that the method of variance estimates recovery may be applied to obtain closed-form confidence intervals. A simulation study showed that this simple approach performs well in small sample sizes in terms of empirical coverage, relatively balanced tail errors, and interval widths as compared to existing methods. The methods are illustrated using data arising from a cluster randomization trial investigating a critical pathway for the treatment of community acquired pneumonia.

Pilot randomized controlled trial of dialectical behavior therapy group skills training for ADHD among college students.

PubMed

Fleming, Andrew P; McMahon, Robert J; Moran, Lyndsey R; Peterson, A Paige; Dreessen, Anthony

2015-03-01

ADHD affects between 2% and 8% of college students and is associated with broad functional impairment. No prior randomized controlled trials with this population have been published. The present study is a pilot randomized controlled trial evaluating dialectical behavior therapy (DBT) group skills training adapted for college students with ADHD. Thirty-three undergraduates with ADHD between ages 18 and 24 were randomized to receive either DBT group skills training or skills handouts during an 8-week intervention phase. ADHD symptoms, executive functioning (EF), and related outcomes were assessed at baseline, post-treatment, and 3-month follow-up. Participants receiving DBT group skills training showed greater treatment response rates (59-65% vs. 19-25%) and clinical recovery rates (53-59% vs. 6-13%) on ADHD symptoms and EF, and greater improvements in quality of life. DBT group skills training may be efficacious, acceptable, and feasible for treating ADHD among college students. A larger randomized trial is needed for further evaluation. © 2014 SAGE Publications.

THE USE OF RANDOMIZED CONTROLLED TRIALS OF IN-HOME DRINKING WATER TREATMENT TO STUDY ENDEMIC WATERBORNE DISEASE

EPA Science Inventory

Randomized trials of water treatment have demonstrated the ability of simple water treatments to significantly reduce the incidence of gastrointestinal illnesses in developing countries where drinking water is of poor quality. Whether or not additional treatment at the tap reduc...

Computer-Assisted Learning in Elementary Reading: A Randomized Control Trial

ERIC Educational Resources Information Center

Shannon, Lisa Cassidy; Styers, Mary Koenig; Wilkerson, Stephanie Baird; Peery, Elizabeth

2015-01-01

This study evaluated the efficacy of Accelerated Reader, a computer-based learning program, at improving student reading. Accelerated Reader is a progress-monitoring, assessment, and practice tool that supports classroom instruction and guides independent reading. Researchers used a randomized controlled trial to evaluate the program with 344…

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…

Cost-Effectiveness of a Long-Term Internet-Delivered Worksite Health Promotion Programme on Physical Activity and Nutrition: A Cluster Randomized Controlled Trial

ERIC Educational Resources Information Center

Robroek, Suzan J. W.; Polinder, Suzanne; Bredt, Folef J.; Burdorf, Alex

2012-01-01

This study aims to evaluate the cost-effectiveness of a long-term workplace health promotion programme on physical activity (PA) and nutrition. In total, 924 participants enrolled in a 2-year cluster randomized controlled trial, with departments (n = 74) within companies (n = 6) as the unit of randomization. The intervention was compared with a…

Is Reducing Uncertain Control the Key to Successful Test Anxiety Intervention for Secondary School Students? Findings from a Randomized Control Trial

ERIC Educational Resources Information Center

Putwain, David W.; Pescod, Marc

2018-01-01

The aim of the study was to conduct a randomized control trial of a targeted, facilitated, test anxiety intervention for a group of adolescent students, and to examine the mediating role of uncertain control. Fifty-six participants (male = 19, white = 21, mean age = 14.7 years) were randomly allocated to an early intervention or wait-list control…

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

Knee osteoarthritis and role for surgical intervention: lessons learned from randomized clinical trials and population-based cohorts.

PubMed

Buchbinder, Rachelle; Richards, Bethan; Harris, Ian

2014-03-01

Over the last decade, there has been increased recognition of the importance of high-quality randomized controlled trials in determining the role of surgery for knee osteoarthritis. This review highlights key findings from the best available studies, and considers whether or not this knowledge has resulted in better evidence-based care. Use of arthroscopy to treat knee osteoarthritis has not declined despite strong evidence-based recommendations that do not sanction its use. A large randomized controlled trial has demonstrated that arthroscopic partial meniscectomy followed by a standardized physical therapy program results in similar improvements in pain and function at 6 and 12 months in comparison to physical therapy alone in patients with knee osteoarthritis and a symptomatic meniscal tear, confirming the findings of two previous trials. Two recent randomized controlled trials have demonstrated that decision aids help people to reach better-informed decisions about total knee arthroplasty. A majority of studies have indicated that for people with obesity the positive results of total knee arthroplasty may be compromised by postoperative complications, particularly infection. More efforts are needed to overcome significant evidence-practice gaps in the surgical management of knee osteoarthritis, particularly arthroscopy. Decision aids are a promising tool.

Selenium and Preeclampsia: a Systematic Review and Meta-analysis.

PubMed

Xu, Min; Guo, Dan; Gu, Hao; Zhang, Li; Lv, Shuyan

2016-06-01

Conflicting results exist between selenium concentration and preeclampsia. The role of selenium in the development of preeclampsia is unclear. We conducted a meta-analysis to compare the blood selenium level in patients with preeclampsia and healthy pregnant women, and to determine the effectiveness of selenium supplementation in preventing preeclampsia. We searched PubMed, ScienceDirect, the Cochrane Library, and relevant references for English language literature up to November 25, 2014. Mean difference from observational studies and relative risk from randomized controlled trials were meta-analyzed by a random-effect model. Thirteen observational studies with 1515 participants and 3 randomized controlled trials with 439 participants were included in the meta-analysis. Using a random-effect model, a statistically significant difference in blood selenium concentration of -6.47 μg/l (95 % confidence interval (CI) -11.24 to -1.7, p = 0.008) was seen after comparing the mean difference of observational studies. In randomized controlled trials, using a random-effect model, the relative risk for preeclampsia was 0.28 (0.09 to 0.84) for selenium supplementation (p = 0.02). Evidence from observational studies indicates an inverse association of blood selenium level and the risk of preeclampsia. Supplementation with selenium significantly reduces the incidence of preeclampsia. However, more prospective clinical trials are required to assess the association between selenium supplementation and preeclampsia and to determine the dose, beginning time, and duration of selenium supplementation.

Follow-up of colorectal cancer patients after resection with curative intent-the GILDA trial.

PubMed

Grossmann, Erik M; Johnson, Frank E; Virgo, Katherine S; Longo, Walter E; Fossati, Rolando

2004-01-01

Surgery remains the primary treatment of colorectal cancer. Data are lacking to delineate the optimal surveillance strategy following resection. A large-scale multi-center European study is underway to address this issue (Gruppo Italiano di Lavoro per la Diagnosi Anticipata-GILDA). Following primary surgery with curative intent, stratification, and randomization at GILDA headquarters, colon cancer patients are then assigned to a more intensive or less intensive surveillance regimen. Rectal cancer patients undergoing curative resection are similarly randomized, with their follow-up regimens placing more emphasis on detection of local recurrence. Target recruitment for the study will be 1500 patients to achieve a statistical power of 80% (assuming an alpha of 0.05 and a hazard-rate reduction of >24%). Since the trial opened in 1998, 985 patients have been randomized from 41 centers as of February 2004. There were 496 patients randomized to the less intensive regimens, and 489 randomized to the more intensive regimens. The mean duration of follow-up is 14 months. 75 relapses (15%) and 32 deaths (7%) had been observed in the two more intensive follow-up arms, while 64 relapses (13%) and 24 deaths (5%) had been observed in the two less intensive arms as of February 2004. This trial should provide the first evidence based on an adequately powered randomized trial to determine the optimal follow-up strategy for colorectal cancer patients. This trial is open to US centers, and recruitment continues.

A randomized trial of enhanced HIV risk reduction and vaccine trial education interventions among HIV-negative, high-risk women who use non-injection drugs: The UNITY Study

PubMed Central

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

2014-01-01

Background 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. Methods The UNITY Study was a two-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 non-injection drug using women. The enhanced vaccine education intervention using pictures along with application vignettes and enhanced risk reduction counseling consisting of three one-on-one counseling sessions were compared to standard conditions. Follow-up visits at one week and one, six and twelve months after randomization included HIV testing and assessment of outcomes. Results 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. Conclusions Further research is needed to boost educational efforts and strengthen risk reduction counseling among high-risk non-injection drug using women. PMID:20190585

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.

The Effect of Trimethoprim on Serum Folate Levels in Humans: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Meidahl Petersen, Kasper; Eplov, Kasper; Kjær Nielsen, Torben; Jimenez-Solem, Espen; Petersen, Morten; Broedbaek, Kasper; Daugaard Popik, Sara; Kallehave Hansen, Lina; Enghusen Poulsen, Henrik; Trærup Andersen, Jon

2016-01-01

Trimethoprim antagonize the actions of folate by inhibition of dihydrofolate reductase. This could diminish serum folate levels in humans and causes folate deficiency in some patients. We conducted a randomized, double-blind, placebo-controlled trial, to investigate the effect of trimethoprim on serum folate levels in healthy participants after a 7-day trial period. Thirty young, healthy males were randomly allocated to receive trimethoprim, 200 mg twice daily, and 30 were randomly allocated to placebo. Before trial initiation, participant numbers were given randomly generated treatment allocations within sealed opaque envelopes. Participants and all staff were kept blinded to treatment allocations during the trial. Serum folate was measured at baseline and at end of trial. In the 58 participants analyzed (30 in the trimethoprim group and 28 in the placebo group), 8 had folate deficiency at baseline. Within the trimethoprim group, serum folate was significantly decreased (P = 0.018) after the trial. We found a mean decrease in serum folate among trimethoprim exposed of 1.95 nmol/L, compared with a 0.21 nmol/L mean increase in the placebo group (P = 0.040). The proportion of folate-deficient participants increased significantly within the trimethoprim group (P = 0.034). No serious adverse events were observed. In conclusion, we found that a daily dose of 400 mg trimethoprim for 7 days significantly lowered serum folate levels in healthy study participants.

Does increased exercise or physical activity alter ad-libitum daily energy intake or macronutrient composition in healthy adults? A systematic review.

PubMed

Donnelly, Joseph E; Herrmann, Stephen D; Lambourne, Kate; Szabo, Amanda N; Honas, Jeffery J; Washburn, Richard A

2014-01-01

The magnitude of the negative energy balance induced by exercise may be reduced due to compensatory increases in energy intake. TO ADDRESS THE QUESTION: Does increased exercise or physical activity alter ad-libitum daily energy intake or macronutrient composition in healthy adults? PubMed and Embase were searched (January 1990-January 2013) for studies that presented data on energy and/or macronutrient intake by level of exercise, physical activity or change in response to exercise. Ninety-nine articles (103 studies) were included. Primary source articles published in English in peer-reviewed journals. Articles that presented data on energy and/or macronutrient intake by level of exercise or physical activity or changes in energy or macronutrient intake in response to acute exercise or exercise training in healthy (non-athlete) adults (mean age 18-64 years). Articles were grouped by study design: cross-sectional, acute/short term, non-randomized, and randomized trials. Considerable heterogeneity existed within study groups for several important study parameters, therefore a meta-analysis was considered inappropriate. Results were synthesized and presented by study design. No effect of physical activity, exercise or exercise training on energy intake was shown in 59% of cross-sectional studies (n = 17), 69% of acute (n = 40), 50% of short-term (n = 10), 92% of non-randomized (n = 12) and 75% of randomized trials (n = 24). Ninety-four percent of acute, 57% of short-term, 100% of non-randomized and 74% of randomized trials found no effect of exercise on macronutrient intake. Forty-six percent of cross-sectional trials found lower fat intake with increased physical activity. The literature is limited by the lack of adequately powered trials of sufficient duration, which have prescribed and measured exercise energy expenditure, or employed adequate assessment methods for energy and macronutrient intake. We found no consistent evidence that increased physical activity or exercise effects energy or macronutrient intake.

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.

A Cluster-Randomized Trial of Restorative Practices: An Illustration to Spur High-Quality Research and Evaluation.

PubMed

Acosta, Joie D; Chinman, Matthew; Ebener, Patricia; Phillips, Andrea; Xenakis, Lea; Malone, Patrick S

2016-01-01

Restorative Practices in schools lack rigorous evaluation studies. As an example of rigorous school-based research, this paper describes the first randomized control trial of restorative practices to date, the Study of Restorative Practices. It is a 5-year, cluster-randomized controlled trial (RCT) of the Restorative Practices Intervention (RPI) in 14 middle schools in Maine to assess whether RPI impacts both positive developmental outcomes and problem behaviors and whether the effects persist during the transition from middle to high school. The two-year RPI intervention began in the 2014-2015 school year. The study's rationale and theoretical concerns are discussed along with methodological concerns including teacher professional development. The theoretical rationale and description of the methods from this study may be useful to others conducting rigorous research and evaluation in this area.

The PREEMPT study - evaluating smartphone-assisted n-of-1 trials in patients with chronic pain: study protocol for a randomized controlled trial.

PubMed

Barr, Colin; Marois, Maria; Sim, Ida; Schmid, Christopher H; Wilsey, Barth; Ward, Deborah; Duan, Naihua; Hays, Ron D; Selsky, Joshua; Servadio, Joseph; Schwartz, Marc; Dsouza, Clyde; Dhammi, Navjot; Holt, Zachary; Baquero, Victor; MacDonald, Scott; Jerant, Anthony; Sprinkle, Ron; Kravitz, Richard L

2015-02-27

Chronic pain is prevalent, costly, and clinically vexatious. Clinicians typically use a trial-and-error approach to treatment selection. Repeated crossover trials in a single patient (n-of-1 trials) may provide greater therapeutic precision. N-of-1 trials are the most direct way to estimate individual treatment effects and are useful in comparing the effectiveness and toxicity of different analgesic regimens. The goal of the PREEMPT study is to test the 'Trialist' mobile health smartphone app, which has been developed to make n-of-1 trials easier to accomplish, and to provide patients and clinicians with tools for individualizing treatments for chronic pain. A randomized controlled trial is being conducted to test the feasibility and effectiveness of the Trialist app. A total of 244 participants will be randomized to either the Trialist app intervention group (122 patients) or a usual care control group (122 patients). Patients assigned to the Trialist app will work with their clinicians to set up an n-of-1 trial comparing two pain regimens, selected from a menu of flexible options. The Trialist app provides treatment reminders and collects data entered daily by the patient on pain levels and treatment side effects. Upon completion of the n-of-1 trial, patients review results with their clinicians and develop a long-term treatment plan. The primary study outcome (comparing Trialist to usual care patients) is pain-related interference with daily functioning at 26 weeks. Trialist will allow patients and clinicians to conduct personalized n-of-1 trials. In prior studies, n-of-1 trials have been shown to encourage greater patient involvement with care, which has in turn been associated with better health outcomes. mHealth technology implemented using smartphones may offer an efficient means of facilitating n-of-1 trials so that more patients can benefit from this approach. ClinicalTrials.gov: NCT02116621 , first registered 15 April 2014.

The effects of ventilation tubes versus no ventilation tubes for recurrent acute otitis media or chronic otitis media with effusion in 9 to 36 month old Greenlandic children, the SIUTIT trial: study protocol for a randomized controlled trial.

PubMed

Demant, Malene Nøhr; Jensen, Ramon Gordon; Jakobsen, Janus Christian; Gluud, Christian; Homøe, Preben

2017-01-19

The prevalence of otitis media in Greenlandic children is one of the highest in the world. International studies have shown that otitis-prone children may benefit from tubulation of the tympanic membrane. However, it is unknown whether these results can be applied to Greenlandic children and trials on the effects of ventilation tubes in high-risk populations have, to our knowledge, never been conducted. The trial is an investigator-initiated, multicentre, randomized, blinded superiority trial of bilateral ventilation tube insertion versus treatment as usual (no tube) in Greenlandic children aged 9-36 months with chronic otitis media with effusion or recurrent acute otitis media. With randomization stratified by otitis media subtype and trial site, a type 1 error of 5% and a power of 80%, a total of 230 participants are needed to detect a decrease of two visits to a health clinic during 2 years, which is considered the minimal clinical relevant difference. The primary outcome measure will be assessed blindly by investigating medical records. Secondary outcome measures are number of episodes of acute otitis media, quality of life, number of episodes of antibiotics administration and proportion of children with tympanic membrane perforations. This trial will provide evidence-based knowledge of the effects of ventilation tubes in children with middle ear infections from the high-risk Greenlandic population. Furthermore, this trial will improve the understanding of conducting randomized clinical trials in remote areas, where management of logistical aspects is particularly challenging. ClinicalTrials.gov, NCT02490332 . Registered on 14 February 2016.

Effects of zinc supplementation on subscales of anorexia in children: A randomized controlled trial

PubMed Central

Khademian, Majid; Farhangpajouh, Neda; Shahsanaee, Armindokht; Bahreynian, Maryam; Mirshamsi, Mehran; Kelishadi, Roya

2014-01-01

Objectives: This study aims to assess the effects of zinc supplementation on improving the appetite and its subscales in children. Methods: This study was conducted in 2013 in Isfahan, Iran. It had two phases. At the first step, after validation of the Child Eating Behaviour Questionaire (CEBQ), it was completed for 300 preschool children, who were randomly selected. The second phase was conducted as a randomized controlled trial. Eighty of these children were randomly selected, and were randomly assigned to two groups of equal number receiving zinc (10 mg/day) or placebo for 12 weeks. Results: Overall 77 children completed the trial (39 in the case and 3 in the control group).The results showed that zinc supplement can improve calorie intake in children by affecting some CEBQ subscales like Emotional over Eating and Food Responsible. Conclusion: Zinc supplementation had positive impact in promoting the calorie intake and some subscales of anorexia. PMID:25674110

Increased Patient Enrollment to a Randomized Surgical Trial Through Equipoise Polling of an Expert Surgeon Panel.

PubMed

Ghogawala, Zoher; Schwartz, J Sanford; Benzel, Edward C; Magge, Subu N; Coumans, Jean Valery; Harrington, J Fred; Gelbs, Jared C; Whitmore, Robert G; Butler, William E; Barker, Fred G

2016-07-01

To determine whether patients who learned the views of an expert surgeons' panel's assessment of equipoise between 2 alternative operative treatments had increased likelihood of consenting to randomization. Difficulty obtaining patient consent to randomization is an important barrier to conducting surgical randomized clinical trials, the gold standard for generating clinical evidence. Observational study of the rate of patient acceptance of randomization within a 5-center randomized clinical trial comparing lumbar spinal decompression versus lumbar spinal decompression plus instrumented fusion for patients with symptomatic grade I degenerative lumbar spondylolisthesis with spinal stenosis. Eligible patients were enrolled in the trial and then asked to accept randomization. A panel of 10 expert spine surgeons was formed to review clinical information and images for individual patients to provide an assessment of suitability for randomization. The expert panel vote was disclosed to the patient by the patient's surgeon before the patient decided whether to accept randomization or not. Randomization acceptance among eligible patients without expert panel review was 40% (19/48) compared with 81% (47/58) among patients undergoing expert panel review (P < 0.001). Among expert-reviewed patients, randomization acceptance was 95% when all experts or all except 1 voted for randomization, 75% when 2 experts voted against randomization, and 20% with 3 or 4 votes against (P < 0.001 for trend). Patients provided with an expert panel's assessment of their own suitability for randomization were twice as likely to agree to randomization compared with patients receiving only their own surgeon's recommendation.

Are Randomized Controlled Trials the (G)old Standard? From Clinical Intelligence to Prescriptive Analytics.

PubMed

Van Poucke, Sven; Thomeer, Michiel; Heath, John; Vukicevic, Milan

2016-07-06

Despite the accelerating pace of scientific discovery, the current clinical research enterprise does not sufficiently address pressing clinical questions. Given the constraints on clinical trials, for a majority of clinical questions, the only relevant data available to aid in decision making are based on observation and experience. Our purpose here is 3-fold. First, we describe the classic context of medical research guided by Poppers' scientific epistemology of "falsificationism." Second, we discuss challenges and shortcomings of randomized controlled trials and present the potential of observational studies based on big data. Third, we cover several obstacles related to the use of observational (retrospective) data in clinical studies. We conclude that randomized controlled trials are not at risk for extinction, but innovations in statistics, machine learning, and big data analytics may generate a completely new ecosystem for exploration and validation.

Are Randomized Controlled Trials the (G)old Standard? From Clinical Intelligence to Prescriptive Analytics

PubMed Central

2016-01-01

Despite the accelerating pace of scientific discovery, the current clinical research enterprise does not sufficiently address pressing clinical questions. Given the constraints on clinical trials, for a majority of clinical questions, the only relevant data available to aid in decision making are based on observation and experience. Our purpose here is 3-fold. First, we describe the classic context of medical research guided by Poppers’ scientific epistemology of “falsificationism.” Second, we discuss challenges and shortcomings of randomized controlled trials and present the potential of observational studies based on big data. Third, we cover several obstacles related to the use of observational (retrospective) data in clinical studies. We conclude that randomized controlled trials are not at risk for extinction, but innovations in statistics, machine learning, and big data analytics may generate a completely new ecosystem for exploration and validation. PMID:27383622

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. Methods and design This will be an open-label randomized, controlled trial conducted at Women’s College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the ‘multiple comparisons with the best’ approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. Discussion Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures. Trial registration ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742. PMID:24010992

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.

The Radical Extent of lymphadenectomy - D2 dissection versus complete mesocolic excision of LAparoscopic Right Colectomy for right-sided colon cancer (RELARC) trial: study protocol for a randomized controlled trial.

PubMed

Lu, Jun-Yang; Xu, Lai; Xue, Hua-Dan; Zhou, Wei-Xun; Xu, Tao; Qiu, Hui-Zhong; Wu, Bin; Lin, Guo-Le; Xiao, Yi

2016-12-08

The extent of lymphadenectomy during laparoscopic right colectomy can affect the oncological outcome and the safety of surgery. The principle of complete mesocolic excision (CME) has been gradually accepted and increasingly applied by colorectal surgeons. The aim of this study is to investigate whether extended lymphadenectomy (CME) in laparoscopic colectomy could improve the oncological outcomes of patients with right-sided colon cancers, compared with D2 lymphadenectomy. The Radical Extent of lympadenectomy: D2 dissection versus complete mesocolic excision of LAparoscopic Right Colectomy for right-sided colon cancer (RELARC) study is a prospective, multicenter, randomized controlled trial in which 1072 eligible patients with right-sided colon cancers will be randomly assigned to the CME group or the D2 dissection group during laparoscopic right colectomy. Inclusion criteria are locally advanced colon cancers situated from the cecum to the right third of the transverse colon and clinically staged as T2-4aN0M0 or TanyN + M0. The primary endpoint of this trial is 3-year disease-free survival. Secondary endpoints include 3-year overall survival, postoperative complication rates, perioperative mortality rates, and rates of positive central lymph nodes (the station 3 nodes). The RELARC trial is a prospective, multicenter, randomized controlled trial that will provide evidence on the optimal extent of lymphadenectomy during laparoscopic right colectomy in terms of better oncological outcome and operation safety. ClinicalTrials.gov: NCT02619942 . Registered on 29 November 2015.

A randomized two-by-two comparison of high-dose bolus tirofiban versus abciximab and unfractionated heparin versus bivalirudin during percutaneous coronary revascularization and stent placement: the tirofiban evaluation of novel dosing versus abciximab with clopidogrel and inhibition of thrombin (TENACITY) study trial.

PubMed

Moliterno, David J

2011-06-01

In the absence of high-dose thienopyridines, placebo-controlled trials have demonstrated a reduction in ischemic events with intravenous glycoprotein IIb/IIIa antagonists during percutaneous coronary intervention (PCI). One head-to-head trial comparing abciximab and tirofiban among PCI patients found tirofiban to be inferior, and laboratory evidence confirmed that the bolus dose of tirofiban tested in that trial to be less effective than abciximab. Whether a higher bolus dose of tirofiban would be as efficacious as abciximab during PCI is uncertain. Patients undergoing PCI were randomized equally to abciximab or to tirofiban, given as high-dose bolus (25 μg/kg) plus 12-hr infusion (0.15 μg/kg/min). All patients received aspirin and clopidogrel and were additionally randomized to unfractionated heparin or bivalirudin. Approximately 8,000 patients were to be studied, but after 383 were enrolled, the study sponsor discontinued the trial for financial reasons. The primary endpoint of 30-day death, myocardial infarction, or urgent target vessel revascularization occurred in 8.8% of patients randomized to abciximab and 6.9% of those randomized to tirofiban. The respective rates of major bleeding were 1.5 and 1.6%. Additionally, the primary endpoint occurred in 8.1% of patients randomized to unfractionated heparin and 7.6% of those randomized to bivalirudin. The respective rates of major bleeding were 2.5% and 0.5%. With limited assessment, this direct comparison of high-dose bolus tirofiban versus abciximab produced encouraging results and suggests that further study of this tirofiban dose regimen is warranted. The limited assessments comparing heparin and bivalirudin are consistent with prior observations. Copyright © 2010 Wiley-Liss, Inc.

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.

A Review of Clinical Trials in Spinal Cord Injury including Biomarkers.

PubMed

Badhiwala, Jetan H; Wilson, Jefferson R; Kwon, Brian K; Casha, Steve; Fehlings, Michael G

2018-06-11

Acute traumatic spinal cord injury (SCI) entered the arena of prospective randomized clinical trials almost 40 years ago, with the undertaking of the National Acute Spinal Cord Study (NASCIS) I trial. Since then, a number of clinical trials have been conducted in the field, spurred by the devastating physical, social, and economic consequences of acute SCI for patients, families, and society at large. Many of these have been controversial and attracted criticism. The current review provides a critical summary of select past and current clinical trials in SCI, focusing in particular on the findings of prospective randomized controlled trials (RCTs), the challenges and barriers encountered, and the valuable lessons learned that can be applied to future trials.

The Heterogeneous Effect of Information on Student Performance: Evidence from a Randomized Control Trial in Mexico. Policy Research Working Paper 7422

ERIC Educational Resources Information Center

Avitabile, Ciro; de Hoyos, Rafael

2015-01-01

A randomized control trial was conducted to study whether providing 10th grade students with information about the returns to upper secondary and tertiary education, and a source of financial aid for tertiary education, can contribute to improve student performance. The study finds that the intervention had no effects on the probability of taking…

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…

Cross-Age Peer Tutoring and Fluency-Based Instruction to Achieve Fluency with Mathematics Computation Skills: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Greene, Irene; Mc Tiernan, Aoife; Holloway, Jennifer

2018-01-01

The current study employed a randomized controlled trial to evaluate the use of peer tutoring and fluency-based instruction to increase mathematics fluency with addition and subtraction computation skills. Forty-one elementary school students between the ages of eight and 12 years participated in the 8-week study using cross-age peer tutoring, Say…

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.

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.

The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials.

PubMed

Morer, Carla; Roques, Christian-François; Françon, Alain; Forestier, Romain; Maraver, Francisco

2017-12-01

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials

NASA Astrophysics Data System (ADS)

Morer, Carla; Roques, Christian-François; Françon, Alain; Forestier, Romain; Maraver, Francisco

2017-12-01

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

Effects of yoga on chronic neck pain: a systematic review of randomized controlled trials

PubMed Central

Kim, Sang-Dol

2016-01-01

[Purpose] The aim of this study was to investigate the effectiveness of yoga in the management of chronic neck pain. [Subjects and Methods] Five electronic databases were searched to identify randomized controlled trials (RCTs) of yoga intervention on chronic neck pain. The trials were published in the English language between January 1966 and December 2015. The Cochrane Risk of Bias Tool was used to assess the quality of the trials. [Results] Three trials were identified and included in this review. A critical appraisal was performed on the trials, and the result indicated a high risk of bias. A narrative description was processed because of the small number of RCTs. Neck pain intensity and functional disability were significantly lower in the yoga groups than in the control groups. [Conclusion] Evidence from the 3 randomly controlled trials shows that yoga may be beneficial for chronic neck pain. The low-quality result of the critical appraisal and the small number of trials suggest that high-quality RCTs are required to examine further the effects of yoga intervention on chronic neck pain relief. PMID:27512290

The effects of AST-120 on chronic kidney disease progression in the United States of America: a post hoc subgroup analysis of randomized controlled trials.

PubMed

Schulman, Gerald; Berl, Tomas; Beck, Gerald J; Remuzzi, Giuseppe; Ritz, Eberhard; Shimizu, Miho; Shobu, Yuko; Kikuchi, Mami

2016-09-30

The orally administered spherical carbon adsorbent AST-120 is used on-label in Asian countries to slow renal disease progression in patients with progressive chronic kidney disease (CKD). Recently, two multinational, randomized, double-blind, placebo-controlled, phase 3 trials (Evaluating Prevention of Progression in Chronic Kidney Disease [EPPIC] trials) examined AST-120's efficacy in slowing CKD progression. This study assessed the efficacy of AST-120 in the subgroup of patients from the United States of America (USA) in the EPPIC trials. In the EPPIC trials, 2035 patients with moderate to severe CKD were studied, of which 583 were from the USA. The patients were randomly assigned to two groups of equal size that were treated with AST-120 or placebo (9 g/day). The primary end point was a composite of dialysis initiation, kidney transplantation, or serum creatinine doubling. The Kaplan-Meier curve for the time to achieve the primary end point in the placebo-treated patients from the USA was similar to that projected before the study. The per protocol subgroup analysis of the population from the USA which included patients with compliance rates of ≥67 % revealed a significant difference between the treatment groups in the time to achieve the primary end point (Hazard Ratio, 0.74; 95 % Confidence Interval, 0.56-0.97). This post hoc subgroup analysis of EPPIC study data suggests that treatment with AST-120 might delay the time to primary end point in CKD patients from the USA. A further randomized controlled trial in progressive CKD patients in the USA is necessary to confirm the beneficial effect of adding AST-120 to standard therapy regimens. ClinicalTrials.gov NCT00500682 ; NCT00501046 .

The effect of primary delivery of the anterior compared with the posterior shoulder on perineal trauma: a study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Approximately 85% of vaginal deliveries are accompanied by perineal trauma. The objective of this trial is to compare the incidence and degree of perineal trauma after primary delivery of the anterior compared with the posterior shoulder during vaginal birth. The hypothesis is that primary delivery of the posterior shoulder reduces the rate and degree of perineal trauma. Methods/design This is a single-centre, randomized controlled trial, with computer-generated randomization in a 1:1 allocation ratio. Women planning their first vaginal delivery (n = 650) are randomized to primary delivery of either the anterior or posterior shoulder. The primary outcome is any perineal trauma. Additional outcomes are the perineal injury subtypes, postpartum bleeding, umbilical artery pH, Apgar score at 5 minutes and any neonatal birth trauma. Perineal trauma is assessed by a midwife or doctor blinded to the method of shoulder delivery. All midwives are trained in the two methods of shoulder delivery and in the grading of perineal tears. The trial is being undertaken at a Danish community hospital with 1,600 yearly deliveries. Data will be analyzed according to the intention-to-treat principle. Recruitment started in January 2013 and the trial is planned to proceed for 24 months. Discussion Most delivery assistance techniques are based on tradition and heritage and lack objective evidence. This trial provides an example of how vaginal delivery techniques can be evaluated in a randomized controlled trial. The results of this trial will clarify the role that delivery of the shoulders has on perineal trauma and thereby provide knowledge to recommendations on birthing technique. Trial registration ClinicalTrials.gov: NCT01937546. PMID:25047001

Role of supplemental calcium in the recurrence of colorectal adenomas: a metaanalysis of randomized controlled trials.

PubMed

Shaukat, Aasma; Scouras, Nicole; Schünemann, Holger J

2005-02-01

Colorectal adenomas are neoplastic growths that are important targets for chemoprevention. Dietary calcium is thought to play an important role in chemoprevention. However, the role of calcium supplementation for preventing recurrence of adenomas is controversial. We performed a systematic review and meta-analysis to study the role of calcium supplementation in preventing recurrence of adenomas. We searched electronic bibliographic databases (Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, CINAHL, EMBASE, and MEDLINE) and contacted authors to identify potentially eligible studies. We identified three trials including 1,485 subjects with previously removed adenomas who were randomized to calcium versus placebo supplementation. The study endpoint was recurrence of adenomas at the end of 3-4 yr in 1,279 patients who completed the trials. We found that the recurrence of adenomas was significantly lower in subjects randomized to calcium supplementation (RR: 0.80, CI: 0.68, 0.93; p-value = 0.004). This systematic review and meta-analysis suggest that calcium supplementation prevents recurrent colorectal adenomas.

Mindfulness-based stress reduction for treating chronic headache: A systematic review and meta-analysis.

PubMed

Anheyer, Dennis; Leach, Matthew J; Klose, Petra; Dobos, Gustav; Cramer, Holger

2018-01-01

Background Mindfulness-based stress reduction/cognitive therapy are frequently used for pain-related conditions, but their effects on headache remain uncertain. This review aimed to assess the efficacy and safety of mindfulness-based stress reduction/cognitive therapy in reducing the symptoms of chronic headache. Data sources and study selection MEDLINE/PubMed, Scopus, CENTRAL, and PsychINFO were searched to 16 June 2017. Randomized controlled trials comparing mindfulness-based stress reduction/cognitive therapy with usual care or active comparators for migraine and/or tension-type headache, which assessed headache frequency, duration or intensity as a primary outcome, were eligible for inclusion. Risk of bias was assessed using the Cochrane Tool. Results Five randomized controlled trials (two on tension-type headache; one on migraine; two with mixed samples) with a total of 185 participants were included. Compared to usual care, mindfulness-based stress reduction/cognitive therapy did not improve headache frequency (three randomized controlled trials; standardized mean difference = 0.00; 95% confidence interval = -0.33,0.32) or headache duration (three randomized controlled trials; standardized mean difference = -0.08; 95% confidence interval = -1.03,0.87). Similarly, no significant difference between groups was found for pain intensity (five randomized controlled trials; standardized mean difference = -0.78; 95% confidence interval = -1.72,0.16). Conclusions Due to the low number, small scale and often high or unclear risk of bias of included randomized controlled trials, the results are imprecise; this may be consistent with either an important or negligible effect. Therefore, more rigorous trials with larger sample sizes are needed.

Interventions for reducing fear of childbirth: A systematic review and meta-analysis of clinical trials.

PubMed

MoghaddamHosseini, Vahideh; Nazarzadeh, Milad; Jahanfar, Shayesteh

2017-11-07

Fear of childbirth is a problematic mental health issue during pregnancy. But, effective interventions to reduce this problem are not well understood. To examine effective interventions for reducing fear of childbirth. The Cochrane Central Register of Controlled Trials, PubMed, Embase and PsycINFO were searched since inception till September 2017 without any restriction. Randomised controlled trials and quasi-randomised controlled trials comparing interventions for treatment of fear of childbirth were included. The standardized mean differences were pooled using random and fixed effect models. The heterogeneity was determined using the Cochran's test and I 2 index and was further explored in meta-regression model and subgroup analyses. Ten studies inclusive of 3984 participants were included in the meta-analysis (2 quasi-randomized and 8 randomized clinical trials). Eight studies investigated education and two studies investigated hypnosis-based intervention. The pooled standardized mean differences of fear for the education intervention and hypnosis group in comparison with control group were -0.46 (95% CI -0.73 to -0.19) and -0.22 (95% CI -0.34 to -0.10), respectively. Both types of interventions were effective in reducing fear of childbirth; however our pooled results revealed that educational interventions may reduce fear with double the effect of hypnosis. Further large scale randomized clinical trials and individual patient data meta-analysis are warranted for assessing the association. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Asthma Self-Management Model: Randomized Controlled Trial

ERIC Educational Resources Information Center

Olivera, Carolina M. X.; Vianna, Elcio Oliveira; Bonizio, Roni C.; de Menezes, Marcelo B.; Ferraz, Erica; Cetlin, Andrea A.; Valdevite, Laura M.; Almeida, Gustavo A.; Araujo, Ana S.; Simoneti, Christian S.; de Freitas, Amanda; Lizzi, Elisangela A.; Borges, Marcos C.; de Freitas, Osvaldo

2016-01-01

Information for patients provided by the pharmacist is reflected in adhesion to treatment, clinical results and patient quality of life. The objective of this study was to assess an asthma self-management model for rational medicine use. This was a randomized controlled trial with 60 asthmatic patients assigned to attend five modules presented by…

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…

Considerations for Designing Group Randomized Trials of Professional Development with Teacher Knowledge Outcomes

ERIC Educational Resources Information Center

Kelcey, Ben; Phelps, Geoffrey

2013-01-01

Despite recent shifts in research emphasizing the value of carefully designed experiments, the number of studies of teacher professional development with rigorous designs has lagged behind its student outcome counterparts. We outline a framework for the design of group randomized trials (GRTs) with teachers' knowledge as the outcome and…

Randomized Controlled Trial of Video Self-Modeling Following Speech Restructuring Treatment for Stuttering

ERIC Educational Resources Information Center

Cream, Angela; O'Brian, Sue; Jones, Mark; Block, Susan; Harrison, Elisabeth; Lincoln, Michelle; Hewat, Sally; Packman, Ann; Menzies, Ross; Onslow, Mark

2010-01-01

Purpose: In this study, the authors investigated the efficacy of video self-modeling (VSM) following speech restructuring treatment to improve the maintenance of treatment effects. Method: The design was an open-plan, parallel-group, randomized controlled trial. Participants were 89 adults and adolescents who undertook intensive speech…

Mixing Methods in Randomized Controlled Trials (RCTs): Validation, Contextualization, Triangulation, and Control

ERIC Educational Resources Information Center

Spillane, James P.; Pareja, Amber Stitziel; Dorner, Lisa; Barnes, Carol; May, Henry; Huff, Jason; Camburn, Eric

2010-01-01

In this paper we described how we mixed research approaches in a Randomized Control Trial (RCT) of a school principal professional development program. Using examples from our study we illustrate how combining qualitative and quantitative data can address some key challenges from validating instruments and measures of mediator variables to…

Anger Management and Intellectual Disabilities: A Systematic Review

ERIC Educational Resources Information Center

Hamelin, Jeffery; Travis, Robert; Sturmey, Peter

2013-01-01

We conducted a systematic literature review of anger management in people with intellectual disabilities (ID). We identified 2 studies that used randomized controlled trials and 6 that used pretest-posttest nonequivalent control group designs. The mean between-group effect size was 1.52 for randomized controlled trials and 0.89 for the other…

Effect of structured physical activity on prevention of serious fall injuries in adults aged 70-89: randomized clinical trial (LIFE Study)

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: To test whether a long term, structured physical activity program compared with a health education program reduces the risk of serious fall injuries among sedentary older people with functional limitations. DESIGN: Multicenter, single blinded randomized trial (Lifestyle Interventions and ...

Evaluation of Parent and Child Enhancement (PACE) Program: Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Lo, Cyrus

2017-01-01

Objective: This study examined the efficacy of the Parent and Child Enhancement (PACE) program on child learning, child behavior problems, and parental stress, using randomized controlled trial design, in social services centers. Methods: Eligibility criteria were (1) children aged 2 years at program commencement, (2) low-income, new immigrant, or…

Explaining Feast or Famine in Randomized Field Trials: Medical Science and Criminology Compared.

ERIC Educational Resources Information Center

Shepherd, Jonathan P.

2003-01-01

Discusses the contrast between the frequency of randomized clinical trials in the health sciences and the relative famine of such studies in criminology. Attributes this difference to the contexts in which research is done and the difference in the status of situational research in the two disciplines. (SLD)

Randomized Control Trial of a CBT Trauma Recovery Program in Palestinian Schools

ERIC Educational Resources Information Center

Barron, Ian G.; Abdallah, Ghassan; Smith, Patrick

2013-01-01

The current study aimed to assess the Teaching Recovery Techniques (TRT) trauma recovery program within the context of ongoing violence. Utilizing a randomized controlled trial, 11-14-year-old students in Nablus, Palestine, were allocated by class to intervention or wait-list control conditions. Standardized measures assessed trauma exposure,…

Moderators of Theory-Based Interventions to Promote Physical Activity in 77 Randomized Controlled Trials

ERIC Educational Resources Information Center

Bernard, Paquito; Carayol, Marion; Gourlan, Mathieu; Boiché, Julie; Romain, Ahmed Jérôme; Bortolon, Catherine; Lareyre, Olivier; Ninot, Gregory

2017-01-01

A meta-analysis of randomized controlled trials (RCTs) has recently showed that theory-based interventions designed to promote physical activity (PA) significantly increased PA behavior. The objective of the present study was to investigate the moderators of the efficacy of these theory-based interventions. Seventy-seven RCTs evaluating…

Moving from Efficacy to Effectiveness in Cognitive Behavioral Therapy for Psychosis: A Randomized Clinical Practice Trial

ERIC Educational Resources Information Center

Lincoln, Tania M.; Ziegler, Michael; Mehl, Stephanie; Kesting, Marie-Luise; Lullmann, Eva; Westermann, Stefan; Rief, Winfried

2012-01-01

Objective: Randomized controlled trials have attested the efficacy of cognitive behavioral therapy (CBT) in reducing psychotic symptoms. Now, studies are needed to investigate its effectiveness in routine clinical practice settings. Method: Eighty patients with schizophrenia spectrum disorders who were seeking outpatient treatment were randomized…

A Randomized Trial Investigating the Effect of a Brief Lifestyle Intervention on Freshman-Year Weight Gain

ERIC Educational Resources Information Center

Middleton, Kathryn R.; Perri, Michael G.

2014-01-01

Objective: The current study was a randomized controlled trial investigating the effect of an innovative, short-term lifestyle intervention on weight gain in female freshman college students. Participants: Ninety-five freshmen were recruited from a large public university in the United States. Methods: Participants completed baseline assessments…

Mainstreaming Remedial Mathematics Students in Introductory Statistics: Results Using a Randomized Controlled Trial

ERIC Educational Resources Information Center

Logue, Alexandra W.; Watanabe-Rose, Mari

2014-01-01

This study used a randomized controlled trial to determine whether students, assessed by their community colleges as needing an elementary algebra (remedial) mathematics course, could instead succeed at least as well in a college-level, credit-bearing introductory statistics course with extra support (a weekly workshop). Researchers randomly…

Randomized Clinical Trial: The Use of SpeechEasy® in Stuttering Treatment

ERIC Educational Resources Information Center

Ritto, Ana Paula; Juste, Fabiola Staróbole; Stuart, Andrew; Kalinowski, Joseph; de Andrade, Claudia Regina Furquim

2016-01-01

Background: Numerous studies have demonstrated the benefit of devices delivering altered auditory feedback (AAF) as a therapeutic alternative for those who stutter. Aims: The effectiveness of a device delivering AAF (SpeechEasy®) was compared with behavioural techniques in the treatment of stuttering in a randomized clinical trial. Methods &…

Leveraging contact network structure in the design of cluster randomized trials.

PubMed

Harling, Guy; Wang, Rui; Onnela, Jukka-Pekka; De Gruttola, Victor

2017-02-01

In settings like the Ebola epidemic, where proof-of-principle trials have provided evidence of efficacy but questions remain about the effectiveness of different possible modes of implementation, it may be useful to conduct trials that not only generate information about intervention effects but also themselves provide public health benefit. Cluster randomized trials are of particular value for infectious disease prevention research by virtue of their ability to capture both direct and indirect effects of intervention, the latter of which depends heavily on the nature of contact networks within and across clusters. By leveraging information about these networks-in particular the degree of connection across randomized units, which can be obtained at study baseline-we propose a novel class of connectivity-informed cluster trial designs that aim both to improve public health impact (speed of epidemic control) and to preserve the ability to detect intervention effects. We several designs for cluster randomized trials with staggered enrollment, in each of which the order of enrollment is based on the total number of ties (contacts) from individuals within a cluster to individuals in other clusters. Our designs can accommodate connectivity based either on the total number of external connections at baseline or on connections only to areas yet to receive the intervention. We further consider a "holdback" version of the designs in which control clusters are held back from re-randomization for some time interval. We investigate the performance of these designs in terms of epidemic control outcomes (time to end of epidemic and cumulative incidence) and power to detect intervention effect, by simulating vaccination trials during an SEIR-type epidemic outbreak using a network-structured agent-based model. We compare results to those of a traditional Stepped Wedge trial. In our simulation studies, connectivity-informed designs lead to a 20% reduction in cumulative incidence compared to comparable traditional study designs, but have little impact on epidemic length. Power to detect intervention effect is reduced in all connectivity-informed designs, but "holdback" versions provide power that is very close to that of a traditional Stepped Wedge approach. Incorporating information about cluster connectivity in the design of cluster randomized trials can increase their public health impact, especially in acute outbreak settings. Using this information helps control outbreaks-by minimizing the number of cross-cluster infections-with very modest cost in terms of power to detect effectiveness.

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.

Predictors of short- and long-term adherence with a Mediterranean-type diet intervention: the PREDIMED randomized trial.

PubMed

Downer, Mary Kathryn; Gea, Alfredo; Stampfer, Meir; Sánchez-Tainta, Ana; Corella, Dolores; Salas-Salvadó, Jordi; Ros, Emilio; Estruch, Ramón; Fitó, Montserrat; Gómez-Gracia, Enrique; Arós, Fernando; Fiol, Miquel; De-la-Corte, Francisco Jose Garcia; Serra-Majem, Lluís; Pinto, Xavier; Basora, Josep; Sorlí, José V; Vinyoles, Ernest; Zazpe, Itziar; Martínez-González, Miguel-Ángel

2016-06-14

Dietary intervention success requires strong participant adherence, but very few studies have examined factors related to both short-term and long-term adherence. A better understanding of predictors of adherence is necessary to improve the design and execution of dietary intervention trials. This study was designed to identify participant characteristics at baseline and study features that predict short-term and long-term adherence with interventions promoting the Mediterranean-type diet (MedDiet) in the PREvención con DIeta MEDiterránea (PREDIMED) randomized trial. Analyses included men and women living in Spain aged 55-80 at high risk for cardiovascular disease. Participants were randomized to the MedDiet supplemented with either complementary extra-virgin olive oil (EVOO) or tree nuts. The control group and participants with insufficient information on adherence were excluded. PREDIMED began in 2003 and ended in 2010. Investigators assessed covariates at baseline and dietary information was updated yearly throughout follow-up. Adherence was measured with a validated 14-point Mediterranean-type diet adherence score. Logistic regression was used to examine associations between baseline characteristics and adherence at one and four years of follow-up. Participants were randomized to the MedDiet supplemented with EVOO (n = 2,543; 1,962 after exclusions) or tree nuts (n = 2,454; 2,236 after exclusions). A higher number of cardiovascular risk factors, larger waist circumference, lower physical activity levels, lower total energy intake, poorer baseline adherence to the 14-point adherence score, and allocation to MedDiet + EVOO each independently predicted poorer adherence. Participants from PREDIMED recruiting centers with a higher total workload (measured as total number of persons-years of follow-up) achieved better adherence. No adverse events or side effects were reported. To maximize dietary adherence in dietary interventions, additional efforts to promote adherence should be used for participants with lower baseline adherence to the intended diet and poorer health status. The design of multicenter nutrition trials should prioritize few large centers with more participants in each, rather than many small centers. This study was registered at controlled-trials.com (http://www.controlled-trials. com/ISRCTN35739639). International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005. parallel randomized trial.

A mathematical model of case-ascertainment bias: Applied to case-control studies nested within a randomized screening trial.

PubMed

Jansen, Rick J; Alexander, Bruce H; Hayes, Richard B; Miller, Anthony B; Wacholder, Sholom; Church, Timothy R

2018-01-01

When some individuals are screen-detected before the beginning of the study, but otherwise would have been diagnosed symptomatically during the study, this results in different case-ascertainment probabilities among screened and unscreened participants, referred to here as lead-time-biased case-ascertainment (LTBCA). In fact, this issue can arise even in risk-factor studies nested within a randomized screening trial; even though the screening intervention is randomly allocated to trial arms, there is no randomization to potential risk-factors and uptake of screening can differ by risk-factor strata. Under the assumptions that neither screening nor the risk factor affects underlying incidence and no other forms of bias operate, we simulate and compare the underlying cumulative incidence and that observed in the study due to LTBCA. The example used will be constructed from the randomized Prostate, Lung, Colorectal, and Ovarian cancer screening trial. The derived mathematical model is applied to simulating two nested studies to evaluate the potential for screening bias in observational lung cancer studies. Because of differential screening under plausible assumptions about preclinical incidence and duration, the simulations presented here show that LTBCA due to chest x-ray screening can significantly increase the estimated risk of lung cancer due to smoking by 1% and 50%. Traditional adjustment methods cannot account for this bias, as the influence screening has on observational study estimates involves events outside of the study observation window (enrollment and follow-up) that change eligibility for potential participants, thus biasing case ascertainment.

Driving with Intuition: A Preregistered Study about the EEG Anticipation of Simulated Random Car Accidents

PubMed Central

Duma, Gian Marco; Mento, Giovanni; Manari, Tommaso; Martinelli, Massimiliano

2017-01-01

The study of neural pre-stimulus or “anticipatory” activity opened a new window for understanding how the brain actively constructs the forthcoming reality. Usually, experimental paradigms designed to study anticipatory activity make use of stimuli. The purpose of the present study is to expand the study of neural anticipatory activity upon the temporal occurrence of dichotomic, statistically unpredictable (random) stimuli within an ecological experimental paradigm. To this purpose, we used a simplified driving simulation including two possible, randomly-presented trial types: a car crash end trial and a no car crash end trial. Event Related Potentials (ERP) were extracted -3,000 ms before stimulus onset. We identified a fronto-central negativity starting around 1,000 ms before car crash presentation. By contrast, a whole-scalp distributed positivity characterized the anticipatory activity observed before the end of the trial in the no car crash end condition. The present data are in line with the hypothesis that the brain may also anticipate dichotomic, statistically unpredictable stimuli, relaying onto different pre-stimulus ERP activity. Possible integration with car-smart-systems is also suggested. PMID:28103303

New Estimates of Design Parameters for Clustered Randomization Studies: Findings from North Carolina and Florida. Working Paper 43

ERIC Educational Resources Information Center

Xu, Zeyu; Nichols, Austin

2010-01-01

The gold standard in making causal inference on program effects is a randomized trial. Most randomization designs in education randomize classrooms or schools rather than individual students. Such "clustered randomization" designs have one principal drawback: They tend to have limited statistical power or precision. This study aims to…

Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial

PubMed Central

2011-01-01

Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis. Discussion This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. Trial registration number Netherlands Trial Register (NTR): NTR2768 PMID:22070744

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.

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…

Effectiveness and cost-effectiveness of telehealthcare for chronic obstructive pulmonary disease: study protocol for a cluster randomized controlled trial.

PubMed

Udsen, Flemming Witt; Lilholt, Pernille Heyckendorff; Hejlesen, Ole; Ehlers, Lars Holger

2014-05-21

Several feasibility studies show promising results of telehealthcare on health outcomes and health-related quality of life for patients suffering from chronic obstructive pulmonary disease, and some of these studies show that telehealthcare may even lower healthcare costs. However, the only large-scale trial we have so far - the Whole System Demonstrator Project in England - has raised doubts about these results since it conclude that telehealthcare as a supplement to usual care is not likely to be cost-effective compared with usual care alone. The present study is known as 'TeleCare North' in Denmark. It seeks to address these doubts by implementing a large-scale, pragmatic, cluster-randomized trial with nested economic evaluation. The purpose of the study is to assess the effectiveness and the cost-effectiveness of a telehealth solution for patients suffering from chronic obstructive pulmonary disease compared to usual practice. General practitioners will be responsible for recruiting eligible participants (1,200 participants are expected) for the trial in the geographical area of the North Denmark Region. Twenty-six municipality districts in the region define the randomization clusters. The primary outcomes are changes in health-related quality of life, and the incremental cost-effectiveness ratio measured from baseline to follow-up at 12 months. Secondary outcomes are changes in mortality and physiological indicators (diastolic and systolic blood pressure, pulse, oxygen saturation, and weight). There has been a call for large-scale clinical trials with rigorous cost-effectiveness assessments in telehealthcare research. This study is meant to improve the international evidence base for the effectiveness and cost-effectiveness of telehealthcare to patients suffering from chronic obstructive pulmonary disease by implementing a large-scale pragmatic cluster-randomized clinical trial. Clinicaltrials.gov, http://NCT01984840, November 14, 2013.

Systematic review and meta-analysis of Saccharomyces boulardii in adult patients.

PubMed

McFarland, Lynne V

2010-05-14

This article reviews the evidence for efficacy and safety of Saccharomyces boulardii (S. boulardii) for various disease indications in adults based on the peer-reviewed, randomized clinical trials and pre-clinical studies from the published medical literature (Medline, Clinical Trial websites and meeting abstracts) between 1976 and 2009. For meta-analysis, only randomized, blinded controlled trials unrestricted by language were included. Pre-clinical studies, volunteer studies and uncontrolled studies were excluded from the review of efficacy and meta-analysis, but included in the systematic review. Of 31 randomized, placebo-controlled treatment arms in 27 trials (encompassing 5029 study patients), S. boulardii was found to be significantly efficacious and safe in 84% of those treatment arms. A meta-analysis found a significant therapeutic efficacy for S. boulardii in the prevention of antibiotic-associated diarrhea (AAD) (RR = 0.47, 95% CI: 0.35-0.63, P < 0.001). In adults, S. boulardii can be strongly recommended for the prevention of AAD and the traveler's diarrhea. Randomized trials also support the use of this yeast probiotic for prevention of enteral nutrition-related diarrhea and reduction of Helicobacter pylori treatment-related symptoms. S. boulardii shows promise for the prevention of C. difficile disease recurrences; treatment of irritable bowel syndrome, acute adult diarrhea, Crohn's disease, giardiasis, human immunodeficiency virus-related diarrhea; but more supporting evidence is recommended for these indications. The use of S. boulardii as a therapeutic probiotic is evidence-based for both efficacy and safety for several types of diarrhea.

Systematic review and meta-analysis of Saccharomyces boulardii in adult patients

PubMed Central

McFarland, Lynne V

2010-01-01

This article reviews the evidence for efficacy and safety of Saccharomyces boulardii (S. boulardii) for various disease indications in adults based on the peer-reviewed, randomized clinical trials and pre-clinical studies from the published medical literature (Medline, Clinical Trial websites and meeting abstracts) between 1976 and 2009. For meta-analysis, only randomized, blinded controlled trials unrestricted by language were included. Pre-clinical studies, volunteer studies and uncontrolled studies were excluded from the review of efficacy and meta-analysis, but included in the systematic review. Of 31 randomized, placebo-controlled treatment arms in 27 trials (encompassing 5029 study patients), S. boulardii was found to be significantly efficacious and safe in 84% of those treatment arms. A meta-analysis found a significant therapeutic efficacy for S. boulardii in the prevention of antibiotic-associated diarrhea (AAD) (RR = 0.47, 95% CI: 0.35-0.63, P < 0.001). In adults, S. boulardii can be strongly recommended for the prevention of AAD and the traveler’s diarrhea. Randomized trials also support the use of this yeast probiotic for prevention of enteral nutrition-related diarrhea and reduction of Heliobacter pylori treatment-related symptoms. S. boulardii shows promise for the prevention of C. difficile disease recurrences; treatment of irritable bowel syndrome, acute adult diarrhea, Crohn’s disease, giardiasis, human immunodeficiency virus-related diarrhea; but more supporting evidence is recommended for these indications. The use of S. boulardii as a therapeutic probiotic is evidence-based for both efficacy and safety for several types of diarrhea. PMID:20458757

Cervical Spondylotic Myelopathy Surgical (CSM-S) Trial: Randomized Controlled Trial Design and Rationale

PubMed Central

Ghogawala, Zoher; Benzel, Edward C.; Heary, Robert F.; Riew, K. Daniel; Albert, Todd J.; Butler, William E.; Barker, Fred G.; Heller, John G.; McCormick, Paul C.; Whitmore, Robert G.; Freund, Karen M.; Schwartz, J. Sanford

2014-01-01

Background Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction in the world. There is significant practice variation and uncertainty as to the optimal surgical approach for treating CSM. Objective The primary objective is to determine if ventral surgery is associated with superior SF-36 Physical Component Summary (PCS) outcome at one year follow-up compared to dorsal (laminectomy/fusion or laminoplasty) surgery for the treatment of CSM. The study will also investigate whether post-operative sagittal balance is an independent predictor of overall outcome and will compare health resource utilization for ventral and dorsal procedures. Methods The study is a randomized, controlled trial with a nonrandomized arm for patients who are eligible but decline randomization. Two hundred fifty patients (159 randomized) with CSM from 11 sites will be recruited over 18 months. The primary outcome is the Short Form-36 PCS score. Secondary outcomes include disease specific outcomes, overall health-related quality of life (EuroQol-5D), and health resource utilization. Expected Outcomes This will be the first randomized controlled trial to compare directly the health-related quality of life outcomes for ventral versus dorsal surgery for treating CSM. Discussion An NIH-funded (1R13AR065834-01) investigator meeting was held prior to initiating the trial in order to bring multiple stakeholders together to finalize the study protocol. Study investigators, coordinators, and major stakeholders were able to attend and discuss strengths, limitations, and concerns regarding the study. The final protocol was approved for funding by PCORI (CE-1304-6173). The RCT began enrollment on April 1, 2014. PMID:24991714

Donepezil treatment and Alzheimer disease: can the results of randomized clinical trials be applied to Alzheimer disease patients in clinical practice?

PubMed

Tinklenberg, Jared R; Kraemer, Helena C; Yaffe, Kristine; Ross, Leslie; Sheikh, Javaid; Ashford, John W; Yesavage, Jerome A; Taylor, Joy L

2007-11-01

To determine if results from randomized clinical trials of donepezil in Alzheimer disease (AD) patients can be applied to AD patients in clinical practice by comparing the findings from a Nordic one-year randomized AD donepezil trial with data from a one-year prospective, observational study of AD patients. AD patients from a consortium of California sites were systematically followed for at least one year. Their treatment regimens, including prescription of donepezil, were determined by their individual physician according to his or her usual criteria. The 148 California patients treated with donepezil had a one-year decline of 1.3 (3.5 SD) points on the Mini-Mental State Exam compared to a decline of 3.3 (4.4 SD) in the 158 AD patients who received no anti-Alzheimer drugs. The Mini-Mental State Exam decline in Nordic sample was approximately 0.25 points for the 91 patients receiving donepezil and approximately 2.2 for the 98 placebo patients. The overall effect sizes were estimated at about 0.49 in both studies. The California data were further analyzed using propensity methods; after taking into account differences that could bias prescribing decisions, benefits associated with taking donepezil remained. A comparison of a randomized clinical trial of donepezil in AD patients and this observational study indicates that if appropriate methodological and statistical precautions are undertaken, then results from randomized clinical trials can be predictive with AD patients in clinical practice. This California study supports the modest effectiveness of donepezil in AD patients having clinical characteristics similar to those of the Nordic study.

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.

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.

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.

Effect of joint mobilization techniques for primary total knee arthroplasty: Study protocol for a randomized controlled trial.

PubMed

Xu, Jiao; Zhang, Juan; Wang, Xue-Qiang; Wang, Xuan-Lin; Wu, Ya; Chen, Chan-Cheng; Zhang, Han-Yu; Zhang, Zhi-Wan; Fan, Kai-Yi; Zhu, Qiang; Deng, Zhi-Wei

2017-12-01

Total knee arthroplasty (TKA) has become the most preferred procedure by patients for the relief of pain caused by knee osteoarthritis. TKA patients aim a speedy recovery after the surgery. Joint mobilization techniques for rehabilitation have been widely used to relieve pain and improve joint mobility. However, relevant randomized controlled trials showing the curative effect of these techniques remain lacking to date. Accordingly, this study aims to investigate whether joint mobilization techniques are valid for primary TKA. We will manage a single-blind, prospective, randomized, controlled trial of 120 patients with unilateral TKA. Patients will be randomized into an intervention group, a physical modality therapy group, and a usual care group. The intervention group will undergo joint mobilization manipulation treatment once a day and regular training twice a day for a month. The physical modality therapy group will undergo physical therapy once a day and regular training twice a day for a month. The usual care group will perform regular training twice a day for a month. Primary outcome measures will be based on the visual analog scale, the knee joint Hospital for Special Surgery score, range of motion, surrounded degree, and adverse effect. Secondary indicators will include manual muscle testing, 36-Item Short Form Health Survey, Berg Balance Scale function evaluation, Pittsburgh Sleep Quality Index, proprioception, and muscle morphology. We will direct intention-to-treat analysis if a subject withdraws from the trial. The important features of this trial for joint mobilization techniques in primary TKA are randomization procedures, single-blind, large sample size, and standardized protocol. This study aims to investigate whether joint mobilization techniques are effective for early TKA patients. The result of this study may serve as a guide for TKA patients, medical personnel, and healthcare decision makers. It has been registered at http://www.chictr.org.cn/showproj.aspx?proj=15262 (Identifier:ChiCTR-IOR-16009192), Registered 11 September 2016. We also could provide the correct URL of the online registry in the WHO Trial Registration. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-IOR-16009192.

Patent Foramen Ovale Closure for Secondary Prevention of Cryptogenic Stroke: Updated Meta-Analysis of Randomized Clinical Trials.

PubMed

Vaduganathan, Muthiah; Qamar, Arman; Gupta, Ankur; Bajaj, Navkaranbir; Golwala, Harsh B; Pandey, Ambarish; Bhatt, Deepak L

2018-05-01

Patent foramen ovale closure represents a potential secondary prevention strategy for cryptogenic stroke, but available trials have varied by size, device studied, and follow-up. We conducted a systematic search of published randomized clinical trials evaluating patent foramen ovale closure versus medical therapy in patients with recent stroke or transient ischemic attack using PubMED, EMBASE, and Cochrane through September 2017. Weighting was by random effects models. Of 480 studies screened, we included 5 randomized clinical trials in the meta-analysis in which 3440 patients were randomized to patent foramen ovale closure (n = 1829) or medical therapy (n = 1611) and followed for an average of 2.0 to 5.9 years. Index stroke/transient ischemic attack occurred within 6 to 9 months of randomization. The primary end point was composite stroke/transient ischemic attack and death (in 3 trials) or stroke alone (in 2 trials). Patent foramen ovale closure reduced the primary end point (0.70 vs 1.48 events per 100 patient-years; risk ratio [RR], 0.52 [0.29-0.91]; I 2  = 55.0%) and stroke/transient ischemic attack (1.04 vs 2.00 events per 100 patient-years; RR, 0.55 [0.37-0.82]; I 2  = 42.2%) with modest heterogeneity compared with medical therapy. Procedural bleeding was not different between study arms (1.8% vs 1.8%; RR, 0.94 [0.49-1.83]; I 2  = 29.2%), but new-onset atrial fibrillation/flutter was increased with patent foramen ovale closure (6.6% vs 0.7%; RR, 4.69 [2.17-10.12]; I 2  = 29.3%). In patients with recent cryptogenic stroke, patent foramen ovale closure reduces recurrent stroke/transient ischemic attack compared with medical therapy, but is associated with a higher risk of new-onset atrial fibrillation/flutter. Copyright © 2018 Elsevier Inc. All rights reserved.

Hypothesis testing in clinical trials.

PubMed

Green, S B

2000-08-01

In designing and analyzing any clinical trial, two issues related to patient heterogeneity must be considered: (1) the effect of chance and (2) the effect of bias. These issues are addressed by enrolling adequate numbers of patients in the study and using randomization for treatment assignment. An "intention-to-treat" analysis of outcome data includes all individuals randomized and counted in the group to which they are randomized. There is an increased risk of spurious results with a greater number of subgroup analyses, particularly when these analyses are data derived. Factorial designs are sometimes appropriate and can lead to efficiencies by addressing more than one comparison of interventions in a single trial.

A randomized trial comparing concise and standard consent forms in the START trial

PubMed Central

Touloumi, Giota; Walker, A. Sarah; Smolskis, Mary; Sharma, Shweta; Babiker, Abdel G.; Pantazis, Nikos; Tavel, Jorge; Florence, Eric; Sanchez, Adriana; Hudson, Fleur; Papadopoulos, Antonios; Emanuel, Ezekiel; Clewett, Megan; Munroe, David; Denning, Eileen

2017-01-01

Background Improving the effectiveness and efficiency of research informed consent is a high priority. Some express concern about longer, more complex, written consent forms creating barriers to participant understanding. A recent meta-analysis concluded that randomized comparisons were needed. Methods We conducted a cluster-randomized non-inferiority comparison of a standard versus concise consent form within a multinational trial studying the timing of starting antiretroviral therapy in HIV+ adults (START). Interested sites were randomized to standard or concise consent forms for all individuals signing START consent. Participants completed a survey measuring comprehension of study information and satisfaction with the consent process. Site personnel reported usual site consent practices. The primary outcome was comprehension of the purpose of randomization (pre-specified 7.5% non-inferiority margin). Results 77 sites (2429 participants) were randomly allocated to use standard consent and 77 sites (2000 participants) concise consent, for an evaluable cohort of 4229. Site and participant characteristics were similar for the two groups. The concise consent was non-inferior to the standard consent on comprehension of randomization (80.2% versus 82%, site adjusted difference: 0.75% (95% CI -3.8%, +5.2%)); and the two groups did not differ significantly on total comprehension score, satisfaction, or voluntariness (p>0.1). Certain independent factors, such as education, influenced comprehension and satisfaction but not differences between consent groups. Conclusions An easier to read, more concise consent form neither hindered nor improved comprehension of study information nor satisfaction with the consent process among a large number of participants. This supports continued efforts to make consent forms more efficient. Trial registration Informed consent substudy was registered as part of START study in clinicaltrials.gov #NCT00867048, and EudraCT # 2008-006439-12 PMID:28445471

Revisited: A Systematic Review of Therapeutic Hypothermia for Adult Patients Following Traumatic Brain Injury.

PubMed

Watson, Hannah I; Shepherd, Andrew A; Rhodes, Jonathan K J; Andrews, Peter J D

2018-06-01

Therapeutic hypothermia has been of topical interest for many years and with the publication of two international, multicenter randomized controlled trials, the evidence base now needs updating. The aim of this systematic review of randomized controlled trials is to assess the efficacy of therapeutic hypothermia in adult traumatic brain injury focusing on mortality, poor outcomes, and new pneumonia. The following databases were searched from January 1, 2011, to January 26, 2018: Cochrane Central Register of Controlled Trial, MEDLINE, PubMed, and EMBASE. Only foreign articles published in the English language were included. Only articles that were randomized controlled trials investigating adult traumatic brain injury sustained following an acute, closed head injury were included. Two authors independently assessed at each stage. Quality was assessed using the Cochrane Collaboration's tool for assessing the risk of bias. All extracted data were combined using the Mantel-Haenszel estimator for pooled risk ratio with 95% CIs. p value of less than 0.05 was considered statistically significant. All statistical analyses were conducted using RevMan 5 (Cochrane Collaboration, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Twenty-two studies with 2,346 patients are included. Randomized controlled trials with a low risk of bias show significantly more mortality in the therapeutic hypothermia group (risk ratio, 1.37; 95% CI, 1.04-1.79; p = 0.02), whereas randomized controlled trials with a high risk of bias show the opposite with a higher mortality in the control group (risk ratio, 0.70; 95% CI, 0.60-0.82; p < 0.00001). Overall, this review is in-keeping with the conclusions published by the most recent randomized controlled trials. High-quality studies show no significant difference in mortality, poor outcomes, or new pneumonia. In addition, this review shows a place for fever control in the management of traumatic brain injury.

A Poisson approach to the validation of failure time surrogate endpoints in individual patient data meta-analyses.

PubMed

Rotolo, Federico; Paoletti, Xavier; Burzykowski, Tomasz; Buyse, Marc; Michiels, Stefan

2017-01-01

Surrogate endpoints are often used in clinical trials instead of well-established hard endpoints for practical convenience. The meta-analytic approach relies on two measures of surrogacy: one at the individual level and one at the trial level. In the survival data setting, a two-step model based on copulas is commonly used. We present a new approach which employs a bivariate survival model with an individual random effect shared between the two endpoints and correlated treatment-by-trial interactions. We fit this model using auxiliary mixed Poisson models. We study via simulations the operating characteristics of this mixed Poisson approach as compared to the two-step copula approach. We illustrate the application of the methods on two individual patient data meta-analyses in gastric cancer, in the advanced setting (4069 patients from 20 randomized trials) and in the adjuvant setting (3288 patients from 14 randomized trials).

Recruitment methods and costs for a randomized, placebo-controlled trial of chiropractic care for lumbar spinal stenosis: a single-site pilot study.

PubMed

Cambron, Jerrilyn A; Dexheimer, Jennifer M; Chang, Mabel; Cramer, Gregory D

2010-01-01

The purpose of this article is to describe the methods for recruitment in a clinical trial on chiropractic care for lumbar spinal stenosis. This randomized, placebo-controlled pilot study investigated the efficacy of different amounts of total treatment dosage over 6 weeks in 60 volunteer subjects with lumbar spinal stenosis. Subjects were recruited for this study through several media venues, focusing on successful and cost-effective strategies. Included in our efforts were radio advertising, newspaper advertising, direct mail, and various other low-cost initiatives. Of the 1211 telephone screens, 60 responders (5.0%) were randomized into the study. The most successful recruitment method was radio advertising, generating more than 64% of the calls (776 subjects). Newspaper and magazine advertising generated approximately 9% of all calls (108 subjects), and direct mail generated less than 7% (79 subjects). The total direct cost for recruitment was $40 740 or $679 per randomized patient. The costs per randomization were highest for direct mail ($995 per randomization) and lowest for newspaper/magazine advertising ($558 per randomization). Success of recruitment methods may vary based on target population and location. Planning of recruitment efforts is essential to the success of any clinical trial. Copyright 2010 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

Impact of Probiotics on Necrotizing Enterocolitis

PubMed Central

Underwood, Mark A.

2016-01-01

A large number of randomized placebo-controlled clinical trials and cohort studies have demonstrated a decrease in the incidence of necrotizing enterocolitis with administration of probiotic microbes. These studies have prompted many neonatologists to adopt routine prophylactic administration of probiotics while others await more definitive studies and/or probiotic products with demonstrated purity and stable numbers of live organisms. Cross-contamination and inadequate sample size limit the value of further traditional placebo-controlled randomized controlled trials. Key areas for future research include mechanisms of protection, optimum probiotic species or strains (or combinations thereof) and duration of treatment, interactions between diet and the administered probiotic, and the influence of genetic polymorphisms in the mother and infant on probiotic response. Next generation probiotics selected based on bacterial genetics rather than ease of production and large cluster-randomized clinical trials hold great promise for NEC prevention. PMID:27836423

Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Sfontouris, Ioannis A; Martins, Wellington P; Nastri, Carolina O; Viana, Iara G R; Navarro, Paula A; Raine-Fenning, Nick; van der Poel, Sheryl; Rienzi, Laura; Racowsky, Catherine

2016-10-01

The purpose of this study was to undertake a review of the available evidence comparing the use of a single medium versus sequential media for embryo culture to the blastocyst stage in clinical IVF. We searched the Cochrane Central, PubMed, Scopus, ClinicalTrials.gov, Current Controlled Trials and WHO International Clinical Trials Registry Platform to identify randomized controlled trials comparing single versus sequential media for blastocyst culture and ongoing pregnancy rate. Included studies randomized either oocytes/zygotes or women. Eligible oocyte/zygote studies were analyzed to assess the risk difference (RD) and 95 % confidence intervals (CI) between the two media systems; eligible woman-based studies were analyzed to assess the risk ratio (RR) and 95 % CI for clinical pregnancy rate. No differences were observed between single and sequential media for either ongoing pregnancy per randomized woman (relative risk (RR) = 0.9, 95 % CI = 0.7 to 1.3, two studies including 246 women, I 2  = 0 %) or clinical pregnancy per randomized woman (RR = 1.0, 95 % CI = 0.7 to 1.4, one study including 100 women); or miscarriage per clinical pregnancy: RR = 1.3, 95 % CI = 0.4 to 4.3, two studies including 246 participants, I 2  = 0 %). Single media use was associated with an increase blastocyst formation per randomized oocyte/zygote (relative distribution (RD) = +0.06, 95 % CI = +0.01 to +0.12, ten studies including 7455 oocytes/zygotes, I 2  = 83 %) but not top/high blastocyst formation (RD = +0.05, 95 % CI = -0.01 to +0.11, five studies including 3879 oocytes/zygotes, I 2  = 93 %). The overall quality of the evidence was very low for all these four outcomes. Although using a single medium for extended culture has some practical advantages and blastocyst formation rates appear to be higher, there is insufficient evidence to recommend either sequential or single-step media as being superior for the culture of embryos to days 5/6. Future studies comparing these two media systems in well-designed trials should be performed.

Impact of Clinical Trial Results on the Temporal Trends of Carotid Endarterectomy and Stenting From 2002 to 2014

PubMed Central

Hussain, Mohamad A.; Mamdani, Muhammad; Tu, Jack V.; Saposnik, Gustavo; Khoushhal, Zeyad; Aljabri, Badr; Verma, Subdoh

2016-01-01

Background and Purpose— Randomized trials provide conflicting data for the efficacy of carotid-artery stenting compared with endarterectomy. The purpose of this study was to examine the impact of conflicting clinical trial publications on the utilization rates of carotid revascularization procedures. Methods— We conducted a population-level time-series analysis of all individuals who underwent carotid endarterectomy and stenting in Ontario, Canada (2002–2014). The primary analysis examined temporal changes in the rates of carotid revascularization procedures after publications of major randomized trials. Secondary analyses examined changes in overall and age, sex, carotid-artery symptom, and operator specialty–specific procedure rates. Results— A total of 16 772 patients were studied (14 394 endarterectomy [86%]; 2378 stenting [14%]). The overall rate of carotid revascularization decreased from 6.0 procedures per 100 000 individuals ≥40 years old in April 2002 to 4.3 procedures in the first quarter of 2014 (29% decrease; P<0.001). The rate of endarterectomy decreased by 36% (P<0.001), whereas the rate of carotid-artery stenting increased by 72% (P=0.006). We observed a marked increase (P=0.01) in stenting after publication of the SAPPHIRE trial (Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy) in 2004, whereas stenting remained relatively unchanged after subsequent randomized trials published in 2006 (P=0.11) and 2010 (P=0.34). In contrast, endarterectomy decreased after trials published in 2006 (P=0.04) and 2010 (P=0.005). Conclusions— Although the overall rates of carotid revascularization and endarterectomy have fallen since 2002, the rate of carotid-artery stenting has risen since the publication of stenting-favorable SAPPHIRE trial. Subsequent conflicting randomized trials were associated with a decreasing rate of carotid endarterectomy. PMID:27834754

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

Nitrofurantoin vs other prophylactic agents in reducing recurrent urinary tract infections in adult women: a systematic review and meta-analysis.

PubMed

Price, Jameca Renee; Guran, Larissa A; Gregory, W Thomas; McDonagh, Marian S

2016-11-01

The clinical and financial burden from bladder infections is significant. Daily antibiotic use is the recommended strategy for recurrent urinary tract infection prevention. Increasing antibiotic resistance rates, however, require immediate identification of innovative alternative prophylactic therapies. This systematic review aims to provide guidance on gaps in evidence to guide future research. The objective of this review was to provide current pooled estimates of randomized control trials comparing the effects of nitrofurantoin vs other agents in reducing recurrent urinary tract infections in adult, nonpregnant women and assess relative adverse side effects. Data sources included the following: MEDLINE, Jan. 1, 1946, to Jan. 31, 2015; Cochrane Central Register of Controlled Trials the Cochrane Database of Systematic Reviews, and web sites of the National Institute for Clinical Excellence, and the National Guideline Clearinghouse from 2000 to 2015. Randomized control trials of women with recurrent urinary tract infections comparing nitrofurantoin with any other treatment were included. A protocol for the study was developed a priori. Published guidance was followed for assessment of study quality. All meta-analyses were performed using random-effects models with Stats Direct Software. Dual review was used for all decisions and data abstraction. Twelve randomized control trials involving 1063 patients were included. One study that had a serious flaw was rated poor in quality, one study rated good, and the remainder fair. No significant differences in prophylactic antibiotic treatment with nitrofurantoin and norfloxacin, trimethoprim, sulfamethoxazole/trimethoprim, methamine hippurate, estriol, or cefaclor were found in clinical or microbiological cure in adult nonpregnant women with recurrent urinary tract infections (9 randomized control trials, 673 patients, relative risk ratio, 1.06; 95% confidence interval, 0.89-1.27; I 2 , 65%; and 12 randomized control trials, 1063 patients, relative risk ratio, 1.06; 95% confidence interval, 0.90-1.26; I 2 , 76%, respectively). Duration of prophylaxis also did not have a significant impact on outcomes. There was a statistically significant difference in overall adverse effects, with nitrofurantoin resulting in greater risk than other prophylactic treatments (10 randomized control trials, 948 patients, relative risk ratio, 2.17; 95% confidence interval, 1.34-3.50; I 2 , 61%). Overall, the majority of nitrofurantoin adverse effects were gastrointestinal, with a significant difference for withdrawals (12 randomized control trials, 1063 patients, relative risk ratio, 2.14; 95% confidence interval, 1.28-3.56; I 2 , 8%). Nitrofurantoin had similar efficacy but a greater risk of adverse events than other prophylactic treatments. Balancing the risks of adverse events, particularly gastrointestinal symptoms, with potential benefits of decreasing collateral ecological damage should be considered if selecting nitrofurantoin. Copyright © 2016 Elsevier Inc. All rights reserved.

Surgery for post-vitrectomy cataract

PubMed Central

Do, Diana V; Gichuhi, Stephen; Vedula, Satyanarayana S; Hawkins, Barbara S

2014-01-01

Background Cataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique for removing the vitreous which is used in the treatment of disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit the benefit from cataract surgery. Objectives The objective of this review was to evaluate the effectiveness and safety of surgery for post-vitrectomy cataract with respect to visual acuity, quality of life, and other outcomes. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE in-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid OLDMED-LINE (January 1946 to May 2013), EMBASE (January 1980 to May 2013, Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2013), PubMed (January 1946 to May 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 May 2013. Selection criteria We planned to include randomized and quasi-randomized controlled trials comparing cataract surgery with no surgery in adult patients who developed cataract following vitrectomy. Data collection and analysis Two authors screened the search results independently according to the standard methodological procedures expected by The Cochrane Collaboration. Main results We found no randomized or quasi-randomized controlled trials comparing cataract surgery with no cataract surgery for patients who developed cataracts following vitrectomy surgery. Authors' conclusions There is no evidence from randomized or quasi-randomized controlled trials on which to base clinical recommendations for surgery for post-vitrectomy cataract. There is a clear need for randomized controlled trials to address this evidence gap. Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the underlying disease process in the contralateral eye. Outcomes assessed in such trials may include gain of vision on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, quality of life, and adverse events such as posterior capsular rupture. Both short-term (six-month) and long-term (one-year or two-year) outcomes should be examined. PMID:24357418

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.

Bayesian adaptive trials offer advantages in comparative effectiveness trials: an example in status epilepticus.

PubMed

Connor, Jason T; Elm, Jordan J; Broglio, Kristine R

2013-08-01

We present a novel Bayesian adaptive comparative effectiveness trial comparing three treatments for status epilepticus that uses adaptive randomization with potential early stopping. The trial will enroll 720 unique patients in emergency departments and uses a Bayesian adaptive design. The trial design is compared to a trial without adaptive randomization and produces an efficient trial in which a higher proportion of patients are likely to be randomized to the most effective treatment arm while generally using fewer total patients and offers higher power than an analogous trial with fixed randomization when identifying a superior treatment. When one treatment is superior to the other two, the trial design provides better patient care, higher power, and a lower expected sample size. Copyright © 2013 Elsevier Inc. All rights reserved.

Methods to Limit Attrition in Longitudinal Comparative Effectiveness Trials: Lessons from the Lithium Use for Bipolar Disorder (LiTMUS) Study

PubMed Central

Sylvia, Louisa G.; Reilly-Harrington, Noreen A.; Leon, Andrew C.; Kansky, Christine I.; Ketter, Terence A.; Calabrese, Joseph R.; Thase, Michael E.; Bowden, Charles L.; Friedman, Edward S.; Ostacher, Michael J.; Iosifescu, Dan V.; Severe, Joanne; Nierenberg, Andrew A.

2013-01-01

Background High attrition rates which occur frequently in longitudinal clinical trials of interventions for bipolar disorder limit the interpretation of results. Purpose The aim of this article is to present design approaches that limited attrition in the Lithium Use for Bipolar Disorder (LiTMUS) Study. Methods LiTMUS was a 6-month randomized, longitudinal multi-site comparative effectiveness trial that examined bipolar participants who were at least mildly ill. Participants were randomized to either low to moderate doses of lithium or no lithium, in addition to other treatments needed for mood stabilization administered in a guideline-informed, empirically supported, and personalized fashion (N=283). Results Components of the study design that may have contributed to the low attrition rate of the study included use of: (1) an intent-to-treat design; (2) a randomized adjunctive single-blind design; (3) participant reimbursement; (4) intent-to-attend the next study visit (includes a discussion of attendance obstacles when intention is low); (5) quality care with limited participant burden; and (6) target windows for study visits. Limitations Site differences and the effectiveness and tolerability data have not been analyzed yet. Conclusions These components of the LiTMUS study design may have reduced the probability of attrition which would inform the design of future randomized clinical effectiveness trials. PMID:22076437

Chlorambucil for the treatment of patients with chronic lymphocytic leukemia (CLL) - a systematic review and meta-analysis of randomized trials.

PubMed

Vidal, Liat; Gurion, Ronit; Ram, Ron; Raanani, Pia; Bairey, Osnat; Robak, Tadeusz; Gafter-Gvili, Anat; Shpilberg, Ofer

2016-09-01

Randomized clinical trials that compared chlorambucil to different regimens, for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) do not support an overall survival (OS) benefit. To assess the efficacy and safety of chlorambucil as frontline treatment, we conducted a systematic review and meta-analysis of randomized controlled trials. OS was the primary outcome. Meta-analysis of 18 trials that compared purine analogs, alkylators, alemtuzumab and ibrutinib to chlorambucil demonstrated no OS benefit for therapy without chlorambucil over chlorambucil (pooled HR 0.99, 95% CI 0.91-1.08; 4133 patients). PFS was longer with purine analogs compared with chlorambucil with an increased risk of infection. The risk of secondary malignancies was not increased with chlorambucil. In conclusion, our study showed that chlorambucil is an acceptable chemotherapy backbone for unfit patients with CLL. Purine analogs should be preferred in fit younger patients because of longer PFS. Future trials should focus on unfit patients who are underrepresented in clinical trials.

The treatment of medial tibial stress syndrome in athletes; a randomized clinical trial

PubMed Central

2012-01-01

Background The only three randomized trials on the treatment of MTSS were all performed in military populations. The treatment options investigated in this study were not previously examined in athletes. This study investigated if functional outcome of three common treatment options for medial tibial stress syndrome (MTSS) in athletes in a non-military setting was the same. Methods The study design was randomized and multi-centered. Physical therapists and sports physicians referred athletes with MTSS to the hospital for inclusion. 81 athletes were assessed for eligibility of which 74 athletes were included and randomized to three treatment groups. Group one performed a graded running program, group two performed a graded running program with additional stretching and strengthening exercises for the calves, while group three performed a graded running program with an additional sports compression stocking. The primary outcome measure was: time to complete a running program (able to run 18 minutes with high intensity) and secondary outcome was: general satisfaction with treatment. Results 74 Athletes were randomized and included of which 14 did not complete the study due a lack of progress (18.9%). The data was analyzed on an intention-to-treat basis. Time to complete a running program and general satisfaction with the treatment were not significantly different between the three treatment groups. Conclusion This was the first randomized trial on the treatment of MTSS in athletes in a non-military setting. No differences were found between the groups for the time to complete a running program. Trial registration CCMO; NL23471.098.08 PMID:22464032

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.

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.

Baseline adjustments for binary data in repeated cross-sectional cluster randomized trials.

PubMed

Nixon, R M; Thompson, S G

2003-09-15

Analysis of covariance models, which adjust for a baseline covariate, are often used to compare treatment groups in a controlled trial in which individuals are randomized. Such analysis adjusts for any baseline imbalance and usually increases the precision of the treatment effect estimate. We assess the value of such adjustments in the context of a cluster randomized trial with repeated cross-sectional design and a binary outcome. In such a design, a new sample of individuals is taken from the clusters at each measurement occasion, so that baseline adjustment has to be at the cluster level. Logistic regression models are used to analyse the data, with cluster level random effects to allow for different outcome probabilities in each cluster. We compare the estimated treatment effect and its precision in models that incorporate a covariate measuring the cluster level probabilities at baseline and those that do not. In two data sets, taken from a cluster randomized trial in the treatment of menorrhagia, the value of baseline adjustment is only evident when the number of subjects per cluster is large. We assess the generalizability of these findings by undertaking a simulation study, and find that increased precision of the treatment effect requires both large cluster sizes and substantial heterogeneity between clusters at baseline, but baseline imbalance arising by chance in a randomized study can always be effectively adjusted for. Copyright 2003 John Wiley & Sons, Ltd.

Does Mass Azithromycin Distribution Impact Child Growth and Nutrition in Niger? A Cluster-Randomized Trial

PubMed Central

Amza, Abdou; Yu, Sun N.; Kadri, Boubacar; Nassirou, Baido; Stoller, Nicole E.; Zhou, Zhaoxia; West, Sheila K.; Bailey, Robin L.; Gaynor, Bruce D.; Keenan, Jeremy D.; Porco, Travis C.; Lietman, Thomas M.

2014-01-01

Background Antibiotic use on animals demonstrates improved growth regardless of whether or not there is clinical evidence of infectious disease. Antibiotics used for trachoma control may play an unintended benefit of improving child growth. Methodology In this sub-study of a larger randomized controlled trial, we assess anthropometry of pre-school children in a community-randomized trial of mass oral azithromycin distributions for trachoma in Niger. We measured height, weight, and mid-upper arm circumference (MUAC) in 12 communities randomized to receive annual mass azithromycin treatment of everyone versus 12 communities randomized to receive biannual mass azithromycin treatments for children, 3 years after the initial mass treatment. We collected measurements in 1,034 children aged 6–60 months of age. Principal Findings We found no difference in the prevalence of wasting among children in the 12 annually treated communities that received three mass azithromycin distributions compared to the 12 biannually treated communities that received six mass azithromycin distributions (odds ratio = 0.88, 95% confidence interval = 0.53 to 1.49). Conclusions/Significance We were unable to demonstrate a statistically significant difference in stunting, underweight, and low MUAC of pre-school children in communities randomized to annual mass azithromycin treatment or biannual mass azithromycin treatment. The role of antibiotics on child growth and nutrition remains unclear, but larger studies and longitudinal trials may help determine any association. PMID:25210836

Randomized trials of high-dose chemotherapy in breast cancer: fraud, the press and the data (or lessons learned in medical policy governing clinical research).

PubMed Central

Antman, Karen

2002-01-01

High dose therapy for breast cancer remains controversial. Of the 15 randomized trials of high dose therapy in breast cancer reported to date, two South African studies have been discredited leaving 13 remaining studies. Mortality was consistently low, in the 0 to 2.5% range, except for the BCNU containing American Intergroup study, which had a 7.4% toxic mortality rate. Seven of the remaining 13 studies randomized fewer than 200 patients. Three of these small studies have significant differences in disease free survival, and a fourth study has a trend in favor of high dose therapy. The other three small studies cannot exclude a survival difference of 20%. Of the 6 remaining moderately large trials of 219 to 885 randomized patients, 5 are adjuvant studies and one included patients with metastatic disease. Of the five adjuvant trials, four have significant differences in relapse rate favoring the high dose arm, and the remaining study has a trend (with a high dose sequential single agent design rather than combination therapy as in the other studies). A planned subset analysis of the first 284 patients in the largest study funded by the Dutch insurance industry showed a significant advantage for high dose therapy. Given the 2-year median time to relapse and an addition 2-year median to death after relapse, the follow up for survival of 3-5 years on these studies is still short. In the only moderately sized metastatic trial from the National Cancer Institute of Canada with a very short median follow-up of 19 months, a significant difference in disease free survival has emerged, with no difference in survival. PMID:12053718

Randomized trials of high-dose chemotherapy in breast cancer: fraud, the press and the data (or lessons learned in medical policy governing clinical research).

PubMed

Antman, Karen

2002-01-01

High dose therapy for breast cancer remains controversial. Of the 15 randomized trials of high dose therapy in breast cancer reported to date, two South African studies have been discredited leaving 13 remaining studies. Mortality was consistently low, in the 0 to 2.5% range, except for the BCNU containing American Intergroup study, which had a 7.4% toxic mortality rate. Seven of the remaining 13 studies randomized fewer than 200 patients. Three of these small studies have significant differences in disease free survival, and a fourth study has a trend in favor of high dose therapy. The other three small studies cannot exclude a survival difference of 20%. Of the 6 remaining moderately large trials of 219 to 885 randomized patients, 5 are adjuvant studies and one included patients with metastatic disease. Of the five adjuvant trials, four have significant differences in relapse rate favoring the high dose arm, and the remaining study has a trend (with a high dose sequential single agent design rather than combination therapy as in the other studies). A planned subset analysis of the first 284 patients in the largest study funded by the Dutch insurance industry showed a significant advantage for high dose therapy. Given the 2-year median time to relapse and an addition 2-year median to death after relapse, the follow up for survival of 3-5 years on these studies is still short. In the only moderately sized metastatic trial from the National Cancer Institute of Canada with a very short median follow-up of 19 months, a significant difference in disease free survival has emerged, with no difference in survival.

The Impact of Classroom Physical Activity Breaks on Middle School Students' Health-Related Fitness: An Xbox One Kinetic Delivered 4-Week Randomized Controlled Trial

ERIC Educational Resources Information Center

Yli-Piipari, S.; Layne, T.; McCollins, T.; Knox, T.

2016-01-01

The aim of the study was to examine the effect of a 4-week classroom physical activity break intervention on middle school students' health-related physical fitness. The study was a randomized controlled trial with students assigned to the experiment and control conditions. A convenience sample comprised 94 adolescents (experiment group n = 52;…

Cluster Randomized Test-Negative Design (CR-TND) Trials: A Novel and Efficient Method to Assess the Efficacy of Community Level Dengue Interventions.

PubMed

Anders, Katherine L; Cutcher, Zoe; Kleinschmidt, Immo; Donnelly, Christl A; Ferguson, Neil M; Indriani, Citra; O'Neill, Scott L; Jewell, Nicholas P; Simmons, Cameron P

2018-05-07

Cluster randomized trials are the gold standard for assessing efficacy of community-level interventions, such as vector control strategies against dengue. We describe a novel cluster randomized trial methodology with a test-negative design, which offers advantages over traditional approaches. It utilizes outcome-based sampling of patients presenting with a syndrome consistent with the disease of interest, who are subsequently classified as test-positive cases or test-negative controls on the basis of diagnostic testing. We use simulations of a cluster trial to demonstrate validity of efficacy estimates under the test-negative approach. This demonstrates that, provided study arms are balanced for both test-negative and test-positive illness at baseline and that other test-negative design assumptions are met, the efficacy estimates closely match true efficacy. We also briefly discuss analytical considerations for an odds ratio-based effect estimate arising from clustered data, and outline potential approaches to analysis. We conclude that application of the test-negative design to certain cluster randomized trials could increase their efficiency and ease of implementation.

A pilot randomized controlled trial of deprescribing.

PubMed

Beer, Christopher; Loh, Poh-Kooi; Peng, Yan Gee; Potter, Kathleen; Millar, Alasdair

2011-04-01

Polypharmacy and adverse drug reactions are frequent and important among older people. Few clinical trials have evaluated systematic withdrawal of medications among older people. This small, open, study was conducted to determine the feasibility of a randomized controlled deprescribing trial. Ten volunteers living in the community (recruited by media advertising) and 25 volunteers living in residential aged-care facilities (RCFs) were randomized to intervention or control groups. The intervention was gradual withdrawal of one target medication. The primary outcome was the number of intervention participants in whom medication withdrawal could be achieved. Other outcomes measures were quality of life, medication adherence, sleep quality, and cognitive impairment. Participants were aged 80 ± 11 years and were taking 9 ± 2 medications. Fifteen participants commenced medication withdrawal and all ceased or reduced the dose of their target medication. Two subjects withdrew; one was referred for clinical review, and one participant declined further dose reductions. A randomized controlled trial of deprescribing was acceptable to participants. Recruitment in RCFs is feasible. Definitive trials of deprescribing are required.

Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available.

PubMed

Hernán, Miguel A; Robins, James M

2016-04-15

Ideally, questions about comparative effectiveness or safety would be answered using an appropriately designed and conducted randomized experiment. When we cannot conduct a randomized experiment, we analyze observational data. Causal inference from large observational databases (big data) can be viewed as an attempt to emulate a randomized experiment-the target experiment or target trial-that would answer the question of interest. When the goal is to guide decisions among several strategies, causal analyses of observational data need to be evaluated with respect to how well they emulate a particular target trial. We outline a framework for comparative effectiveness research using big data that makes the target trial explicit. This framework channels counterfactual theory for comparing the effects of sustained treatment strategies, organizes analytic approaches, provides a structured process for the criticism of observational studies, and helps avoid common methodologic pitfalls. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Educational interventions in childhood obesity: a systematic review with meta-analysis of randomized clinical trials.

PubMed

Sbruzzi, Graciele; Eibel, Bruna; Barbiero, Sandra M; Petkowicz, Rosemary O; Ribeiro, Rodrigo A; Cesa, Claudia C; Martins, Carla C; Marobin, Roberta; Schaan, Camila W; Souza, Willian B; Schaan, Beatriz D; Pellanda, Lucia C

2013-05-01

To assess the effectiveness of educational interventions including behavioral modification, nutrition and physical activity to prevent or treat childhood obesity through a systematic review and meta-analysis of randomized trials. A search of databases (PubMed, EMBASE and Cochrane CENTRAL) and references of published studies (from inception until May 2012) was conducted. Eligible studies were randomized trials enrolling children 6 to 12 years old and assessing the impact of educational interventions during 6 months or longer on waist circumference, body mass index (BMI), blood pressure and lipid profile to prevent or treat childhood obesity. Calculations were performed using a random effects method and pooled-effect estimates were obtained using the final values. Of 22.852 articles retrieved, 26 trials (23.617 participants) were included. There were no differences in outcomes assessed in prevention studies. However, in treatment studies, educational interventions were associated with a significant reduction in waist circumference [-3.21 cm (95%CI -6.34, -0.07)], BMI [-0.86 kg/m(2) (95%CI -1.59, -0.14)] and diastolic blood pressure [-3.68 mmHg (95%CI -5.48, -1.88)]. Educational interventions are effective in treatment, but not prevention, of childhood obesity and its consequences. Copyright © 2013 Elsevier Inc. All rights reserved.

Child language interventions in public health: a systematic literature review.

PubMed

De Cesaro, Bruna Campos; Gurgel, Léia Gonçalves; Nunes, Gabriela Pisoni Canedo; Reppold, Caroline Tozzi

2013-01-01

Systematically review the literature on interventions in children's language in primary health care. One searched the electronic databases (January 1980 to March 2013) MEDLINE (accessed by PubMed), Scopus, Lilacs and Scielo. The search terms used were "child language", "primary health care", "randomized controlled trial" and "intervention studies" (in English, Portuguese and Spanish). There were included any randomized controlled trials that addressed the issues child language and primary health care. The analysis was based on the type of language intervention conducted in primary health care. Seven studies were included and used intervention strategies such as interactive video, guidance for parents and group therapy. Individuals of both genders were included in the seven studies. The age of the children participant in the samples of the articles included in this review ranged from zero to 11 years. These seven studies used approaches that included only parents, parents and children or just children. The mainly intervention in language on primary health care, used in randomized controlled trials, involved the use of interactional video. Several professionals, beyond speech and language therapist, been inserted in the language interventions on primary health care, demonstrating the importance of interdisciplinary work. None of the articles mentioned aspects related to hearing. There was scarcity of randomized controlled trials that address on language and public health, either in Brazil or internationally.

Learning From Past Failures of Oral Insulin Trials.

PubMed

Michels, Aaron W; Gottlieb, Peter A

2018-07-01

Very recently one of the largest type 1 diabetes prevention trials using daily administration of oral insulin or placebo was completed. After 9 years of study enrollment and follow-up, the randomized controlled trial failed to delay the onset of clinical type 1 diabetes, which was the primary end point. The unfortunate outcome follows the previous large-scale trial, the Diabetes Prevention Trial-Type 1 (DPT-1), which again failed to delay diabetes onset with oral insulin or low-dose subcutaneous insulin injections in a randomized controlled trial with relatives at risk for type 1 diabetes. These sobering results raise the important question, "Where does the type 1 diabetes prevention field move next?" In this Perspective, we advocate for a paradigm shift in which smaller mechanistic trials are conducted to define immune mechanisms and potentially identify treatment responders. The stage is set for these interventions in individuals at risk for type 1 diabetes as Type 1 Diabetes TrialNet has identified thousands of relatives with islet autoantibodies and general population screening for type 1 diabetes risk is under way. Mechanistic trials will allow for better trial design and patient selection based upon molecular markers prior to large randomized controlled trials, moving toward a personalized medicine approach for the prevention of type 1 diabetes. © 2018 by the American Diabetes Association.

Statistical lessons learned for designing cluster randomized pragmatic clinical trials from the NIH Health Care Systems Collaboratory Biostatistics and Design Core.

PubMed

Cook, Andrea J; Delong, Elizabeth; Murray, David M; Vollmer, William M; Heagerty, Patrick J

2016-10-01

Pragmatic clinical trials embedded within health care systems provide an important opportunity to evaluate new interventions and treatments. Networks have recently been developed to support practical and efficient studies. Pragmatic trials will lead to improvements in how we deliver health care and promise to more rapidly translate research findings into practice. The National Institutes of Health (NIH) Health Care Systems Collaboratory was formed to conduct pragmatic clinical trials and to cultivate collaboration across research areas and disciplines to develop best practices for future studies. Through a two-stage grant process including a pilot phase (UH2) and a main trial phase (UH3), investigators across the Collaboratory had the opportunity to work together to improve all aspects of these trials before they were launched and to address new issues that arose during implementation. Seven Cores were created to address the various considerations, including Electronic Health Records; Phenotypes, Data Standards, and Data Quality; Biostatistics and Design Core; Patient-Reported Outcomes; Health Care Systems Interactions; Regulatory/Ethics; and Stakeholder Engagement. The goal of this article is to summarize the Biostatistics and Design Core's lessons learned during the initial pilot phase with seven pragmatic clinical trials conducted between 2012 and 2014. Methodological issues arose from the five cluster-randomized trials, also called group-randomized trials, including consideration of crossover and stepped wedge designs. We outlined general themes and challenges and proposed solutions from the pilot phase including topics such as study design, unit of randomization, sample size, and statistical analysis. Our findings are applicable to other pragmatic clinical trials conducted within health care systems. Pragmatic clinical trials using the UH2/UH3 funding mechanism provide an opportunity to ensure that all relevant design issues have been fully considered in order to reliably and efficiently evaluate new interventions and treatments. The integrity and generalizability of trial results can only be ensured if rigorous designs and appropriate analysis choices are an essential part of their research protocols. © The Author(s) 2016.

When is informed consent required in cluster randomized trials in health research?

PubMed Central

2011-01-01

This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the cluster trial is to be set on a firm ethical foundation. This paper addresses the second of the questions posed, namely, from whom, when, and how must informed consent be obtained in CRTs in health research? The ethical principle of respect for persons implies that researchers are generally obligated to obtain the informed consent of research subjects. Aspects of CRT design, including cluster randomization, cluster level interventions, and cluster size, present challenges to obtaining informed consent. Here we address five questions related to consent and CRTs: How can a study proceed if informed consent is not possible? Is consent to randomization always required? What information must be disclosed to potential subjects if their cluster has already been randomized? Is passive consent a valid substitute for informed consent? Do health professionals have a moral obligation to participate as subjects in CRTs designed to improve professional practice? We set out a framework based on the moral foundations of informed consent and international regulatory provisions to address each of these questions. First, when informed consent is not possible, a study may proceed if a research ethics committee is satisfied that conditions for a waiver of consent are satisfied. Second, informed consent to randomization may not be required if it is not possible to approach subjects at the time of randomization. Third, when potential subjects are approached after cluster randomization, they must be provided with a detailed description of the interventions in the trial arm to which their cluster has been randomized; detailed information on interventions in other trial arms need not be provided. Fourth, while passive consent may serve a variety of practical ends, it is not a substitute for valid informed consent. Fifth, while health professionals may have a moral obligation to participate as subjects in research, this does not diminish the necessity of informed consent to study participation. PMID:21906277

Sensitivity analysis for missing dichotomous outcome data in multi-visit randomized clinical trial with randomization-based covariance adjustment.

PubMed

Li, Siying; Koch, Gary G; Preisser, John S; Lam, Diana; Sanchez-Kam, Matilde

2017-01-01

Dichotomous endpoints in clinical trials have only two possible outcomes, either directly or via categorization of an ordinal or continuous observation. It is common to have missing data for one or more visits during a multi-visit study. This paper presents a closed form method for sensitivity analysis of a randomized multi-visit clinical trial that possibly has missing not at random (MNAR) dichotomous data. Counts of missing data are redistributed to the favorable and unfavorable outcomes mathematically to address possibly informative missing data. Adjusted proportion estimates and their closed form covariance matrix estimates are provided. Treatment comparisons over time are addressed with Mantel-Haenszel adjustment for a stratification factor and/or randomization-based adjustment for baseline covariables. The application of such sensitivity analyses is illustrated with an example. An appendix outlines an extension of the methodology to ordinal endpoints.

Assessing the comparative effectiveness of Tai Chi versus physical therapy for knee osteoarthritis: design and rationale for a randomized trial.

PubMed

Wang, Chenchen; Iversen, Maura D; McAlindon, Timothy; Harvey, William F; Wong, John B; Fielding, Roger A; Driban, Jeffrey B; Price, Lori Lyn; Rones, Ramel; Gamache, Tressa; Schmid, Christopher H

2014-09-08

Knee osteoarthritis (OA) causes pain and long-term disability with annual healthcare costs exceeding $185 billion in the United States. Few medical remedies effectively influence the course of the disease. Finding effective treatments to maintain function and quality of life in patients with knee OA is one of the national priorities identified by the Institute of Medicine. We are currently conducting the first comparative effectiveness and cost-effectiveness randomized trial of Tai Chi versus a physical-therapy regimen in a sample of patients with symptomatic and radiographically confirmed knee OA. This article describes the design and conduct of this trial. A single-center, 52-week, comparative effectiveness randomized controlled trial of Tai Chi versus a standardized physical-therapy regimen is being conducted at an urban tertiary medical center in Boston, Massachusetts. The study population consists of adults ≥ 40 years of age with symptomatic and radiographic knee OA (American College of Rheumatology criteria). Participants are randomly allocated to either 12 weeks of Tai Chi (2x/week) or Physical Therapy (2x/week for 6 weeks, followed by 6 weeks of rigorously monitored home exercise). The primary outcome measure is pain (Western Ontario and McMaster Universities WOMAC) subscale at 12 weeks. Secondary outcomes include WOMAC stkiffness and function domain scores, lower extremity strength and power, functional balance, physical performance tests, psychological and psychosocial functioning, durability effects, health related quality of life, and healthcare utilization at 12, 24 and 52 weeks. This study will be the first randomized comparative-effectiveness and cost-effectiveness trial of Tai Chi versus Physical Therapy in a large symptomatic knee OA population with long-term follow up. We present here a robust and well-designed randomized comparative-effectiveness trial that also explores multiple outcomes to elucidate the potential mechanisms of mind-body effect for a major disabling disease with substantial health burdens and economic costs. Results of this study are expected to have important public health implications for the large and growing population with knee OA. ClinicalTrials.gov identifier: NCT01258985.

Wrist-ankle acupuncture (WAA) for primary dysmenorrhea (PD) of young females: study protocol for a randomized controlled trial.

PubMed

Chen, Yingfan; Tian, Sinan; Tian, Jing; Shu, Shi

2017-08-22

Primary dysmenorrhea (PD) is one of the most common health complaints all over the world, specifically among young females. Acupuncture has been employed to relieve the pain-based symptoms and to avoid the side effects of conventional medication, and wrist-ankle acupuncture (WAA) has confirmed analgesic efficacy for various types of pain. The aim of this study is to evaluate the immediate analgesia effect of WAA on PD of young females. This study will carry out a randomized parallel controlled single-blind trial to observe the immediate analgesia effect of WAA in PD of young females. Sixty participants who meet inclusion criteria will be recruited from September 2016 to September 2017 in Changhai hospital of China. They are randomly assigned to WAA therapy or sham acupuncture groups (30 patients for each group), and then receive real or sham acupuncture treatment, respectively. In this trial, the primary outcome measure is simple form of McGill pain questionnaire (SF-MPQ), while expectation and treatment credibility scale (ETCS), safety assessment, the COX menstrual symptom scale (CMSS), questionnaire about the feeling of being punctured are included in the secondary outcomes. This trial will be the first study protocol designed to evaluate the immediate analgesia effect of WAA in PD of young females. The strengths in methodology, including rigorous randomized, sham-controlled, participants-blinded and assessors-blinded, will guarantee the quality of this study. WAA doesn't require any needling sensation, so non-penetrating sham acupuncture can serve as an effective placebo intervention in this trial. Chinese Clinical Trial Registry (identifier: ChiCTR-IOR-16008546 ; registration date: 27 May 2016).

Practical health co-operation - the impact of a referral template on quality of care and health care co-operation: study protocol for a cluster randomized controlled trial.

PubMed

Wåhlberg, Henrik; Valle, Per Christian; Malm, Siri; Broderstad, Ann Ragnhild

2013-01-07

The referral letter plays a key role both in the communication between primary and secondary care, and in the quality of the health care process. Many studies have attempted to evaluate and improve the quality of these referral letters, but few have assessed the impact of their quality on the health care delivered to each patient. A cluster randomized trial, with the general practitioner office as the unit of randomization, has been designed to evaluate the effect of a referral intervention on the quality of health care delivered. Referral templates have been developed covering four diagnostic groups: dyspepsia, suspected colonic malignancy, chest pain, and chronic obstructive pulmonary disease. Of the 14 general practitioner offices primarily served by University Hospital of North Norway Harstad, seven were randomized to the intervention group. The primary outcome is a collated quality indicator score developed for each diagnostic group. Secondary outcomes include: quality of the referral, health process outcome such as waiting times, and adequacy of prioritization. In addition, information on patient satisfaction will be collected using self-report questionnaires. Outcome data will be collected on the individual level and analyzed by random effects linear regression. Poor communication between primary and secondary care can lead to inappropriate investigations and erroneous prioritization. This study's primary hypothesis is that the use of a referral template in this communication will lead to a measurable increase in the quality of health care delivered. This trial has been registered at ClinicalTrials.gov. The trial registration number is NCT01470963.

[Randomized, controlled clinical trials with observational follow-up investigations for evaluating efficacy of antihyperglycaemic treatment. II. Features of and lessons from the follow-up investigations].

PubMed

Jermendy, György

2018-04-01

Although the outcomes of the follow-up investigation period of the randomized clinical studies for evaluating the efficacy of a treatment or an antidiabetic drug may be confounded or potentially biased by several factors, the results are widely accepted by the diabetes community. In line with the theory of metabolic memory or metabolic legacy, early and intensive antihyperglycaemic treatment should be provided for all diabetic patients as this strategy can result in beneficial effects even in the long run. The recent cardiovascular safety trials with new, innovative antidiabetic drugs differ in several aspects from the former efficacy studies. Ten cardiovascular safety trials were completed so far enabling to define their unique and common features. It can be anticipated that the era of randomized, controlled efficacy studies with observational follow-up investigations came to an end in diabetes research. Nowadays, cardiovascular safety trials are in the focus of clinical research in diabetology and results of several ongoing studies are expected with interest in the near future. Orv Hetil. 2018; 159(16): 615-619.

Web-Based Intervention for Women With Type 1 Diabetes in Pregnancy and Early Motherhood: Critical Analysis of Adherence to Technological Elements and Study Design.

PubMed

Berg, Marie; Linden, Karolina; Adolfsson, Annsofie; Sparud Lundin, Carina; Ranerup, Agneta

2018-05-02

Numerous Web-based interventions have been implemented to promote health and health-related behaviors in persons with chronic conditions. Using randomized controlled trials to evaluate such interventions creates a range of challenges, which in turn can influence the study outcome. Applying a critical perspective when evaluating Web-based health interventions is important. The objective of this study was to critically analyze and discuss the challenges of conducting a Web-based health intervention as a randomized controlled trial. The MODIAB-Web study was critically examined using an exploratory case study methodology and the framework for analysis offered through the Persuasive Systems Design model. Focus was on technology, study design, and Web-based support usage, with special focus on the forum for peer support. Descriptive statistics and qualitative content analysis were used. The persuasive content and technological elements in the design of the randomized controlled trial included all four categories of the Persuasive Systems Design model, but not all design principles were implemented. The study duration was extended to a period of four and a half years. Of 81 active participants in the intervention group, a maximum of 36 women were simultaneously active. User adherence varied greatly with a median of 91 individual log-ins. The forum for peer support was used by 63 participants. Although only about one-third of the participants interacted in the forum, there was a fairly rich exchange of experiences and advice between them. Thus, adherence in terms of social interactions was negatively affected by limited active participation due to prolonged recruitment process and randomization effects. Lessons learned from this critical analysis are that technology and study design matter and might mutually influence each other. In Web-based interventions, the use of design theories enables utilization of the full potential of technology and promotes adherence. The randomization element in a randomized controlled trial design can become a barrier to achieving a critical mass of user interactions in Web-based interventions, especially when social support is included. For extended study periods, the technology used may need to be adapted in line with newly available technical options to avoid the risk of becoming outdated in the user realm, which in turn might jeopardize study validity in terms of randomized controlled trial designs. On the basis of lessons learned in this randomized controlled trial, we give recommendations to consider when designing and evaluating Web-based health interventions. ©Marie Berg, Karolina Linden, Annsofie Adolfsson, Carina Sparud Lundin, Agneta Ranerup. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 02.05.2018.

Therapeutic Plasma Transfusion in Bleeding Patients: A Systematic Review.

PubMed

Levy, Jerrold H; Grottke, Oliver; Fries, Dietmar; Kozek-Langenecker, Sibylle

2017-04-01

Plasma products, including fresh frozen plasma, are administered extensively in a variety of settings from massive transfusion to vitamin K antagonist reversal. Despite the widespread use of plasma as a hemostatic agent in bleeding patients, its effect in comparison with other available choices of hemostatic therapies is unclear. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed Central, and databases of ongoing trials for randomized controlled trials that assessed the efficacy and/or safety of therapeutic plasma as an intervention to treat bleeding patients compared with other interventions or placebo. Of 1243 unique publications retrieved in our initial search, no randomized controlled trials were identified. Four nonrandomized studies described the effect of therapeutic plasma in bleeding patients; however, data gathered from these studies did not allow for comparison with other therapeutic interventions primarily as a result of the low number of patients and the use of different (or lack of) comparators. We identified two ongoing trials investigating the efficacy and safety of therapeutic plasma, respectively; however, no data have been released as yet. Although plasma is used extensively in the treatment of bleeding patients, evidence from randomized controlled trials comparing its effect with those of other therapeutic interventions is currently lacking.

Fluoxetine, Smoking, and History of Major Depression: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Spring, Bonnie; Doran, Neal; Pagoto, Sherry; McChargue, Dennis; Cook, Jessica Werth; Bailey, Katherine; Crayton, John; Hedeker, Donald

2007-01-01

The study was a randomized placebo-controlled trial testing whether fluoxetine selectively enhances cessation for smokers with a history of depression. Euthymic smokers with (H+, n = 109) or without (H-, n = 138) a history of major depression received 60 mg fluoxetine or placebo plus group behavioral quit-smoking treatment for 12 weeks. Fluoxetine…

Can Findings from Randomized Controlled Trials of Social Skills Training in Autism Spectrum Disorder Be Generalized? The Neglected Dimension of External Validity

ERIC Educational Resources Information Center

Jonsson, Ulf; Olsson, Nora Choque; Bölte, Sven

2016-01-01

Systematic reviews have traditionally focused on internal validity, while external validity often has been overlooked. In this study, we systematically reviewed determinants of external validity in the accumulated randomized controlled trials of social skills group interventions for children and adolescents with autism spectrum disorder. We…

Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial

USDA-ARS?s Scientific Manuscript database

Knee osteoarthritis (OA), a disorder of cartilage and periarticular bone, is a public health problem without effective medical treatments. Some studies have suggested that vitamin D may protect against structural progression. A 2-year randomized, placebo-controlled, double-blind, clinical trial invo...

Three Randomized Controlled Trials of Early Long-Chain Polyunsaturated Fatty Acid Supplementation on Means-End Problem Solving in 9-Month-Olds

ERIC Educational Resources Information Center

Drover, James; Hoffman, Dennis R.; Castaneda, Yolanda S.; Morale, Sarah E.; Birch, Eileen E.

2009-01-01

This study examines whether feeding infants formula supplemented with long-chain polyunsaturated fatty acids (LCPUFA) improves cognitive function of 9-month-olds. Participants included 229 infants from 3 randomized controlled trials. Children received either formula supplemented with docosahexaenoic acid and arachidonic acid, or a control formula…

Randomized, Controlled Trial of a Comprehensive Program for Young Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Young, Helen E.; Falco, Ruth A.; Hanita, Makoto

2016-01-01

This randomized, controlled trial, comparing the Comprehensive Autism Program (CAP) and business as usual programs, studied outcomes for 3-5 year old students with autism spectrum disorder (ASD). Participants included 84 teachers and 302 students with ASD and their parents. CAP utilized specialized curricula and training components to implement…

Positive Family Intervention for Severe Challenging Behavior I: A Multisite Randomized Clinical Trial

ERIC Educational Resources Information Center

Durand, V. Mark; Hieneman, Meme; Clarke, Shelley; Wang, Mo; Rinaldi, Melissa L.

2013-01-01

The present study was a multisite randomized clinical trial assessing the effects of adding a cognitive-behavioral intervention to positive behavior support (PBS). Fifty-four families who met the criteria of (a) having a child with a developmental disability, (b) whose child displayed serious challenging behavior (e.g., aggression, self-injury,…

An Intervention for Sensory Difficulties in Children with Autism: A Randomized Trial

ERIC Educational Resources Information Center

Schaaf, Roseann C.; Benevides, Teal; Mailloux, Zoe; Faller, Patricia; Hunt, Joanne; van Hooydonk, Elke; Freeman, Regina; Leiby, Benjamin; Sendecki, Jocelyn; Kelly, Donna

2014-01-01

This study evaluated a manualized intervention for sensory difficulties for children with autism, ages 4-8 years, using a randomized trial design. Diagnosis of autism was confirmed using gold standard measures. Results show that the children in the treatment group (n = 17) who received 30 sessions of the occupational therapy intervention scored…

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…

Remediating Organizational Functioning in Children with ADHD: Immediate and Long-Term Effects from a Randomized Controlled Trial

ERIC Educational Resources Information Center

Abikoff, Howard; Gallagher, Richard; Wells, Karen C.; Murray, Desiree W.; Huang, Lei; Lu, Feihan; Petkova, Eva

2013-01-01

Objective: The study compared the efficacy of 2 behavioral interventions to ameliorate organization, time management, and planning (OTMP) difficulties in 3rd- to 5th-grade children with attention-deficit/hyperactivity disorder (ADHD). Method: In a dual-site randomized controlled trial, 158 children were assigned to organizational skills training…

A Randomized Trial of a Multimodal Community-Based Prisoner Reentry Program Emphasizing Substance Abuse Treatment

ERIC Educational Resources Information Center

Grommon, Eric; Davidson, William S., II; Bynum, Timothy S.

2013-01-01

Prisoner reentry programs continue to be developed and implemented to ease the process of transition into the community and to curtail fiscal pressures. This study describes and provides relapse and recidivism outcome findings related to a randomized trial evaluating a multimodal, community-based reentry program that prioritized substance abuse…

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,…

The Effectiveness of Two Grammar Treatment Procedures for Children with SLI: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Smith-Lock, Karen M.; Leitão, Suze; Prior, Polly; Nickels, Lyndsey

2015-01-01

Purpose: This study compared the effectiveness of two grammar treatment procedures for children with specific language impairment. Method: A double-blind superiority trial with cluster randomization was used to compare a cueing procedure, designed to elicit a correct production following an initial error, to a recasting procedure, which required…

Efficacy of a Universal Parent Training Program (HOPE-20): Cluster Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Kwan, H. W.

2017-01-01

Objective: This study examined the efficacy of Hands-On Parent Empowerment-20 (HOPE-20) program. Methods: Eligible participants were parents residing in Hong Kong with target children aged 2 years attending nursery schools. Cluster randomized control trial was adopted, with 10 schools (110 participants) assigned to intervention group and 8 schools…

Treatment of Co-Occurring Substance Abuse and Suicidality among Adolescents: A Randomized Trial

ERIC Educational Resources Information Center

Esposito-Smythers, Christianne; Spirito, Anthony; Kahler, Christopher W.; Hunt, Jeffrey; Monti, Peter

2011-01-01

Objective: This study tested a cognitive-behavioral treatment protocol for adolescents with a co-occurring alcohol or other drug use disorder (AOD) and suicidality in a randomized clinical trial. Method: Forty adolescents (M[subscript age] = 15 years; 68% female, 89% White) and their families recruited from an inpatient psychiatric hospital were…

Effectiveness of a Web-Based Intervention to Reduce Alcohol Consumption among French Hazardous Drinkers: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Guillemont, Juliette; Cogordan, Chloé; Nalpas, Bertrand; Nguyen-Thanh, Vi?t; Richard, Jean-Baptiste; Arwidson, Pierre

2017-01-01

This study aims to evaluate the effectiveness of a web-based intervention to reduce alcohol consumption among hazardous drinkers. A two-group parallel randomized controlled trial was conducted among adults identified as hazardous drinkers according to the Alcohol Use Disorders Identification Test. The intervention delivers personalized normative…

Group Lidcombe Program Treatment for Early Stuttering: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Arnott, Simone; Onslow, Mark; O'Brian, Sue; Packman, Ann; Jones, Mark; Block, Susan

2014-01-01

Purpose: This study adds to the Lidcombe Program evidence base by comparing individual and group treatment of preschoolers who stutter. Method: A randomized controlled trial of 54 preschoolers was designed to establish whether group delivery outcomes were not inferior to the individual model. The group arm used a rolling group model, in which a…

An Empirical Comparison of Randomized Control Trials and Regression Discontinuity Estimations

ERIC Educational Resources Information Center

Barrera-Osorio, Felipe; Filmer, Deon; McIntyre, Joe

2014-01-01

Randomized controlled trials (RCTs) and regression discontinuity (RD) studies both provide estimates of causal effects. A major difference between the two is that RD only estimates local average treatment effects (LATE) near the cutoff point of the forcing variable. This has been cited as a drawback to RD designs (Cook & Wong, 2008).…

Motivational Pathways to Leisure-Time Physical Activity Participation in Urban Physical Education: A Cluster-Randomized Trial

ERIC Educational Resources Information Center

Yli-Piipari, Sami; Layne, Todd; Hinson, Janet; Irwin, Carol

2018-01-01

Purpose: Grounded in the trans-contextual model of motivation framework, this cluster-randomized trial examined the effectiveness of an autonomy supportive physical education (PE) instruction on student motivation and physical activity (PA). Method: The study comprised six middle schools and 408 students (M[subscript age] = 12.29), with primary…

Cognitive-Behavioral Therapy for Intermittent Explosive Disorder: A Pilot Randomized Clinical Trial

ERIC Educational Resources Information Center

McCloskey, Michael S.; Noblett, Kurtis L.; Deffenbacher, Jerry L.; Gollan, Jackie K.; Coccaro, Emil F.

2008-01-01

No randomized clinical trials have evaluated the efficacy of psychotherapy for intermittent explosive disorder (IED). In the present study, the authors tested the efficacy of 12-week group and individual cognitive-behavioral therapies (adapted from J. L. Deffenbacher & M. McKay, 2000) by comparing them with a wait-list control in a randomized…

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…

Comprehensive genotyping in dyslipidemia: mendelian dyslipidemias caused by rare variants and Mendelian randomization studies using common variants.

PubMed

Tada, Hayato; Kawashiri, Masa-Aki; Yamagishi, Masakazu

2017-04-01

Dyslipidemias, especially hyper-low-density lipoprotein cholesterolemia and hypertriglyceridemia, are important causal risk factors for coronary artery disease. Comprehensive genotyping using the 'next-generation sequencing' technique has facilitated the investigation of Mendelian dyslipidemias, in addition to Mendelian randomization studies using common genetic variants associated with plasma lipids and coronary artery disease. The beneficial effects of low-density lipoprotein cholesterol-lowering therapies on coronary artery disease have been verified by many randomized controlled trials over the years, and subsequent genetic studies have supported these findings. More recently, Mendelian randomization studies have preceded randomized controlled trials. When the on-target/off-target effects of rare variants and common variants exhibit the same direction, novel drugs targeting molecules identified by investigations of rare Mendelian lipid disorders could be promising. Such a strategy could aid in the search for drug discovery seeds other than those for dyslipidemias.

Radiation Therapy Intensification for Solid Tumors: A Systematic Review of Randomized Trials

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

Yamoah, Kosj; Showalter, Timothy N.; Ohri, Nitin, E-mail: ohri.nitin@gmail.com

Purpose: To systematically review the outcomes of randomized trials testing radiation therapy (RT) intensification, including both dose escalation and/or the use of altered fractionation, as a strategy to improve disease control for a number of malignancies. Methods and Materials: We performed a literature search to identify randomized trials testing RT intensification for cancers of the central nervous system, head and neck, breast, lung, esophagus, rectum, and prostate. Findings were described qualitatively. Where adequate data were available, pooled estimates for the effect of RT intensification on local control (LC) or overall survival (OS) were obtained using the inverse variance method. Results: Inmore » primary central nervous system tumors, esophageal cancer, and rectal cancer, randomized trials have not demonstrated that RT intensification improves clinical outcomes. In breast cancer and prostate cancer, dose escalation has been shown to improve LC or biochemical disease control but not OS. Radiation therapy intensification may improve LC and OS in head and neck and lung cancers, but these benefits have generally been limited to studies that did not incorporate concurrent chemotherapy. Conclusions: In randomized trials, the benefits of RT intensification have largely been restricted to trials in which concurrent chemotherapy was not used. Novel strategies to optimize the incorporation of RT in the multimodality treatment of solid tumors should be explored.« less

Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for suspected malignant hilar obstruction: study protocol for a randomized controlled trial.

PubMed

Al-Kawas, Firas; Aslanian, Harry; Baillie, John; Banovac, Filip; Buscaglia, Jonathan M; Buxbaum, James; Chak, Amitabh; Chong, Bradford; Coté, Gregory A; Draganov, Peter V; Dua, Kulwinder; Durkalski, Valerie; Elmunzer, B Joseph; Foster, Lydia D; Gardner, Timothy B; Geller, Brian S; Jamidar, Priya; Jamil, Laith H; Keswani, Rajesh N; Khashab, Mouen A; Lang, Gabriel D; Law, Ryan; Lichtenstein, David; Lo, Simon K; McCarthy, Sean; Melo, Silvio; Mullady, Daniel; Nieto, Jose; Bayne Selby, J; Singh, Vikesh K; Spitzer, Rebecca L; Strife, Brian; Tarnaksy, Paul; Taylor, Jason R; Tokar, Jeffrey; Wang, Andrew Y; Williams, April; Willingham, Field; Yachimski, Patrick

2018-02-14

The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO). The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded. The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial. ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1 June 2017.

Using Minitel Network and New Software Engineering Techniques for Randomized Clinical Trials Management

PubMed Central

Lepage, E.; Tavernier, H.; Bouhaddou, O.; Jais, JP.; Gisselbrecht, C.; Aurengo, A.; Boiron, M.

1989-01-01

The usual Randomized Clinical Trials (RCT) management using an anachronic procedure involving a flowsheet exchange between the remote centers and the coordinating center presents a number of inadequacies. Eligibility criteria are not always verified by the coordinating center before inclusion in the trial and randomization. Laboratory tests and therapeutic adjustments are frequently decided from memory by the clinician which often leads to data oversight and variability of therapeutic decisions. This results in protocol deviations and alteration of the efficiency of the RCT. HICREN is a medical consultation system designed to take into account the different difficulties encountered during RCT driving. The system integrates a clinical database with artificial intelligence technics to manage clinical trial data on non-expensive and widely available Minitel® terminals. Randomization is then possible, after eligibility criteria are satisfied, anytime and anywhere in France through the national telematic network. HICREN also includes an intuitive graphic interface to increase physician's compliance: a user friendly dialogue manager supports on line data entry with multi-windowing facilities and pull down menus. Interactive data validation is achieved through an interface to dedicated C programs. Patient follow up is achieved by an expert system that proposes appropriate dose of treatment according to the rules defined in the trial. At present, HICREN is implemented on the CISARC system for conducting three randomized clinical trials and one epidemiologic study.

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

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

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.

Systematic review of physiotherapy interventions to improve gross motor capacity and performance in children and adolescents with an acquired brain injury.

PubMed

Baque, Emmah; Sakzewski, Leanne; Barber, Lee; Boyd, Roslyn N

2016-01-01

To systematically review the efficacy of physiotherapy interventions to improve gross motor capacity, performance and societal participation in children aged 5-17 years with an acquired brain injury (ABI). Randomized and non-randomized controlled trials, cohort, case series, case-control and case studies were included and classified according to grades of evidence. Methodological quality of studies was assessed using the Downs and Black (D&B) scale and quantitative data was analysed using effect sizes. Two home-based studies investigated functional strength training (one randomized controlled trial, n = 20, level 2b, D&B = 16/32 and one non-randomized self-control study, n = 19, level 4, D&B = 15/32). Four studies evaluated virtual reality including: one pilot study, n = 50, level 4, D&B = 22/32; one single-subject, non-concurrent, randomized multiple baseline study, n = 3, level 4, D&B = 15/32; one case series study, n = 2, level 4, D&B = 15/32; one case study, n = 1, level 4, D&B = 15/32. Effect sizes for the randomized controlled trial ranged between 0.30-1.29 for the Functional Reach and Timed Up and Go outcome measures. There is preliminary evidence to support the efficacy of physiotherapy interventions to improve gross motor outcomes in children with an ABI. Both functional strength training and virtual-reality based therapy are potential treatment options for clinicians to prescribe in either home or clinical settings.

Demographic variables, design characteristics, and effect sizes of randomized, placebo-controlled, monotherapy trials of major depressive disorder and bipolar depression.

PubMed

Papakostas, George I; Martinson, Max A; Fava, Maurizio; Iovieno, Nadia

2016-05-01

The aim of this work is to compare the efficacy of pharmacologic agents for the treatment of major depressive disorder (MDD) and bipolar depression. MEDLINE/PubMed databases were searched for studies published in English between January 1980 and September 2014 by cross-referencing the search term placebo with each of the antidepressant agents identified and with bipolar. The search was supplemented by manual bibliography review. We selected double-blind, randomized, placebo-controlled trials of antidepressant monotherapies for the treatment of MDD and of oral drug monotherapies for the treatment of bipolar depression. 196 trials in MDD and 19 trials in bipolar depression were found eligible for inclusion in our analysis. Data were extracted by one of the authors and checked for accuracy by a second one. Data extracted included year of publication, number of patients randomized, probability of receiving placebo, duration of the trial, baseline symptom severity, dosing schedule, study completion rates, and clinical response rates. Response rates for drug versus placebo in trials of MDD and bipolar depression were 52.7% versus 37.5% and 54.7% versus 40.5%, respectively. The random-effects meta-analysis indicated that drug therapy was more effective than placebo in both MDD (risk ratio for response = 1.373; P < .001) and bipolar depression (risk ratio = 1.257; P < .001) trials. The meta-regression analysis suggested a statistically significant difference in the risk ratio of responding to drug versus placebo between MDD and bipolar depression trials in favor of MDD (P = .008). Although a statistically significantly greater treatment effect size was noted in MDD relative to bipolar depression studies, the absolute magnitude of the difference was numerically small. Therefore, the present study suggests no clinically significant differences in the overall short-term efficacy of pharmacologic monotherapies for MDD and bipolar depression. © Copyright 2016 Physicians Postgraduate Press, Inc.

Comparison of efficacy and tolerance between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer: Study protocol for a randomized controlled trial.

PubMed

Lee, Keun-Wook; Zang, Dae Young; Ryu, Min-Hee; Kim, Ki Hyang; Kim, Mi-Jung; Han, Hye Sook; Koh, Sung Ae; Park, Jin Hyun; Kim, Jin Won; Nam, Byung-Ho; Choi, In Sil

2017-12-01

The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

Two controlled trials to increase participant retention in a randomized controlled trial of mobile phone-based smoking cessation support in the United Kingdom.

PubMed

Severi, Ettore; Free, Caroline; Knight, Rosemary; Robertson, Steven; Edwards, Philip; Hoile, Elizabeth

2011-10-01

Loss to follow-up of trial participants represents a threat to research validity. To date, interventions designed to increase participants' awareness of benefits to society of completing follow-up, and the impact of a telephone call from a senior female clinician and researcher requesting follow-up have not been evaluated robustly. Trial 1 aimed to evaluate the effect on trial follow-up of written information regarding the benefits of participation to society. Trial 2 aimed to evaluate the effect on trial follow-up of a telephone call from a senior female clinician and researcher. Two single-blind randomized controlled trials were nested within a larger trial, Txt2stop. In Trial 1, participants were allocated using minimization to receive a refrigerator magnet and a text message emphasizing the benefits to society of completing follow-up, or to a control group receiving a simple reminder regarding follow-up. In Trial 2, participants were randomly allocated to receive a telephone call from a senior female clinician and researcher, or to a control group receiving standard Txt2stop follow-up procedures. Trial 1: 33.5% (327 of 976) of the intervention group and 33.8% (329 of 974) of the control group returned the questionnaire within 26 weeks of randomization, risk ratio (RR) 0.99; 95% confidence interval (CI) 0.88-1.12. In all, 83.3% (813 of 976) of the intervention group and 82.2% (801 of/974) of the control group sent back the questionnaire within 30 weeks of randomization, RR 1.01; 95% CI 0.97, 1.05. Trial 2: 31% (20 of 65) of the intervention group and 32% (20 of 62) of the control group completed trial follow-up, RR 0.93; 95%CI 0.44, 1.98. In presence of other methods to increase follow-up neither experimental method (refrigerator magnet and text message emphasizing participation's benefits to society nor a telephone call from study's principal investigator) increased participant follow-up in the Txt2stop trial.

The role of vitamin D in the prevention of late-life depression.

PubMed

Okereke, Olivia I; Singh, Ankura

2016-07-01

In this article, we review current evidence regarding potential benefits of vitamin D for improving mood and reducing depression risk in older adults. We summarize gaps in knowledge and describe future efforts that may clarify the role of vitamin D in late-life depression prevention. MEDLINE and PsychINFO databases were searched for all articles on vitamin D and mood that had been published up to and including May 2015. Observational studies and randomized trials with 50 or more participants were included. We excluded studies that involved only younger adults and/or exclusively involved persons with current depression. Twenty observational (cross-sectional and prospective) studies and 10 randomized trials (nine were randomized placebo-controlled trials [RCTs]; one was a randomized blinded comparison trial) were reviewed. Inverse associations of vitamin D blood level or vitamin D intake with depression were found in 13 observational studies; three identified prospective relations. Results from all but one of the RCTs showed no statistically significant differences in depression outcomes between vitamin D and placebo groups. Observational studies were mostly cross-sectional and frequently lacked adequate control of confounding. RCTs often featured low treatment doses, suboptimal post-intervention changes in biochemical levels of vitamin D, and/or short trial durations. Vitamin D level-mood associations were observed in most, but not all, observational studies; results indicated that vitamin D deficiency may be a risk factor for late-life depression. However, additional data from well-designed RCTs are required to determine the impact of vitamin D in late-life depression prevention. Copyright © 2016 Elsevier B.V. All rights reserved.

'Huang Qi Elixir' for proteinuria in patients with diabetic nephropathy: a study protocol for a randomized controlled pilot trial.

PubMed

Tu, Xiang; Liu, Fang; Jordan, James B; Ye, Xue Feng; Fu, Ping; Wang, Fei; Zhong, Sen

2013-07-18

Diabetic nephropathy (DN) is the major complication of diabetes; proteinuria is the hall mark of DN. Currently, the treatment for proteinuria is mainly limited to angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). According to Traditional Chinese Medicine (TCM) theory, Chinese medicinals 'securing essence and tonifying the kidney' may be appropriate for proteinuria. The most promising Chinese medicinals and formulae are introduced in the present study to form a potent formula for DN proteinuria. To make oral administration convenient, the formula will be processed in the form of granules. A randomized, multi-center pilot trial will be conducted. Forty eight participants with DN will be randomly assigned to one of four treatment groups: 1. A granule group, at 10 grams, three times daily (G10 group, n = 12); 2. A granule group, at 20 grams, three times daily (G20 group, n = 12); 3. A decoction group (D group, n = 12); and 4. An irbesartan group (Aprovel group, n = 12).The following outcome measures will be used: the percentage change of the albumin-to-creatinine ratio; and the changes in serum creatinine, glomerular filtration rate, fasting plasma glucose and hemoglobulin from baseline to the end of the trial. It is notable that most published clinical trials which assessed the efficacy of TCM on DN were of poor methodology and, therefore, their results have been invalidated. It is necessary to carry out well-designed clinical trials to provide sound evidence. The present trial is a study with potentially great value, for it will provide the parameters for future randomized, placebo-controlled, clinical trials with large sample sizes. The trial is registered on the Chinese Clinical Trial Registry: ChiCTR-TRC-12002718 (http://www.chictr.org/cn/proj/show.aspx?proj=3820).

Does Increased Exercise or Physical Activity Alter Ad-Libitum Daily Energy Intake or Macronutrient Composition in Healthy Adults? A Systematic Review

PubMed Central

Donnelly, Joseph E.; Herrmann, Stephen D.; Lambourne, Kate; Szabo, Amanda N.; Honas, Jeffery J.; Washburn, Richard A.

2014-01-01

Background The magnitude of the negative energy balance induced by exercise may be reduced due to compensatory increases in energy intake. Objective To address the question: Does increased exercise or physical activity alter ad-libitum daily energy intake or macronutrient composition in healthy adults? Data Sources PubMed and Embase were searched (January 1990–January 2013) for studies that presented data on energy and/or macronutrient intake by level of exercise, physical activity or change in response to exercise. Ninety-nine articles (103 studies) were included. Study Eligibility Criteria Primary source articles published in English in peer-reviewed journals. Articles that presented data on energy and/or macronutrient intake by level of exercise or physical activity or changes in energy or macronutrient intake in response to acute exercise or exercise training in healthy (non-athlete) adults (mean age 18–64 years). Study Appraisal and Synthesis Methods Articles were grouped by study design: cross-sectional, acute/short term, non-randomized, and randomized trials. Considerable heterogeneity existed within study groups for several important study parameters, therefore a meta-analysis was considered inappropriate. Results were synthesized and presented by study design. Results No effect of physical activity, exercise or exercise training on energy intake was shown in 59% of cross-sectional studies (n = 17), 69% of acute (n = 40), 50% of short-term (n = 10), 92% of non-randomized (n = 12) and 75% of randomized trials (n = 24). Ninety-four percent of acute, 57% of short-term, 100% of non-randomized and 74% of randomized trials found no effect of exercise on macronutrient intake. Forty-six percent of cross-sectional trials found lower fat intake with increased physical activity. Limitations The literature is limited by the lack of adequately powered trials of sufficient duration, which have prescribed and measured exercise energy expenditure, or employed adequate assessment methods for energy and macronutrient intake. Conclusions We found no consistent evidence that increased physical activity or exercise effects energy or macronutrient intake. PMID:24454704

Culturally-Tailored Smoking Cessation for American Indians: Study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Cigarette smoking is the number one cause of preventable death among American Indian and Alaska Natives, AI/ANs. Two out of every five AI/AN will die from tobacco-related diseases if the current smoking rates of AI/ANs (40.8%) persist. Currently, there is no proven, effective culturally-tailored smoking cessation program designed specifically for a heterogeneous population of AI. The primary aim of this group randomized clinical trial is to test the efficacy of "All Nations Breath of Life" (ANBL) program compared to a non-tailored "Current Best Practices" smoking cessation program among AI smokers. Methods We will randomize 56 groups (8 smokers per group) to the tailored program or non-tailored program for a total sample size of 448 American Indian smokers. All participants in the proposed study will be offered pharmacotherapy, regardless of group assignment. This study is the first controlled trial to examine the efficacy of a culturally-tailored smoking cessation program for American Indians. If the intervention is successful, the potential health impact is significant because the prevalence of smoking is the highest in this population. Trial Registration ClinicalTrials.gov: NCT01106456 PMID:21592347

Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

PubMed

Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula

2018-01-20

The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.

Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials

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

Logan, Jennifer K.; Tang, Chad; Liao, Zhongxing

Purpose: Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. Methods and Materials: From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials inmore » NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results: A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Conclusion: Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design.« less

Personalized contact strategies and predictors of time to survey completion: analysis of two sequential randomized trials.

PubMed

Dinglas, Victor D; Huang, Minxuan; Sepulveda, Kristin A; Pinedo, Mariela; Hopkins, Ramona O; Colantuoni, Elizabeth; Needham, Dale M

2015-01-09

Effective strategies for contacting and recruiting study participants are critical in conducting clinical research. In this study, we conducted two sequential randomized controlled trials of mail- and telephone-based strategies for contacting and recruiting participants, and evaluated participant-related variables' association with time to survey completion and survey completion rates. Subjects eligible for this study were survivors of acute lung injury who had been previously enrolled in a 12-month observational follow-up study evaluating their physical, cognitive and mental health outcomes, with their last study visit completed at a median of 34 months previously. Eligible subjects were contacted to complete a new research survey as part of two randomized trials, initially using a randomized mail-based contact strategy, followed by a randomized telephone-based contact strategy for non-responders to the mail strategy. Both strategies focused on using either a personalized versus a generic approach. In addition, 18 potentially relevant subject-related variables (e.g., demographics, last known physical and mental health status) were evaluated for association with time to survey completion. Of 308 eligible subjects, 67% completed the survey with a median (IQR) of 3 (2, 5) contact attempts required. There was no significant difference in the time to survey completion for either randomized trial of mail- or phone-based contact strategy. Among all subject-related variables, age ≤40 years and minority race were independently associated with a longer time to survey completion. We found that age ≤40 years and minority race were associated with a longer time to survey completion, but personalized versus generic approaches to mail- and telephone-based contact strategies had no significant effect. Repeating both mail and telephone contact attempts was important for increasing survey completion rate. NCT00719446.

Using a partially randomized patient preference study design to evaluate the therapeutic effect of acupuncture and cupping therapy for fibromyalgia: study protocol for a partially randomized controlled trial

PubMed Central

2014-01-01

Background Conducting randomized controlled trials on traditional Chinese non-drug therapies has been limited by factors such as patient preference to specific treatment modality. The aim of this study is to investigate the feasibility of applying a partially randomized patient preference (PRPP) trial model in evaluating the efficacy of two types of traditional Chinese medicine therapies, acupuncture and cupping, for fibromyalgia while accounting for patients’ preference of either therapeutic modality. Methods This protocol was approved by the Institutional Ethics Committee of affiliated Dongfang Hospital, Beijing University of Chinese Medicine (approval number: 2013052104-2). One hundred participants with fibromyalgia will be included in this study. Diagnosis of fibromyalgia will be based on the American College of Rheumatology criteria. Before treatment, participants will be interviewed for their preference toward acupuncture or cupping therapy. Fifty participants with no preference will be randomly assigned to one of the two groups and another 50 participants with strong preference to either acupuncture or cupping will receive what they choose. For acupuncture and cupping therapy, the main acupoints used will be tender points (Ashi). Treatment will be three times a week for 5 consecutive weeks with a follow-up period of 12 weeks. Outcome measures will be qualitative (patient expectation and satisfaction) and quantitative (pain intensity, quality of life, depression assessment). Trial registration number NCT01869712 (in clinicaltrials.gov, on 22nd May 2013). PMID:25012121

Long-Term Follow-up of Participants with Heart Failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

PubMed Central

Piller, Linda B.; Baraniuk, Sarah; Simpson, Lara M.; Cushman, William C.; Massie, Barry M.; Einhorn, Paula T.; Oparil, Suzanne; Ford, Charles E.; Graumlich, James F.; Dart, Richard A.; Parish, David C.; Retta, Tamrat M.; Cuyjet, Aloysius B.; Jafri, Syed Z.; Furberg, Curt D.; Saklayen, Mohammad G.; Thadani, Udho; Probstfield, Jeffrey L.; Davis, Barry R.

2011-01-01

Background In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in high-risk hypertensive participants, risk of new-onset heart failure (HF) was higher in the amlodipine (2.5-10 mg/day) and lisinopril (10-40 mg/day) arms compared with the chlorthalidone (12.5-25 mg/day) arm . Similar to other studies, mortality rates following new-onset HF were very high (≥50% at 5 years), and were similar across randomized treatment arms. After the randomized phase of the trial ended in 2002, outcomes were determined from administrative databases. Methods and Results Using national databases, post-trial follow-up mortality through 2006 was obtained on participants who developed new-onset HF during the randomized (in-trial) phase of ALLHAT. Mean follow-up for the entire period was 8.9 years. Of 1761 participants with incident HF in-trial, 1348 died. Post-HF all-cause mortality was similar across treatment groups with adjusted hazard ratios (95% confidence intervals) of 0.95 (0.81-1.12) and 1.05 (0.89-1.25), respectively, for amlodipine and lisinopril compared with chlorthalidone, and 10-year adjusted rates of 86%, 87%, and 83%, respectively. All-cause mortality rates were also similar among those with reduced ejection fractions (84%) and preserved ejection fractions (81%) with no significant differences by randomized treatment arm. Conclusions Once HF develops, risk of death is high and consistent across randomized treatment groups. Measures to prevent the development of HF, especially blood pressure control, must be a priority if mortality associated with development of HF is to be addressed. PMID:21969009

Electroacupuncture for tapering off long-term benzodiazepine use: study protocol of randomized controlled trial.

PubMed

Yeung, Wing-Fai; Chung, Ka-Fai; Zhang, Zhang-Jin; Chan, Wai-Chi; Zhang, Shi-Ping; Ng, Roger Man-Kin; Chan, Connie Lai-Wah; Ho, Lai-Ming; Yu, Yee-Man; Lao, Li-Xing

2017-03-31

Conventional approaches for benzodiazepine tapering have their limitations. Anecdotal studies have shown that acupuncture is a potential treatment for facilitating successful benzodiazepine tapering. As of today, there was no randomized controlled trial examining its efficacy and safety. The purpose of the study is to evaluate the efficacy of using electroacupuncture as an adjunct treatment to gradual tapering of benzodiazepine doses in complete benzodiazepine cessation in long-term benzodiazepine users. The study protocol of a randomized, assessor- and subject-blinded, controlled trial is presented. One hundred and forty-four patients with histories of using benzodiazepines in ≥50% of days for more than 3 months will be randomly assigned in a 1:1 ratio to receive either electroacupuncture or placebo electroacupuncture combined with gradual benzodiazepine tapering schedule. Both experimental and placebo treatments will be delivered twice per week for 4 weeks. Major assessments will be conducted at baseline, week 6 and week 16 post-randomization. Primary outcome is the cessation rate of benzodiazepine use. Secondary outcomes include the percentage change in the doses of benzodiazepine usage and the severity of withdrawal symptoms experienced based on the Benzodiazepine Withdrawal Symptom Questionnaire, insomnia as measured by the Insomnia Severity Index, and anxiety and depressive symptoms as evaluated by the Hospital Anxiety and Depression Scale. Adverse events will also be measured at each study visit. Results of this study will provide high quality evidence of the efficacy and safety of electroacupuncture as an adjunct treatment for benzodiazepine tapering in long-term users. ClinicalTrials.gov NCT02475538 .

Clinical trials in rheumatoid arthritis: a status report from the ClinicalTrials.gov website.

PubMed

Paul, Jisna R; Ranganathan, Prabha

2012-06-01

The aims of this study are to describe the characteristics of clinical trials in rheumatoid arthritis (RA) listed in ClinicalTrials.gov and examine existing trends in study design, funding sources, outcomes, and drugs under investigation. We conducted a survey of ongoing clinical trials in RA registered in the ClinicalTrials.gov website. We used the advanced search option and applied the following inclusion criteria, "rheumatoid arthritis", "open studies", "interventional", and "adults 18 years or older". Of 127 eligible trials, 53.5% of the studies were either phase 3 or 4, and 40.2% were phase 1, 2, and 2/3. Two-thirds of the trials were randomized (70.9%), and over half were, in addition, double-blinded (53.5%) and placebo-controlled (53.5%). Universities were listed as the primary sponsor for 18.9% of the trials and pharmaceutical industry for 73.2%. Majority of the trials were multi-center studies (93%) conducted outside the United States (54.3%). The most frequently used endpoint was drug efficacy (54.3%) followed by drug safety (25.2%). Most industry-funded trials were open for less than 12 months, whereas most university-funded trials were open for more than 24 months (58% each). Biologic therapies were the focus of most trials in the registry (78.5%). Randomized, double-blinded, placebo-controlled, phase 3 and 4 trials form the majority of ongoing clinical trials in RA. The preponderance of industry funding of RA trials and the short duration of such trials are troubling trends which need to be addressed.

Efficacy of electroacupuncture for symptoms of menopausal transition: study protocol for a randomized controlled trial.

PubMed

Liu, Zhishun; Wang, Yang; Xu, Huanfang; Wu, Jiani; He, Liyun; Jiang, John Yi; Yan, Shiyan; Du, Ruosang; Liu, Baoyan

2014-06-21

Previous studies have shown that acupuncture can alleviate postmenopausal symptoms, such as hot flashes, but few studies have assessed symptoms during the menopausal transition (MT) period. Thus, the effect of acupuncture upon MT symptoms is unclear. We designed a large-scale trial aimed at evaluating the efficacy of electroacupuncture for MT symptoms compared with sham electroacupuncture and at observing the safety of electroacupuncture. In this multicenter randomized controlled trial, 360 women will be randomized to either an electroacupuncture group or a sham electroacupuncture group. During the 8-week-long treatment, a menopause rating scale, average 24-hour hot flash score, Menopause-Specific Quality of Life Questionnaire score, and level of female hormones will be observed. Follow-ups at the 20th and 32nd week will be made. Though there is no completely inert placebo acupuncture and blinding is difficult in acupuncture trials, the placebo effect of EA can still be partially excluded in this study. For the placebo control, we use non-points and a tailor-made sham needle. This needle is different from a retractable needle, which is usually used for sham acupuncture. The needle in this trial is more simply constructed and more acceptable to Chinese people. We expect to evaluate the efficacy of electroacupuncture for MT symptoms and clarify its effect on these symptoms. ClinicalTrials.gov Identifier: NCT01849172 (Date of registration: 05/05/2013).

Effect of Frequent or Extended Hemodialysis on Cardiovascular Parameters: A Meta-analysis

PubMed Central

Susantitaphong, Paweena; Koulouridis, Ioannis; Balk, Ethan M.; Madias, Nicolaos E.; Jaber, Bertrand L.

2012-01-01

Background Increased left ventricular (LV) mass is a risk factor for cardiovascular mortality in patients with chronic kidney failure. More frequent or extended hemodialysis (HD) has been hypothesized to have a beneficial effect on LV mass. Study Design Meta-analysis. Setting & Population MEDLINE literature search (inception-April 2011), Cochrane Central Register of Controlled Trials and ClinicalTrials.gov using the search terms “short daily HD”, “daily HD”, “quotidian HD”, “frequent HD”, “intensive HD”, “nocturnal HD”, and “home HD”. Selection Criteria for Studies Single-arm cohort studies (with pre- and post-study evaluations) and randomized controlled trials examining the effect of frequent or extended HD on cardiac morphology and function, and blood pressure parameters. Studies of hemofiltration, hemodiafiltration and peritoneal dialysis were excluded. Intervention Frequent (2–8 hours,> thrice weekly) or extended (>4 hours, thrice weekly) HD as compared with conventional (≤ 4 hours, thrice weekly) HD. Outcomes Absolute changes in cardiac morphology and function, including LV mass index (LVMI) (primary), and blood pressure parameters (secondary). Results We identified 38 single-arm studies, 5 crossover trials and 3 randomized controlled trials. By meta-analysis of 23 study arms, frequent or extended HD significantly reduced LVMI from baseline (−31.2 g/m2, 95% CI, −39.8 to −22.5; P<0.001).The 3 randomized trials found a less pronounced net reduction in LVMI (−7.0 g/m2; 95% CI, −10.2 to −3.7; P<0.001). LV ejection fraction improved by 6.7% (95% CI, 1.6 to 11.9; P=0.01). Other cardiac morphological parameters displayed similar improvements. There were also significant decreases in systolic, diastolic, and mean blood pressure, and mean number of anti-hypertensive medications. Limitations Paucity of randomized controlled trials. Conclusions Conversion from conventional to frequent or extended HD is associated with an improvement in cardiac morphology and function, including LVMI and LV ejection fraction, respectively, and in several blood pressure parameters, which collectively might confer long-term cardiovascular benefit. Trials with long-term clinical outcomes are needed. PMID:22370022

Mortality risk of darbepoetin alfa versus epoetin alfa in patients with CKD: systematic review and meta-analysis.

PubMed

Wilhelm-Leen, Emilee R; Winkelmayer, Wolfgang C

2015-07-01

Epoetin alfa (EPO) and darbepoetin alfa (DPO) are erythropoiesis-stimulating agents that are widely and interchangeably used for the treatment of anemia in patients with advanced chronic kidney disease and end-stage renal disease. No study has specifically compared the risks of hard study outcomes between EPO and DPO, including mortality. Systematic review of the literature and meta-analysis. Patients enrolled in randomized trials comparing EPO versus DPO for the treatment of anemia in adults with chronic kidney disease, including those requiring dialysis. We conducted a systematic search of the literature (PubMed, CENTRAL, SCOPUS, and EMBASE, all years) and industry resources, using predefined search terms and data abstraction tools. We then summarized key characteristics and findings of these trials and performed a random-effects meta-analysis of trials with at least 3 months' duration to identify the summary OR of mortality between patients randomly assigned to DPO versus EPO. DPO versus EPO. All-cause mortality. We identified 9 trials that met the stated inclusion criteria. Overall, 2,024 patients were included in the meta-analysis, of whom 126 died during follow-up, which ranged from 20 to 52 weeks. We found no significant difference in mortality between patients randomly assigned to DPO versus EPO (OR, 1.33; 95% CI, 0.88-2.01). No treatment heterogeneity across studies was detected (Q statistic=4.60; P=0.8). Generalizability to nontrial populations is uncertain. Few trials directly comparing DPO and EPO have been conducted and follow-up was limited. In aggregate, no effect of specific erythropoiesis-stimulating agent on mortality was identified, but the confidence limits were wide and remained compatible with considerable harm from DPO. Absent adequately powered randomized trials, observational postmarketing comparative effectiveness studies comparing these erythropoiesis-stimulating agents are required to better characterize the long-term safety profiles of these agents. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Spine device clinical trials: design and sponsorship.

PubMed

Cher, Daniel J; Capobianco, Robyn A

2015-05-01

Multicenter prospective randomized clinical trials represent the best evidence to support the safety and effectiveness of medical devices. Industry sponsorship of multicenter clinical trials is purported to lead to bias. To determine what proportion of spine device-related trials are industry-sponsored and the effect of industry sponsorship on trial design. Analysis of data from a publicly available clinical trials database. Clinical trials of spine devices registered on ClinicalTrials.gov, a publicly accessible trial database, were evaluated in terms of design, number and location of study centers, and sample size. The relationship between trial design characteristics and study sponsorship was evaluated using logistic regression and general linear models. One thousand six hundred thrity-eight studies were retrieved from ClinicalTrials.gov using the search term "spine." Of the 367 trials that focused on spine surgery, 200 (54.5%) specifically studied devices for spine surgery and 167 (45.5%) focused on other issues related to spine surgery. Compared with nondevice trials, device trials were far more likely to be sponsored by the industry (74% vs. 22.2%, odds ratio (OR) 9.9 [95% confidence interval 6.1-16.3]). Industry-sponsored device trials were more likely multicenter (80% vs. 29%, OR 9.8 [4.8-21.1]) and had approximately four times as many participating study centers (p<.0001) and larger sample sizes. There were very few US-based multicenter randomized trials of spine devices not sponsored by the industry. Most device-related spine research is industry-sponsored. Multicenter trials are more likely to be industry-sponsored. These findings suggest that previously published studies showing larger effect sizes in industry-sponsored vs. nonindustry-sponsored studies may be biased as a result of failure to take into account the marked differences in design and purpose. Copyright © 2015 Elsevier Inc. All rights reserved.

Outcomes following vaginal prolapse repair and mid urethral sling (OPUS) trial--design and methods.

PubMed

Wei, John; Nygaard, Ingrid; Richter, Holly; Brown, Morton; Barber, Matthew; Xiao Xu; Kenton, Kimberly; Nager, Charles; Schaffer, Joseph; Visco, Anthony; Weber, Anne

2009-04-01

The primary aims of this trial are to determine whether the use of a concomitant prophylactic anti-incontinence procedure may prevent stress urinary incontinence symptom development in women undergoing vaginal prolapse surgery and to evaluate the cost-effectiveness of this prophylactic approach. To present the rationale and design of a randomized controlled surgical trial (RCT), the Outcomes following vaginal Prolapse repair and mid Urethral Sling (OPUS) Trial highlighting the challenges in the design and implementation. The challenges of implementing this surgical trial combined with a cost-effectiveness study and patient preference group are discussed including the study design, ethical issues regarding use of sham incision, maintaining the masking of study staff, and pragmatic difficulties encountered in the collection of cost data. The trial is conducted by the NICHD-funded Pelvic Floor Disorders Network. The ongoing OPUS trial started enrollment in May 2007 with a planned accrual of 350. The use of sham incision was generally well accepted but the collection of cost data using conventional billing forms was found to potentially unmask key study personnel. This necessitated changes in the study forms and planned timing for collection of cost data. To date, the enrollment to the patient preference group has been lower than the limit established by the protocol suggesting a willingness on the part of women to participate in the randomization. Given the invasive nature of surgical intervention trials, potential participants may be reluctant to accept random assignment, potentially impacting generalizability. Findings from the OPUS trial will provide important information that will help surgeons to better counsel women on the benefits and risks of concomitant prophylactic anti-incontinence procedure at the time of vaginal surgery for prolapse. The implementation of the OPUS trial has necessitated that investigators consider ethical issues up front, remain flexible with regards to data collection and be constantly aware of unanticipated opportunities for unmasking. Future surgical trials should be aware of potential challenges in maintaining masking and collection of cost-related information.

Sleep-Disordered Breathing in Chronic SCI: A Randomized Controlled Trial of Treatment Impact on Cognition, Quality of Life, and Cardiovascular Disease

DTIC Science & Technology

2015-10-01

randomized controlled trial, we will objectively measure sleep disordered breathing ( SDB ) in chronic SCI patients using portable sleep studies, and...systematically evaluate the association between SDB , cognitive performance, mood, pain, and CV measures. We will randomize participants to 4 months of PAP...TERMS SDB , SCI, PAP, CV 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a

Sleep Disordered Breathing in Chronic SCI: A Randomized Controlled Trial of Treatment Impact on Cognition, Quality of Life, and Cardiovascular Disease

DTIC Science & Technology

2015-11-30

randomized controlled trial, we will objectively measure sleep disordered breathing ( SDB ) in chronic SCI patients using portable sleep studies, and...systematically evaluate the association between SDB , cognitive performance, mood, pain, and CV measures. We will randomize participants to 4 months of PAP...TERMS SDB , SCI, PAP, CV 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a

Enhancing Adherence among Older African American Men Enrolled in a Longitudinal Cancer Screening Trial

ERIC Educational Resources Information Center

Ford, Marvella E.; Havstad, Suzanne; Vernon, Sally W.; Davis, Shawna D.; Kroll, David; Lamerato, Lois; Swanson, G. Marie

2006-01-01

Purpose: The purpose of this study was to enhance adherence among older (aged 55 years and older) African American men enrolled in a cancer screening trial for prostate, lung, and colorectal cancer. For this study, we defined "adherence" as completing the trial screenings. Design and Methods: We used a randomized trial design. Case managers…

Web-Based Decision Aid to Assist Help-Seeking Choices for Young People Who Self-Harm: Outcomes From a Randomized Controlled Feasibility Trial

PubMed Central

Patel, Krisna; French, Rebecca S; Henderson, Claire; Ougrin, Dennis; Slade, Mike; Moran, Paul

2018-01-01

Background Adolescents who self-harm are often unsure how or where to get help. We developed a Web-based personalized decision aid (DA) designed to support young people in decision making about seeking help for their self-harm. Objective The aim of this study was to evaluate the feasibility and acceptability of the DA intervention and the randomized controlled trial (RCT) in a school setting. Methods We conducted a two-group, single blind, randomized controlled feasibility trial in a school setting. Participants aged 12 to 18 years who reported self-harm in the past 12 months were randomized to either a Web-based DA or to general information about mood and feelings. Feasibility of recruitment, randomization, and follow-up rates were assessed, as was acceptability of the intervention and study procedures. Descriptive data were collected on outcome measures examining decision making and help-seeking behavior. Qualitative interviews were conducted with young people, parents or carers, and staff and subjected to thematic analysis to explore their views of the DA and study processes. Results Parental consent was a significant barrier to young people participating in the trial, with only 17.87% (208/1164) of parents or guardians who were contacted for consent responding to study invitations. Where parental consent was obtained, we were able to recruit 81.7% (170/208) of young people into the study. Of those young people screened, 13.5% (23/170) had self-harmed in the past year. Ten participants were randomized to receiving the DA, and 13 were randomized to the control group. Four-week follow-up assessments were completed with all participants. The DA had good acceptability, but qualitative interviews suggested that a DA that addressed broader mental health problems such as depression, anxiety, and self-harm may be more beneficial. Conclusions A broad-based mental health DA addressing a wide range of psychosocial problems may be useful for young people. The requirement for parental consent is a key barrier to intervention research on self-harm in the school setting. Adaptations to the research design and the intervention are needed before generalizable research about DAs can be successfully conducted in a school setting. Trial Registration International Standard Randomized Controlled Trial registry: ISRCTN11230559; http://www.isrctn.com/ISRCTN11230559 (Archived by WebCite at http://www.webcitation.org/6wqErsYWG) PMID:29382626

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

Hospital Inpatient versus HOme-based rehabilitation after knee arthroplasty (The HIHO study): study protocol for a randomized controlled trial.

PubMed

Buhagiar, Mark A; Naylor, Justine M; Harris, Ian A; Xuan, Wei; Kohler, Friedbert; Wright, Rachael J; Fortunato, Renee

2013-12-17

Formal rehabilitation programs are often assumed to be required after total knee arthroplasty to optimize patient recovery. Inpatient rehabilitation is a costly rehabilitation option after total knee arthroplasty and, in Australia, is utilized most frequently for privately insured patients. With the exception of comparisons with domiciliary services, no randomized trial has compared inpatient rehabilitation to any outpatient based program. The Hospital Inpatient versus HOme (HIHO) study primarily aims to determine whether 10 days of post-acute inpatient rehabilitation followed by a hybrid home program provides superior recovery of functional mobility on the 6-minute walk test (6MWT) compared to a hybrid home program alone following total knee arthroplasty. Secondarily, the trial aims to determine whether inpatient rehabilitation yields superior recovery in patient-reported function. This is a two-arm parallel randomized controlled trial (RCT), with a third, non-randomized, observational group. One hundred and forty eligible, consenting participants who have undergone a primary total knee arthroplasty at a high-volume joint replacement center will be randomly allocated when cleared for discharge from acute care to either 10 days of inpatient rehabilitation followed by usual care (a 6-week hybrid home program) or to usual care. Seventy participants in each group (140 in total) will provide 80% power at a significance level of 5% to detect an increase in walking capacity from 400 m to 460 m between the Home and Inpatient groups, respectively, in the 6MWT at 6 months post-surgery, assuming a SD of 120 m and a drop-out rate of <10%.The outcome assessor will assess participants at 10, 26 and 52 weeks post-operatively, and will remain blind to group allocation for the duration of the study, as will the statistician. Participant preference for rehabilitation mode stated prior to randomization will be accounted for in the analysis together with any baseline differences in potentially confounding characteristics as required. The HIHO Trial will be the first RCT to investigate the efficacy of inpatient rehabilitation compared to any outpatient alternative following total knee arthroplasty. U.S. National Institutes of Health Clinical Trials Registry (http://clinicaltrials.gov) ref: NCT01583153.

Prevention of EP Migratory Contamination in a Cluster Randomized Trial to Increase tPA Use in Stroke (The INSTINCT Trial)

PubMed Central

Weston, Victoria C.; Meurer, William J.; Frederiksen, Shirley M.; Fox, Allison K.; Scott, Phillip A.

2016-01-01

Objectives Cluster randomized trials (CRTs) are increasingly utilized to evaluate quality improvement interventions aimed at healthcare providers. In trials testing emergency department interventions, migration of emergency physicians (EPs) between hospitals is an important concern, as contamination may affect both internal and external validity. We hypothesized that geographically isolating emergency departments would prevent migratory contamination in a CRT designed to increase ED delivery of tPA in stroke (The INSTINCT Trial). Methods INSTINCT was a prospective, cluster randomized, controlled trial. 24 Michigan community hospitals were randomly selected in matched pairs for study. Contamination was defined at the cluster level, with substantial contamination defined a priori as >10% of EPs affected. Non-adherence, total crossover (contamination + non-adherence), migration distance and characteristics were determined. Results 307 emergency physicians were identified at all sites. Overall, 7 (2.3%) changed study sites. 1 moved between control sites, leaving 6 (2.0%) total crossovers. Of these, 2 (0.7%) moved from intervention to control (contamination) and 4 (1.3%) moved from control to intervention (non-adherence). Contamination was observed in 2 of 12 control sites, with 17% and 9% contamination of the total site EP workforce at follow-up, respectively. Average migration distance was 42 miles for all EPs moving in the study and 35 miles for EPs moving from intervention to control sites. Conclusion The mobile nature of emergency physicians should be considered in the design of quality improvement CRTs. Increased reporting of contamination in CRTs is encouraged to clarify thresholds and facilitate CRT design. PMID:25440230

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.

A systematic review of randomized clinical trials published in Malaria Journal between 2008 and 2013.

PubMed

Martínez-Alonso, E; Ramos, J M

2016-06-01

Randomized controlled trials (RCT) are a key component in clinical research and they provide the highest quality clinical results. The objective of this study was to describe the main characteristics of RCTs published in Malaria Journal, including research topics, study population and design, funding sources and collaboration between institutions. This may help researchers and funders define future research priorities in this field. A retrospective analysis was performed on the RCTs published in Malaria Journal between January 1, 2008 and December 31, 2013. A key-word search by "Randomized controlled trial" or "Random*" was carried out in PubMed. RCT indexed to MEDLINE were selected for the analysis. A total of 108 published articles containing RCTs were analysed. Treatment of uncomplicated Plasmodium falciparum malaria (n=45, 41.6%), especially the efficacy and safety of antimalarial drugs, and malaria prevention (n=34, 31.5%) were the two main research topics. The majority of trials were conducted in Africa (62.2%) and Asia (27%) and received external funding (private, 42.3% and/or public, 38.6%). Paediatric population was the primary study group (n=63, 58.3%), followed by adults (n=29, 26.9%). Pregnant women (n=7) and geriatric population (n=1) remain underrepresented. Nearly 75% of trials were conducted in individual subjects and 25% in groups of subjects (cluster RCTs). A considerable collaboration between researchers and institutions is noteworthy. RCTs published in Malaria Journal address a wide range of research topics. Paediatric trials conducted in Africa and Asia are frequently performed, and a significant worldwide collaboration to fight against malaria has been identified.

The Effectiveness and Cost-Effectiveness of Spinal Cord Stimulation for Refractory Angina (RASCAL Study): A Pilot Randomized Controlled Trial.

PubMed

Eldabe, Sam; Thomson, Simon; Duarte, Rui; Brookes, Morag; deBelder, Mark; Raphael, Jon; Davies, Ed; Taylor, Rod

2016-01-01

Patients with "refractory angina" (RA) unsuitable for coronary revascularization experience high levels of hospitalization and poor health-related quality of life. Randomized trials have shown spinal cord stimulation (SCS) to be a promising treatment for chronic stable angina and RA; however, none has compared SCS with usual care (UC). The aim of this pilot study was to address the key uncertainties of conducting a definitive multicenter trial to assess the clinical and cost-effectiveness of SCS in RA patients, i.e., recruitment and retention of patients, burden of outcome measures, our ability to standardize UC in a UK NHS setting. RA patients deemed suitable were randomized in a 1:1 ratio to SCS plus UC (SCS group) or UC alone (UC group). We sought to assess: recruitment, uptake, and retention of patients; feasibility and acceptability of SCS treatment; the feasibility and acceptability of standardizing UC; and the feasibility and acceptability of the proposed trial outcome measures. Patient outcomes were assessed at baseline (prerandomization) and three and six months postrandomization. We failed to meet our planned recruitment target (45 patients) and randomized 29 patients (15 SCS group, 14 UC group) over a 42-month period across four sites. None of the study participants chose to withdraw following consent and randomization. With exception of two deaths, all completed evaluation at baseline and follow-up. Although the study was not formally powered to compare outcomes between groups, we saw a trend toward larger improvements in both primary and secondary outcomes in the SCS group. While patient recruitment was found to be challenging, levels of participant retention, outcome completion, and acceptability of SCS therapy were high. A number of lessons are presented in order to take forward a future definitive pragmatic randomized trial. © 2015 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.

A randomized trial comparing primary angioplasty versus stent placement for symptomatic intracranial stenosis

PubMed Central

Qureshi, Adnan I; Chaudhry, Saqib A; Siddiq, Farhan; Majidi, Shahram; Rodriguez, Gustavo J; Suri, M Fareed K

2013-01-01

Background: Both primary angioplasty alone and angioplasty with a self-expanding stent have been compared in non-randomized concurrent clinical studies that suggest equivalent results. However, there is no randomized trial that has compared the two procedures in patients with symptomatic high grade intracranial stenosis. Objective: The primary aim of the randomized trial was to compare the clinical and angiographic efficacy of primary angioplasty and angioplasty followed by stent placement in preventing restenosis, stroke, requirement for second treatment, and death in patients with symptomatic intracranial stenosis. Methods: The study prospectively evaluated efficacy and safety of the two existing neurointerventional techniques for treatment of moderate intracranial stenosis (stenosis ≥ 50%) with documented failure of medical treatment or severe stenosis (≥70%) with or without failure of medical treatment. Results: A total of 18 patients were recruited in the study (mean age [±SD] was 64.7 ± 15.1 years); out of these, 12 were men. Of these 18, 10 were treated with primary angioplasty and 8 were treated with angioplasty followed by self-expanding stent. The technical success rates of intracranial angioplasty and stent placements defined as ability to achieve <30% residual stenosis when assessed by immediate post-procedure angiography was 5 of 10 and 5 of 8 patients, respectively. The total fluoroscopic time (mean [±SD]) was lower in patients undergoing primary angioplasty 37 [±11] min versus those undergoing angioplasty followed by self-expanding stent 42 [±15] min, P = 0.4321. The stroke and death rate within 1 month was very low in both patient groups (1 of 10 versus 0 of 8 patients). One patient randomized to stent placement continued to have recurrent ischemic symptoms requiring another angioplasty in the vertebral artery on post-procedure Day 2. Conclusions: The trial suggests that a randomized trial comparing primary angioplasty to angioplasty followed by stent placement is feasible. The immediate procedural outcomes with primary angioplasty are comparable to stent placement and warrant further studies. PMID:24358415

Diarrhea and dengue control in rural primary schools in Colombia: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Diarrheal diseases and dengue fever are major global health problems. Where provision of clean water is inadequate, water storage is crucial. Fecal contamination of stored water is a common source of diarrheal illness, but stored water also provides breeding sites for dengue vector mosquitoes. Poor household water management and sanitation are therefore potential determinants of both diseases. Little is known of the role of stored water for the combined risk of diarrhea and dengue, yet a joint role would be important for developing integrated control and management efforts. Even less is known of the effect of integrating control of these diseases in school settings. The objective of this trial was to investigate whether interventions against diarrhea and dengue will significantly reduce diarrheal disease and dengue entomological risk factors in rural primary schools. Methods/design This is a 2×2 factorial cluster randomized controlled trial. Eligible schools were rural primary schools in La Mesa and Anapoima municipalities, Cundinamarca, Colombia. Eligible pupils were school children in grades 0 to 5. Schools were randomized to one of four study arms: diarrhea interventions (DIA); dengue interventions (DEN); combined diarrhea and dengue interventions (DIADEN); and control (C). Schools were allocated publicly in each municipality (strata) at the start of the trial, obviating the need for allocation concealment. The primary outcome for diarrhea is incidence rate of diarrhea in school children and for dengue it is density of adult female Aedes aegypti per school. Approximately 800 pupils from 34 schools were enrolled in the trial with eight schools in the DIA arm, nine in the DEN, eight in the DIADEN, and nine in the control arms. The trial status as of June 2012 was: completed baseline data collections; enrollment, randomization, and allocation of schools. The trial was funded by the Research Council of Norway and the Lazos de Calandaima Foundation. Discussion This is the first trial investigating the effect of a set of integrated interventions to control both dengue and diarrhea. This is also the first trial to study the combination of diarrhea-dengue disease control in school settings. Trial registration Current Controlled Trials ISRCTN40195031 PMID:23034084

Recruitment and Retention for a Weight Loss Maintenance Trial Involving Weight Loss Prior to Randomization

PubMed Central

Grubber, J. M.; McVay, M. A.; Olsen, M. K.; Bolton, J.; Gierisch, J. M.; Taylor, S. S.; Maciejewski, M. L.; Yancy, W. S.

2016-01-01

Abstract Objective A weight loss maintenance trial involving weight loss prior to randomization is challenging to implement due to the potential for dropout and insufficient weight loss. We examined rates and correlates of non‐initiation, dropout, and insufficient weight loss during a weight loss maintenance trial. Methods The MAINTAIN trial involved a 16‐week weight loss program followed by randomization among participants losing at least 4 kg. Psychosocial measures were administered during a screening visit. Weight was obtained at the first group session and 16 weeks later to determine eligibility for randomization. Results Of 573 patients who screened as eligible, 69 failed to initiate the weight loss program. In adjusted analyses, failure to initiate was associated with lower age, lack of a support person, and less encouragement for making dietary changes. Among participants who initiated, 200 dropped out, 82 lost insufficient weight, and 222 lost sufficient weight for randomization. Compared to losing sufficient weight, dropping out was associated with younger age and tobacco use, whereas losing insufficient weight was associated with non‐White race and controlled motivation for physical activity. Conclusions Studies should be conducted to evaluate strategies to maximize recruitment and retention of subgroups that are less likely to initiate and be retained in weight loss maintenance trials. PMID:28090340

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.

Effectiveness of the Self-Regulation eHealth Intervention "MyPlan1.0." on Physical Activity Levels of Recently Retired Belgian Adults: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Van Dyck, Delfien; Plaete, Jolien; Cardon, Greet; Crombez, Geert; De Bourdeaudhuij, Ilse

2016-01-01

The study purpose was to test the effectiveness of the self-regulation eHealth intervention "MyPlan1.0." to increase physical activity (PA) in recently retired Belgian adults. This study was a randomized controlled trial with three points of follow-up/modules (baseline to 1-week to 1-month follow-up). In total, 240 recently retired…

Omega-3/Omega-6 Fatty Acids for Attention Deficit Hyperactivity Disorder: A Randomized Placebo-Controlled Trial in Children and Adolescents

ERIC Educational Resources Information Center

Johnson, Mats; Ostlund, Sven; Fransson, Gunnar; Kadesjo, Bjorn; Gillberg, Christopher

2009-01-01

Objective: The aim of the study was to assess omega 3/6 fatty acids (eye q) in attention deficit hyperactivity disorder (ADHD). Method: The study included a randomized, 3-month, omega 3/6 placebo-controlled, one-way crossover trial with 75 children and adolescents (8-18 years), followed by 3 months with omega 3/6 for all. Investigator-rated ADHD…

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.

Is there a role for e-cigarettes in smoking cessation?

PubMed

Leduc, Charlotte; Quoix, Elisabeth

2016-04-01

The use of e-cigarettes has dramatically increased over the past few years and their role in smoking cessation remains controversial. Several clinical studies have evaluated their efficacy in smoking cessation but most of them are prospective cohort studies. Only two randomized, controlled trials have compared e-cigarettes versus placebo or patches. A meta-analysis of these two randomized, controlled trials has been performed. Nicotine-containing e-cigarettes appear to help smokers unable to stop smoking altogether to reduce their cigarette consumption when compared with placebo. However, these results are rated 'low' by GRADE standards. Many cohort studies have been conducted, with contradictory results. For some, e-cigarettes could increase the risk of nonsmokers developing nicotine dependence and of current smokers maintaining their dependence. The debate remains open and more randomized trials are needed with long-term data about the efficacy and safety of e-cigarettes. © The Author(s), 2015.

A Cluster-Randomized Trial of Restorative Practices: An Illustration to Spur High-Quality Research and Evaluation

PubMed Central

Acosta, Joie D.; Chinman, Matthew; Ebener, Patricia; Phillips, Andrea; Xenakis, Lea; Malone, Patrick S.

2017-01-01

Restorative Practices in schools lack rigorous evaluation studies. As an example of rigorous school-based research, this paper describes the first randomized control trial of restorative practices to date, the Study of Restorative Practices. It is a 5-year, cluster-randomized controlled trial (RCT) of the Restorative Practices Intervention (RPI) in 14 middle schools in Maine to assess whether RPI impacts both positive developmental outcomes and problem behaviors and whether the effects persist during the transition from middle to high school. The two-year RPI intervention began in the 2014–2015 school year. The study’s rationale and theoretical concerns are discussed along with methodological concerns including teacher professional development. The theoretical rationale and description of the methods from this study may be useful to others conducting rigorous research and evaluation in this area. PMID:28936104

Study design and rationale of the 'Balloon-Expandable Cobalt Chromium SCUBA Stent versus Self-Expandable COMPLETE-SE Nitinol Stent for the Atherosclerotic ILIAC Arterial Disease (SENS-ILIAC Trial) Trial': study protocol for a randomized controlled trial.

PubMed

Choi, Woong Gil; Rha, Seung Woon; Choi, Cheol Ung; Kim, Eung Ju; Oh, Dong Joo; Cho, Yoon Hyung; Park, Sang Ho; Lee, Seung Jin; Hur, Ae Yong; Ko, Young Guk; Park, Sang Min; Kim, Ki Chang; Kim, Joo Han; Kim, Min Woong; Kim, Sang Min; Bae, Jang Ho; Bong, Jung Min; Kang, Won Yu; Seo, Jae Bin; Jung, Woo Yong; Cho, Jang Hyun; Kim, Do Hoi; Ahn, Ji Hoon; Kim, Soo Hyun; Jang, Ji Yong

2016-06-25

The self-expandable COMPLETE™ stent (Medtronic) has greater elasticity, allowing it to regain its shape after the compression force reduces, and has higher trackability, thus is easier to maneuver through tortuous vessels, whereas the balloon-expandable SCUBA™ stent (Medtronic) has higher radial stiffness and can afford more accurate placement without geographic miss, which is important in aortoiliac bifurcation lesions. To date, there have been no randomized control trials comparing efficacy and safety between the self-expanding stent and balloon-expandable stent in advanced atherosclerotic iliac artery disease. The purpose of our study is to examine primary patency (efficacy) and incidence of stent fracture and geographic miss (safety) between two different major representative stents, the self-expanding nitinol stent (COMPLETE-SE™) and the balloon-expanding cobalt-chromium stent (SCUBA™), in stenotic or occlusive iliac arterial lesions. This trial is designed as a prospective, randomized, multicenter trial to demonstrate a noninferiority of SCUBA™ stent to COMPLETE-SE™ stent following balloon angioplasty in iliac arterial lesions, and a total of 280 patients will be enrolled. The primary end point of this study is the rate of primary patency in the treated segment at 12 months after intervention as determined by catheter angiography, computed tomography angiography, or duplex ultrasound. The SENS-ILIAC trial will give powerful insight into whether the stent choice according to deployment mechanics would impact stent patency, geographic miss, or stent fracture in patients undergoing stent implantation in iliac artery lesions. National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT01834495 ), registration date: May 8, 2012.

COMPUTERIZED EXPERT SYSTEM FOR EVALUATION OF AUTOMATED VISUAL FIELDS FROM THE ISCHEMIC OPTIC NEUROPATHY DECOMPRESSION TRIAL: METHODS, BASELINE FIELDS, AND SIX-MONTH LONGITUDINAL FOLLOW-UP

PubMed Central

Feldon, Steven E

2004-01-01

ABSTRACT Purpose To validate a computerized expert system evaluating visual fields in a prospective clinical trial, the Ischemic Optic Neuropathy Decompression Trial (IONDT). To identify the pattern and within-pattern severity of field defects for study eyes at baseline and 6-month follow-up. Design Humphrey visual field (HVF) change was used as the outcome measure for a prospective, randomized, multi-center trial to test the null hypothesis that optic nerve sheath decompression was ineffective in treating nonarteritic anterior ischemic optic neuropathy and to ascertain the natural history of the disease. Methods An expert panel established criteria for the type and severity of visual field defects. Using these criteria, a rule-based computerized expert system interpreted HVF from baseline and 6-month visits for patients randomized to surgery or careful follow-up and for patients who were not randomized. Results A computerized expert system was devised and validated. The system was then used to analyze HVFs. The pattern of defects found at baseline for patients randomized to surgery did not differ from that of patients randomized to careful follow-up. The most common pattern of defect was a superior and inferior arcuate with central scotoma for randomized eyes (19.2%) and a superior and inferior arcuate for nonrandomized eyes (30.6%). Field patterns at 6 months and baseline were not different. For randomized study eyes, the superior altitudinal defects improved (P = .03), as did the inferior altitudinal defects (P = .01). For nonrandomized study eyes, only the inferior altitudinal defects improved (P = .02). No treatment effect was noted. Conclusions A novel rule-based expert system successfully interpreted visual field defects at baseline of eyes enrolled in the IONDT. PMID:15747764

The effects of Bifidobacterium animalis ssp. lactis B94 on gastrointestinal wellness in adults with Prader-Willi syndrome: study protocol for a randomized controlled trial.

PubMed

Alyousif, Zainab; Miller, Jennifer L; Sandoval, Mariana Y; MacPherson, Chad W; Nagulesapillai, Varuni; Dahl, Wendy J

2018-04-27

Constipation is a frequent problem in adults with Prader-Willi syndrome. Certain probiotics have been shown to improve transit and gastrointestinal symptoms of adults with functional constipation. The aim of this study is to determine the effect of daily consumption of Bifidobacterium animalis ssp. lactis B94 (B. lactis B94) on stool frequency, stool form, and gastrointestinal symptoms in adults with Prader-Willi syndrome. Adults with Prader-Willi syndrome (18-75 years old, n = 36) will be recruited and enrolled in a 20-week, randomized, double-blind, placebo-controlled, crossover study. Study subjects will be randomized to B. lactis B94 or placebo each for a 4-week period, preceded by a 4-week baseline and followed by 4-week washouts. Subjects will complete daily records of stool frequency and stool form (a proxy of transit time). Dietary intake data also will be collected. Stools, one in each period, will be collected for exploratory microbiota analyses. To our knowledge, this is the first randomized controlled trial evaluating the effectiveness of B. lactis in adults with Prader-Willi syndrome. The results of this study will provide evidence of efficacy for future clinical trials in patient populations with constipation. ClinicalTrials.gov ( NCT03277157 ). Registered on 08 September 2017.

Vitamin D status and weight loss: a systematic review and meta-analysis of randomized and nonrandomized controlled weight-loss trials.

PubMed

Mallard, Simonette R; Howe, Anna S; Houghton, Lisa A

2016-10-01

Obesity is associated with lower concentrations of serum 25-hydroxyvitamin D; however, uncertainty exists as to the direction of causation. To date, meta-analyses of randomized controlled vitamin D-supplementation trials have shown no effect of raising circulating vitamin D on body weight, although several weight-loss-intervention trials have reported an increase in circulating vitamin D after weight reduction. We undertook a systematic review and meta-analysis of randomized and nonrandomized controlled trials to determine whether weight loss compared with weight maintenance leads to an increase in serum 25-hydroxyvitamin D. A systematic search for controlled weight-loss-intervention studies published up to 31 March 2016 was performed. Studies that included participants of any age with changes in adiposity and serum 25-hydroxyvitamin D as primary or secondary outcomes were considered eligible. We identified 4 randomized controlled trials (n = 2554) and 11 nonrandomized controlled trials (n = 917) for inclusion in the meta-analysis. Random assignment to weight loss compared with weight maintenance resulted in a greater increase in serum 25-hydroxyvitamin D with a mean difference of 3.11 nmol/L (95% CI: 1.38, 4.84 nmol/L) between groups, whereas a mean difference of 4.85 nmol/L (95% CI: 2.59, 7.12 nmol/L) was observed in nonrandomized trials. No evidence for a dose-response effect of weight loss on the change in serum 25-hydroxyvitamin D was shown overall. Our results indicate that vitamin D status may be marginally improved with weight loss in comparison with weight maintenance under similar conditions of supplemental vitamin D intake. Although additional studies in unsupplemented individuals are needed to confirm these findings, our results support the view that the association between obesity and lower serum 25-hydroxyvitamin D may be due to reversed causation with increased adiposity leading to suboptimal concentrations of circulating vitamin D. This trial was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42015023836. © 2016 American Society for Nutrition.

Grey literature in meta-analyses of randomized trials of health care interventions.

PubMed

Hopewell, S; McDonald, S; Clarke, M; Egger, M

2007-04-18

The inclusion of grey literature (i.e. literature that has not been formally published) in systematic reviews may help to overcome some of the problems of publication bias, which can arise due to the selective availability of data. To review systematically research studies, which have investigated the impact of grey literature in meta-analyses of randomized trials of health care interventions. We searched the Cochrane Methodology Register (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to 20 May 2005), the Science Citation Index (June 2005) and contacted researchers who may have carried out relevant studies. A study was considered eligible for this review if it compared the effect of the inclusion and exclusion of grey literature on the results of a cohort of meta-analyses of randomized trials. Data were extracted from each report independently by two reviewers. The main outcome measure was an estimate of the impact of trials from the grey literature on the pooled effect estimates of the meta-analyses. Information was also collected on the area of health care, the number of meta-analyses, the number of trials, the number of trial participants, the year of publication of the trials, the language and country of publication of the trials, the number and type of grey and published literature, and methodological quality. Five studies met the inclusion criteria. All five studies showed that published trials showed an overall greater treatment effect than grey trials. This difference was statistically significant in one of the five studies. Data could be combined for three of the five studies. This showed that, on average, published trials showed a 9% greater treatment effect than grey trials (ratio of odds ratios for grey versus published trials 1.09; 95% CI 1.03-1.16). Overall there were more published trials included in the meta-analyses than grey trials (median 224 (IQR 108-365) versus 45(IQR 40-102)). Published trials had more participants on average. The most common types of grey literature were abstracts (55%) and unpublished data (30%). There is limited evidence to show whether grey trials are of poorer methodological quality than published trials. This review shows that published trials tend to be larger and show an overall greater treatment effect than grey trials. This has important implications for reviewers who need to ensure they identify grey trials, in order to minimise the risk of introducing bias into their review.

A novel comparative effectiveness study of Tai Chi versus aerobic exercise for fibromyalgia: study protocol for a randomized controlled trial.

PubMed

Wang, Chenchen; McAlindon, Timothy; Fielding, Roger A; Harvey, William F; Driban, Jeffrey B; Price, Lori Lyn; Kalish, Robert; Schmid, Anna; Scott, Tammy M; Schmid, Christopher H

2015-01-30

Fibromyalgia is a chronic musculoskeletal pain syndrome that causes substantial physical and psychological impairment and costs the US healthcare system over $25 billion annually. Current pharmacological therapies may cause serious adverse effects, are expensive, and fail to effectively improve pain and function. Finding new and effective non-pharmacological treatments for fibromyalgia patients is urgently needed. We are currently conducting the first comparative effectiveness randomized trial of Tai Chi versus aerobic exercise (a recommended component of the current standard of care) in a large fibromyalgia population. This article describes the design and conduct of this trial. A single-center, 52-week, randomized controlled trial of Tai Chi versus aerobic exercise is being conducted at an urban tertiary medical center in Boston, Massachusetts. We plan to recruit 216 patients with fibromyalgia. The study population consists of adults ≥21 years of age with fibromyalgia who meet American College of Rheumatology 1990 and 2010 diagnostic criteria. Participants are randomized to one of four Tai Chi intervention groups: 12 or 24 weeks of supervised Tai Chi held once or twice per week, or a supervised aerobic exercise control held twice per week for 24 weeks. The primary outcome is the change in Revised Fibromyalgia Impact Questionnaire total score from baseline to 24 weeks. Secondary outcomes include measures of widespread pain, symptom severity, functional performance, balance, muscle strength and power, psychological functioning, sleep quality, self-efficacy, durability effects, and health-related quality of life at 12, 24, and 52 week follow-up. This study is the first comparative effectiveness randomized trial of Tai Chi versus aerobic exercise in a large fibromyalgia population with long-term follow up. We present here a robust and well-designed trial to determine the optimal frequency and duration of a supervised Tai Chi intervention with regard to short- and long-term effectiveness. The trial also explores multiple outcomes to elucidate the potential mechanisms of Tai Chi and aerobic exercise and the generalizability of these interventions across instructors. Results of this study are expected to have important public health implications for patients with a major disabling disease that incurs substantial health burdens and economic costs. ClinicalTrials.gov identifier: NCT01420640 , registered 18 August 2011.

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.

Methodological Overview of an African American Couple-Based HIV/STD Prevention Trial

PubMed Central

2010-01-01

Objective To provide an overview of the NIMH Multisite HIV/STD Prevention Trial for African American Couples conducted in four urban areas: Atlanta, Los Angeles, New York, and Philadelphia. The rationale, study design methods, proposed data analyses, and study management are described. Design This is a two arm randomized Trial, implementing a modified randomized block design, to evaluate the efficacy of a couples based intervention designed for HIV serodiscordant African American couples. Methods The study phases consisted of formative work, pilot studies, and a randomized clinical trial. The sample is 535 HIV serodiscordant heterosexual African American couples. There are two theoretically derived behavioral interventions with eight group and individual sessions: the Eban HIV/STD Risk Reduction Intervention (treatment) versus the Eban Health Promotion Intervention (control). The treatment intervention was couples based and focused on HIV/STD risk reduction while the control was individual based and focused on health promotion. The two study conditions were structurally similar in length and types of activities. At baseline, participants completed an Audio Computer-assisted Self Interview (ACASI) interview as well as interviewer-administered questionnaire, and provided biological specimens to assess for STDs. Similar follow-up assessments were conducted immediately after the intervention, at 6 months, and at 12 months. Results The Trial results will be analyzed across the four sites by randomization assignment. Generalized estimating equations (GEE) and mixed effects modeling (MEM) are planned to test: (1) the effects of the intervention on STD incidence and condom use as well as on mediator variables of these outcomes, and (2) whether the effects of the intervention differ depending on key moderator variables (e.g., gender of the HIV-seropositive partners, length of relationship, psychological distress, sexual abuse history, and substance abuse history). Conclusions The lessons learned from the design and conduct of this clinical trial provide guidelines for future couples based clinical trials in HIV/STD risk reduction and can be generalized to other couples based behavioral interventions. PMID:18724188

Using the MEDiPORT humanoid robot to reduce procedural pain and distress in children with cancer: A pilot randomized controlled trial.

PubMed

Jibb, Lindsay A; Birnie, Kathryn A; Nathan, Paul C; Beran, Tanya N; Hum, Vanessa; Victor, J Charles; Stinson, Jennifer N

2018-06-12

Subcutaneous port needle insertions are painful and distressing for children with cancer. The interactive MEDiPORT robot has been programmed to implement psychological strategies to decrease pain and distress during this procedure. This study assessed the feasibility of a future MEDiPORT trial. The secondary aim was to determine the preliminary effectiveness of MEDiPORT in reducing child pain and distress during subcutaneous port accesses. This 5-month pilot randomized controlled trial used a web-based service to randomize 4- to 9-year-olds with cancer to the MEDiPORT cognitive-behavioral arm (robot using evidence-based cognitive-behavioral interventions) or active distraction arm (robot dancing and singing) while a nurse conducted a needle insertion. We assessed accrual and retention; technical difficulties; outcome measure completion by children, parents, and nurses; time taken to complete the study and clinical procedure; and child-, parent-, and nurse-rated acceptability. Descriptive analyses, with exploratory inferential testing of child pain and distress data, were used to address study aims. Forty children were randomized across study arms. Most (85%) eligible children participated and no children withdrew. Technical difficulties were more common in the cognitive-behavioral arm. Completion times for the study and needle insertion were acceptable and >96% of outcome measure items were completed. Overall, MEDiPORT and the study were acceptable to participants. There was no difference in pain between arms, but distress during the procedure was less pronounced in the active distraction arm. The MEDiPORT study appears feasible to implement as an adequately-powered effectiveness-assessing trial following modifications to the intervention and study protocol. ClinicalTrials.gov NCT02611739. © 2018 Wiley Periodicals, Inc.

An Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective Randomized Control Trials

PubMed Central

Logan, Jennifer K; Tang, Chad; Liao, Zhongxing; Lee, J. Jack; Heymach, John V.; Swisher, Stephen G.; Welsh, James W.; Zhang, Jianjun; Lin, Steven H.; Gomez, Daniel R.

2018-01-01

Purpose Effective clinical trial enrollment can be difficult in a protocol designs that contain one treatment arm that is perceived as being more “aggressive” or “favorable.” There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to enrollment, particularly the influence of timing, in context of three prospective randomized oncology trials where one arm was considered more aggressive. Methods and materials From June 2011 to March 2015, patients who were enrolled on three prospective institutional protocols (an oligometastatic non-small cell lung cancer (NSCLC) trial, and two proton vs. intensity-modulated radiation therapy (IMRT) trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher’s exact test, Student’s t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results 309 eligible patients were approached about trial enrollment. The enrollment success rate (ESR) during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligomet protocol: 5 vs. 3 appointments (P<0.001), NSCLC protocol: 4 vs. 3 appointments (P = 0.0018), esophageal protocol: 3 vs. 2 appointments (P = 0.0086No other factors or patient characteristics significantly affected ESR. Conclusion Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success, and may help overcome accrual barriers without compromising trial design. PMID:28244413

Hospital Inpatient versus HOme-based rehabilitation after knee arthroplasty (The HIHO study): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Formal rehabilitation programs are often assumed to be required after total knee arthroplasty to optimize patient recovery. Inpatient rehabilitation is a costly rehabilitation option after total knee arthroplasty and, in Australia, is utilized most frequently for privately insured patients. With the exception of comparisons with domiciliary services, no randomized trial has compared inpatient rehabilitation to any outpatient based program. The Hospital Inpatient versus HOme (HIHO) study primarily aims to determine whether 10 days of post-acute inpatient rehabilitation followed by a hybrid home program provides superior recovery of functional mobility on the 6-minute walk test (6MWT) compared to a hybrid home program alone following total knee arthroplasty. Secondarily, the trial aims to determine whether inpatient rehabilitation yields superior recovery in patient-reported function. Methods/Design This is a two-arm parallel randomized controlled trial (RCT), with a third, non-randomized, observational group. One hundred and forty eligible, consenting participants who have undergone a primary total knee arthroplasty at a high-volume joint replacement center will be randomly allocated when cleared for discharge from acute care to either 10 days of inpatient rehabilitation followed by usual care (a 6-week hybrid home program) or to usual care. Seventy participants in each group (140 in total) will provide 80% power at a significance level of 5% to detect an increase in walking capacity from 400 m to 460 m between the Home and Inpatient groups, respectively, in the 6MWT at 6 months post-surgery, assuming a SD of 120 m and a drop-out rate of <10%. The outcome assessor will assess participants at 10, 26 and 52 weeks post-operatively, and will remain blind to group allocation for the duration of the study, as will the statistician. Participant preference for rehabilitation mode stated prior to randomization will be accounted for in the analysis together with any baseline differences in potentially confounding characteristics as required. Discussion The HIHO Trial will be the first RCT to investigate the efficacy of inpatient rehabilitation compared to any outpatient alternative following total knee arthroplasty. Trial registration U.S. National Institutes of Health Clinical Trials Registry (http://clinicaltrials.gov) ref: NCT01583153 PMID:24341348

Use of electronic healthcare records in large-scale simple randomized trials at the point of care for the documentation of value-based medicine.

PubMed

van Staa, T-P; Klungel, O; Smeeth, L

2014-06-01

A solid foundation of evidence of the effects of an intervention is a prerequisite of evidence-based medicine. The best source of such evidence is considered to be randomized trials, which are able to avoid confounding. However, they may not always estimate effectiveness in clinical practice. Databases that collate anonymized electronic health records (EHRs) from different clinical centres have been widely used for many years in observational studies. Randomized point-of-care trials have been initiated recently to recruit and follow patients using the data from EHR databases. In this review, we describe how EHR databases can be used for conducting large-scale simple trials and discuss the advantages and disadvantages of their use. © 2014 The Association for the Publication of the Journal of Internal Medicine.

A randomized controlled trial of the effectiveness of a pre-recruitment primer letter to increase participation in a study of colorectal screening and surveillance.

PubMed

Paul, Christine; Courtney, Ryan; Sanson-Fisher, Rob; Carey, Mariko; Hill, David; Simmons, Jody; Rose, Shiho

2014-04-01

Recruiting cancer patients is a barrier often encountered in research trials. However, very few randomized trials explore strategies to improve participation rates. The purpose of this study was to evaluate the effectiveness of a pre-recruitment primer letter to recruit persons diagnosed with colorectal cancer for a research trial. Potentially eligible participants were identified by the Victorian Cancer Registry. A total of 1,062 participants were randomized to receive either a mailed explanatory primer letter designed to encourage research participation, or no primer letter. Two weeks after the intervention, the Victorian Cancer Registry sought permission from patients to release their contact details to researchers. Those who agreed were contacted and invited to the study. Pre-recruitment encouragement was not effective at increasing recruitment, with no significant differences demonstrated between experimental groups. Overall, 40% (n = 425) consented to participate, 25% (n = 243) refused and 35% (n = 394) did not respond. While this study demonstrated disappointing outcomes, pre-recruitment letters should not be ruled out as an approach altogether. Rather, future research should explore whether other factors to increase motivation, such as intensity and timing, are feasible and acceptable for contacting cancer patients. Australian and New Zealand Clinical Trials Registry, ACTRN12609000628246.

Systematic Review of Integrative Health Care Research: Randomized Control Trials, Clinical Controlled Trials, and Meta-Analysis

DTIC Science & Technology

2010-01-01

to usual care (control). Also, in the pilot study of the 4 individual Noetic therapies, off-site prayer was associated with the lowest absolute...mortality in-hospital and at 6 months [16]. The parallel randomization to 4 different Noetic therapies across 5 study arms limited the assessment of...interventional cardiac care: the Monitoring and Actualisation of Noetic Trainings (MANTRA) II randomised study ,” Lancet, vol. 366, no. 9481, pp. 211–217, 2005. [18

Study protocol of a mixed-methods evaluation of a cluster randomized trial to improve the safety of NSAID and antiplatelet prescribing: data-driven quality improvement in primary care.

PubMed

Grant, Aileen; Dreischulte, Tobias; Treweek, Shaun; Guthrie, Bruce

2012-08-28

Trials of complex interventions are criticized for being 'black box', so the UK Medical Research Council recommends carrying out a process evaluation to explain the trial findings. We believe it is good practice to pre-specify and publish process evaluation protocols to set standards and minimize bias. Unlike protocols for trials, little guidance or standards exist for the reporting of process evaluations. This paper presents the mixed-method process evaluation protocol of a cluster randomized trial, drawing on a framework designed by the authors. This mixed-method evaluation is based on four research questions and maps data collection to a logic model of how the data-driven quality improvement in primary care (DQIP) intervention is expected to work. Data collection will be predominately by qualitative case studies in eight to ten of the trial practices, focus groups with patients affected by the intervention and quantitative analysis of routine practice data, trial outcome and questionnaire data and data from the DQIP intervention. We believe that pre-specifying the intentions of a process evaluation can help to minimize bias arising from potentially misleading post-hoc analysis. We recognize it is also important to retain flexibility to examine the unexpected and the unintended. From that perspective, a mixed-methods evaluation allows the combination of exploratory and flexible qualitative work, and more pre-specified quantitative analysis, with each method contributing to the design, implementation and interpretation of the other.As well as strengthening the study the authors hope to stimulate discussion among their academic colleagues about publishing protocols for evaluations of randomized trials of complex interventions. DATA-DRIVEN QUALITY IMPROVEMENT IN PRIMARY CARE TRIAL REGISTRATION: ClinicalTrials.gov: NCT01425502.

Methods of pushing during vaginal delivery and pelvic floor and perineal outcomes: a review.

PubMed

de Tayrac, Renaud; Letouzey, Vincent

2016-12-01

Over the past 20 years, several randomized studies have compared Valsalva and spontaneous pushing techniques during vaginal delivery. This review summarizes current medical knowledge concerning their maternal and fetal consequences, focusing on pelvic and perineal outcomes. We selected nine randomized controlled trials comparing Valsalva and spontaneous pushing, and a secondary analysis of a randomized controlled trial comparing different methods of perineal protection. Two trials showed that spontaneous pushing reduces the risk of perineal tears, but no firm conclusions can be drawn given the heterogeneity and inconsistent results of these studies. Conflicting results have been reported regarding the duration of the second stage of labor. Pushing technique does not seem to affect episiotomy, instrumental delivery or cesarean rates. Maternal satisfaction seems to be better after spontaneous pushing. Spontaneous pushing appears to have no adverse effects on neonatal well being, and one study showed a significant improvement in prenatal fetal parameters during the expulsive phase. Valsalva and spontaneous pushing techniques currently appear comparable in terms of duration, pelvic floor, perineal, and neonatal outcomes. In the absence of strong evidence in favor of either technique, the decision should be guided by patient preference and the clinical situation. Additional, well-designed randomized controlled trials are required.

Rationale and study design of PROVHILO - a worldwide multicenter randomized controlled trial on protective ventilation during general anesthesia for open abdominal surgery.

PubMed

Hemmes, Sabrine N T; Severgnini, Paolo; Jaber, Samir; Canet, Jaume; Wrigge, Hermann; Hiesmayr, Michael; Tschernko, Edda M; Hollmann, Markus W; Binnekade, Jan M; Hedenstierna, Göran; Putensen, Christian; de Abreu, Marcelo Gama; Pelosi, Paolo; Schultz, Marcus J

2011-05-06

Post-operative pulmonary complications add to the morbidity and mortality of surgical patients, in particular after general anesthesia >2 hours for abdominal surgery. Whether a protective mechanical ventilation strategy with higher levels of positive end-expiratory pressure (PEEP) and repeated recruitment maneuvers; the "open lung strategy", protects against post-operative pulmonary complications is uncertain. The present study aims at comparing a protective mechanical ventilation strategy with a conventional mechanical ventilation strategy during general anesthesia for abdominal non-laparoscopic surgery. The PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure ("PROVHILO") trial is a worldwide investigator-initiated multicenter randomized controlled two-arm study. Nine hundred patients scheduled for non-laparoscopic abdominal surgery at high or intermediate risk for post-operative pulmonary complications are randomized to mechanical ventilation with the level of PEEP at 12 cmH(2)O with recruitment maneuvers (the lung-protective strategy) or mechanical ventilation with the level of PEEP at maximum 2 cmH(2)O without recruitment maneuvers (the conventional strategy). The primary endpoint is any post-operative pulmonary complication. The PROVHILO trial is the first randomized controlled trial powered to investigate whether an open lung mechanical ventilation strategy in short-term mechanical ventilation prevents against postoperative pulmonary complications. ISRCTN: ISRCTN70332574.

Randomized Trial of Behavioral Activation, Cognitive Therapy, and Antidepressant Medication in the Prevention of Relapse and Recurrence in Major Depression

ERIC Educational Resources Information Center

Dobson, Keith S.; Hollon, Steven D.; Dimidjian, Sona; Schmaling, Karen B.; Kohlenberg, Robert J.; Gallop, Robert J.; Rizvi, Shireen L.; Gollan, Jackie K.; Dunner, David L.; Jacobson, Neil S.

2008-01-01

This study followed treatment responders from a randomized controlled trial of adults with major depression. Patients treated with medication but withdrawn onto pill-placebo had more relapse through 1 year of follow-up compared to patients who received prior behavioral activation, prior cognitive therapy, or continued medication. Prior…

Alcohol-Specific Parenting within a Cluster-Randomized Effectiveness Trial of a Swedish Primary Prevention Program

ERIC Educational Resources Information Center

Strandberg, Anna K.; Bodin, Maria C.

2011-01-01

Purpose: Within the framework of an ongoing cluster-randomized effectiveness trial of a parental prevention program, the aim of the present study is to investigate attitudes towards under-age drinking and use of program components, i.e. alcohol-specific parenting behaviors, in parents who did and did not take part in the programme.…

The YouthMood Project: A Cluster Randomized Controlled Trial of an Online Cognitive Behavioral Program with Adolescents

ERIC Educational Resources Information Center

Calear, Alison L.; Christensen, Helen; Mackinnon, Andrew; Griffiths, Kathleen M.; O'Kearney, Richard

2009-01-01

The aim in the current study was to investigate the effectiveness of an online, self-directed cognitive-behavioral therapy program (MoodGYM) in preventing and reducing the symptoms of anxiety and depression in an adolescent school-based population. A cluster randomized controlled trial was conducted with 30 schools (N = 1,477) from across…

Installing the Communities that Care Prevention System: Implementation Progress and Fidelity in a Randomized Controlled Trial

ERIC Educational Resources Information Center

Quinby, Rose K.; Hanson, Koren; Brooke-Weiss, Blair; Arthur, Michael W.; Hawkins, J. David; Fagan, Abigail A.

2008-01-01

This article describes the degree to which high fidelity implementation of the Communities That Care (CTC) prevention operating system was reached during the first 18 months of intervention in 12 communities in the Community Youth Development Study, a 5-year group randomized controlled trial designed to test the efficacy of the CTC system. CTC…

A Multicenter, Randomized Clinical Trial of a Cognitive Remediation Program for Childhood Survivors of a Pediatric Malignancy

ERIC Educational Resources Information Center

Butler, Robert W.; Copeland, Donna R.; Fairclough, Diane L.; Mulhern, Raymond K.; Katz, Ernest R.; Kazak, Anne E.; Noll, Robert B.; Patel, Sunita K.; Sahler, Olle Jane Z.

2008-01-01

Survivors of childhood cancer whose malignancy and/or treatment involved the central nervous system may demonstrate a consistent pattern of neurocognitive deficits. The present study evaluated a randomized clinical trial of the Cognitive Remediation Program (CRP). Participants were 6- to 17-year-old survivors of childhood cancer (N = 161; 35%…

Examination of Individual Differences in Outcomes from a Randomized Controlled Clinical Trial Comparing Formal and Informal Individual Auditory Training Programs

ERIC Educational Resources Information Center

Smith, Sherri L.; Saunders, Gabrielle H.; Chisolm, Theresa H.; Frederick, Melissa; Bailey, Beth A.

2016-01-01

Purpose: The purpose of this study was to determine if patient characteristics or clinical variables could predict who benefits from individual auditory training. Method: A retrospective series of analyses were performed using a data set from a large, multisite, randomized controlled clinical trial that compared the treatment effects of at-home…

Assessment Data-Informed Guidance to Individualize Kindergarten Reading Instruction: Findings from a Cluster-Randomized Control Field Trial

ERIC Educational Resources Information Center

Al Otaiba, Stephanie; Connor, Carol M.; Folsom, Jessica S.; Greulich, Luana; Meadows, Jane; Li, Zhi

2011-01-01

The purpose of this cluster-randomized control field trial was to examine whether kindergarten teachers could learn to differentiate classroom reading instruction using Individualized Student Instruction for Kindergarten (ISI-K) and to test the efficacy of differentiation on reading outcomes. The study involved 14 schools, 23 ISI-K (n = 305…

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…

Cognitive Behavioral Treatment of PTSD in Residents of Battered Women's Shelters: Results of a Randomized Clinical Trial

ERIC Educational Resources Information Center

Johnson, Dawn M.; Zlotnick, Caron; Perez, Sara

2011-01-01

Objective: This study was designed to explore the acceptability, feasibility, and initial efficacy of a new shelter-based treatment for victims of intimate partner violence (IPV; i.e., Helping to Overcome PTSD through Empowerment [HOPE]). Method: A Phase I randomized clinical trial comparing HOPE (n = 35) with standard shelter services (SSS) (n =…

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…

Parent Training with High-Risk Immigrant Chinese Families: A Pilot Group Randomized Trial Yielding Practice-Based Evidence

ERIC Educational Resources Information Center

Lau, Anna S.; Fung, Joey J.; Ho, Lorinda Y.; Liu, Lisa L.; Gudino, Omar G.

2011-01-01

We studied the efficacy and implementation outcomes of a culturally responsive parent training (PT) program. Fifty-four Chinese American parents participated in a wait-list controlled group randomized trial (32 immediate treatment, 22 delayed treatment) of a 14-week intervention designed to address the needs of high-risk immigrant families.…

Reducing Conduct Problems among Children Exposed to Intimate Partner Violence: A Randomized Clinical Trial Examining Effects of Project Support

ERIC Educational Resources Information Center

Jouriles, Ernest N.; McDonald, Renee; Rosenfield, David; Stephens, Nanette; Corbitt-Shindler, Deborah; Miller, Pamela C.

2009-01-01

This study was a randomized clinical trial of Project Support, an intervention designed to reduce conduct problems among children exposed to intimate partner violence. Participants were 66 families (mothers and children) with at least 1 child exhibiting clinical levels of conduct problems. Families were recruited from domestic violence shelters.…

Experiences Recruiting Indian Worksites for an Integrated Health Protection and Health Promotion Randomized Control Trial in Maharashtra, India

ERIC Educational Resources Information Center

Shulman Cordeira, L.; Pednekar, M. S.; Nagler, E. M.; Gautam, J.; Wallace, L.; Stoddard, A. M.; Gupta, P. C.; Sorensen, G. C.

2015-01-01

This article provides an overview of the recruitment strategies utilized in the Mumbai Worksites Tobacco Control Study, a cluster randomized trial testing the effectiveness of an integrated tobacco control and occupational safety and health program in Indian manufacturing worksites. From June 2012 to June 2013, 20 companies were recruited.…

Randomized Trial of Treatment for Children with Sexual Behavior Problems: Ten-Year Follow-Up

ERIC Educational Resources Information Center

Carpentier, Melissa Y.; Silovsky, Jane F.; Chaffin, Mark

2006-01-01

This study prospectively follows 135 children 5-12 years of age with sexual behavior problems from a randomized trial comparing a 12-session group cognitive-behavioral therapy (CBT) with group play therapy and follows 156 general clinic children with nonsexual behavior problems. Ten-year follow-up data on future juvenile and adult arrests and…

A Parent-Mediated Intervention that Targets Responsive Parental Behaviors Increases Attachment Behaviors in Children with ASD: Results from a Randomized Clinical Trial

ERIC Educational Resources Information Center

Siller, Michael; Swanson, Meghan; Gerber, Alan; Hutman, Ted; Sigman, Marian

2014-01-01

The current study is a randomized clinical trial evaluating the efficacy of Focused Playtime Intervention (FPI) in a sample of 70 children with Autism Spectrum Disorder. This parent-mediated intervention has previously been shown to significantly increase responsive parental communication (Siller et al. in "J Autism Dev Disord"…

A Clustered Randomized Controlled Trial to Determine Impacts of the Harvest of the Month Program

ERIC Educational Resources Information Center

LaChausse, Robert G.

2017-01-01

The study purpose was to examine the impact of the Harvest of the Month (HOTM) program on fruit and vegetable (FV) consumption, FV preferences, other eating behaviors, physical activity and other variables related to healthy eating. A clustered randomized controlled trial was employed in 28 elementary schools. After parental consent was obtained,…

Intervention for First Graders with Limited Number Knowledge: Large-Scale Replication of a Randomized Controlled Trial

ERIC Educational Resources Information Center

Gersten, Russell; Rolfhus, Eric; Clarke, Ben; Decker, Lauren E.; Wilkins, Chuck; Dimino, Joseph

2015-01-01

Replication studies are extremely rare in education. This randomized controlled trial (RCT) is a scale-up replication of Fuchs et al., which in a sample of 139 found a statistically significant positive impact for Number Rockets, a small-group intervention for at-risk first graders that focused on building understanding of number operations. The…

Benefits and Harms of Sick Leave: Lack of Randomized, Controlled Trials

ERIC Educational Resources Information Center

Axelsson, Inge; Marnetoft, Sven-Uno

2010-01-01

The aim of this study was to try to identify those randomized controlled trials that compare sick leave with no sick leave or a different duration or degree of sick leave. A comprehensive, systematic, electronic search of Clinical Evidence, the Cochrane Library and PubMed, and a manual search of the Campbell Library and a journal supplement was…

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…

Pathways to Health: A Cluster Randomized Trial of Nicotine Gum and Motivational Interviewing for Smoking Cessation in Low-Income Housing

ERIC Educational Resources Information Center

Okuyemi, Kolawole S.; James, Aimee S.; Mayo, Matthew S.; Nollen, Nicole; Catley, Delwyn; Choi, Won S.; Ahluwalia, Jasjit S.

2007-01-01

Despite high smoking rates among those living in poverty, few cessation studies are conducted in these populations. This cluster-randomized trial tested nicotine gum plus motivational interviewing (MI) for smoking cessation in 20 low-income housing developments (HDs). Intervention participants (10 HDs, n = 66) received educational materials, 8…

Canadian Phase III Randomized Trial of Stereotactic Body Radiotherapy Versus Conventionally Hypofractionated Radiotherapy for Stage I, Medically Inoperable Non-Small-Cell Lung Cancer - Rationale and Protocol Design for the Ontario Clinical Oncology Group (OCOG)-LUSTRE Trial.

PubMed

Swaminath, Anand; Wierzbicki, Marcin; Parpia, Sameer; Wright, James R; Tsakiridis, Theodoros K; Okawara, Gordon S; Kundapur, Vijayananda; Bujold, Alexis; Ahmed, Naseer; Hirmiz, Khalid; Kurien, Elizabeth; Filion, Edith; Gabos, Zsolt; Faria, Sergio; Louie, Alexander V; Owen, Timothy; Wai, Elaine; Ramchandar, Kevin; Chan, Elisa K; Julian, Jim; Cline, Kathryn; Whelan, Timothy J

2017-03-01

We describe a Canadian phase III randomized controlled trial of stereotactic body radiotherapy (SBRT) versus conventionally hypofractionated radiotherapy (CRT) for the treatment of stage I medically inoperable non-small-cell lung cancer (OCOG-LUSTRE Trial). Eligible patients are randomized in a 2:1 fashion to either SBRT (48 Gy in 4 fractions for peripherally located lesions; 60 Gy in 8 fractions for centrally located lesions) or CRT (60 Gy in 15 fractions). The primary outcome of the study is 3-year local control, which we hypothesize will improve from 75% with CRT to 87.5% with SBRT. With 85% power to detect a difference of this magnitude (hazard ratio = 0.46), a 2-sided α = 0.05 and a 2:1 randomization, we require a sample size of 324 patients (216 SBRT, 108 CRT). Important secondary outcomes include overall survival, disease-free survival, toxicity, radiation-related treatment death, quality of life, and cost-effectiveness. A robust radiation therapy quality assurance program has been established to assure consistent and high quality SBRT and CRT delivery. Despite widespread interest and adoption of SBRT, there still remains a concern regarding long-term control and risks of toxicity (particularly in patients with centrally located lesions). The OCOG-LUSTRE study is the only randomized phase III trial testing SBRT in a medically inoperable population, and the results of this trial will attempt to prove that the benefits of SBRT outweigh the potential risks. Copyright © 2016 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.

Prevalence and factors associated with use of placebo control groups in randomized controlled trials in psoriasis: a cross-sectional study.

PubMed

Katz, Kenneth A; Karlawish, Jason H; Chiang, David S; Bognet, Rachel A; Propert, Katherine J; Margolis, David J

2006-11-01

The ethics and science of using placebo control groups in clinical trials have been widely debated. Few studies, however, have examined factors associated with choice of control group. Our aim was to assess the prevalence of use of placebo controls in randomized controlled trials in psoriasis and to identify factors associated with use of placebo controls in these trials. This is a cross-sectional study of randomized controlled trials in psoriasis published from January 1, 2001 to December 20, 2005 and indexed in the Cochrane Central Register of Controlled Trials. We extracted data on types of control groups used, design issues (number of patients enrolled, primary end point), disease characteristics (psoriasis type and severity), and extrascientific issues (trial location, funding source, and year of publication). We used bivariable and multivariable logistic regression to determine factors associated with use of a placebo control group. Of 194 citations, 187 were available for review. One hundred thirty-five trials from 134 articles in 38 journals met inclusion criteria. Eighty-three trials (61.5%) enrolling 8171 subjects (41.7%) used active controls only, and 52 trials (38.5%) enrolling 11,406 subjects (58.3%) used placebo controls. Adjusted for trial location and funding source, trials significantly more likely to have used placebo controls included those conducted in the United States (odds ratio [OR], 5.79; 95% confidence interval [CI], 2.45-13.68; P < .001) and those funded by pharmaceutical companies (OR, 2.61; 95% CI, 1.19-5.73; P = .02). Predicted frequencies of placebo use ranged from 77.6% (industry-funded, conducted trials in the United States) to 18.6% (non-industry-funded trials not conducted in the United States). Our searches may not have identified all published trials, and we did not have access to data from unpublished trials. Use of placebo controls has been more common in psoriasis trials conducted in the United States and funded by pharmaceutical companies. The findings suggest that ethical and scientific issues related to choice of control group in psoriasis trials are interpreted markedly differently depending on trial location and funding source.

A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics.

PubMed

Koethe, John R; Westfall, Andrew O; Luhanga, Dora K; Clark, Gina M; Goldman, Jason D; Mulenga, Priscilla L; Cantrell, Ronald A; Chi, Benjamin H; Zulu, Isaac; Saag, Michael S; Stringer, Jeffrey S A

2010-03-12

The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree). Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months. From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites. A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings. Clinicaltrials.gov NCT00929604.

Design and challenges of a randomized controlled trial for reducing risk factors of metabolic syndrome in Mexican women through water intake

PubMed Central

Hernández-Cordero, Sonia; González-Castell, Dinorah; Rodríguez-Ramírez, Sonia; Villanueva-Borbolla, María Ángeles; Unar, Mishel; Barquera, Simón; de Cossío, Teresita González; Rivera-Dommarco, Juan; Popkin, Barry M

2014-01-01

Objective To describe the design, methods, and challenges encountered during a randomized clinical trial aimed to promote water intake for reducing risks of metabolic syndrome in Mexican women. Materials and methods In a randomized clinical trial in Cuernavaca, Mexico, overweight and obese (body mass index [BMI] ≥ 25 < 39) women, 18 – < 45 years old with an intake of sugar-sweetened beverages ≥ 250 kilocalories per day (kcal/day) were randomly allocated to the water and education provision group (n = 120) or the education provision only group (n = 120). Results We screened 1 756 women. The main difficulties encountered were identifying participants with the recruitment criteria, delivering water to participants, and the time demanded from the study participants. Conclusions The trial’s main challenges were difficulties surrounding recruitment, delivery of the intervention, and the time demanded from the study participants. Modifications were effectively implemented without jeopardizing the original protocol. PMID:24715012

Effect of intervention programs in schools to reduce screen time: a meta-analysis.

PubMed

Friedrich, Roberta Roggia; Polet, Jéssica Pinto; Schuch, Ilaine; Wagner, Mário Bernardes

2014-01-01

to evaluate the effects of intervention program strategies on the time spent on activities such as watching television, playing videogames, and using the computer among schoolchildren. a search for randomized controlled trials available in the literature was performed in the following electronic databases: PubMed, Lilacs, Embase, Scopus, Web of Science, and Cochrane Library using the following Keywords randomized controlled trial, intervention studies, sedentary lifestyle, screen time, and school. A summary measure based on the standardized mean difference was used with a 95% confidence interval. a total of 1,552 studies were identified, of which 16 were included in the meta-analysis. The interventions in the randomized controlled trials (n=8,785) showed a significant effect in reducing screen time, with a standardized mean difference (random effect) of: -0.25 (-0.37, -0.13), p<0.01. interventions have demonstrated the positive effects of the decrease of screen time among schoolchildren. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Selective decontamination of the digestive tract in gastrointestinal surgery: useful in infection prevention? A systematic review.

PubMed

Abis, Gabor S A; Stockmann, Hein B A C; van Egmond, Marjolein; Bonjer, Hendrik J; Vandenbroucke-Grauls, Christina M J E; Oosterling, Steven J

2013-12-01

Gastrointestinal surgery is associated with a high incidence of infectious complications. Selective decontamination of the digestive tract is an antimicrobial prophylaxis regimen that aims to eradicate gastrointestinal carriage of potentially pathogenic microorganisms and represents an adjunct to regular prophylaxis in surgery. Relevant studies were identified using bibliographic searches of MEDLINE, EMBASE, and the Cochrane database (period from 1970 to November 1, 2012). Only studies investigating selective decontamination of the digestive tract in gastrointestinal surgery were included. Two randomized clinical trials and one retrospective case-control trial showed significant benefit in terms of infectious complications and anastomotic leakage in colorectal surgery. Two randomized controlled trials in esophageal surgery and two randomized clinical trials in gastric surgery reported lower levels of infectious complications. Selective decontamination of the digestive tract reduces infections following esophageal, gastric, and colorectal surgeries and also appears to have beneficial effects on anastomotic leakage in colorectal surgery. We believe these results provide the basis for a large multicenter prospective study to investigate the role of selective decontamination of the digestive tract in colorectal surgery.

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.

Role of Internal Mammary Node Radiation as a Part of Modern Breast Cancer Radiation Therapy: A Systematic Review

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

Verma, Vivek; Vicini, Frank; Tendulkar, Rahul D.

Purpose: Despite data from multiple randomized trials, the role of internal mammary lymph node irradiation as a part of regional nodal irradiation (IMLN RT–RNI) remains unanswered. Recent noteworthy data and modern RT techniques might identify a subset of patients who will benefit from IMLN RT–RNI, lending insight into the balance between improved outcomes and acceptable toxicity. We evaluated the current role of IMLN RT–RNI by analyzing randomized, prospective, and retrospective data. Methods and Materials: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a review of the published data was performed using PubMed to evaluate publishedmore » studies from 1994 to 2015. The information evaluated included the number of patients, follow-up period, technical aspects of RT, and outcomes (clinical outcomes, complications/toxicity). Results: We included 16 studies (4 randomized, 4 nonrandomized, 7 retrospective, and 1 meta-analysis). Although older randomized trials failed to show differences in clinical outcomes or toxicity with IMLN RT–RNI, recent randomized data suggest the potential for improved outcomes, including overall survival, with IMLN RT–RNI. Furthermore, nonrandomized data have suggested a potential benefit for central tumors with IMLN RT–RNI. Although recent data have suggested a potential increase in pulmonary complications with IMLN RT–RNI with the use of advanced radiation techniques, toxicity rates remain low with limited cardiac toxicity data available. Conclusions: Increasing data from recent randomized trials support the use of IMLN RT–RNI. IMLN RT can be considered based on the inclusion of IMLN RT as a part of RNI in recent trials and the inclusion criteria from IMLN RT–RNI trials and for patients with central or medial tumors and axillary disease.« less

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

Patent foramen ovale closure and medical treatments for secondary stroke prevention: a systematic review of observational and randomized evidence.

PubMed

Kitsios, Georgios D; Dahabreh, Issa J; Abu Dabrh, Abd Moain; Thaler, David E; Kent, David M

2012-02-01

Patients discovered to have a patent foramen ovale in the setting of a cryptogenic stroke may be treated with percutaneous closure, antiplatelet therapy, or anticoagulants. A recent randomized trial (CLOSURE I) did not detect any benefit of closure over medical treatment alone; the optimal medical therapy is also unknown. We synthesized the available evidence on secondary stroke prevention in patients with patent foramen ovale and cryptogenic stroke. A MEDLINE search was performed for finding longitudinal studies investigating medical treatment or closure, meta-analysis of incidence rates (IR), and IR ratios of recurrent cerebrovascular events. Fifty-two single-arm studies and 7 comparative nonrandomized studies and the CLOSURE I trial were reviewed. The summary IR of recurrent stroke was 0.36 events (95% confidence interval [CI], 0.24-0.56) per 100 person-years with closure versus 2.53 events (95% CI, 1.91-3.35) per 100 person-years with medical therapy. In comparative observational studies, closure was superior to medical therapy (IR ratio=0.19; 95% CI, 0.07-0.54). The IR for the closure arm of the CLOSURE I trial was higher than the summary estimate from observational studies; there was no significant benefit of closure over medical treatment (P=0.002 comparing efficacy estimates between observational studies and the trial). Observational and randomized data (9 studies) comparing medical therapies were consistent and suggested that anticoagulants are superior to antiplatelets for preventing stroke recurrence (IR ratio=0.42; 95% CI, 0.18-0.98). Although further randomized trial data are needed to precisely determine the effects of closure on stroke recurrence, the results of CLOSURE I challenge the credibility of a substantial body of observational evidence strongly favoring mechanical closure over medical therapy.

Propensity Score Matching: Retrospective Randomization?

PubMed

Jupiter, Daniel C

Randomized controlled trials are viewed as the optimal study design. In this commentary, we explore the strength of this design and its complexity. We also discuss some situations in which these trials are not possible, or not ethical, or not economical. In such situations, specifically, in retrospective studies, we should make every effort to recapitulate the rigor and strength of the randomized trial. However, we could be faced with an inherent indication bias in such a setting. Thus, we consider the tools available to address that bias. Specifically, we examine matching and introduce and explore a new tool: propensity score matching. This tool allows us to group subjects according to their propensity to be in a particular treatment group and, in so doing, to account for the indication bias. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Thromboprophylaxis using combined intermittent pneumatic compression and pharmacologic prophylaxis versus pharmacologic prophylaxis alone in critically ill patients: study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen M; Alsolamy, Sami; Al-Dawood, Abdulaziz; Al-Omari, Awad; Al-Hameed, Fahad; Burns, Karen E A; Almaani, Mohammed; Lababidi, Hani; Al Bshabshe, Ali; Mehta, Sangeeta; Al-Aithan, Abdulsalam M; Mandourah, Yasser; Almekhlafi, Ghaleb; Finfer, Simon; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Sadat, Musharaf

2016-08-03

Venous thromboembolism (VTE) remains a common problem in critically ill patients. Pharmacologic prophylaxis is currently the standard of care based on high-level evidence from randomized controlled trials. However, limited evidence exists regarding the effectiveness of intermittent pneumatic compression (IPC) devices. The Pneumatic compREssion for preventing VENous Thromboembolism (PREVENT trial) aims to determine whether the adjunct use of IPC with pharmacologic prophylaxis compared to pharmacologic prophylaxis alone in critically ill patients reduces the risk of VTE. The PREVENT trial is a multicenter randomized controlled trial, which will recruit 2000 critically ill patients from over 20 hospitals in three countries. The primary outcome is the incidence of proximal lower extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the scans are blinded to intervention allocation, whereas the patients and caregivers are unblinded. The trial has 80 % power to detect a 3 % absolute risk reduction in proximal DVT from 7 to 4 %. The first patient was enrolled in July 2014. As of May 2015, a total of 650 patients have been enrolled from 13 centers in Saudi Arabia, Canada and Australia. The first interim analysis is anticipated in July 2016. We expect to complete recruitment by 2018. Clinicaltrials.gov: NCT02040103 (registered on 3 November 2013). Current controlled trials: ISRCTN44653506 (registered on 30 October 2013).

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

Recruitment and accrual of women in a placebo-controlled clinical pilot study on manual therapy.

PubMed

Cambron, Jerrilyn A; Hawk, Cheryl; Evans, Roni; Long, Cynthia R

2004-06-01

To investigate the accrual rates and recruitment processes among 3 Midwestern sites during a pilot study on manual therapy for chronic pelvic pain. Multisite pilot study for a randomized, placebo-controlled clinical trial. Three chiropractic institutions in or near major metropolitan cities in the Midwestern United States. Thirty-nine women aged 18 to 45 with chronic pelvic pain of at least 6 months duration, diagnosed by a board certified gynecologist. The method of recruitment was collected for each individual who responded to an advertisement and completed an interviewer-administered telephone screen. Participants who were willing and eligible after 3 baseline visits were entered into a randomized clinical trial. The number of responses and accrual rates were determined for the overall study, each of the 3 treatment sites, and each of the 5 recruitment efforts. In this study, 355 women were screened over the telephone and 39 were randomized, making the rate of randomization approximately 10%. The most effective recruitment methods leading to randomization were direct mail (38%) and radio advertisements (34%). However, success of the recruitment process differed by site. Based on the accrual of this multisite pilot study, a full-scale trial would not be feasible using this study's parameters. However, useful information was gained on recruitment effectiveness, eligibility criteria, and screening protocols among the 3 metropolitan sites.

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.

Relapse prevention interventions for smoking cessation.

PubMed

Hajek, Peter; Stead, Lindsay F; West, Robert; Jarvis, Martin; Hartmann-Boyce, Jamie; Lancaster, Tim

2013-08-20

A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been proposed to help prevent relapse. To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. We searched the Cochrane Tobacco Addiction Group trials register in May 2013 for studies mentioning relapse prevention or maintenance in title, abstracts or keywords. Randomized or quasi-randomized controlled trials of relapse prevention interventions with a minimum follow-up of six months. We included smokers who quit on their own, were undergoing enforced abstinence, or were participating in treatment programmes. We included trials that compared relapse prevention interventions with a no intervention control, or that compared a cessation programme with additional relapse prevention components with a cessation programme alone. Studies were screened and data extracted by one review author, and checked by a second. Disagreements were resolved by discussion or by referral to a third review author. Sixty-three studies met inclusion criteria but were heterogeneous in terms of populations and interventions. We considered 41 studies that randomly assigned abstainers separately from studies that randomly assigned participants before their quit date.Upon looking at studies of behavioural interventions that randomly assigned abstainers, we detected no benefit of brief and 'skills-based' relapse prevention methods for women who had quit smoking because of pregnancy, or for smokers undergoing a period of enforced abstinence during hospitalisation or military training. We also failed to detect significant effects of behavioural interventions in trials in unselected groups of smokers who had quit on their own or through a formal programme. Amongst trials randomly assigning smokers before their quit date and evaluating the effects of additional relapse prevention components, we found no evidence of benefit of behavioural interventions or combined behavioural and pharmacotherapeutic interventions in any subgroup. Overall, providing training in skills thought to be needed for relapse avoidance did not reduce relapse, but most studies did not use experimental designs best suited to the task and had limited power to detect expected small differences between interventions. For pharmacological interventions, extended treatment with varenicline significantly reduced relapse in one trial (risk ratio (RR) 1.18, 95% confidence interval (CI) 1.03 to 1.36). Pooling of six studies of extended treatment with bupropion failed to detect a significant effect (RR 1.15, 95% CI 0.98 to 1.35). Two small trials of oral nicotine replacement treatment (NRT) failed to detect an effect, but treatment compliance was low, and in two other trials of oral NRT in which short-term abstainers were randomly assigned, a significant effect of intervention was noted. At the moment, there is insufficient evidence to support the use of any specific behavioural intervention to help smokers who have successfully quit for a short time to avoid relapse. The verdict is strongest for interventions focused on identifying and resolving tempting situations, as most studies were concerned with these. Little research is available regarding other behavioural approaches.Extended treatment with varenicline may prevent relapse. Extended treatment with bupropion is unlikely to have a clinically important effect. Studies of extended treatment with nicotine replacement are needed.

Bayesian randomized clinical trials: From fixed to adaptive design.

PubMed

Yin, Guosheng; Lam, Chi Kin; Shi, Haolun

2017-08-01

Randomized controlled studies are the gold standard for phase III clinical trials. Using α-spending functions to control the overall type I error rate, group sequential methods are well established and have been dominating phase III studies. Bayesian randomized design, on the other hand, can be viewed as a complement instead of competitive approach to the frequentist methods. For the fixed Bayesian design, the hypothesis testing can be cast in the posterior probability or Bayes factor framework, which has a direct link to the frequentist type I error rate. Bayesian group sequential design relies upon Bayesian decision-theoretic approaches based on backward induction, which is often computationally intensive. Compared with the frequentist approaches, Bayesian methods have several advantages. The posterior predictive probability serves as a useful and convenient tool for trial monitoring, and can be updated at any time as the data accrue during the trial. The Bayesian decision-theoretic framework possesses a direct link to the decision making in the practical setting, and can be modeled more realistically to reflect the actual cost-benefit analysis during the drug development process. Other merits include the possibility of hierarchical modeling and the use of informative priors, which would lead to a more comprehensive utilization of information from both historical and longitudinal data. From fixed to adaptive design, we focus on Bayesian randomized controlled clinical trials and make extensive comparisons with frequentist counterparts through numerical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Guidance and examination by ultrasound versus landmark and radiographic method for placement of subclavian central venous catheters: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Central venous catheters play an important role in patient care. Real-time ultrasound-guided subclavian central venous (SCV) cannulation may reduce the incidence of complications and the time between skin penetration and the aspiration of venous blood into the syringe. Ultrasonic diagnosis of catheter misplacement and pneumothorax related to central venous catheterization is rapid and accurate. It is unclear, however, whether ultrasound real-time guidance and examination can reduce procedure times and complication rates when compared with landmark guidance and radiographic examination for SCV catheterization. Methods/Design The Subclavian Central Venous Catheters Guidance and Examination by UltraSound (SUBGEUS) study is an investigator-initiated single center, randomized, controlled two-arm trial. Three hundred patients undergoing SCV catheter placement will be randomized to ultrasound real-time guidance and examination or landmark guidance and radiographic examination. The primary outcome is the time between the beginning of the procedure and control of the catheter. Secondary outcomes include the times required for the six components of the total procedure, the occurrence of complications (pneumothorax, hemothorax, or misplacement), failure of the technique and occurrence of central venous catheter infections. Discussion The SUBGEUS trial is the first randomized controlled study to investigate whether ultrasound real-time guidance and examination for SCV catheter placement reduces all procedure times and the rate of complications. Trial registration ClinicalTrials.gov Identifier: NCT01888094 PMID:24885789

Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies.

PubMed

Moran, T; Wei, J; Cobo, M; Qian, X; Domine, M; Zou, Z; Bover, I; Wang, L; Provencio, M; Yu, L; Chaib, I; You, C; Massuti, B; Song, Y; Vergnenegre, A; Lu, H; Lopez-Vivanco, G; Hu, W; Robinet, G; Yan, J; Insa, A; Xu, X; Majem, M; Chen, X; de Las Peñas, R; Karachaliou, N; Sala, M A; Wu, Q; Isla, D; Zhou, Y; Baize, N; Zhang, F; Garde, J; Germonpre, P; Rauh, S; ALHusaini, H; Sanchez-Ronco, M; Drozdowskyj, A; Sanchez, J J; Camps, C; Liu, B; Rosell, R

2014-11-01

In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS). Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82). Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches. NCT00617656/GECP-BREC and ChiCTR-TRC-12001860/BREC-CHINA. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

The effectiveness of foot reflexology in inducing ovulation: a sham-controlled randomized trial.

PubMed

Holt, Jane; Lord, Jonathan; Acharya, Umesh; White, Adrian; O'Neill, Nyree; Shaw, Steve; Barton, Andy

2009-06-01

To determine whether foot reflexology, a complementary therapy, has an effect greater than sham reflexology on induction of ovulation. Sham-controlled randomized trial with patients and statistician blinded. Infertility clinic in Plymouth, United Kingdom. Forty-eight women attending the clinic with anovulation. Women were randomized to receive eight sessions of either genuine foot reflexology or sham reflexology with gentle massage over 10 weeks. The primary outcome was ovulation detected by serum progesterone level of >30 nmol/L during the study period. Twenty-six patients were randomized to genuine reflexology and 22 to sham (one randomized patient was withdrawn). Patients remained blinded throughout the trial. The rate of ovulation during true reflexology was 11 out of 26 (42%), and during sham reflexology it was 10 out of 22 (46%). Pregnancy rates were 4 out of 26 in the true group and 2 out of 22 in the control group. Because of recruitment difficulties, the required sample size of 104 women was not achieved. Patient blinding of reflexology studies is feasible. Although this study was too small to reach a definitive conclusion on the specific effect of foot reflexology, the results suggest that any effect on ovulation would not be clinically relevant. Sham reflexology may have a beneficial general effect, which this study was not designed to detect.

Glutamine Randomized Studies in Early Life: The Unsolved Riddle of Experimental and Clinical Studies

PubMed Central

Briassouli, Efrossini; Briassoulis, George

2012-01-01

Glutamine may have benefits during immaturity or critical illness in early life but its effects on outcome end hardpoints are controversial. Our aim was to review randomized studies on glutamine supplementation in pups, infants, and children examining whether glutamine affects outcome. Experimental work has proposed various mechanisms of glutamine action but none of the randomized studies in early life showed any effect on mortality and only a few showed some effect on inflammatory response, organ function, and a trend for infection control. Although apparently safe in animal models (pups), premature infants, and critically ill children, glutamine supplementation does not reduce mortality or late onset sepsis, and its routine use cannot be recommended in these sensitive populations. Large prospectively stratified trials are needed to better define the crucial interrelations of “glutamine-heat shock proteins-stress response” in critical illness and to identify the specific subgroups of premature neonates and critically ill infants or children who may have a greater need for glutamine and who may eventually benefit from its supplementation. The methodological problems noted in the reviewed randomized experimental and clinical trials should be seriously considered in any future well-designed large blinded randomized controlled trial involving glutamine supplementation in critical illness. PMID:23019424

The C-seal trial: colorectal anastomosis protected by a biodegradable drain fixed to the anastomosis by a circular stapler, a multi-center randomized controlled trial

PubMed Central

2012-01-01

Background Anastomotic leakage is a major complication in colorectal surgery and with an incidence of 11% the most common cause of morbidity and mortality. In order to reduce the incidence of anastomotic leakage the C-seal is developed. This intraluminal biodegradable drain is stapled to the anastomosis with a circular stapler and prevents extravasation of intracolonic content in case of an anastomotic dehiscence. The aim of this study is to evaluate the efficacy of the C-seal in reducing anastomotic leakage in stapled colorectal anastomoses, as assessed by anastomotic leakage leading to invasive treatment within 30 days postoperative. Methods The C-seal trial is a prospective multi-center randomized controlled trial with primary endpoint, anastomotic leakage leading to re-intervention within 30 days after operation. In this trial 616 patients will be randomized to the C-seal or control group (1:1), stratified by center, anastomotic height (proximal or distal of peritoneal reflection) and the intention to create a temporary deviating ostomy. Interim analyses are planned after 50% and 75% of patient inclusion. Eligible patients are at least 18 years of age, have any colorectal disease requiring a colorectal anastomosis to be made with a circular stapler in an elective setting, with an ASA-classification < 4. Oral mechanical bowel preparation is mandatory and patients with signs of peritonitis are excluded. The C-seal student team will perform the randomization procedure, supports the operating surgeon during the C-seal application and achieves the monitoring of the trial. Patients are followed for one year after randomization en will be analyzed on an intention to treat basis. Discussion This Randomized Clinical trial is designed to evaluate the effectiveness of the C-seal in preventing clinical anastomotic leakage. Trial registration NTR3080 PMID:23153188

Randomized Clinical Trials of Gene Transfer for Heart Failure with Reduced Ejection Fraction.

PubMed

Penny, William F; Hammond, H Kirk

2017-05-01

Despite improvements in drug and device therapy for heart failure, hospitalization rates and mortality have changed little in the past decade. Randomized clinical trials using gene transfer to improve function of the failing heart are the focus of this review. Four randomized clinical trials of gene transfer in heart failure with reduced ejection fraction (HFrEF) have been published. Each enrolled patients with stable symptomatic HFrEF and used either intracoronary delivery of a virus vector or endocardial injection of a plasmid. The initial CUPID trial randomized 14 subjects to placebo and 25 subjects to escalating doses of adeno-associated virus type 1 encoding sarcoplasmic reticulum calcium ATPase (AAV1.SERCA2a). AAV1.SERCA2a was well tolerated, and the high-dose group met a 6 month composite endpoint. In the subsequent CUPID-2 study, 243 subjects received either placebo or the high dose of AAV1.SERCA2a. AAV1.SERCA2a administration, while safe, failed to meet the primary or any secondary endpoints. STOP-HF used plasmid endocardial injection of stromal cell-derived factor-1 to promote stem-cell recruitment. In a 93-subject trial of patients with ischemic etiology heart failure, the primary endpoint (symptoms and 6 min walk distance) failed, but subgroup analyses showed improvements in subjects with the lowest ejection fractions. A fourth trial randomized 14 subjects to placebo and 42 subjects to escalating doses of adenovirus-5 encoding adenylyl cyclase 6 (Ad5.hAC6). There were no safety concerns, and patients in the two highest dose groups (combined) showed improvements in left ventricular function (left ventricular ejection fraction and -dP/dt). The safety data from four randomized clinical trials of gene transfer in patients with symptomatic HFrEF suggest that this approach can be conducted with acceptable risk, despite invasive delivery techniques in a high-risk population. Additional trials are necessary before the approach can be endorsed for clinical practice.

Choice of Moisturiser for Eczema Treatment (COMET): study protocol for a randomized controlled trial.

PubMed

Ridd, Matthew J; Redmond, Niamh M; Hollinghurst, Sandra; Ball, Nicola; Shaw, Lindsay; Guy, Richard; Wilson, Victoria; Metcalfe, Chris; Purdy, Sarah

2015-07-15

Eczema is common in children and in the UK most cases are managed in primary care. The foundation of all treatment is the regular use of leave-on emollients to preserve and restore moisture to the skin. This not only improves comfort but may also reduce the need for rescue treatment for 'flares', such as topical corticosteroids. However, clinicians can prescribe many different types of emollient and there is a paucity of evidence to guide this choice. One reason for this may be the challenges of conducting a clinical trial: are parents or carers of young children willing to be randomly allocated an emollient and followed up for a meaningful amount of time? This is a single-centre feasibility study of a pragmatic, four-arm, single-masked, randomized trial. Children with eczema who are eligible (from 1 month to less than 5 years of age, not known to be sensitive or allergic to any of study emollients or their constituents) are recruited via their general practices. Participants are allocated Aveeno® lotion, Diprobase® cream, Doublebase® gel or Hydromol® ointment via a web-based system, using a simple randomization process in a 1:1:1:1 fashion. Researchers are masked to the study emollient. Participants are assessed at baseline and followed up for 3 months. Data are collected by daily diaries, monthly researcher visits and review of electronic medical records. Because this is a feasibility study, a formal sample size calculation for the estimation of treatment effectiveness has not be made but we aim to recruit 160 participants. Recruitment is on-going. At the end of the study, as well as being able to answer the question, 'Is it is possible to recruit and retain children with eczema from primary care into a four-arm randomized trial of emollients?', we will also have collected important data on the acceptability and effectiveness of four commonly used emollients. Current Controlled Trials ISRCTN21828118 and Clinical Trials Register EudraCT2013-003001-26.

Right versus left atrial pacing in patients with sick sinus syndrome and paroxysmal atrial fibrillation (Riverleft study): study protocol for randomized controlled trial.

PubMed

Ramdjan, Tanwier T T K; van der Does, Lisette J M E; Knops, Paul; Res, Jan C J; de Groot, Natasja M S

2014-11-17

The incidence of sick sinus syndrome will increase due to population ageing. Consequently, this will result in an increase in the number of pacemaker implantations. The atrial lead is usually implanted in the right atrial appendage, but this position may be ineffective for prevention of atrial fibrillation. It has been suggested that pacing distally in the coronary sinus might be more successful in preventing atrial fibrillation episodes. The aim of this trial is to study the efficacy of distal coronary sinus versus right atrial appendage pacing in preventing atrial fibrillation episodes in patients with sick sinus syndrome. This study is designed as a multicenter, randomized controlled trial. Patients with sick sinus syndrome and at least one atrial fibrillation episode of 30 seconds or more in the six months before recruitment will be eligible for participation in this study.All participants will be randomized between pacing distally in the coronary sinus and right atrial appendage. Randomization is stratified for all participating centers. Conventional dual-chamber pacemakers with advanced home monitoring functionality will be implanted. The ventricular lead will be implanted in the right ventricular apex. The first three months of the 36-month follow-up period are considered as run-in time. During the pre-randomization visit and follow-up, an interview, electrocardiogram and pacemaker assessment will be performed, prescribed antiarrhythmic medication will be reviewed and patients will be asked to complete an SF-36 questionnaire. An echocardiographic examination will be conducted in the pre-randomization phase and at the end of each follow-up year. Home monitoring will be used to send daily reports in case of atrial fibrillation episodes. This randomized controlled trial is the first in which home monitoring will be used to compare atrial fibrillation recurrences between pacing in the distal coronary sinus or right atrial appendage. Home monitoring gives the opportunity to accurately detect atrial fibrillation episodes and to study characteristics of atrial fibrillation episodes. Should distal coronary sinus pacing significantly diminish atrial fibrillation recurrences, this study will redefine the preferential location of an atrial lead for preventive pacing. Current Controlled Trials ISRCTN65911661, registered on 8 July 2013.

A LARGE-SCALE CLUSTER RANDOMIZED TRIAL TO DETERMINE THE EFFECTS OF COMMUNITY-BASED DIETARY SODIUM REDUCTION – THE CHINA RURAL HEALTH INITIATIVE SODIUM REDUCTION STUDY

PubMed Central

Li, Nicole; Yan, Lijing L.; Niu, Wenyi; Labarthe, Darwin; Feng, Xiangxian; Shi, Jingpu; Zhang, Jianxin; Zhang, Ruijuan; Zhang, Yuhong; Chu, Hongling; Neiman, Andrea; Engelgau, Michael; Elliott, Paul; Wu, Yangfeng; Neal, Bruce

2013-01-01

Background Cardiovascular diseases are the leading cause of death and disability in China. High blood pressure caused by excess intake of dietary sodium is widespread and an effective sodium reduction program has potential to improve cardiovascular health. Design This study is a large-scale, cluster-randomized, trial done in five Northern Chinese provinces. Two counties have been selected from each province and 12 townships in each county making a total of 120 clusters. Within each township one village has been selected for participation with 1:1 randomization stratified by county. The sodium reduction intervention comprises community health education and a food supply strategy based upon providing access to salt substitute. Subsidization of the price of salt substitute was done in 30 intervention villages selected at random. Control villages continued usual practices. The primary outcome for the study is dietary sodium intake level estimated from assays of 24 hour urine. Trial status The trial recruited and randomized 120 townships in April 2011. The sodium reduction program was commenced in the 60 intervention villages between May and June of that year with outcome surveys scheduled for October to December 2012. Baseline data collection shows that randomisation achieved good balance across groups. Discussion The establishment of the China Rural Health Initiative has enabled the launch of this large-scale trial designed to identify a novel, scalable strategy for reduction of dietary sodium and control of blood pressure. If proved effective, the intervention could plausibly be implemented at low cost in large parts of China and other countries worldwide. PMID:24176436

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…

Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies

USDA-ARS?s Scientific Manuscript database

Background: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies; and the causal relationship remains ill defined. Using the Mendelian randomization (MR) approach and meta-analysis of selected randomized controlled trials (RCTs), we...

Effect of periodontal treatment on the clinical parameters of patients with rheumatoid arthritis: study protocol of the randomized, controlled ESPERA trial

PubMed Central

2013-01-01

Background Rheumatoid arthritis (RA) is a chronic inflammatory disorder that leads to joint damage, deformity, and pain. It affects approximately 1% of adults in developed countries. Periodontitis is a chronic oral infection, caused by inflammatory reactions to gram-negative anaerobic bacteria, and affecting about 35 to 50% of adults. If left untreated, periodontitis can lead to tooth loss. A significant association has been shown to exist between periodontitis and RA in observational studies. Some intervention studies have suggested that periodontal treatment can reduce serum inflammatory biomarkers such as C-reactive protein, or erythrocyte sedimentation rate. We hypothesize that periodontitis could be an aggravating factor in patients with RA, and that its treatment would improve RA outcomes. The aim of this clinical trial is to assess the effect of periodontal treatment on the biological and clinical parameters of patients with RA. Methods/design The ESPERA (Experimental Study of Periodontitis and Rheumatoid Arthritis) study is an open-label, randomized, controlled trial. Subjects with both RA and periodontitis will be recruited at two university hospitals in southwestern France. In total, 40 subjects will be randomized into two arms (intervention and control groups), and will be followed up for 3 months. Intervention will consist of full-mouth supra-gingival and sub-gingival non-surgical scaling and root planing, followed by systemic antibiotic therapy, local antiseptics, and oral hygiene instructions. After the 3-month follow-up period, the same intervention will be applied to the subjects randomized to the control group. The primary outcome will be change of in Disease Activity Score in 28 Joints (DAS28) at the end of the follow-up period. Secondary outcomes will be the percentages of subjects with 20%, 50%, and 70% improvement in disease according to the American College of Rheumatology criteria. Health-related quality of life assessments (the Health Assessment Questionnaire and the Geriatric Oral Health Assessment Index) will also be compared between the two groups. Discussion Evidence-based management of potential aggravating factors in subjects with active RA could be of clinical importance, yet there are few randomized controlled trials on the effect of periodontal treatment on the clinical parameters of RA. The ESPERA trial is designed to determine if non-surgical periodontal treatment could improve clinical outcomes in patients with active RA, and the quality of life of these patients. Trial registration The ESPERA Trial was registered in Current Controlled Trials [ISRCTN79186420] on 2012/03/20. The trial started recruiting on 2012/03/06. PMID:23945051

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

Investigation of the contextual interference effect in the manipulation of the motor parameter of over-all force.

PubMed

Goodwin, J E; Meeuwsen, H J

1996-12-01

This investigation examined the contextual interference effect when manipulating over-all force in a golf-putting task. Undergraduate women (N = 30) were randomly assigned to a Random, Blocked-Random, or Blocked practice condition and practiced golf putting from distances of 2.43 m, 3.95 m, and 5.47 m during acquisition. Subjects in the Random condition practiced trials in a quasirandom sequence and those in the Blocked-Random condition practiced trials initially in a blocked sequence with the remainder of the trials practiced in a quasirandom sequence. In the Blocked condition subjects practiced trials in a blocked sequence. A 24-hr. transfer test consisted of 30 trials with 10 trials each from 1.67 m, 3.19 m, and 6.23 m. Transfer scores supported the Magill and Hall (1990) hypothesis that, when task variations involve learning parameters of a generalized motor program, the benefit of random practice over blocked practice would not be found.

The Design of Phase II Clinical Trials Testing Cancer Therapeutics: Consensus Recommendations from the Clinical Trial Design Task Force of the National Cancer Institute Investigational Drug Steering Committee

PubMed Central

Seymour, Lesley; Ivy, S. Percy; Sargent, Daniel; Spriggs, David; Baker, Laurence; Rubinstein, Larry; Ratain, Mark J; Le Blanc, Michael; Stewart, David; Crowley, John; Groshen, Susan; Humphrey, Jeffrey S; West, Pamela; Berry, Donald

2010-01-01

The optimal design of phase II studies continues to be the subject of vigorous debate, especially with regards to studies of newer molecularly targeted agents. The observations that many new therapeutics ‘fail’ in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials further emphasizes the critical importance of robust and efficient phase II design. The Clinical Trial Design Task Force(CTD-TF)of the NCI Investigational Drug Steering Committee (IDSC) has published a series of discussion papers on Phase II trial design in Clinical Cancer Research. The IDSC has developed formal recommendations regarding aspects of phase II trial design which are the subject of frequent debate such as endpoints(response vs. progression free survival), randomization(single arm designs vs. randomization), inclusion of biomarkers, biomarker based patient enrichment strategies, and statistical design(e.g. two stage designs vs. multiple-group adaptive designs). While these recommendations in general encourage the use of progression-free survival as the primary endpoint, the use of randomization, the inclusion of biomarkers and the incorporation of newer designs, we acknowledge that objective response as an endpoint, and single arm designs, remain relevant in certain situations. The design of any clinical trial should always be carefully evaluated and justified based on the characteristic specific to the situation. PMID:20215557

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.

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.

A theory of eu-estrogenemia: a unifying concept

PubMed Central

Turner, Ralph J.; Kerber, Irwin J.

2017-01-01

Abstract Objective: The aim of the study was to propose a unifying theory for the role of estrogen in postmenopausal women through examples in basic science, randomized controlled trials, observational studies, and clinical practice. Methods: Review and evaluation of the literature relating to estrogen. Discussion: The role of hormone therapy and ubiquitous estrogen receptors after reproductive senescence gains insight from basic science models. Observational studies and individualized patient care in clinical practice may show outcomes that are not reproduced in randomized clinical trials. The understanding gained from the timing hypothesis for atherosclerosis, the critical window theory in neurosciences, randomized controlled trials, and numerous genomic and nongenomic actions of estrogen discovered in basic science provides new explanations to clinical challenges that practitioners face. Consequences of a hypo-estrogenemic duration in women's lives are poorly understood. The Study of Women Across the Nation suggests its magnitude is greater than was previously acknowledged. We propose that the healthy user bias was the result of surgical treatment (hysterectomy with oophorectomy) for many gynecological maladies followed by pharmacological and physiological doses of estrogen to optimize patient quality of life. The past decade of research has begun to demonstrate the role of estrogen in homeostasis. Conclusions: The theory of eu-estrogenemia provides a robust framework to unify the timing hypothesis, critical window theory, randomized controlled trials, the basic science of estrogen receptors, and clinical observations of patients over the past five decades. PMID:28562489

A pilot randomized placebo-controlled trial of adjunctive aripiprazole for chronic PTSD in US military Veterans resistant to antidepressant treatment.

PubMed

Naylor, Jennifer C; Kilts, Jason D; Bradford, Daniel W; Strauss, Jennifer L; Capehart, Bruce P; Szabo, Steven T; Smith, Karen D; Dunn, Charlotte E; Conner, Kathryn M; Davidson, Jonathan R T; Wagner, Henry Ryan; Hamer, Robert M; Marx, Christine E

2015-05-01

Many individuals with post-traumatic stress disorder (PTSD) experience persistent symptoms despite pharmacological treatment with antidepressants. Several open-label monotherapy and adjunctive studies have suggested that aripiprazole (a second-generation antipsychotic) may have clinical utility in PTSD. However, there have been no randomized placebo-controlled trials of aripiprazole use for PTSD. We thus conducted a pilot randomized controlled trial of adjunctive aripiprazole versus placebo among Veterans with chronic PTSD serving in the US military since 11 September 2001 to assess the feasibility, safety, tolerability, and therapeutic potential of aripiprazole. Sixteen Veterans were randomized, and 14 completed at least 4 weeks of the study; 12 completed the entire 8-week trial. Outcome measures included the Clinician-Administered PTSD Scale (CAPS), PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores. Aripiprazole was well-tolerated in this cohort, and improvements in CAPS, PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores were as hypothesized. Although CAPS change scores did not reach statistical significance, aripiprazole outperformed placebo by 9 points on the CAPS in the last observation carried forward analysis compared with the placebo group (n = 7 per group), and by 20 points in the group randomized to aripiprazole that completed the entire study (n = 5) compared with the placebo group (n = 7). Results suggest promise for aripiprazole as an adjunctive strategy for the treatment of PTSD.

Diarrhea and dengue control in rural primary schools in Colombia: study protocol for a randomized controlled trial.

PubMed

Overgaard, Hans J; Alexander, Neal; Mátiz, Maria Ines; Jaramillo, Juan Felipe; Olano, Victor Alberto; Vargas, Sandra; Sarmiento, Diana; Lenhart, Audrey; Seidu, Razak; Stenström, Thor Axel

2012-10-03

Diarrheal diseases and dengue fever are major global health problems. Where provision of clean water is inadequate, water storage is crucial. Fecal contamination of stored water is a common source of diarrheal illness, but stored water also provides breeding sites for dengue vector mosquitoes. Poor household water management and sanitation are therefore potential determinants of both diseases. Little is known of the role of stored water for the combined risk of diarrhea and dengue, yet a joint role would be important for developing integrated control and management efforts. Even less is known of the effect of integrating control of these diseases in school settings. The objective of this trial was to investigate whether interventions against diarrhea and dengue will significantly reduce diarrheal disease and dengue entomological risk factors in rural primary schools. This is a 2×2 factorial cluster randomized controlled trial. Eligible schools were rural primary schools in La Mesa and Anapoima municipalities, Cundinamarca, Colombia. Eligible pupils were school children in grades 0 to 5. Schools were randomized to one of four study arms: diarrhea interventions (DIA); dengue interventions (DEN); combined diarrhea and dengue interventions (DIADEN); and control (C). Schools were allocated publicly in each municipality (strata) at the start of the trial, obviating the need for allocation concealment. The primary outcome for diarrhea is incidence rate of diarrhea in school children and for dengue it is density of adult female Aedes aegypti per school. Approximately 800 pupils from 34 schools were enrolled in the trial with eight schools in the DIA arm, nine in the DEN, eight in the DIADEN, and nine in the control arms. The trial status as of June 2012 was: completed baseline data collections; enrollment, randomization, and allocation of schools. The trial was funded by the Research Council of Norway and the Lazos de Calandaima Foundation. This is the first trial investigating the effect of a set of integrated interventions to control both dengue and diarrhea. This is also the first trial to study the combination of diarrhea-dengue disease control in school settings. Current Controlled Trials ISRCTN40195031.

Customizing chemotherapy in non-small cell lung cancer: the promise is still unmet

PubMed Central

2015-01-01

A combination of cytotoxic agents with cis-platin remains the cornerstone of treatment for the vast majority of patients with non-small cell lung cancer (NSCLC). Molecular analysis of the primary may lead better prognostication and eventually in more accurate therapeutic approaches. Data from retrospective analysis of randomized trials as well as large patients’ series have suggested that chemotherapy may be customized upon molecular-genetic analysis of the tumor cells. The Spanish Lung Cancer Group (SLCG) in collaboration with French lung Cancer Group (FLCG) had conduct randomized, phase III, biomarkers-driven trial and supported simultaneously a randomized phase II trial in collaborating centers in China. Despite the evidence from the preclinical data and the results from the retrospective studies, the results of these trials published recently in Annals of Oncology were in favor of ‘standard approach’. The present commentary tries to give some explanation for the disappointing results, provide potential solution for the future trials and explain why the vision of customizing treatment is still alive. PMID:26629440

Safety and effectiveness of antiretroviral drugs during pregnancy, delivery and breastfeeding for prevention of mother-to-child transmission of HIV-1: the Kesho Bora Multicentre Collaborative Study rationale, design, and implementation challenges.

PubMed

2011-01-01

To evaluate strategies to reduce HIV-1 transmission through breastfeeding, a multicentre study including a nested randomized controlled trial was implemented in five research sites in West, East and South Africa (The Kesho Bora Study). The aim was to optimize the use of antiretroviral (ARV) drugs during pregnancy, delivery and breastfeeding to prevent mother-to-child transmission of HIV-1 (PMTCT) and to preserve the health of the HIV-1-infected mother. The study included long-term ARV treatment for women with advanced disease, and short-course ARV prophylaxis stopped at delivery for women with early disease. Women with intermediate disease participated in a randomized controlled trial to compare safety and efficacy of triple-ARV prophylaxis prolonged during breastfeeding with short-course ARV prophylaxis stopped at delivery. Between January 2005 and August 2008 a total of 1140 women were enrolled. This paper describes the study design, interventions and protocol amendments introduced to adapt to evolving scientific knowledge, international guidelines and availability of ARV treatment. The paper highlights the successes and challenges during the conduct of the trial. The Kesho Bora Study included one of the few randomized controlled trials to assess safety and efficacy of ARV prophylaxis continued during breastfeeding and the only randomized trial to assess maternal prophylaxis started during pregnancy. The findings have been important for informing international and national guidelines on MTCT prevention in developing countries where, due to poverty, lack of reliable and affordable supply of replacement feed and stigma associated with HIV/AIDS, HIV-infected women have little or no option other than to breastfeed their infants. (ISRCTN71468401). Copyright © 2010 Elsevier Inc. All rights reserved.

Mediterranean dietary pattern and depression: the PREDIMED randomized trial

PubMed Central

2013-01-01

Background A few observational studies have found an inverse association between adherence to a Mediterranean diet and the risk of depression. Randomized trials with an intervention based on this dietary pattern could provide the most definitive answer to the findings reported by observational studies. The aim of this study was to compare in a randomized trial the effects of two Mediterranean diets versus a low-fat diet on depression risk after at least 3 years of intervention. Methods This was a multicenter, randomized, primary prevention field trial of cardiovascular disease (Prevención con Dieta Mediterránea (PREDIMED Study)) based on community-dwelling men aged 55 to 80 years and women aged 60 to 80 years at high risk of cardiovascular disease (51% of them had type 2 diabetes; DM2) attending primary care centers affiliated with 11 Spanish teaching hospitals. Primary analyses were performed on an intention-to-treat basis. Cox regression models were used to assess the relationship between the nutritional intervention groups and the incidence of depression. Results We identified 224 new cases of depression during follow-up. There was an inverse association with depression for participants assigned to a Mediterranean diet supplemented with nuts (multivariate hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.55 to 1.10) compared with participants assigned to the control group, although this was not significant. However, when the analysis was restricted to participants with DM2, the magnitude of the effect of the intervention with the Mediterranean diet supplemented with nuts did reach statistical significance (multivariate HR = 0.59; 95% CI 0.36 to 0.98). Conclusions The result suggest that a Mediterranean diet supplemented with nuts could exert a beneficial effect on the risk of depression in patients with DM2. Trial registration This trial has been registered in the Current Controlled Trials with the number ISRCTN 35739639 PMID:24229349

Evaluation of Electromyographic Biofeedback for the Quadriceps Femoris: A Systematic Review

PubMed Central

Wasielewski, Noah J.; Parker, Tonya M.; Kotsko, Kevin M.

2011-01-01

Objective: To critically review evidence for the effectiveness of electromyographic biofeedback (EMGB) of the quadriceps femoris muscle in treating various knee conditions. Data Sources: Databases used to locate randomized controlled trials included PubMed (1980–2010), Cumulative Index of Nursing and Allied Health Literature (CINAHL, 1995–2007), Web of Science (1986–2010), SPORTDiscus (1990–2007), and Physiotherapy Evidence Database (PEDro). Key words were knee and biofeedback. Study Selection: The criteria for selection were clinical randomized controlled trials in which EMGB of the quadriceps femoris was used for various knee conditions of musculoskeletal origin. Trials were excluded because of research designs other than randomized controlled trials, articles published in a non-English language, inclusion of healthy research participants, inability to identify EMGB as the source of clinical improvement, and lack of pain, functional outcome, or quadriceps torque as outcome measures. Data Extraction: Twenty specific data points were abstracted from each clinical trial under the broad categories of attributes of the patient and injury, treatment variables for the EMGB group, treatment variables for the control group, and attributes of the research design. Data Synthesis: Eight trials yielded a total of 319 participants with patellofemoral pain syndrome (n = 86), anterior cruciate ligament reconstruction (n = 52), arthroscopic surgery (n = 91), or osteoarthritis (n = 90). The average methodologic score of the included studies was 4.6/10 based on PEDro criteria. Pooled analyses demonstrated heterogeneity of the included studies, rendering the interpretation of the pooled data inappropriate. The EMGB appeared to benefit short-term postsurgical pain or quadriceps strength in 3 of 4 postsurgical investigations but was ineffective for chronic knee conditions such as patellofemoral pain and osteoarthritis in all 4 studies. Because the findings are based on limited data, caution is warranted until more randomized controlled trials are conducted to support or refute the general trends observed in this report. PMID:22488142

Using resource use logs to reduce the amount of missing data in economic evaluations alongside trials.

PubMed

Marques, Elsa; Johnson, Emma C; Gooberman-Hill, Rachael; Blom, Ashley W; Noble, Sian

2013-01-01

Economic evaluations alongside randomized controlled trials that collect data using patient-completed questionnaires are prone to missing data. Our objective was to determine whether giving patients a resource use log (RUL) at baseline would improve the odds of completing questions in a follow-up resource use questionnaire (RUQ) and to identify patients' views on RUL's usefulness and acceptability. The RUL study was a randomized controlled trial and qualitative study nested within a larger randomized controlled trial (the Arthroplasty Pain Experience Study trial). Eighty-five patients were randomized at baseline to receive or not receive an RUL. At 3-month follow-up, all participants received a postal RUQ. We created dummy variables for 13 resource use categories indicating whether complete information had been given for each category. We compared the completion rates between arms by using descriptive statistics and logistic regression. We explored patients' experience of using the RUL by interviewing a different subsample of Arthroplasty Pain Experience Study patients (n = 24) at 2- to 4-week follow-up. At 3 months, 74 of the 85 (87% in each arm) patients returned the RUQ. Patients in the RUL arm were 3.5 times more likely to complete the National Health Service community-based services category (P = 0.08). The RUL was positively received by patients and was generally seen as a useful memory aid. The RUL is a useful and acceptable tool in reducing the amount of missing data for some types of resource use. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

A focus group study to understand biases and confounders in a cluster randomized controlled trial on low back pain in primary care in Norway.

PubMed

Werner, Erik L; Løchting, Ida; Storheim, Kjersti; Grotle, Margreth

2018-05-22

Cluster randomized controlled trials are often used in research in primary care but creates challenges regarding biases and confounders. We recently presented a study on low back pain from primary care in Norway with equal effects in the intervention and the control group. In order to understand the specific mechanisms that may produce biases in a cluster randomized trial we conducted a focus group study among the participating health care providers. The aim of this study was to understand how the participating providers themselves influenced on the study and thereby possibly on the results of the cluster randomized controlled trial. The providers were invited to share their experiences from their participation in the COPE study, from recruitment of patients to accomplishment of either the intervention or control consultations. Six clinicians from the intervention group and four from the control group took part in the focus group interviews. The group discussions focused on feasibility of the study in primary care and particularly on identifying potential biases and confounders in the study. The audio-recorded interviews were transcribed verbatim and analyzed according to a systematic text condensation. The themes for the analysis emerged from the group discussions. A personal interest for back pain, logistic factors at the clinics and an assessment of the patients' capacity to accomplish the study prior to their recruitment was reported. The providers were allowed to provide additional therapy to the intervention and it turned out that some of these could be regarded as opposed to the messages of the intervention. The providers seemed to select different items from the educational package according to personal beliefs and their perception of the patients' acceptance. The study disclosed several potential biases to the COPE study which may have impacted on the study results. Awareness of these is highly important when planning and conducting a cluster randomized controlled trial. Procedures in the recruitment of both providers and patients seem to be key factors and the providers should be aware of their role in a scientific study in order to standardize the provision of the intervention.

Progestogens in singleton gestations with preterm prelabor rupture of membranes: a systematic review and metaanalysis of randomized controlled trials.

PubMed

Quist-Nelson, Johanna; Parker, Pamela; Mokhtari, Neggin; Di Sarno, Rossana; Saccone, Gabriele; Berghella, Vincenzo

2018-03-31

Preterm prelabor rupture of membranes occurs in 3% of all pregnancies. Neonatal benefit is seen in uninfected women who do not deliver immediately after preterm prelabor rupture of membranes. The purpose of this study was to evaluate whether the administration of progestogens in singleton pregnancies prolongs pregnancy after preterm prelabor rupture of membranes. Searches were performed in MEDLINE, OVID, Scopus, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of keywords and text words related to "progesterone," "progestogen," "prematurity," and "preterm premature rupture of membranes" from the inception of the databases until January 2018. We included all randomized controlled trials of singleton gestations after preterm prelabor rupture of membranes that were randomized to either progestogens or control (either placebo or no treatment). Exclusion criteria were trials that included women who had contraindications to expectant management after preterm prelabor rupture of membranes (ie, chorioamnionitis, severe preeclampsia, and nonreassuring fetal status) and trials on multiple gestations. We planned to include all progestogens, including but not limited to 17-α hydroxyprogesterone caproate, and natural progesterone. The primary outcome was latency from randomization to delivery. Metaanalysis was performed with the use of the random effects model of DerSimonian and Laird to produce relative risk with 95% confidence interval. Analysis was performed for each mode of progestogen administration separately. Six randomized controlled trials (n=545 participants) were included. Four of the included trials assessed the efficacy of 17-α hydroxyprogesterone caproate; 1 trial assessed rectal progestogen, and 1 trial had 3 arms that compared 17-α hydroxyprogesterone caproate, rectal progestogen, and placebo. The mean gestational age at time randomization was 26.9 weeks in the 17-α hydroxyprogesterone caproate group and 27.3 weeks in the control group. 17-α Hydroxyprogesterone caproate administration was not found to prolong the latency period between randomization and delivery (mean difference, 0.11 days; 95% confidence interval, -3.30 to 3.53). There were no differences in mean gestational age at delivery, mode of delivery, or maternal or neonatal outcomes between the 2 groups. Similarly, there was no difference in latency for those women who received rectal progesterone (mean difference, 4.00 days; 95% confidence interval, -0.72 to 8.72). Progestogen administration does not prolong pregnancy in singleton gestations with preterm prelabor rupture of membranes. Copyright © 2018 Elsevier Inc. All rights reserved.

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).

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2011-09-01

placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer. In Year 3 of the...risk. Our study is nested within the Prostate Cancer Prevention Trial (PCPT), a randomized placebo-controlled clinical trial to determine if finasteride

Evaluation of a standardized treatment regimen of anti-tuberculosis drugs for patients with multi-drug-resistant tuberculosis (STREAM): study protocol for a randomized controlled trial.

PubMed

Nunn, Andrew J; Rusen, I D; Van Deun, Armand; Torrea, Gabriela; Phillips, Patrick P J; Chiang, Chen-Yuan; Squire, S Bertel; Madan, Jason; Meredith, Sarah K

2014-09-09

In contrast to drug-sensitive tuberculosis, the guidelines for the treatment of multi-drug-resistant tuberculosis (MDR-TB) have a very poor evidence base; current recommendations, based on expert opinion, are that patients should be treated for a minimum of 20 months. A series of cohort studies conducted in Bangladesh identified a nine-month regimen with very promising results. There is a need to evaluate this regimen in comparison with the currently recommended regimen in a randomized controlled trial in a variety of settings, including patients with HIV-coinfection. STREAM is a multi-centre randomized trial of non-inferiority design comparing a nine-month regimen to the treatment currently recommended by the World Health Organization in patients with MDR pulmonary TB with no evidence on line probe assay of fluoroquinolone or kanamycin resistance. The nine-month regimen includes clofazimine and high-dose moxifloxacin and can be extended to 11 months in the event of delay in smear conversion. The primary outcome is based on the bacteriological status of the patients at 27 months post-randomization. Based on the assumption that the nine-month regimen will be slightly more effective than the control regimen and, given a 10% margin of non-inferiority, a total of 400 patients are required to be enrolled. Health economics data are being collected on all patients in selected sites. The results from the study in Bangladesh and cohorts in progress elsewhere are encouraging, but for this regimen to be recommended more widely than in a research setting, robust evidence is needed from a randomized clinical trial. Results from the STREAM trial together with data from ongoing cohorts should provide the evidence necessary to revise current recommendations for the treatment for MDR-TB. This trial was registered with clincaltrials.gov (registration number: ISRCTN78372190) on 14 October 2010.

Review of Recent Methodological Developments in Group-Randomized Trials: Part 1—Design

PubMed Central

Li, Fan; Gallis, John A.; Prague, Melanie; Murray, David M.

2017-01-01

In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have highlighted the developments of the past 13 years in design with a companion article to focus on developments in analysis. As a pair, these articles update the 2004 review. We have discussed developments in the topics of the earlier review (e.g., clustering, matching, and individually randomized group-treatment trials) and in new topics, including constrained randomization and a range of randomized designs that are alternatives to the standard parallel-arm GRT. These include the stepped-wedge GRT, the pseudocluster randomized trial, and the network-randomized GRT, which, like the parallel-arm GRT, require clustering to be accounted for in both their design and analysis. PMID:28426295

Review of Recent Methodological Developments in Group-Randomized Trials: Part 1-Design.

PubMed

Turner, Elizabeth L; Li, Fan; Gallis, John A; Prague, Melanie; Murray, David M

2017-06-01

In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have highlighted the developments of the past 13 years in design with a companion article to focus on developments in analysis. As a pair, these articles update the 2004 review. We have discussed developments in the topics of the earlier review (e.g., clustering, matching, and individually randomized group-treatment trials) and in new topics, including constrained randomization and a range of randomized designs that are alternatives to the standard parallel-arm GRT. These include the stepped-wedge GRT, the pseudocluster randomized trial, and the network-randomized GRT, which, like the parallel-arm GRT, require clustering to be accounted for in both their design and analysis.

Statistical analysis plan of the head position in acute ischemic stroke trial pilot (HEADPOST pilot).

PubMed

Olavarría, Verónica V; Arima, Hisatomi; Anderson, Craig S; Brunser, Alejandro; Muñoz-Venturelli, Paula; Billot, Laurent; Lavados, Pablo M

2017-02-01

Background The HEADPOST Pilot is a proof-of-concept, open, prospective, multicenter, international, cluster randomized, phase IIb controlled trial, with masked outcome assessment. The trial will test if lying flat head position initiated in patients within 12 h of onset of acute ischemic stroke involving the anterior circulation increases cerebral blood flow in the middle cerebral arteries, as measured by transcranial Doppler. The study will also assess the safety and feasibility of patients lying flat for ≥24 h. The trial was conducted in centers in three countries, with ability to perform early transcranial Doppler. A feature of this trial was that patients were randomized to a certain position according to the month of admission to hospital. Objective To outline in detail the predetermined statistical analysis plan for HEADPOST Pilot study. Methods All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be classified, and for each item, appropriate descriptive statistical analyses are planned with comparisons made between randomized groups. For the outcomes, statistical comparisons to be made between groups are planned and described. Results This statistical analysis plan was developed for the analysis of the results of the HEADPOST Pilot study to be transparent, available, verifiable, and predetermined before data lock. Conclusions We have developed a statistical analysis plan for the HEADPOST Pilot study which is to be followed to avoid analysis bias arising from prior knowledge of the study findings. Trial registration The study is registered under HEADPOST-Pilot, ClinicalTrials.gov Identifier NCT01706094.

Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis123

PubMed Central

Thompson-Paul, Angela M; Bazzano, Lydia A

2013-01-01

Background: Coenzyme Q10 (CoQ10; also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of CoQ10 on CHF with inconclusive results. Objective: The objective of this meta-analysis was to evaluate the impact of CoQ10 supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF. Design: A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ10 supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol. Results: Supplementation with CoQ10 resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and −0.30 (95% CI: −0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ10/d and in patients with less severe CHF. These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup. Conclusions: Pooled analyses of available randomized controlled trials suggest that CoQ10 may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed. PMID:23221577

Metal-backed versus all-polyethylene tibial components in primary total knee arthroplasty

PubMed Central

2011-01-01

Background and purpose The choice of either all-polyethylene (AP) tibial components or metal-backed (MB) tibial components in total knee arthroplasty (TKA) remains controversial. We therefore performed a meta-analysis and systematic review of randomized controlled trials that have evaluated MB and AP tibial components in primary TKA. Methods The search strategy included a computerized literature search (Medline, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials) and a manual search of major orthopedic journals. A meta-analysis and systematic review of randomized or quasi-randomized trials that compared the performance of tibial components in primary TKA was performed using a fixed or random effects model. We assessed the methodological quality of studies using Detsky quality scale. Results 9 randomized controlled trials (RCTs) published between 2000 and 2009 met the inclusion quality standards for the systematic review. The mean standardized Detsky score was 14 (SD 3). We found that the frequency of radiolucent lines in the MB group was significantly higher than that in the AP group. There were no statistically significant differences between the MB and AP tibial components regarding component positioning, knee score, knee range of motion, quality of life, and postoperative complications. Interpretation Based on evidence obtained from this study, the AP tibial component was comparable with or better than the MB tibial component in TKA. However, high-quality RCTs are required to validate the results. PMID:21895503

A random walk model for evaluating clinical trials involving serial observations.

PubMed

Hopper, J L; Young, G P

1988-05-01

For clinical trials where the variable of interest is ordered and categorical (for example, disease severity, symptom scale), and where measurements are taken at intervals, it might be possible to achieve a greater discrimination between the efficacy of treatments by modelling each patient's progress as a stochastic process. The random walk is a simple, easily interpreted model that can be fitted by maximum likelihood using a maximization routine with inference based on standard likelihood theory. In general the model can allow for randomly censored data, incorporates measured prognostic factors, and inference is conditional on the (possibly non-random) allocation of patients. Tests of fit and of model assumptions are proposed, and application to two therapeutic trials of gastroenterological disorders are presented. The model gave measures of the rate of, and variability in, improvement for patients under different treatments. A small simulation study suggested that the model is more powerful than considering the difference between initial and final scores, even when applied to data generated by a mechanism other than the random walk model assumed in the analysis. It thus provides a useful additional statistical method for evaluating clinical trials.

Feasibility, design and conduct of a pragmatic randomized controlled trial to reduce overweight and obesity in children: The electronic games to aid motivation to exercise (eGAME) study

PubMed Central

Maddison, Ralph; Foley, Louise; Ni Mhurchu, Cliona; Jull, Andrew; Jiang, Yannan; Prapavessis, Harry; Rodgers, Anthony; Vander Hoorn, Stephen; Hohepa, Maea; Schaaf, David

2009-01-01

Background Childhood obesity has reached epidemic proportions in developed countries. Sedentary screen-based activities such as video gaming are thought to displace active behaviors and are independently associated with obesity. Active video games, where players physically interact with images onscreen, may have utility as a novel intervention to increase physical activity and improve body composition in children. The aim of the Electronic Games to Aid Motivation to Exercise (eGAME) study is to determine the effects of an active video game intervention over 6 months on: body mass index (BMI), percent body fat, waist circumference, cardio-respiratory fitness, and physical activity levels in overweight children. Methods/Design Three hundred and thirty participants aged 10–14 years will be randomized to receive either an active video game upgrade package or to a control group (no intervention). Discussion An overview of the eGAME study is presented, providing an example of a large, pragmatic randomized controlled trial in a community setting. Reflection is offered on key issues encountered during the course of the study. In particular, investigation into the feasibility of the proposed intervention, as well as robust testing of proposed study procedures is a critical step prior to implementation of a large-scale trial. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12607000632493 PMID:19450288

Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

PubMed Central

Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

2010-01-01

Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

The Ethics of Randomized Controlled Trials in Social Settings: Can Social Trials Be Scientifically Promising and Must There Be Equipoise?

ERIC Educational Resources Information Center

Fives, Allyn; Russell, Daniel W.; Canavan, John; Lyons, Rena; Eaton, Patricia; Devaney, Carmel; Kearns, Norean; O'Brien, Aoife

2015-01-01

In a randomized controlled trial (RCT), treatments are assigned randomly and treatments are withheld from participants. Is it ethically permissible to conduct an RCT in a social setting? This paper addresses two conditions for justifying RCTs: that there should be a state of equipoise and that the trial should be scientifically promising.…

Using re-randomization to increase the recruitment rate in clinical trials - an assessment of three clinical areas.

PubMed

Kahan, Brennan C

2016-12-13

Patient recruitment in clinical trials is often challenging, and as a result, many trials are stopped early due to insufficient recruitment. The re-randomization design allows patients to be re-enrolled and re-randomized for each new treatment episode that they experience. Because it allows multiple enrollments for each patient, this design has been proposed as a way to increase the recruitment rate in clinical trials. However, it is unknown to what extent recruitment could be increased in practice. We modelled the expected recruitment rate for parallel-group and re-randomization trials in different settings based on estimates from real trials and datasets. We considered three clinical areas: in vitro fertilization, severe asthma exacerbations, and acute sickle cell pain crises. We compared the two designs in terms of the expected time to complete recruitment, and the sample size recruited over a fixed recruitment period. Across the different scenarios we considered, we estimated that re-randomization could reduce the expected time to complete recruitment by between 4 and 22 months (relative reductions of 19% and 45%), or increase the sample size recruited over a fixed recruitment period by between 29% and 171%. Re-randomization can increase recruitment most for trials with a short follow-up period, a long trial recruitment duration, and patients with high rates of treatment episodes. Re-randomization has the potential to increase the recruitment rate in certain settings, and could lead to quicker and more efficient trials in these scenarios.

Are glucose levels, glucose variability and autonomic control influenced by inspiratory muscle exercise in patients with type 2 diabetes? Study protocol for a randomized controlled trial.

PubMed

Schein, Aso; Correa, Aps; Casali, Karina Rabello; Schaan, Beatriz D

2016-01-20

Physical exercise reduces glucose levels and glucose variability in patients with type 2 diabetes. Acute inspiratory muscle exercise has been shown to reduce these parameters in a small group of patients with type 2 diabetes, but these results have yet to be confirmed in a well-designed study. The aim of this study is to investigate the effect of acute inspiratory muscle exercise on glucose levels, glucose variability, and cardiovascular autonomic function in patients with type 2 diabetes. This study will use a randomized clinical trial crossover design. A total of 14 subjects will be recruited and randomly allocated to two groups to perform acute inspiratory muscle loading at 2 % of maximal inspiratory pressure (PImax, placebo load) or 60 % of PImax (experimental load). Inspiratory muscle training could be a novel exercise modality to be used to decrease glucose levels and glucose variability. ClinicalTrials.gov NCT02292810 .

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.

Online CBT life skills programme for low mood and anxiety: study protocol for a pilot randomized controlled trial.

PubMed

Williams, Christopher; McClay, Carrie-Anne; Martinez, Rebeca; Morrison, Jill; Haig, Caroline; Jones, Ray; Farrand, Paul

2016-04-27

Low mood is a common mental health problem with significant health consequences. Studies have shown that cognitive behavioural therapy (CBT) is an effective treatment for low mood and anxiety when delivered one-to-one by an expert practitioner. However, access to this talking therapy is often limited and waiting lists can be long, although a range of low-intensity interventions that can increase access to services are available. These include guided self-help materials delivered via books, classes and online packages. This project aims to pilot a randomized controlled trial of an online CBT-based life skills course with community-based individuals experiencing low mood and anxiety. Individuals with elevated symptoms of depression will be recruited directly from the community via online and newspaper advertisements. Participants will be remotely randomized to receive either immediate access or delayed access to the Living Life to the Full guided online CBT-based life skills package, with telephone or email support provided whilst they use the online intervention. The primary end point will be at 3 months post-randomization, at which point the delayed-access group will be offered the intervention. Levels of depression, anxiety, social functioning and satisfaction will be assessed. This pilot study will test the trial design, and ability to recruit and deliver the intervention. Drop-out rates will be assessed and the completion and acceptability of the package will be investigated. The study will also inform a sample size power calculation for a subsequent substantive randomized controlled trial. ISRCTN ISRCTN12890709.

Robotic-assisted versus laparoscopic colorectal surgery: a meta-analysis of four randomized controlled trials

PubMed Central

2014-01-01

Background Robotic-assisted laparoscopy is popularly performed for colorectal disease. The objective of this meta-analysis was to compare the safety and efficacy of robotic-assisted colorectal surgery (RCS) and laparoscopic colorectal surgery (LCS) for colorectal disease based on randomized controlled trial studies. Methods Literature searches of electronic databases (Pubmed, Web of Science, and Cochrane Library) were performed to identify randomized controlled trial studies that compared the clinical or oncologic outcomes of RCS and LCS. This meta-analysis was performed using the Review Manager (RevMan) software (version 5.2) that is provided by the Cochrane Collaboration. The data used were mean differences and odds ratios for continuous and dichotomous variables, respectively. Fixed-effects or random-effects models were adopted according to heterogeneity. Results Four randomized controlled trial studies were identified for this meta-analysis. In total, 110 patients underwent RCS, and 116 patients underwent LCS. The results revealed that estimated blood losses (EBLs), conversion rates and times to the recovery of bowel function were significantly reduced following RCS compared with LCS. There were no significant differences in complication rates, lengths of hospital stays, proximal margins, distal margins or harvested lymph nodes between the two techniques. Conclusions RCS is a promising technique and is a safe and effective alternative to LCS for colorectal surgery. The advantages of RCS include reduced EBLs, lower conversion rates and shorter times to the recovery of bowel function. Further studies are required to define the financial effects of RCS and the effects of RCS on long-term oncologic outcomes. PMID:24767102

Substance Use and Delinquency among Middle School Girls in Foster Care: A Three-Year Follow-Up of a Randomized Controlled Trial

ERIC Educational Resources Information Center

Kim, Hyoun K.; Leve, Leslie D.

2011-01-01

Objective: The present study evaluated the efficacy of the Middle School Success intervention (MSS) for reducing substance use and delinquency among girls in foster care, using a randomized controlled trial design. The program was designed to fill a service gap during the summer prior to the middle school transition and to prevent delinquency,…

Treatment of Posttraumatic Stress Disorder by Trained Lay Counselors in an African Refugee Settlement: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Neuner, Frank; Onyut, Patience Lamaro; Ertl, Verena; Odenwald, Michael; Schauer, Elisabeth; Elbert, Thomas

2008-01-01

Traumatic stress due to conflict and war causes major mental health problems in many resource-poor countries. The objective of this study was to examine whether trained lay counselors can carry out effective treatment of posttraumatic stress disorder (PTSD) in a refugee settlement. In a randomized controlled dissemination trial in Uganda with 277…

The Long-Term Effectiveness of a Selective, Personality-Targeted Prevention Program in Reducing Alcohol Use and Related Harms: A Cluster Randomized Controlled Trial

ERIC Educational Resources Information Center

Newton, Nicola C.; Conrod, Patricia J.; Slade, Tim; Carragher, Natacha; Champion, Katrina E.; Barrett, Emma L.; Kelly, Erin V.; Nair, Natasha K.; Stapinski, Lexine; Teesson, Maree

2016-01-01

Background: This study investigated the long-term effectiveness of Preventure, a selective personality-targeted prevention program, in reducing the uptake of alcohol, harmful use of alcohol, and alcohol-related harms over a 3-year period. Methods: A cluster randomized controlled trial was conducted to assess the effectiveness of Preventure.…

The PEDALS Stationary Cycling Intervention and Health-Related Quality of Life in Children with Cerebral Palsy: A Randomized Controlled Trial

ERIC Educational Resources Information Center

DeMuth, Sharon K.; Knutson, Loretta M.; Fowler, Eileen G.

2012-01-01

Aim: The aim of this study was to assess health-related quality of life (HRQOL) following a stationary cycling intervention in children with cerebral palsy (CP). Method: This was a phase I multisite randomized controlled trial with single blinding. HRQOL was evaluated using the Pediatric Quality of Life Inventory SF15 (PedsQL; children) and…

Mapping Evidence-Based Treatments for Children and Adolescents: Application of the Distillation and Matching Model to 615 Treatments from 322 Randomized Trials

ERIC Educational Resources Information Center

Chorpita, Bruce F.; Daleiden, Eric L.

2009-01-01

This study applied the distillation and matching model to 322 randomized clinical trials for child mental health treatments. The model involved initial data reduction of 615 treatment protocol descriptions by means of a set of codes describing discrete clinical strategies, referred to as practice elements. Practice elements were then summarized in…

Effects of a Web-Based Decision Aid Regarding Diagnostic Self-Testing. A Single-Blind Randomized Controlled Trial

ERIC Educational Resources Information Center

Ickenroth, Martine H. P.; Grispen, J. E. J.; de Vries, N. K.; Dinant, G. J.; Ronda, G.; van der Weijden, T.

2016-01-01

Currently, there are many diagnostic self-tests on body materials available to consumers. The aim of this study was to assess the effect of an online decision aid on diagnostic self-testing for cholesterol and diabetes on knowledge among consumers with an intention to take these tests. A randomized controlled trial was designed. A total of 1259…

Cluster-Randomized Controlled Trial Evaluating the Effectiveness of Computer-Assisted Intervention Delivered by Educators for Children with Speech Sound Disorders

ERIC Educational Resources Information Center

McLeod, Sharynne; Baker, Elise; McCormack, Jane; Wren, Yvonne; Roulstone, Sue; Crowe, Kathryn; Masso, Sarah; White, Paul; Howland, Charlotte

2017-01-01

Purpose: The aim was to evaluate the effectiveness of computer-assisted input-based intervention for children with speech sound disorders (SSD). Method: The Sound Start Study was a cluster-randomized controlled trial. Seventy-nine early childhood centers were invited to participate, 45 were recruited, and 1,205 parents and educators of 4- and…

The Effects of Coach Training on Fear of Failure in Youth Swimmers: A Latent Growth Curve Analysis from a Randomized, Controlled Trial

ERIC Educational Resources Information Center

Conroy, David E.; Coatsworth, Douglas J.

2004-01-01

The present study was a randomized trial of the efficacy of psychosocial and injury prevention-based coach training programs for reducing fear of failure (FF) among youth swimmers aged 7 to 18 years. Results revealed that (a) psychosocial training increased coaches' use of reward/reinforcement, (b) the FF measure demonstrated strong factorial…

A Randomized Controlled Trial of a Home-Visiting Intervention Aimed at Preventing Relationship Problems in Depressed Mothers and Their Infants

ERIC Educational Resources Information Center

van Doesum, Karin T. M.; Riksen-Walraven, J. Marianne; Hosman, Clemens M. H.; Hoefnagels, Cees

2008-01-01

This study examined the effect of a mother-baby intervention on the quality of mother-child interaction, infant-mother attachment security, and infant socioemotional functioning in a group of depressed mothers with infants aged 1-12 months. A randomized controlled trial compared an experimental group (n = 35) receiving the intervention (8-10 home…