Mobile access to virtual randomization for investigator-initiated trials.

PubMed

Deserno, Thomas M; Keszei, András P

2017-08-01

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

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.

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.

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.

Randomization Methods in Emergency Setting Trials: A Descriptive Review

ERIC Educational Resources Information Center

Corbett, Mark Stephen; Moe-Byrne, Thirimon; Oddie, Sam; McGuire, William

2016-01-01

Background: Quasi-randomization might expedite recruitment into trials in emergency care settings but may also introduce selection bias. Methods: We searched the Cochrane Library and other databases for systematic reviews of interventions in emergency medicine or urgent care settings. We assessed selection bias (baseline imbalances) in prognostic…

Random forests of interaction trees for estimating individualized treatment effects in randomized trials.

PubMed

Su, Xiaogang; Peña, Annette T; Liu, Lei; Levine, Richard A

2018-04-29

Assessing heterogeneous treatment effects is a growing interest in advancing precision medicine. Individualized treatment effects (ITEs) play a critical role in such an endeavor. Concerning experimental data collected from randomized trials, we put forward a method, termed random forests of interaction trees (RFIT), for estimating ITE on the basis of interaction trees. To this end, we propose a smooth sigmoid surrogate method, as an alternative to greedy search, to speed up tree construction. The RFIT outperforms the "separate regression" approach in estimating ITE. Furthermore, standard errors for the estimated ITE via RFIT are obtained with the infinitesimal jackknife method. We assess and illustrate the use of RFIT via both simulation and the analysis of data from an acupuncture headache trial. Copyright © 2018 John Wiley & Sons, Ltd.

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

Post-trial follow-up methodology in large randomized controlled trials: a systematic review protocol.

PubMed

Llewellyn-Bennett, Rebecca; Bowman, Louise; Bulbulia, Richard

2016-12-15

Clinical trials typically have a relatively short follow-up period, and may both underestimate potential benefits of treatments investigated, and fail to detect hazards, which can take much longer to emerge. Prolonged follow-up of trial participants after the end of the scheduled trial period can provide important information on both efficacy and safety outcomes. This protocol describes a systematic review to qualitatively compare methods of post-trial follow-up used in large randomized controlled trials. A systematic search of electronic databases and clinical trial registries will use a predefined search strategy. All large (more than 1000 adult participants) randomized controlled trials will be evaluated. Two reviewers will screen and extract data according to this protocol with the aim of 95% concordance of papers checked and discrepancies will be resolved by a third reviewer. Trial methods, participant retention rates and prevalence of missing data will be recorded and compared. The potential for bias will be evaluated using the Cochrane Risk of Bias tool (applied to the methods used during the in-trial period) with the aim of investigating whether the quality of the post-trial follow-up methodology might be predicted by the quality of the methods used for the original trial. Post-trial follow-up can provide valuable information about the long-term benefits and hazards of medical interventions. However, it can be logistically challenging and costly. The aim of this systematic review is to describe how trial participants have been followed-up post-trial in order to inform future post-trial follow-up designs. Not applicable for PROSPERO registration.

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

Evaluation of active and passive recruitment methods used in randomized controlled trials targeting pediatric obesity.

PubMed

Raynor, Hollie A; Osterholt, Kathrin M; Hart, Chantelle N; Jelalian, Elissa; Vivier, Patrick; Wing, Rena R

2009-01-01

Evaluate enrollment numbers, randomization rates, costs, and cost-effectiveness of active versus passive recruitment methods for parent-child dyads into two pediatric obesity intervention trials. Recruitment methods were categorized into active (pediatrician referral and targeted mailings, with participants identified by researcher/health care provider) versus passive methods (newspaper, bus, internet, television, and earning statements; fairs/community centers/schools; and word of mouth; with participants self-identified). Numbers of enrolled and randomized families and costs/recruitment method were monitored throughout the 22-month recruitment period. Costs (in USD) per recruitment method included staff time, mileage, and targeted costs of each method. A total of 940 families were referred or made contact, with 164 families randomized (child: 7.2+/-1.6 years, 2.27+/-0.61 standardized body mass index [zBMI], 86.6% obese, 61.7% female, 83.5% Caucasian; parent: 38.0+/-5.8 years, 32.9+/-8.4 BMI, 55.2% obese, 92.7% female, 89.6% caucasian). Pediatrician referral, followed by targeted mailings, produced the largest number of enrolled and randomized families (both methods combined producing 87.2% of randomized families). Passive recruitment methods yielded better retention from enrollment to randomization (p<0.05), but produced few families (21 in total). Approximately $91,000 was spent on recruitment, with cost per randomized family at $554.77. Pediatrician referral was the most cost-effective method, $145.95/randomized family, but yielded only 91 randomized families over 22-months of continuous recruitment. Pediatrician referral and targeted mailings, which are active recruitment methods, were the most successful strategies. However, recruitment demanded significant resources. Successful recruitment for pediatric trials should use several strategies. NCT00259324, NCT00200265.

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

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

PubMed

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

2014-01-01

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

Testing Mediators of Intervention Effects in Randomized Controlled Trials: An Evaluation of Three Depression Prevention Programs

ERIC Educational Resources Information Center

Stice, Eric; Rohde, Paul; Seeley, John R.; Gau, Jeff M.

2010-01-01

Objective: Evaluate a new 5-step method for testing mediators hypothesized to account for the effects of depression prevention programs. Method: In this indicated prevention trial, at-risk teens with elevated depressive symptoms were randomized to a group cognitive-behavioral (CB) intervention, group supportive expressive intervention, CB…

Run-Reversal Equilibrium for Clinical Trial Randomization

PubMed Central

Grant, William C.

2015-01-01

In this paper, we describe a new restricted randomization method called run-reversal equilibrium (RRE), which is a Nash equilibrium of a game where (1) the clinical trial statistician chooses a sequence of medical treatments, and (2) clinical investigators make treatment predictions. RRE randomization counteracts how each investigator could observe treatment histories in order to forecast upcoming treatments. Computation of a run-reversal equilibrium reflects how the treatment history at a particular site is imperfectly correlated with the treatment imbalance for the overall trial. An attractive feature of RRE randomization is that treatment imbalance follows a random walk at each site, while treatment balance is tightly constrained and regularly restored for the overall trial. Less predictable and therefore more scientifically valid experiments can be facilitated by run-reversal equilibrium for multi-site clinical trials. PMID:26079608

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

PubMed Central

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

2014-01-01

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

[Methodological quality and reporting quality evaluation of randomized controlled trials published in China Journal of Chinese Materia Medica].

PubMed

Yu, Dan-Dan; Xie, Yan-Ming; Liao, Xing; Zhi, Ying-Jie; Jiang, Jun-Jie; Chen, Wei

2018-02-01

To evaluate the methodological quality and reporting quality of randomized controlled trials(RCTs) published in China Journal of Chinese Materia Medica, we searched CNKI and China Journal of Chinese Materia webpage to collect RCTs since the establishment of the magazine. The Cochrane risk of bias assessment tool was used to evaluate the methodological quality of RCTs. The CONSORT 2010 list was adopted as reporting quality evaluating tool. Finally, 184 RCTs were included and evaluated methodologically, of which 97 RCTs were evaluated with reporting quality. For the methodological evaluating, 62 trials(33.70%) reported the random sequence generation; 9(4.89%) trials reported the allocation concealment; 25(13.59%) trials adopted the method of blinding; 30(16.30%) trials reported the number of patients withdrawing, dropping out and those lost to follow-up;2 trials （1.09%） reported trial registration and none of the trial reported the trial protocol; only 8(4.35%) trials reported the sample size estimation in details. For reporting quality appraising, 3 reporting items of 25 items were evaluated with high-quality,including: abstract, participants qualified criteria, and statistical methods; 4 reporting items with medium-quality, including purpose, intervention, random sequence method, and data collection of sites and locations; 9 items with low-quality reporting items including title, backgrounds, random sequence types, allocation concealment, blindness, recruitment of subjects, baseline data, harms, and funding;the rest of items were of extremely low quality(the compliance rate of reporting item<10%). On the whole, the methodological and reporting quality of RCTs published in the magazine are generally low. Further improvement in both methodological and reporting quality for RCTs of traditional Chinese medicine are warranted. It is recommended that the international standards and procedures for RCT design should be strictly followed to conduct high-quality trials. At the same time, in order to improve the reporting quality of randomized controlled trials, CONSORT standards should be adopted in the preparation of research reports and submissions. Copyright© by the Chinese Pharmaceutical Association.

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.

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.

Generalizing Evidence From Randomized Clinical Trials to Target Populations

PubMed Central

Cole, Stephen R.; Stuart, Elizabeth A.

2010-01-01

Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results. PMID:20547574

EEG Neurofeedback for ADHD: Double-Blind Sham-Controlled Randomized Pilot Feasibility Trial

ERIC Educational Resources Information Center

Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara

2013-01-01

Objective: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. Method: Unmedicated 6- to 12-year-olds with "Diagnostic and Statistical Manual of…

The Sonoma Water Evaluation Trial (SWET): A randomized drinking water intervention trial to reduce gastrointestinal illness in older adults

EPA Science Inventory

Objectives. We estimate the risk of highly credible gastrointestinal illness (HCGI) among adults 55 and older in a community drinking tap water meeting current U.S. standards. Methods. We conducted a randomized, triple-blinded, crossover trial in 714 households (988 indiv...

The prompted optional randomization trial: a new design for comparative effectiveness research.

PubMed

Flory, James; Karlawish, Jason

2012-12-01

Randomized controlled trials are the gold standard for medical evidence because randomization provides the best-known protection against confounding of results. Randomization has practical and ethical problems that limit the number of trials that can be conducted, however. A different method for collecting clinical data retains the statistically useful properties of randomization without incurring its practical and ethical challenges. A computerized prompt introduces a random element into clinical decision-making that can be instantly overridden if it conflicts with optimal patient care. This creates a weak form of randomization that still eliminates the effect of all confounders, can be carried out without disturbing routine clinical care, and arguably will not require research-grade informed consent.

[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.

Lack of Interaction between Sensing-Intuitive Learning Styles and Problem-First versus Information-First Instruction: A Randomized Crossover Trial

ERIC Educational Resources Information Center

Cook, David A.; Thompson, Warren G.; Thomas, Kris G.; Thomas, Matthew R.

2009-01-01

Background: Adaptation to learning styles has been proposed to enhance learning. Objective: We hypothesized that learners with sensing learning style would perform better using a problem-first instructional method while intuitive learners would do better using an information-first method. Design: Randomized, controlled, crossover trial. Setting:…

Randomized Controlled Trial of a Preventive Intervention for Perinatal Depression in High-Risk Latinas

ERIC Educational Resources Information Center

Le, Huynh-Nhu; Perry, Deborah F.; Stuart, Elizabeth A.

2011-01-01

Objective: A randomized controlled trial was conducted to evaluate the efficacy of a cognitive-behavioral (CBT) intervention to prevent perinatal depression in high-risk Latinas. Method: A sample of 217 participants, predominantly low-income Central American immigrants who met demographic and depression risk criteria, were randomized into usual…

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…

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…

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

ERIC Educational Resources Information Center

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

2016-01-01

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

Sydney Playground Project: A Cluster-Randomized Trial to Increase Physical Activity, Play, and Social Skills

ERIC Educational Resources Information Center

Bundy, Anita; Engelen, Lina; Wyver, Shirley; Tranter, Paul; Ragen, Jo; Bauman, Adrian; Baur, Louise; Schiller, Wendy; Simpson, Judy M.; Niehues, Anita N.; Perry, Gabrielle; Jessup, Glenda; Naughton, Geraldine

2017-01-01

Background: We assessed the effectiveness of a simple intervention for increasing children's physical activity, play, perceived competence/social acceptance, and social skills. Methods: A cluster-randomized controlled trial was conducted, in which schools were the clusters. Twelve Sydney (Australia) primary schools were randomly allocated to…

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

PubMed

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

2014-04-01

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

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.

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

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.

Complementary nonparametric analysis of covariance for logistic regression in a randomized clinical trial setting.

PubMed

Tangen, C M; Koch, G G

1999-03-01

In the randomized clinical trial setting, controlling for covariates is expected to produce variance reduction for the treatment parameter estimate and to adjust for random imbalances of covariates between the treatment groups. However, for the logistic regression model, variance reduction is not obviously obtained. This can lead to concerns about the assumptions of the logistic model. We introduce a complementary nonparametric method for covariate adjustment. It provides results that are usually compatible with expectations for analysis of covariance. The only assumptions required are based on randomization and sampling arguments. The resulting treatment parameter is a (unconditional) population average log-odds ratio that has been adjusted for random imbalance of covariates. Data from a randomized clinical trial are used to compare results from the traditional maximum likelihood logistic method with those from the nonparametric logistic method. We examine treatment parameter estimates, corresponding standard errors, and significance levels in models with and without covariate adjustment. In addition, we discuss differences between unconditional population average treatment parameters and conditional subpopulation average treatment parameters. Additional features of the nonparametric method, including stratified (multicenter) and multivariate (multivisit) analyses, are illustrated. Extensions of this methodology to the proportional odds model are also made.

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

ERIC Educational Resources Information Center

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

2011-01-01

Objective: To determine the effectiveness of brief strategic family therapy (BSFT; an evidence-based family therapy) compared to treatment as usual (TAU) as provided in community-based adolescent outpatient drug abuse programs. Method: A randomized effectiveness trial in the National Drug Abuse Treatment Clinical Trials Network compared BSFT to…

A Mixed-Methods Randomized Controlled Trial of Financial Incentives and Peer Networks to Promote Walking among Older Adults

ERIC Educational Resources Information Center

Kullgren, Jeffrey T.; Harkins, Kristin A.; Bellamy, Scarlett L.; Gonzales, Amy; Tao, Yuanyuan; Zhu, Jingsan; Volpp, Kevin G.; Asch, David A.; Heisler, Michele; Karlawish, Jason

2014-01-01

Background: Financial incentives and peer networks could be delivered through eHealth technologies to encourage older adults to walk more. Methods: We conducted a 24-week randomized trial in which 92 older adults with a computer and Internet access received a pedometer, daily walking goals, and weekly feedback on goal achievement. Participants…

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,…

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…

Randomized Controlled Trial in Clinical Settings to Evaluate Effectiveness of Coping Skills Education Used with Progressive Tinnitus Management

ERIC Educational Resources Information Center

Henry, James A.; Thielman, Emily J.; Zaugg, Tara L.; Kaelin, Christine; Schmidt, Caroline J.; Griest, Susan; McMillan, Garnett P.; Myers, Paula; Rivera, Izel; Baldwin, Robert; Carlson, Kathleen

2017-01-01

Purpose: This randomized controlled trial evaluated, within clinical settings, the effectiveness of coping skills education that is provided with progressive tinnitus management (PTM). Method: At 2 Veterans Affairs medical centers, N = 300 veterans were randomized to either PTM intervention or 6-month wait-list control. The PTM intervention…

Marital Status and Satisfaction Five Years Following a Randomized Clinical Trial Comparing Traditional versus Integrative Behavioral Couple Therapy

ERIC Educational Resources Information Center

Christensen, Andrew; Atkins, David C.; Baucom, Brian; Yi, Jean

2010-01-01

Objective: To follow distressed married couples for 5 years after their participation in a randomized clinical trial. Method: A total of 134 chronically and seriously distressed married couples were randomly assigned to approximately 8 months of either traditional behavioral couple therapy (TBCT; Jacobson & Margolin, 1979) or integrative…

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…

Effects of Cognitive Enhancement Therapy on Employment Outcomes in Early Schizophrenia: Results from a 2-Year Randomized Trial

ERIC Educational Resources Information Center

Eack, Shaun M.; Hogarty, Gerard E.; Greenwald, Deborah P.; Hogarty, Susan S.; Keshavan, Matcheri S.

2011-01-01

Objective: To examine the effects of psychosocial cognitive rehabilitation on employment outcomes in a randomized controlled trial for individuals with early course schizophrenia. Method: Early course schizophrenia outpatients (N = 58) were randomly assigned to cognitive enhancement therapy (CET) or an enriched supportive therapy (EST) control and…

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…

Methodological Reporting of Randomized Trials in Five Leading Chinese Nursing Journals

PubMed Central

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

2014-01-01

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

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 general method for handling missing binary outcome data in randomized controlled trials

PubMed Central

Jackson, Dan; White, Ian R; Mason, Dan; Sutton, Stephen

2014-01-01

Aims The analysis of randomized controlled trials with incomplete binary outcome data is challenging. We develop a general method for exploring the impact of missing data in such trials, with a focus on abstinence outcomes. Design We propose a sensitivity analysis where standard analyses, which could include ‘missing = smoking’ and ‘last observation carried forward’, are embedded in a wider class of models. Setting We apply our general method to data from two smoking cessation trials. Participants A total of 489 and 1758 participants from two smoking cessation trials. Measurements The abstinence outcomes were obtained using telephone interviews. Findings The estimated intervention effects from both trials depend on the sensitivity parameters used. The findings differ considerably in magnitude and statistical significance under quite extreme assumptions about the missing data, but are reasonably consistent under more moderate assumptions. Conclusions A new method for undertaking sensitivity analyses when handling missing data in trials with binary outcomes allows a wide range of assumptions about the missing data to be assessed. In two smoking cessation trials the results were insensitive to all but extreme assumptions. PMID:25171441

Effects of a Psychological Intervention in a Primary Health Care Center for Caregivers of Dependent Relatives: A Randomized Trial

ERIC Educational Resources Information Center

Rodriguez-Sanchez, Emiliano; Patino-Alonso, Maria C.; Mora-Simon, Sara; Gomez-Marcos, Manuel A.; Perez-Penaranda, Anibal; Losada-Baltar, Andres; Garcia-Ortiz, Luis

2013-01-01

Purpose: To assess, in the context of Primary Health Care (PHC), the effect of a psychological intervention in mental health among caregivers (CGs) of dependent relatives. Design and Methods: Randomized multicenter, controlled clinical trial. The 125 CGs included in the trial were receiving health care in PHC. Inclusion criteria: Identifying…

Estimates of Intraclass Correlation Coefficients from Longitudinal Group-Randomized Trials of Adolescent HIV/STI/Pregnancy Prevention Programs

ERIC Educational Resources Information Center

Glassman, Jill R.; Potter, Susan C.; Baumler, Elizabeth R.; Coyle, Karin K.

2015-01-01

Introduction: Group-randomized trials (GRTs) are one of the most rigorous methods for evaluating the effectiveness of group-based health risk prevention programs. Efficiently designing GRTs with a sample size that is sufficient for meeting the trial's power and precision goals while not wasting resources exceeding them requires estimates of the…

Clamp-Crushing versus stapler hepatectomy for transection of the parenchyma in elective hepatic resection (CRUNSH) - A randomized controlled trial (NCT01049607)

PubMed Central

2011-01-01

Background Hepatic resection is still associated with significant morbidity. Although the period of parenchymal transection presents a crucial step during the operation, uncertainty persists regarding the optimal technique of transection. It was the aim of the present randomized controlled trial to evaluate the efficacy and safety of hepatic resection using the technique of stapler hepatectomy compared to the simple clamp-crushing technique. Methods/Design The CRUNSH Trial is a prospective randomized controlled single-center trial with a two-group parallel design. Patients scheduled for elective hepatic resection without extrahepatic resection at the Department of General-, Visceral- and Transplantation Surgery, University of Heidelberg are enrolled into the trial and randomized intraoperatively to hepatic resection by the clamp-crushing technique and stapler hepatectomy, respectively. The primary endpoint is total intraoperative blood loss. A set of general and surgical variables are documented as secondary endpoints. Patients and outcome-assessors are blinded for the treatment intervention. Discussion The CRUNSH Trial is the first randomized controlled trial to evaluate efficacy and safety of stapler hepatectomy compared to the clamp-crushing technique for parenchymal transection during elective hepatic resection. Trial Registration ClinicalTrials.gov: NCT01049607 PMID:21888669

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.

Lay public's understanding of equipoise and randomisation in randomised controlled trials.

PubMed

Robinson, E J; Kerr, C E P; Stevens, A J; Lilford, R J; Braunholtz, D A; Edwards, S J; Beck, S R; Rowley, M G

2005-03-01

To research the lay public's understanding of equipoise and randomisation in randomised controlled trials (RCTs) and to look at why information on this may not be not taken in or remembered, as well as the effects of providing information designed to overcome barriers. Investigations were informed by an update of systematic review on patients' understanding of consent information in clinical trials, and by relevant theory and evidence from experimental psychology. Nine investigations were conducted with nine participants. Access (return to education), leisure and vocational courses at Further Education Colleges in the Midlands, UK. Healthy adults with a wide range of educational backgrounds and ages. Participants read hypothetical scenarios and wrote brief answers to subsequent questions. Sub-samples of participants were interviewed individually to elaborate on their written answers. Participants' background assumptions concerning equipoise and randomisation were examined and ways of helping participants recognise the scientific benefits of randomisation were explored. Judgments on allocation methods; treatment preferences; the acceptability of random allocation; whether or not individual doctors could be completely unsure about the best treatment; whether or not doctors should reveal treatment preferences under conditions of collective equipoise; and how sure experts would be about the best treatment following random allocation vs doctor/patient choice. Assessments of understanding hypothetical trial information. Recent literature continues to report trial participants' failure to understand or remember information about randomisation and equipoise, despite the provision of clear and readable trial information leaflets. In current best practice, written trial information describes what will happen without offering accessible explanations. As a consequence, patients may create their own incorrect interpretations and consent or refusal may be inadequately informed. In six investigations, most participants identified which methods of allocation were random, but judged the random allocation methods to be unacceptable in a trial context; the mere description of a treatment as new was insufficient to engender a preference for it over a standard treatment; around half of the participants denied that a doctor could be completely unsure about the best treatment. A majority of participants judged it unacceptable for a doctor to suggest letting chance decide when uncertain of the best treatment, and, in the absence of a justification for random allocation, participants did not recognise scientific benefits of random allocation over normal treatment allocation methods. The pattern of results across three intervention studies suggests that merely supplementing written trial information with an explanation is unlikely to be helpful. However, when people manage to focus on the trial's aim of increasing knowledge (as opposed to making treatment decisions about individuals), and process an explanation actively, they may be helped to understand the scientific reasons for random allocation. This research was not carried out in real healthcare settings. However, participants who could correctly identify random allocation methods, yet judged random allocation unacceptable, doubted the possibility of individual equipoise and saw no scientific benefits of random allocation over doctor/patient choice, are unlikely to draw upon contrasting views if invited to enter a real clinical trial. This suggests that many potential trial participants may have difficulty understanding and remembering trial information that conforms to current best practice in its descriptions of randomisation and equipoise. Given the extent of the disparity between the assumptions underlying trial design and the assumptions held by the lay public, the solution is unlikely to be simple. Nevertheless, the results suggest that including an accessible explanation of the scientific benefits of randomisation may be beneficial provided potential participants are also enabled to reflect on the trial's aim of advancing knowledge, and to think actively about the information presented. Further areas for consideration include: the identification of effective combinations of written and oral information; helping participants to reflect on the aim of advancing knowledge; and an evidence-based approach to leaflet construction.

A Cluster Randomized Controlled Trial Testing the Effectiveness of Houvast: A Strengths-Based Intervention for Homeless Young Adults

ERIC Educational Resources Information Center

Krabbenborg, Manon A. M.; Boersma, Sandra N.; van der Veld, William M.; van Hulst, Bente; Vollebergh, Wilma A. M.; Wolf, Judith R. L. M.

2017-01-01

Objective: To test the effectiveness of Houvast: a strengths-based intervention for homeless young adults. Method: A cluster randomized controlled trial was conducted with 10 Dutch shelter facilities randomly allocated to an intervention and a control group. Homeless young adults were interviewed when entering the facility and when care ended.…

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

ERIC Educational Resources Information Center

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

2009-01-01

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

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…

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.

Effective Recruitment of Schools for Randomized Clinical Trials: Role of School Nurses.

PubMed

Petosa, R L; Smith, L

2017-01-01

In school settings, nurses lead efforts to improve the student health and well-being to support academic success. Nurses are guided by evidenced-based practice and data to inform care decisions. The randomized controlled trial (RCT) is considered the gold standard of scientific rigor for clinical trials. RCTs are critical to the development of evidence-based health promotion programs in schools. The purpose of this article is to present practical solutions to implementing principles of randomization to RCT trials conducted in school settings. Randomization is a powerful sampling method used to build internal and external validity. The school's daily organization and educational mission provide several barriers to randomization. Based on the authors' experience in conducting school-based RCTs, they offer a host of practical solutions to working with schools to successfully implement randomization procedures. Nurses play a critical role in implementing RCTs in schools to promote rigorous science in support of evidence-based practice.

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

PubMed

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

2009-01-01

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

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

Differential Susceptibility to Prevention: GABAergic, Dopaminergic, and Multilocus Effects

ERIC Educational Resources Information Center

Brody, Gene H.; Chen, Yi-fu; Beach, Steven R. H.

2013-01-01

Background: Randomized prevention trials provide a unique opportunity to test hypotheses about the interaction of genetic predispositions with contextual processes to create variations in phenotypes over time. Methods: Using two longitudinal, randomized prevention trials, molecular genetic and alcohol use outcome data were gathered from more than…

Recruitment strategies in two Reproductive Medicine Network infertility trials

PubMed Central

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

2016-01-01

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

Recruitment 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.

Blocking for Sequential Political Experiments

PubMed Central

Moore, Sally A.

2013-01-01

In typical political experiments, researchers randomize a set of households, precincts, or individuals to treatments all at once, and characteristics of all units are known at the time of randomization. However, in many other experiments, subjects “trickle in” to be randomized to treatment conditions, usually via complete randomization. To take advantage of the rich background data that researchers often have (but underutilize) in these experiments, we develop methods that use continuous covariates to assign treatments sequentially. We build on biased coin and minimization procedures for discrete covariates and demonstrate that our methods outperform complete randomization, producing better covariate balance in simulated data. We then describe how we selected and deployed a sequential blocking method in a clinical trial and demonstrate the advantages of our having done so. Further, we show how that method would have performed in two larger sequential political trials. Finally, we compare causal effect estimates from differences in means, augmented inverse propensity weighted estimators, and randomization test inversion. PMID:24143061

Recruiting Unmotivated Smokers into a Smoking Induction Trial

ERIC Educational Resources Information Center

Harris, Kari Jo; Bradley-Ewing, Andrea; Goggin, Kathy; Richter, Kimber P.; Patten, Christi; Williams, Karen; Lee, Hyoung S.; Staggs, Vincent S.; Catley, Delwyn

2016-01-01

Little is known about effective methods to recruit unmotivated smokers into cessation induction trials, the reasons unmotivated smokers agree to participate, and the impact of those reasons on study outcomes. A mixed-method approach was used to examine recruitment data from a randomized controlled cessation induction trial that enrolled 255 adult…

Improved Cardiovascular Prevention Using Best CME Practices: A Randomized Trial

ERIC Educational Resources Information Center

Laprise, Rejean; Thivierge, Robert; Gosselin, Gilbert; Bujas-Bobanovic, Maja; Vandal, Sylvie; Paquette, Daniel; Luneau, Micheline; Julien, Pierre; Goulet, Serge; Desaulniers, Jean; Maltais, Paule

2009-01-01

Introduction: It was hypothesized that after a continuing medical education (CME) event, practice enablers and reinforcers addressing main clinical barriers to preventive care would be more effective in improving general practitioners' (GPs) adherence to cardiovascular guidelines than a CME event only. Methods: A cluster-randomized trial was…

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

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.

A general method for handling missing binary outcome data in randomized controlled trials.

PubMed

Jackson, Dan; White, Ian R; Mason, Dan; Sutton, Stephen

2014-12-01

The analysis of randomized controlled trials with incomplete binary outcome data is challenging. We develop a general method for exploring the impact of missing data in such trials, with a focus on abstinence outcomes. We propose a sensitivity analysis where standard analyses, which could include 'missing = smoking' and 'last observation carried forward', are embedded in a wider class of models. We apply our general method to data from two smoking cessation trials. A total of 489 and 1758 participants from two smoking cessation trials. The abstinence outcomes were obtained using telephone interviews. The estimated intervention effects from both trials depend on the sensitivity parameters used. The findings differ considerably in magnitude and statistical significance under quite extreme assumptions about the missing data, but are reasonably consistent under more moderate assumptions. A new method for undertaking sensitivity analyses when handling missing data in trials with binary outcomes allows a wide range of assumptions about the missing data to be assessed. In two smoking cessation trials the results were insensitive to all but extreme assumptions. © 2014 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

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.

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.

Comparison of Time-to-First Event and Recurrent Event Methods in Randomized Clinical Trials.

PubMed

Claggett, Brian; Pocock, Stuart; Wei, L J; Pfeffer, Marc A; McMurray, John J V; Solomon, Scott D

2018-03-27

Background -Most Phase-3 trials feature time-to-first event endpoints for their primary and/or secondary analyses. In chronic diseases where a clinical event can occur more than once, recurrent-event methods have been proposed to more fully capture disease burden and have been assumed to improve statistical precision and power compared to conventional "time-to-first" methods. Methods -To better characterize factors that influence statistical properties of recurrent-events and time-to-first methods in the evaluation of randomized therapy, we repeatedly simulated trials with 1:1 randomization of 4000 patients to active vs control therapy, with true patient-level risk reduction of 20% (i.e. RR=0.80). For patients who discontinued active therapy after a first event, we assumed their risk reverted subsequently to their original placebo-level risk. Through simulation, we varied a) the degree of between-patient heterogeneity of risk and b) the extent of treatment discontinuation. Findings were compared with those from actual randomized clinical trials. Results -As the degree of between-patient heterogeneity of risk was increased, both time-to-first and recurrent-events methods lost statistical power to detect a true risk reduction and confidence intervals widened. The recurrent-events analyses continued to estimate the true RR=0.80 as heterogeneity increased, while the Cox model produced estimates that were attenuated. The power of recurrent-events methods declined as the rate of study drug discontinuation post-event increased. Recurrent-events methods provided greater power than time-to-first methods in scenarios where drug discontinuation was ≤30% following a first event, lesser power with drug discontinuation rates of ≥60%, and comparable power otherwise. We confirmed in several actual trials in chronic heart failure that treatment effect estimates were attenuated when estimated via the Cox model and that increased statistical power from recurrent-events methods was most pronounced in trials with lower treatment discontinuation rates. Conclusions -We find that the statistical power of both recurrent-events and time-to-first methods are reduced by increasing heterogeneity of patient risk, a parameter not included in conventional power and sample size formulas. Data from real clinical trials are consistent with simulation studies, confirming that the greatest statistical gains from use of recurrent-events methods occur in the presence of high patient heterogeneity and low rates of study drug discontinuation.

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.

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 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…

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…

The Cost-Effectiveness of Education Interventions in Poor Countries. Policy Insight, Volume 2, Issue 4

ERIC Educational Resources Information Center

Evans, David K.; Ghosh, Arkadipta

2008-01-01

Poor countries need development programs that are both effective and cost-effective. To assess effectiveness, researchers are increasingly using randomized trials (or quasi-experimental methods that imitate randomized trials), which provide a clear picture of which outcomes are attributable to the program being evaluated. This "Policy Insight"…

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…

A Randomized Effectiveness Trial of Brief Cognitive-Behavioral Therapy for Depressed Adolescents Receiving Antidepressant Medication

ERIC Educational Resources Information Center

Clarke, Gregory; DeBar, Lynn; Lynch, Frances; Powell, James; Gale, John; O'Connor, Elizabeth; Ludman, Evette; Bush, Terry; Lin, Elizabeth H. B.; Von Korff, Michael; Hertert, Stephanie

2005-01-01

Objective: To test a collaborative-care, cognitive-behavioral therapy (CBT) program adjunctive to selective serotonin reuptake inhibitor (SSRI) treatment in HMO pediatric primary care. Method: A randomized effectiveness trial comparing a treatment-as-usual (TAU) control condition consisting primarily of SSRI medication delivered outside the…

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…

A Compound Herbal Preparation (CHP) in the Treatment of Children with ADHD: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Katz, M.; Adar Levine, A.; Kol-Degani, H.; Kav-Venaki, L.

2010-01-01

Objective: Evaluation of the efficacy of a patented, compound herbal preparation (CHP) in improving attention, cognition, and impulse control in children with ADHD. Method: Design: A randomized, double-blind, placebo-controlled trial. Setting: University-affiliated tertiary medical center. Participants: 120 children newly diagnosed with ADHD,…

Randomized, Controlled Trial of Atomoxetine for Attention-Deficit/Hyperactivity Disorder in Adolescents with Substance Use Disorder

ERIC Educational Resources Information Center

Thurstone, Christian; Riggs, Paula D.; Salomonsen-Sautel, Stacy; Mikulich-Gilbertson, Susan K.

2010-01-01

Objective: To evaluate the effect of atomoxetine hydrochloride versus placebo on attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) in adolescents receiving motivational interviewing/cognitive behavioral therapy (MI/CBT) for SUD. Method: This single-site, randomized, controlled trial was conducted between December…

Intervention for Verb Argument Structure in Children with Persistent SLI: A Randomized Control Trial

ERIC Educational Resources Information Center

Ebbels, Susan H.; van der Lely, Heather K. J.; Dockrell, Julie E.

2007-01-01

Purpose: The authors aimed to establish whether 2 theoretically motivated interventions could improve use of verb argument structure in pupils with persistent specific language impairment (SLI). Method: Twenty-seven pupils with SLI (ages 11;0-16;1) participated in this randomized controlled trial with "blind" assessment. Participants were randomly…

Methods of Learning in Statistical Education: A Randomized Trial of Public Health Graduate Students

ERIC Educational Resources Information Center

Enders, Felicity Boyd; Diener-West, Marie

2006-01-01

A randomized trial of 265 consenting students was conducted within an introductory biostatistics course: 69 received eight small group cooperative learning sessions; 97 accessed internet learning sessions; 96 received no intervention. Effect on examination score (95% CI) was assessed by intent-to-treat analysis and by incorporating reported…

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…

Interpretation Training in Individuals with Generalized Social Anxiety Disorder: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Amir, Nader; Taylor, Charles T.

2012-01-01

Objective: To examine the efficacy of a multisession computerized interpretation modification program (IMP) in the treatment of generalized social anxiety disorder (GSAD). Method: The sample comprised 49 individuals meeting diagnostic criteria for GSAD who were enrolled in a randomized, double-blind placebo-controlled trial comparing IMP (n = 23)…

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 &…

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

Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods

PubMed Central

2010-01-01

Objective To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents. Methods Following a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described. Results CAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years) with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance. Conclusions CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI) treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results of CAMS will hold important implications for informing practice-relevant decisions regarding the initial treatment of youth with anxiety disorders. Trial registration ClinicalTrials.gov NCT00052078. PMID:20051130

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.

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

PubMed Central

2013-01-01

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

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

A randomized controlled trial of acupuncture and moxibustion to treat Bell's palsy according to different stages: design and protocol.

PubMed

Chen, Xiaoqin; Li, Ying; Zheng, Hui; Hu, Kaming; Zhang, Hongxing; Zhao, Ling; Li, Yan; Liu, Lian; Mang, Lingling; Yu, Shuyuan

2009-07-01

Acupuncture to treat Bell's palsy is one of the most commonly used methods in China. There are a variety of acupuncture treatment options to treat Bell's palsy in clinical practice. Since Bell's palsy has three different path-stages (acute stage, resting stage and restoration stage), so whether acupuncture is effective in the different path-stages and which acupuncture treatment is the best method are major issues in acupuncture clinical trials about Bell's palsy. In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with acupuncture. There are five acupuncture groups, with four according to different path-stages and one not. In total, 900 patients with Bell's palsy are enrolled in this study. These patients are randomly assigned to receive one of the following four treatment groups according to different path-stages, i.e. 1) staging acupuncture group, 2) staging acupuncture and moxibustion group, 3) staging electro-acupuncture group, 4) staging acupuncture along yangming musculature group or non-staging acupuncture control group. The outcome measurements in this trial are the effect comparison achieved among these five groups in terms of House-Brackmann scale (Global Score and Regional Score), Facial Disability Index scale, Classification scale of Facial Paralysis, and WHOQOL-BREF scale before randomization (baseline phase) and after randomization. The result of this trial will certify the efficacy of using staging acupuncture and moxibustion to treat Bell's palsy, and to approach a best acupuncture treatment among these five different methods for treating Bell's palsy.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis.

PubMed

Messier, S P; Callahan, L F; Golightly, Y M; Keefe, F J

2015-05-01

The objective was to develop a set of "best practices" for use as a primer for those interested in entering the clinical trials field for lifestyle diet and/or exercise interventions in osteoarthritis (OA), and as a set of recommendations for experienced clinical trials investigators. A subcommittee of the non-pharmacologic therapies committee of the OARSI Clinical Trials Working Group was selected by the Steering Committee to develop a set of recommended principles for non-pharmacologic diet/exercise OA randomized clinical trials. Topics were identified for inclusion by co-authors and reviewed by the subcommittee. Resources included authors' expert opinions, traditional search methods including MEDLINE (via PubMed), and previously published guidelines. Suggested steps and considerations for study methods (e.g., recruitment and enrollment of participants, study design, intervention and assessment methods) were recommended. The recommendations set forth in this paper provide a guide from which a research group can design a lifestyle diet/exercise randomized clinical trial in patients with OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Inference of median difference based on the Box-Cox model in randomized clinical trials.

PubMed

Maruo, K; Isogawa, N; Gosho, M

2015-05-10

In randomized clinical trials, many medical and biological measurements are not normally distributed and are often skewed. The Box-Cox transformation is a powerful procedure for comparing two treatment groups for skewed continuous variables in terms of a statistical test. However, it is difficult to directly estimate and interpret the location difference between the two groups on the original scale of the measurement. We propose a helpful method that infers the difference of the treatment effect on the original scale in a more easily interpretable form. We also provide statistical analysis packages that consistently include an estimate of the treatment effect, covariance adjustments, standard errors, and statistical hypothesis tests. The simulation study that focuses on randomized parallel group clinical trials with two treatment groups indicates that the performance of the proposed method is equivalent to or better than that of the existing non-parametric approaches in terms of the type-I error rate and power. We illustrate our method with cluster of differentiation 4 data in an acquired immune deficiency syndrome clinical trial. Copyright © 2015 John Wiley & Sons, Ltd.

Cluster randomized trials in comparative effectiveness research: randomizing hospitals to test methods for prevention of healthcare-associated infections.

PubMed

Platt, Richard; Takvorian, Samuel U; Septimus, Edward; Hickok, Jason; Moody, Julia; Perlin, Jonathan; Jernigan, John A; Kleinman, Ken; Huang, Susan S

2010-06-01

The need for evidence about the effectiveness of therapeutics and other medical practices has triggered new interest in methods for comparative effectiveness research. Describe an approach to comparative effectiveness research involving cluster randomized trials in networks of hospitals, health plans, or medical practices with centralized administrative and informatics capabilities. We discuss the example of an ongoing cluster randomized trial to prevent methicillin-resistant Staphylococcus aureus (MRSA) infection in intensive care units (ICUs). The trial randomizes 45 hospitals to: (a) screening cultures of ICU admissions, followed by Contact Precautions if MRSA-positive, (b) screening cultures of ICU admissions followed by decolonization if MRSA-positive, or (c) universal decolonization of ICU admissions without screening. All admissions to adult ICUs. The primary outcome is MRSA-positive clinical cultures occurring >or=2 days following ICU admission. Secondary outcomes include blood and urine infection caused by MRSA (and, separately, all pathogens), as well as the development of resistance to decolonizing agents. Recruitment of hospitals is complete. Data collection will end in Summer 2011. This trial takes advantage of existing personnel, procedures, infrastructure, and information systems in a large integrated hospital network to conduct a low-cost evaluation of prevention strategies under usual practice conditions. This approach is applicable to many comparative effectiveness topics in both inpatient and ambulatory settings.

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.

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

PubMed

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

2016-10-01

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

Clinical trial design for orthodontists.

PubMed

Pandis, Nikolaos; Cobourne, Martyn T

2013-06-01

High-quality research should form the basis of all clinical practice. Randomized controlled trials currently provide the gold standard for investigating the effectiveness of treatment interventions and these are increasingly being used in orthodontics. Here we discuss the reasons why this form of investigation provides the most useful evidence for assessing treatment outcome. The methods available to achieve true randomization, a fundamental component in the design of these trials, are also discussed. In addition, we focus on how to minimize bias in clinical research, not only during the design and management of a trial, but also when disseminating results. We focus on the importance of using control groups correctly and describe methods that are available to adequately power a trial. Finally, we emphasise the importance of accurate and transparent reporting, which facilitates correct communication and assessment of the evidence.

Cost-effectiveness of Recruitment Methods in an Obesity Prevention Trial for Young Children

PubMed Central

Robinson, Jodie L.; Fuerch, Janene H.; Winiewicz, Dana D.; Salvy, Sarah J.; Roemmich, James N.; Epstein, Leonard H.

2007-01-01

Background Recruitment of participants for clinical trials requires considerable effort and cost. There is no research on the cost-effectiveness of recruitment methods for an obesity prevention trial of young children. Methods This study determined the cost-effectiveness of recruiting 70 families with a child aged 4 to 7 (5.9 ± 1.3) years in Western New York from February, 2003 to November, 2004, for a two year randomized obesity prevention trial to reduce television watching in the home. Results Of the 70 randomized families, 65.7% (n = 46) were obtained through direct mailings, 24.3% (n = 17) were acquired through newspaper advertisements, 7.1 % (n = 5) from other sources (e.g. word of mouth), and 2.9% (n = 2) through posters and brochures. Costs of each recruitment method were computed by adding the cost of materials, staff time, and media expenses. Cost-effectiveness (money spent per randomized participant) was US $0 for other sources, US $227.76 for direct mailing, US $546.95 for newspaper ads, and US $3,020.84 for posters and brochures. Conclusion Of the methods with associated costs, direct mailing was the most cost effective in recruiting families with young children, which supports the growing literature of the effectiveness of direct mailing. PMID:17475318

Effect of Atomoxetine on Executive Function Impairments in Adults with ADHD

ERIC Educational Resources Information Center

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

2011-01-01

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

A Randomized Controlled Trial of Koru: A Mindfulness Program for College Students and Other Emerging Adults

ERIC Educational Resources Information Center

Greeson, Jeffrey M.; Juberg, Michael K.; Maytan, Margaret; James, Kiera; Rogers, Holly

2014-01-01

Objective: To evaluate the effectiveness of Koru, a mindfulness training program for college students and other emerging adults. Participants: Ninety students (66% female, 62% white, 71% graduate students) participated between Fall 2012 and Spring 2013. Methods: Randomized controlled trial. It was hypothesized that Koru, compared with a wait-list…

Nasal Oxytocin for Social Deficits in Childhood Autism: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Dadds, Mark R.; MacDonald, Elayne; Cauchi, Avril; Williams, Katrina; Levy, Florence; Brennan, John

2014-01-01

The last two decades have witnessed a surge in research investigating the application of oxytocin as a method of enhancing social behaviour in humans. Preliminary evidence suggests oxytocin may have potential as an intervention for autism. We evaluated a 5-day "live-in" intervention using a double-blind randomized control trial. 38 male…

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…

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…

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…

Attachment-Based Family Therapy for Adolescents with Suicidal Ideation: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Diamond, Guy S.; Wintersteen, Matthew B.; Brown, Gregory K.; Diamond, Gary M.; Gallop, Robert; Shelef, Karni; Levy, Suzanne

2010-01-01

Objective: To evaluate whether Attachment-Based Family Therapy (ABFT) is more effective than Enhanced Usual Care (EUC) for reducing suicidal ideation and depressive symptoms in adolescents. Method: This was a randomized controlled trial of suicidal adolescents between the ages of 12 and 17, identified in primary care and emergency departments. Of…

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…

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…

A Double-Blind, Randomized, Placebo-Controlled Trial of Escitalopram in the Treatment of Pediatric Depression

ERIC Educational Resources Information Center

Wagner, Karen Dineen; Jonas, Jeffrey; Findling, Robert L.; Ventura, Daniel; Saikali, Khalil

2006-01-01

Objective: Escitalopram is a selective serotonin reuptake inhibitor antidepressant indicated for use in adults. This trial examined the efficacy and safety of escitalopram in pediatric depression. Method: Patients (6-17 years old) with major depressive disorder were randomized to receive 8 weeks of double-blind flexibly dosed treatment with…

Randomized Controlled Trial Examining the Effectiveness of a Tailored Self-Help Smoking-Cessation Intervention for Postsecondary Smokers

ERIC Educational Resources Information Center

Travis, Heather E.; Lawrance, Kelli-an G.

2009-01-01

Objective: Between September 2002 and February 2003, the authors assessed the effectiveness of a new, age-tailored, self-help smoking-cessation program for college students. Participants: College student smokers (N = 216) from 6 Ontario universities participated. Methods: The researchers used a randomized controlled trial with a 3-month telephone…

Cancer Screening Knowledge Changes: Results from a Randomized Control Trial of Women with Developmental Disabilities

ERIC Educational Resources Information Center

Parish, Susan L.; Rose, Roderick A.; Luken, Karen; Swaine, Jamie G.; O'Hare, Lindsey

2012-01-01

Background: Women with developmental disabilities are much less likely than nondisabled women to receive cervical and breast cancer screening according to clinical guidelines. One barrier to receipt of screenings is a lack of knowledge about preventive screenings. Method: To address this barrier, we used a randomized control trial (n = 175 women)…

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.…

Cognitive Behavioral Therapy for 4- to 7-Year-Old Children with Anxiety Disorders: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Hirshfeld-Becker, Dina R.; Masek, Bruce; Henin, Aude; Blakely, Lauren Raezer; Pollock-Wurman, Rachel A.; McQuade, Julia; DePetrillo, Lillian; Briesch, Jacquelyn; Ollendick, Thomas H.; Rosenbaum, Jerrold F.; Biederman, Joseph

2010-01-01

Objective: To examine the efficacy of a developmentally appropriate parent-child cognitive behavioral therapy (CBT) protocol for anxiety disorders in children ages 4-7 years. Method: Design: Randomized wait-list controlled trial. Conduct: Sixty-four children (53% female, mean age 5.4 years, 80% European American) with anxiety disorders were…

Reporting of embryo transfer methods in IVF research: a cross-sectional study.

PubMed

Gambadauro, Pietro; Navaratnarajah, Ramesan

2015-02-01

The reporting of embryo transfer methods in IVF research was assessed through a cross-sectional analysis of randomized controlled trials (RCTs) published between 2010 and 2011. A systematic search identified 325 abstracts; 122 RCTs were included in the study. Embryo transfer methods were described in 42 out of 122 articles (34%). Catheters (32/42 [76%]) or ultrasound guidance (31/42 [74%]) were most frequently mentioned. Performer 'blinding' (12%) or technique standardization (7%) were seldom reported. The description of embryo transfer methods was significantly more common in trials published by journals with lower impact factor (less than 3, 39.6%; 3 or greater, 21.5%; P = 0.037). Embryo transfer methods were reported more often in trials with pregnancy as the main end-point (33% versus 16%) or with positive outcomes (37.8% versus 25.0%), albeit not significantly. Multivariate logistic regression confirmed that RCTs published in higher impact factor journals are less likely to describe embryo transfer methods (OR 0.371; 95% CI 0.143 to 0.964). Registered trials, trials conducted in an academic setting, multi-centric studies or full-length articles were not positively associated with embryo transfer methods reporting rate. Recent reports of randomized IVF trials rarely describe embryo transfer methods. The under-reporting of research methods might compromise reproducibility and suitability for meta-analysis. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Clinical Knowledge from Observational Studies: Everything You Wanted to Know but Were Afraid to Ask.

PubMed

Gershon, Andrea S; Jafarzadeh, S Reza; Wilson, Kevin C; Walkey, Allan J

2018-05-07

Well-done randomized trials provide accurate estimates of treatment effect by producing groups that are similar on all measures except for the intervention of interest. However, inferences of efficacy in tightly-controlled experimental settings may not translate into similar effectiveness in real-world settings. Observational studies generally enable inferences over a wider range of patient characteristics and evaluation of a broader range of outcomes over a longer period than randomized trials. However, clinicians are often reluctant to incorporate the findings of observational studies into clinical practice. Reason for uncertainty regarding observational studies include a lack of familiarity with observational research methods, occasional disagreements between results of observational studies and randomized trials, the perceived risk of spurious results from systematic bias, and prior teaching that randomized trials are the most reliable source of medical evidence. We propose that a better understanding of observational research will enhance clinicians' ability to distinguish reliable observational studies from those that are subjected to biases and, therefore, provide more confidence to apply observational research results into clinical practice when appropriate. Herein, we explain why observational studies may be perceived as less conclusive than randomized trials, address situations in which observational research and randomized trials produced different findings, and provide information on observational study design so that quality can be evaluated. We conclude that observational research is a valuable source of medical evidence and that clinical action is strongest when supported by both high quality observational studies and randomized trials.

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

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.

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

PubMed Central

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

1977-01-01

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

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

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

PubMed Central

2013-01-01

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

A reanalysis of cluster randomized trials showed interrupted time-series studies were valuable in health system evaluation.

PubMed

Fretheim, Atle; Zhang, Fang; Ross-Degnan, Dennis; Oxman, Andrew D; Cheyne, Helen; Foy, Robbie; Goodacre, Steve; Herrin, Jeph; Kerse, Ngaire; McKinlay, R James; Wright, Adam; Soumerai, Stephen B

2015-03-01

There is often substantial uncertainty about the impacts of health system and policy interventions. Despite that, randomized controlled trials (RCTs) are uncommon in this field, partly because experiments can be difficult to carry out. An alternative method for impact evaluation is the interrupted time-series (ITS) design. Little is known, however, about how results from the two methods compare. Our aim was to explore whether ITS studies yield results that differ from those of randomized trials. We conducted single-arm ITS analyses (segmented regression) based on data from the intervention arm of cluster randomized trials (C-RCTs), that is, discarding control arm data. Secondarily, we included the control group data in the analyses, by subtracting control group data points from intervention group data points, thereby constructing a time series representing the difference between the intervention and control groups. We compared the results from the single-arm and controlled ITS analyses with results based on conventional aggregated analyses of trial data. The findings were largely concordant, yielding effect estimates with overlapping 95% confidence intervals (CI) across different analytical methods. However, our analyses revealed the importance of a concurrent control group and of taking baseline and follow-up trends into account in the analysis of C-RCTs. The ITS design is valuable for evaluation of health systems interventions, both when RCTs are not feasible and in the analysis and interpretation of data from C-RCTs. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Sample Size Calculations for Micro-randomized Trials in mHealth

PubMed Central

Liao, Peng; Klasnja, Predrag; Tewari, Ambuj; Murphy, Susan A.

2015-01-01

The use and development of mobile interventions are experiencing rapid growth. In “just-in-time” mobile interventions, treatments are provided via a mobile device and they are intended to help an individual make healthy decisions “in the moment,” and thus have a proximal, near future impact. Currently the development of mobile interventions is proceeding at a much faster pace than that of associated data science methods. A first step toward developing data-based methods is to provide an experimental design for testing the proximal effects of these just-in-time treatments. In this paper, we propose a “micro-randomized” trial design for this purpose. In a micro-randomized trial, treatments are sequentially randomized throughout the conduct of the study, with the result that each participant may be randomized at the 100s or 1000s of occasions at which a treatment might be provided. Further, we develop a test statistic for assessing the proximal effect of a treatment as well as an associated sample size calculator. We conduct simulation evaluations of the sample size calculator in various settings. Rules of thumb that might be used in designing a micro-randomized trial are discussed. This work is motivated by our collaboration on the HeartSteps mobile application designed to increase physical activity. PMID:26707831

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

Thymectomy in Myasthenia Gravis

PubMed Central

Aydin, Yener; Ulas, Ali Bilal; Mutlu, Vahit; Colak, Abdurrahim; Eroglu, Atilla

2017-01-01

In recent years, thymectomy has become a widespread procedure in the treatment of myasthenia gravis (MG). Likelihood of remission was highest in preoperative mild disease classification (Osserman classification 1, 2A). In absence of thymoma or hyperplasia, there was no relationship between age and gender in remission with thymectomy. In MG treatment, randomized trials that compare conservative treatment with thymectomy have started, recently. As with non-randomized trials, remission with thymectomy in MG treatment was better than conservative treatment with only medication. There are four major methods for the surgical approach: transcervical, minimally invasive, transsternal, and combined transcervical transsternal thymectomy. Transsternal approach with thymectomy is the accepted standard surgical approach for many years. In recent years, the incidence of thymectomy has been increasing with minimally invasive techniques using thoracoscopic and robotic methods. There are not any randomized, controlled studies which are comparing surgical techniques. However, when comparing non-randomized trials, it is seen that minimally invasive thymectomy approaches give similar results to more aggressive approaches. PMID:28416933

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 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

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.

A Randomized Controlled Trial of Internet-Delivered Cognitive Behavior Therapy and Acceptance and Commitment Therapy in the Treatment of Tinnitus

ERIC Educational Resources Information Center

Hesser, Hugo; Gustafsson, Tore; Lunden, Charlotte; Henrikson, Oskar; Fattahi, Kidjan; Johnsson, Erik; Westin, Vendela Zetterqvist; Carlbring, Per; Maki-Torkko, Elina; Kaldo, Viktor; Andersson, Gerhard

2012-01-01

Objective: Our aim in this randomized controlled trial was to investigate the effects on global tinnitus severity of 2 Internet-delivered psychological treatments, acceptance and commitment therapy (ACT) and cognitive behavior therapy (CBT), in guided self-help format. Method: Ninety-nine participants (mean age = 48.5 years; 43% female) who were…

Rigorous Program Evaluations on a Budget: How Low-Cost Randomized Controlled Trials Are Possible in Many Areas of Social Policy

ERIC Educational Resources Information Center

Coalition for Evidence-Based Policy, 2012

2012-01-01

The increasing ability of social policy researchers to conduct randomized controlled trials (RCTs) at low cost could revolutionize the field of performance-based government. RCTs are widely judged to be the most credible method of evaluating whether a social program is effective, overcoming the demonstrated inability of other, more common methods…

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…

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 =…

Randomized Controlled Trial of Problem-Solving Therapy for Minor Depression in Home Care

ERIC Educational Resources Information Center

Gellis, Zvi D.; McGinty, Jean; Tierney, Lynda; Jordan, Cindy; Burton, Jean; Misener, Elizabeth

2008-01-01

Objective: Data are presented from a pilot research program initiated to develop, refine, and test the outcomes of problem-solving therapy that targets the needs of older adults with minor depression in home care settings. Method: A pilot randomized clinical trial compares the impact of problem-solving therapy for home care to treatment as usual…

Effects of a Worksite Weight-Control Programme in Obese Male Workers: A Randomized Controlled Crossover Trial

ERIC Educational Resources Information Center

Iriyama, Yae; Murayama, Nobuko

2014-01-01

Objective: We conducted a randomized controlled crossover trial to evaluate the effects of a new worksite weight-control programme designed for men with or at risk of obesity using a combination of nutrition education and nutrition environmental interventions. Subjects and methods: Male workers with or at risk of obesity were recruited for this…

The Efficacy of Fast ForWord Language Intervention in School-Age Children with Language Impairment: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Gillam, Ronald B.; Loeb, Diane Frome; Hoffman, LaVae M.; Bohman, Thomas; Champlin, Craig A.; Thibodeau, Linda; Widen, Judith; Brandel, Jayne; Friel-Patti, Sandy

2008-01-01

Purpose: A randomized controlled trial was conducted to compare the language and auditory processing outcomes of children assigned to receive the Fast ForWord Language intervention (FFW-L) with the outcomes of children assigned to nonspecific or specific language intervention comparison treatments that did not contain modified speech. Method: Two…

Personality-Targeted Interventions Delay Uptake of Drinking and Decrease Risk of Alcohol-Related Problems when Delivered by Teachers

ERIC Educational Resources Information Center

O'Leary-Barrett, Maeve; Mackie, Clare J.; Castellanos-Ryan, Natalie; Al-Khudhairy, Nadia; Conrod, Patricia J.

2010-01-01

Objective: This trial examined the efficacy of teacher-delivered personality-targeted interventions for alcohol-misuse over a 6-month period. Method: This randomized controlled trial randomly allocated participating schools to intervention (n = 11) or control (n = 7) conditions. A total of 2,506 (mean age, 13.7 years) were assessed for elevated…

Does Maintenance CBT Contribute to Long-Term Treatment Response of Panic Disorder with or without Agoraphobia? A Randomized Controlled Clinical Trial

ERIC Educational Resources Information Center

White, Kamila S.; Payne, Laura A.; Gorman, Jack M.; Shear, M. Katherine; Woods, Scott W.; Saksa, John R.; Barlow, David H.

2013-01-01

Objective: We examined the possibility that maintenance cognitive behavior therapy (M-CBT) may improve the likelihood of sustained improvement and reduced relapse in a multi-site randomized controlled clinical trial of patients who met criteria for panic disorder with or without agoraphobia. Method: Participants were all patients (N = 379) who…

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

ERIC Educational Resources Information Center

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

2012-01-01

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

"Right from the Start": Randomized Trial Comparing an Attachment Group Intervention to Supportive Home Visiting

ERIC Educational Resources Information Center

Niccols, Alison

2008-01-01

Background: Infant attachment security is a protective factor for future mental health, and may be promoted by individual interventions. Given service demands, it is important to determine if a group-based intervention for parents could be used to enhance infant attachment security. Methods: In a randomized trial involving 76 mothers, an 8-session…

A Randomized Controlled Trial of Cognitive-Behavioral Therapy for Generalized Anxiety Disorder with Integrated Techniques from Emotion-Focused and Interpersonal Therapies

ERIC Educational Resources Information Center

Newman, Michelle G.; Castonguay, Louis G.; Borkovec, Thomas D.; Fisher, Aaron J.; Boswell, James F.; Szkodny, Lauren E.; Nordberg, Samuel S.

2011-01-01

Objective: Recent models suggest that generalized anxiety disorder (GAD) symptoms may be maintained by emotional processing avoidance and interpersonal problems. Method: This is the first randomized controlled trial to test directly whether cognitive-behavioral therapy (CBT) could be augmented with the addition of a module targeting interpersonal…

Cluster Randomized-Controlled Trial of Interventions to Improve Health for Adults with Intellectual Disability Who Live in Private Dwellings

ERIC Educational Resources Information Center

Lennox, Nicholas; Bain, Chris; Rey-Conde, Therese; Taylor, Miriam; Boyle, Frances M.; Purdie, David M.; Ware, Robert S.

2010-01-01

Background: People with intellectual disability who live in the community often have poor health and healthcare, partly as a consequence of poor communication, recall difficulties and incomplete patient health information. Materials and Methods: A cluster randomized-controlled trial with 2 x 2 factorial design was conducted with adults with…

The Acute Effect of Methylphenidate in Brazilian Male Children and Adolescents with ADHD: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Szobot, C. M.; Ketzer, C.; Parente, M. A.; Biederman, J.; Rohde, L. A.

2004-01-01

Objective: To evaluate the acute efficacy of methylphenidate (MPH) in Brazilian male children and adolescents with ADHD. Method: In a 4-day, double-blind, placebo-controlled, randomized, fix dose escalating, parallel-group trial, 36 ADHD children and adolescents were allocated to two groups: MPH (n = 19) and placebo (n = 17). Participants were…

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.

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.

Evaluation of the acceptability, feasibility and effectiveness of two methods of involving patients with disability in developing clinical guidelines: study protocol of a randomized pragmatic pilot trial.

PubMed

Lamontagne, Marie-Eve; Perreault, Kadija; Gagnon, Marie-Pierre

2014-04-10

Despite growing interest in the importance of, and challenges associated with the involvement of patient and population (IPP) in the process of developing and adapting clinical practice guidelines (CPGs), there is a lack of knowledge about the best method to use. This is especially problematic in the field of rehabilitation, where individuals with disabilities might face many barriers to their involvement in the guideline development and adaptation process. The goal of this pilot trial is to document the acceptability, feasibility and effectiveness of two methods of involving patients with a disability (traumatic brain injury) in CPG development. A single-blind, randomized, crossover pragmatic trial will be performed with 20 patients with traumatic brain injury (TBI). They will be randomized into two groups, and each will try two alternative methods of producing recommendations; a discussion group (control intervention) and a Wiki, a webpage that can be modified by those who have access to it (experimental intervention). The participants will rate the acceptability of the two methods, and feasibility will be assessed using indicators such as the number of participants who accessed and completed the two methods, and the number of support interventions required. Twenty experts, blinded to the method of producing the recommendations, will independently rate the recommendations produced by the participants for clarity, accuracy, appropriateness and usefulness. Our trial will allow for the use of optimal IPP methods in a larger project of adapting guidelines for the rehabilitation of individuals with TBI. Ultimately the results will inform the science of CPG development and contribute to the growing knowledge about IPP in rehabilitation settings. Clinical trial KT Canada 87776.

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

Cost effectiveness of recruitment methods in an obesity prevention trial for young children.

PubMed

Robinson, Jodie L; Fuerch, Janene H; Winiewicz, Dana D; Salvy, Sarah J; Roemmich, James N; Epstein, Leonard H

2007-06-01

Recruitment of participants for clinical trials requires considerable effort and cost. There is no research on the cost effectiveness of recruitment methods for an obesity prevention trial of young children. This study determined the cost effectiveness of recruiting 70 families with a child aged 4 to 7 (5.9+/-1.3) years in Western New York from February 2003 to November 2004, for a 2-year randomized obesity prevention trial to reduce television watching in the home. Of the 70 randomized families, 65.7% (n=46) were obtained through direct mailings, 24.3% (n=17) were acquired through newspaper advertisements, 7.1% (n=5) from other sources (e.g., word of mouth), and 2.9% (n=2) through posters and brochures. Costs of each recruitment method were computed by adding the cost of materials, staff time, and media expenses. Cost effectiveness (money spent per randomized participant) was US $0 for other sources, US $227.76 for direct mailing, US $546.95 for newspaper ads, and US $3,020.84 for posters and brochures. Of the methods with associated costs, direct mailing was the most cost effective in recruiting families with young children, which supports the growing literature of the effectiveness of direct mailing.

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).

Methodological and ethical aspects of randomized controlled clinical trials in minors with malignant diseases.

PubMed

Rothenberger, Lillian G; Henschel, Andreas Dirk; Schrey, Dominik; Becker, Andreas; Boos, Joachim

2011-10-01

Due to the new European regulations for pediatric medications, future clinical trials will include an increasing number of minors. It is therefore important to reconsider and evaluate recent methodological and ethical aspects of clinical trials in minors. The following questions were investigated: How are randomized controlled clinical trials (RCTs) performed in practice? Do investigators take into consideration biomedical ethical principles, explicated for example by Beauchamp and Childress, when planning and conducting a trial? The study was conducted in a descriptive manner. A systematic, algorithm-guided search focusing on RCTs in minors with malignant diseases was carried out in PubMed. One-thousand-nine-hundred-sixty-two publications from 2001 to 2005 were randomized in sequence. The first 1,000 publications were screened according to a priori defined inclusion criteria. One hundred seventy-five publications met the criteria and were reviewed using the SIGN methodological checklist (2004), the CONSORT Statement (2001, section Methods, items 3-12) and indicators for ethical aspects. Seventeen publications were checked by two raters. Information on randomization and blinding was often equivocal. The publications were mainly rated positive for the criteria of the SIGN checklist, and mostly rated negative for the additional items of the CONSORT Statement. Regarding the ethical principles, only few contributions were found in the publications. Inter-rater reliability was good. In the publications analyzed, we found only limited information concerning methods and reflections on ethical principles of the trials. Improvements are thus necessary and possible. We suggest how such trials and their respective publications can be optimized for these aspects. Copyright © 2011 Wiley-Liss, Inc.

A Comparison of Single Sample and Bootstrap Methods to Assess Mediation in Cluster Randomized Trials

ERIC Educational Resources Information Center

Pituch, Keenan A.; Stapleton, Laura M.; Kang, Joo Youn

2006-01-01

A Monte Carlo study examined the statistical performance of single sample and bootstrap methods that can be used to test and form confidence interval estimates of indirect effects in two cluster randomized experimental designs. The designs were similar in that they featured random assignment of clusters to one of two treatment conditions and…

A Bayesian sequential design with adaptive randomization for 2-sided hypothesis test.

PubMed

Yu, Qingzhao; Zhu, Lin; Zhu, Han

2017-11-01

Bayesian sequential and adaptive randomization designs are gaining popularity in clinical trials thanks to their potentials to reduce the number of required participants and save resources. We propose a Bayesian sequential design with adaptive randomization rates so as to more efficiently attribute newly recruited patients to different treatment arms. In this paper, we consider 2-arm clinical trials. Patients are allocated to the 2 arms with a randomization rate to achieve minimum variance for the test statistic. Algorithms are presented to calculate the optimal randomization rate, critical values, and power for the proposed design. Sensitivity analysis is implemented to check the influence on design by changing the prior distributions. Simulation studies are applied to compare the proposed method and traditional methods in terms of power and actual sample sizes. Simulations show that, when total sample size is fixed, the proposed design can obtain greater power and/or cost smaller actual sample size than the traditional Bayesian sequential design. Finally, we apply the proposed method to a real data set and compare the results with the Bayesian sequential design without adaptive randomization in terms of sample sizes. The proposed method can further reduce required sample size. Copyright © 2017 John Wiley & Sons, Ltd.

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

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

PubMed

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

2010-06-01

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

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

PubMed Central

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

2008-01-01

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

Usual and Unusual Care: Existing Practice Control Groups In Randomized Controlled Trials of Behavioral Interventions

PubMed Central

Freedland, Kenneth E.; Mohr, David C.; Davidson, Karina W.; Schwartz, Joseph E.

2011-01-01

Objective To examine the use of existing practice control groups in randomized controlled trials of behavioral interventions, and the role of extrinsic healthcare services in the design and conduct of behavioral trials. Method Selective qualitative review. Results Extrinsic healthcare services, also known as nonstudy care, have important but under-recognized effects on the design and conduct of behavioral trials. Usual care, treatment as usual, standard of care, and other existing practice control groups pose a variety of methodological and ethical challenges, but they play a vital role in behavioral intervention research. Conclusion This review highlights the need for a scientific consensus statement on control groups in behavioral trials. PMID:21536837

[METHODS OF EVALUATION OF MUSCLE MASS: A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS].

PubMed

Moreira, Osvaldo Costa; de Oliveira, Cláudia Eliza Patrocínio; Candia-Luján, Ramón; Romero-Pérez, Ena Monserrat; de Paz Fernandez, José Antonio

2015-09-01

in recent years, research about muscle mass has gained popularity for their relationship to health. Thus precise measurement of muscle mass may have clinical application once may interfere with the diagnosis and prescription drug or drug treatment. to conduct a systematic review of the methods most used for evaluation of muscle mass in randomized controlled trials, with its advantages and disadvantages. we conducted a search of the data bases Pub- Med, Web of Science and Scopus, with words "muscle mass", "measurement", "assessment" and "evaluation", combined in this way: "muscle mass" AND (assessment OR measurement OR evaluation). 23 studies were recovered and analyzed, all in English. 69.56% only used a method for quantification of muscle mass; 69.57% used dual X-ray absorptiometry (DXA); in 45.46% the type of measure used was the body lean mass; and 51.61% chose the whole body as a site of measurement. in the randomized controlled trials analyzed the majority used just one method of assessment, with the DXA being the method most used, the body lean mass the measurement type most used and total body the most common site of measure. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Comparative Effectiveness of Medication versus Cognitive-Behavioral Therapy in a Randomized Controlled Trial of Low-Income Young Minority Women with Depression

ERIC Educational Resources Information Center

Siddique, Juned; Chung, Joyce Y.; Brown, C. Hendricks; Miranda, Jeanne

2012-01-01

Objective: To examine whether there are latent trajectory classes in response to treatment and whether they moderate the effects of medication versus psychotherapy. Method: Data come from a 1-year randomized controlled trial of 267 low-income, young (M = 29 years), minority (44% Black, 50% Latina, 6% White) women with current major depression…

Vitamin D3 supplementation increases spine bone mineral density in adolescents and young adults with HIV infection being treated with tenofovir disoproxil fumarate: a randomized, placebo controlled trial

USDA-ARS?s Scientific Manuscript database

Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized vitamin D3 (VITD3) would increase BMD in adolescents/young adults receiving TDF. Methods: Randomized double-blind placebo-controlled trial of directly observed VITD3 50,000 IU vs. placebo every 4 ...

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…

The Effects of Including Observed Means or Latent Means as Covariates in Multilevel Models for Cluster Randomized Trials

ERIC Educational Resources Information Center

Aydin, Burak; Leite, Walter L.; Algina, James

2016-01-01

We investigated methods of including covariates in two-level models for cluster randomized trials to increase power to detect the treatment effect. We compared multilevel models that included either an observed cluster mean or a latent cluster mean as a covariate, as well as the effect of including Level 1 deviation scores in the model. A Monte…

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…

Indicated Prevention and Early Intervention for Childhood Anxiety: A Randomized Trial with Caucasian and Hispanic/Latino Youth

ERIC Educational Resources Information Center

Pina, Armando A.; Zerr, Argero A.; Villalta, Ian K.; Gonzales, Nancy A.

2012-01-01

Objective: This trial of a randomized indicated anxiety prevention and early intervention explored initial program effects as well as the role of ethnicity and language on measured outcomes. Method: A total of 88 youth (M = 10.36 years; 45 girls, 52 Latino) received 1 of 2 protocols with varying degrees of parent involvement, and response was…

Randomized Controlled Trial to Increase Physical Activity among Insufficiently Active Women Following Their Participation in a Mass Event

ERIC Educational Resources Information Center

Lane, Aoife; Murphy, Niamh; Bauman, Adrian; Chey, Tien

2010-01-01

Objective: To assess the impact of a community based, low-contact intervention on the physical activity habits of insufficiently active women. Design: Randomized controlled trial. Participants: Inactive Irish women. Method: A population sample of women participating in a mass 10 km event were up followed at 2 and 6 months, and those who had…

Paradigm War Revived? On the Diagnosis of Resistance to Randomized Controlled Trials and Systematic Review in Education

ERIC Educational Resources Information Center

Hammersley, Martyn

2008-01-01

There has been considerable discussion in recent years about the role in educational research of randomized controlled trials (RCTs) and systematic reviews (SR). Advocacy of these methods arose partly as a result of the spread of the notion of evidence-based practice from medicine into other fields, and of the rise of the "new public…

Baduanjin Exercise for Stroke Rehabilitation: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

PubMed Central

Wang, Chaoyi; Chen, Xiaoan; Wang, Huiru

2018-01-01

Objective: The purpose of this review was to objectively evaluate the effects of Baduanjin exercise on rehabilitative outcomes in stroke patients. Methods: Both Chinese and English electronic databases were searched for potentially relevant trials. Two review authors independently screened eligible trials against the inclusion criteria, extracted data, and assessed the methodological quality by using the revised PEDro scale. Meta-analysis was only performed for balance function. Results: In total, there were eight randomized controlled trials selected in this systematic review. The aggregated result of four trials has shown a significant benefit in favor of Baduanjin on balance function (Hedges’ g = 2.39, 95% CI 2.14 to 2.65, p < 0.001, I2 = 61.54). Additionally, Baduanjin exercise effectively improved sensorimotor function of lower extremities and ability of daily activities as well as reduced depressive level, leading to improved quality of life. Conclusion: Baduanjin exercise as an adjunctive and safe method may be conducive to help stroke patients achieve the best possible short-term outcome and should be integrated with mainstream rehabilitation programs. More rigorous randomized controlled trials with long-term intervention periods among a large sample size of stroke patients are needed to draw a firm conclusion regarding the rehabilitative effects for this population. PMID:29584623

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.

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial

PubMed Central

Nel, Annaléne; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Background Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. Objectives This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. Methods 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. Results No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. Conclusions The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides. PMID:29813074

The effectiveness and cost-evaluation of manual therapy and physical therapy in patients with sub-acute and chronic non specific neck pain. Rationale and design of a Randomized Controlled Trial (RCT)

PubMed Central

2010-01-01

Background Manual Therapy applied to patients with non specific neck pain has been investigated several times. In the Netherlands, manual therapy as applied according to the Utrecht School of Manual Therapy (MTU) has not been the subject of a randomized controlled trial. MTU differs in diagnoses and treatment from other forms of manual therapy. Methods/Design This is a single blind randomized controlled trial in patients with sub-acute and chronic non specific neck pain. Patients with neck complaints existing for two weeks (minimum) till one year (maximum) will participate in the trial. 180 participants will be recruited in thirteen primary health care centres in the Netherlands. The experimental group will be treated with MTU during a six week period. The control group will be treated with physical therapy (standard care, mainly active exercise therapy), also for a period of six weeks. Primary outcomes are Global Perceived Effect (GPE) and functional status (Neck Disability Index (NDI-DV)). Secondary outcomes are neck pain (Numeric Rating Scale (NRS)), Eurocol, costs and quality of life (SF36). Discussion This paper presents details on the rationale of MTU, design, methods and operational aspects of the trial. Trial registration ClinicalTrials.gov Identifier: NCT00713843 PMID:20096136

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 effect of berberine on insulin resistance in women with polycystic ovary syndrome: detailed statistical analysis plan (SAP) for a multicenter randomized controlled trial.

PubMed

Zhang, Ying; Sun, Jin; Zhang, Yun-Jiao; Chai, Qian-Yun; Zhang, Kang; Ma, Hong-Li; Wu, Xiao-Ke; Liu, Jian-Ping

2016-10-21

Although Traditional Chinese Medicine (TCM) has been widely used in clinical settings, a major challenge that remains in TCM is to evaluate its efficacy scientifically. This randomized controlled trial aims to evaluate the efficacy and safety of berberine in the treatment of patients with polycystic ovary syndrome. In order to improve the transparency and research quality of this clinical trial, we prepared this statistical analysis plan (SAP). The trial design, primary and secondary outcomes, and safety outcomes were declared to reduce selection biases in data analysis and result reporting. We specified detailed methods for data management and statistical analyses. Statistics in corresponding tables, listings, and graphs were outlined. The SAP provided more detailed information than trial protocol on data management and statistical analysis methods. Any post hoc analyses could be identified via referring to this SAP, and the possible selection bias and performance bias will be reduced in the trial. This study is registered at ClinicalTrials.gov, NCT01138930 , registered on 7 June 2010.

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.

An observational study showed that explaining randomization using gambling-related metaphors and computer-agency descriptions impeded randomized clinical trial recruitment.

PubMed

Jepson, Marcus; Elliott, Daisy; Conefrey, Carmel; Wade, Julia; Rooshenas, Leila; Wilson, Caroline; Beard, David; Blazeby, Jane M; Birtle, Alison; Halliday, Alison; Stein, Rob; Donovan, Jenny L

2018-07-01

To explore how the concept of randomization is described by clinicians and understood by patients in randomized controlled trials (RCTs) and how it contributes to patient understanding and recruitment. Qualitative analysis of 73 audio recordings of recruitment consultations from five, multicenter, UK-based RCTs with identified or anticipated recruitment difficulties. One in 10 appointments did not include any mention of randomization. Most included a description of the method or process of allocation. Descriptions often made reference to gambling-related metaphors or similes, or referred to allocation by a computer. Where reference was made to a computer, some patients assumed that they would receive the treatment that was "best for them". Descriptions of the rationale for randomization were rarely present and often only came about as a consequence of patients questioning the reason for a random allocation. The methods and processes of randomization were usually described by recruiters, but often without clarity, which could lead to patient misunderstanding. The rationale for randomization was rarely mentioned. Recruiters should avoid problematic gambling metaphors and illusions of agency in their explanations and instead focus on clearer descriptions of the rationale and method of randomization to ensure patients are better informed about randomization and RCT participation. Copyright © 2018 University of Bristol. Published by Elsevier Inc. All rights reserved.

Randomization in cancer clinical trials: permutation test and development of a computer program.

PubMed Central

Ohashi, Y

1990-01-01

When analyzing cancer clinical trial data where the treatment allocation is done using dynamic balancing methods such as the minimization method for balancing the distribution of important prognostic factors in each arm, conservativeness occurs if such a randomization scheme is ignored and a simple unstratified analysis is carried out. In this paper, the above conservativeness is demonstrated by computer simulation, and the development of a computer program that carries out permutation tests of the log-rank statistics for clinical trial data where the allocation is done by the minimization method or a stratified permuted block design is introduced. We are planning to use this program in practice to supplement a usual stratified analysis and model-based methods such as the Cox regression. The most serious problem in cancer clinical trials in Japan is how to carry out the quality control or data management in trials that are initiated and conducted by researchers without support from pharmaceutical companies. In the final section of this paper, one international collaborative work for developing international guidelines on data management in clinical trials of bladder cancer is briefly introduced, and the differences between the system adopted in US/European statistical centers and the Japanese system is described. PMID:2269216

Randomized Multicenter Feasibility Trial of Myofascial Physical Therapy for Treatment of Urologic Chronic Pelvic Pain Syndrome

PubMed Central

FitzGerald, Mary P; Anderson, Rodney U; Potts, Jeannette; Payne, Christopher K; Peters, Kenneth M; Clemens, J Quentin; Kotarinos, Rhonda; Fraser, Laura; Cosby, Annamarie; Fortman, Carole; Neville, Cynthia; Badillo, Suzanne; Odabachian, Lisa; Sanfield, Anna; O’Dougherty, Betsy; Halle-Podell, Rick; Cen, Liyi; Chuai, Shannon; Landis, J Richard; Kusek, John W; Nyberg, Leroy M

2010-01-01

Objectives To determine the feasibility of conducting a randomized clinical trial designed to compare two methods of manual therapy (myofascial physical therapy (MPT) and global therapeutic massage (GTM)) among patients with urologic chronic pelvic pain syndromes. Materials and Methods Our goal was to recruit 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at six clinical centers. Eligible patients were randomized to either MPT or GTM and were scheduled to receive up to 10 weekly treatments, each 1 hour in duration. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events which occurred during study treatment, and rate of response to therapy as assessed by the Patient Global Response Assessment (GRA). Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. Results Twenty-three (49%) men and 24 (51%) women were randomized over a six month period. Twenty-four (51%) patients were randomized to GTM, 23 (49%) to MPT; 44 (94%) patients completed the study. Therapist adherence to the treatment protocols was excellent. The GRA response rate of 57% in the MPT group was significantly higher than the rate of 21% in the GTM treatment group (p=0.03). Conclusions The goals to judge feasibility of conducting a full-scale trial of physical therapy methods were met. The preliminary findings of a beneficial effect of MPT warrants further study. PMID:19535099

Participant recruitment and retention in longitudinal preconception randomized trials: lessons learnt from the Calcium And Pre-eclampsia (CAP) trial.

PubMed

Lawrie, Theresa A; Betrán, Ana Pilar; Singata-Madliki, Mandisa; Ciganda, Alvaro; Hofmeyr, G Justus; Belizán, José M; Purnat, Tina Dannemann; Manyame, Sarah; Parker, Catherine; Cormick, Gabriela

2017-10-26

The preconception period has the potential to influence pregnancy outcomes and randomized controlled trials (RCTs) are needed to evaluate a variety of potentially beneficial preconception interventions. However, RCTs commencing before pregnancy have significant participant recruitment and retention challenges. The Calcium And Pre-eclampsia trial (CAP trial) is a World Health Organization multi-country RCT of calcium supplementation commenced before pregnancy to prevent recurrent pre-eclampsia in which non-pregnant participants are recruited and followed up until childbirth. This sub-study explores recruitment methods and preconception retention of participants of the CAP trial to inform future trials. Recruiters at the study sites in Argentina, South Africa and Zimbabwe completed post-recruitment phase questionnaires on recruitment methods used. Qualitative data from these questionnaires and quantitative data on pre-pregnancy trial visit attendance and pregnancy rates up to September 2016 are reported in this paper. RStudio (Version 0.99.903 https://www.rstudio.org ) statistical software was used for summary statistics. Between July 2011 and 8 September 2016, 1354 women with previous pre-eclampsia were recruited. Recruitment took 2 years longer than expected and was facilitated mainly through medical record/register and maternity ward/clinic-based strategies. Recruiters highlighted difficulties associated with inadequate medical records, redundant patient contact details, and follow-up of temporarily ineligible women as some of the challenges faced. Whilst the attendance rates at pre-pregnancy visits were high (78% or more), visits often occurred later than scheduled. Forty-five percent of participants became pregnant (614/1354), 33.5% (454/1354) within 1 year of randomization. In preconception trials, both retrospective and prospective methods are useful for recruiting eligible women with certain conditions. However, these are time-consuming in low-resource settings with suboptimal medical records and other challenges. Trial planners should ensure that trial budgets cover sufficient on-site researchers with pre-trial training, and should consider using mobile phone and web-based electronic tools to optimize recruitment and retention. This should lead to greater efficiency and shorter trial durations. Pan-African Clinical Trials Registry, Registration Number: PACTR201105000267371 . The trial was registered on 6 December 2016.

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

PubMed

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

2016-02-09

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

A cluster-randomized, placebo-controlled, maternal vitamin a or beta-carotene supplementation trial in bangladesh: design and methods

PubMed Central

2011-01-01

Background We present the design, methods and population characteristics of a large community trial that assessed the efficacy of a weekly supplement containing vitamin A or beta-carotene, at recommended dietary levels, in reducing maternal mortality from early gestation through 12 weeks postpartum. We identify challenges faced and report solutions in implementing an intervention trial under low-resource, rural conditions, including the importance of population choice in promoting generalizability, maintaining rigorous data quality control to reduce inter- and intra- worker variation, and optimizing efficiencies in information and resources flow from and to the field. Methods This trial was a double-masked, cluster-randomized, dual intervention, placebo-controlled trial in a contiguous rural area of ~435 sq km with a population of ~650,000 in Gaibandha and Rangpur Districts of Northwestern Bangladesh. Approximately 120,000 married women of reproductive age underwent 5-weekly home surveillance, of whom ~60,000 were detected as pregnant, enrolled into the trial and gave birth to ~44,000 live-born infants. Upon enrollment, at ~ 9 weeks' gestation, pregnant women received a weekly oral supplement containing vitamin A (7000 ug retinol equivalents (RE)), beta-carotene (42 mg, or ~7000 ug RE) or a placebo through 12 weeks postpartum, according to prior randomized allocation of their cluster of residence. Systems described include enlistment and 5-weekly home surveillance for pregnancy based on menstrual history and urine testing, weekly supervised supplementation, periodic risk factor interviews, maternal and infant vital outcome monitoring, birth defect surveillance and clinical/biochemical substudies. Results The primary outcome was pregnancy-related mortality assessed for 3 months following parturition. Secondary outcomes included fetal loss due to miscarriage or stillbirth, infant mortality under three months of age, maternal obstetric and infectious morbidity, infant infectious morbidity, maternal and infant micronutrient status, fetal and infant growth and prematurity, external birth defects and postnatal infant growth to 3 months of age. Conclusion Aspects of study site selection and its "resonance" with national and rural qualities of Bangladesh, the trial's design, methods and allocation group comparability achieved by randomization, field procedures and innovative approaches to solving challenges in trial conduct are described and discussed. This trial is registered with http://Clinicaltrials.gov as protocol NCT00198822. PMID:21510905

Methodological Issues in Trials of Complementary and Alternative Medicine Interventions

PubMed Central

Sikorskii, Alla; Wyatt, Gwen; Victorson, David; Faulkner, Gwen; Rahbar, Mohammad Hossein

2010-01-01

Background Complementary and alternative medicine (CAM) use is widespread among cancer patients. Information on safety and efficacy of CAM therapies is needed for both patients and health care providers. Well-designed randomized clinical trials (RCTs) of CAM therapy interventions can inform both clinical research and practice. Objectives To review important issues that affect the design of RCTs for CAM interventions. Methods Using the methods component of the Consolidated Standards for Reporting Trials (CONSORT) as a guiding framework, and a National Cancer Institute-funded reflexology study as an exemplar, methodological issues related to participants, intervention, objectives, outcomes, sample size, randomization, blinding, and statistical methods were reviewed. Discussion Trials of CAM interventions designed and implemented according to appropriate methodological standards will facilitate the needed scientific rigor in CAM research. Interventions in CAM can be tested using proposed methodology, and the results of testing will inform nursing practice in providing safe and effective supportive care and improving the well-being of patients. PMID:19918155

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

PubMed Central

Perraton, Luke; Machotka, Zuzana; Kumar, Saravana

2009-01-01

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

Meta-analysis of Laparoscopic Versus Open Repair of Perforated Peptic Ulcer

PubMed Central

Antoniou, George A.; Koch, Oliver O.; Pointner, Rudolph; Granderath, Frank A.

2013-01-01

Background and Objectives: Laparoscopic treatment of perforated peptic ulcer (PPU) has been introduced as an alternative procedure to open surgery. It has been postulated that the minimally invasive approach involves less operative stress and results in decreased morbidity and mortality. Methods: We conducted a meta-analysis of randomized trials to test this hypothesis. Medline, EMBASE, and the Cochrane Central Register of Randomized Trials databases were searched, with no date or language restrictions. Results: Our literature search identified 4 randomized trials, with a cumulative number of 289 patients, that compared the laparoscopic approach with open sutured repair of perforated ulcer. Analysis of outcomes did not favor either approach in terms of morbidity, mortality, and reoperation rate, although odds ratios seemed to consistently support the laparoscopic approach. Results did not determine the comparative efficiency and safety of laparoscopic or open approach for PPU. Conclusion: In view of an increased interest in the laparoscopic approach, further randomized trials are considered essential to determine the relative effectiveness of laparoscopic and open repair of PPU. PMID:23743368

Omega 3/6 Fatty Acids for Reading in Children: A Randomized, Double-Blind, Placebo-Controlled Trial in 9-Year-Old Mainstream Schoolchildren in Sweden

ERIC Educational Resources Information Center

Johnson, Mats; Fransson, Gunnar; Östlund, Sven; Areskoug, Björn; Gillberg, Christopher

2017-01-01

Background: Previous research has shown positive effects of Omega 3/6 fatty acids in children with inattention and reading difficulties. We aimed to investigate if Omega 3/6 improved reading ability in mainstream schoolchildren. Methods: We performed a 3-month parallel, randomized, double-blind, placebo-controlled trial followed by 3-month active…

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.

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.

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.

Using Audit Information to Adjust Parameter Estimates for Data Errors in Clinical Trials

PubMed Central

Shepherd, Bryan E.; Shaw, Pamela A.; Dodd, Lori E.

2013-01-01

Background Audits are often performed to assess the quality of clinical trial data, but beyond detecting fraud or sloppiness, the audit data is generally ignored. In earlier work using data from a non-randomized study, Shepherd and Yu (2011) developed statistical methods to incorporate audit results into study estimates, and demonstrated that audit data could be used to eliminate bias. Purpose In this manuscript we examine the usefulness of audit-based error-correction methods in clinical trial settings where a continuous outcome is of primary interest. Methods We demonstrate the bias of multiple linear regression estimates in general settings with an outcome that may have errors and a set of covariates for which some may have errors and others, including treatment assignment, are recorded correctly for all subjects. We study this bias under different assumptions including independence between treatment assignment, covariates, and data errors (conceivable in a double-blinded randomized trial) and independence between treatment assignment and covariates but not data errors (possible in an unblinded randomized trial). We review moment-based estimators to incorporate the audit data and propose new multiple imputation estimators. The performance of estimators is studied in simulations. Results When treatment is randomized and unrelated to data errors, estimates of the treatment effect using the original error-prone data (i.e., ignoring the audit results) are unbiased. In this setting, both moment and multiple imputation estimators incorporating audit data are more variable than standard analyses using the original data. In contrast, in settings where treatment is randomized but correlated with data errors and in settings where treatment is not randomized, standard treatment effect estimates will be biased. And in all settings, parameter estimates for the original, error-prone covariates will be biased. Treatment and covariate effect estimates can be corrected by incorporating audit data using either the multiple imputation or moment-based approaches. Bias, precision, and coverage of confidence intervals improve as the audit size increases. Limitations The extent of bias and the performance of methods depend on the extent and nature of the error as well as the size of the audit. This work only considers methods for the linear model. Settings much different than those considered here need further study. Conclusions In randomized trials with continuous outcomes and treatment assignment independent of data errors, standard analyses of treatment effects will be unbiased and are recommended. However, if treatment assignment is correlated with data errors or other covariates, naive analyses may be biased. In these settings, and when covariate effects are of interest, approaches for incorporating audit results should be considered. PMID:22848072

A comparison of confidence interval methods for the intraclass correlation coefficient in community-based cluster randomization trials with a binary outcome.

PubMed

Braschel, Melissa C; Svec, Ivana; Darlington, Gerarda A; Donner, Allan

2016-04-01

Many investigators rely on previously published point estimates of the intraclass correlation coefficient rather than on their associated confidence intervals to determine the required size of a newly planned cluster randomized trial. Although confidence interval methods for the intraclass correlation coefficient that can be applied to community-based trials have been developed for a continuous outcome variable, fewer methods exist for a binary outcome variable. The aim of this study is to evaluate confidence interval methods for the intraclass correlation coefficient applied to binary outcomes in community intervention trials enrolling a small number of large clusters. Existing methods for confidence interval construction are examined and compared to a new ad hoc approach based on dividing clusters into a large number of smaller sub-clusters and subsequently applying existing methods to the resulting data. Monte Carlo simulation is used to assess the width and coverage of confidence intervals for the intraclass correlation coefficient based on Smith's large sample approximation of the standard error of the one-way analysis of variance estimator, an inverted modified Wald test for the Fleiss-Cuzick estimator, and intervals constructed using a bootstrap-t applied to a variance-stabilizing transformation of the intraclass correlation coefficient estimate. In addition, a new approach is applied in which clusters are randomly divided into a large number of smaller sub-clusters with the same methods applied to these data (with the exception of the bootstrap-t interval, which assumes large cluster sizes). These methods are also applied to a cluster randomized trial on adolescent tobacco use for illustration. When applied to a binary outcome variable in a small number of large clusters, existing confidence interval methods for the intraclass correlation coefficient provide poor coverage. However, confidence intervals constructed using the new approach combined with Smith's method provide nominal or close to nominal coverage when the intraclass correlation coefficient is small (<0.05), as is the case in most community intervention trials. This study concludes that when a binary outcome variable is measured in a small number of large clusters, confidence intervals for the intraclass correlation coefficient may be constructed by dividing existing clusters into sub-clusters (e.g. groups of 5) and using Smith's method. The resulting confidence intervals provide nominal or close to nominal coverage across a wide range of parameters when the intraclass correlation coefficient is small (<0.05). Application of this method should provide investigators with a better understanding of the uncertainty associated with a point estimator of the intraclass correlation coefficient used for determining the sample size needed for a newly designed community-based trial. © The Author(s) 2015.

Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

PubMed

Takahashi, Fumihiro; Morita, Satoshi

2018-02-08

Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.

A Prospective Randomized Trial of Two Different Prostate Biopsy Schemes

ClinicalTrials.gov

2016-07-03

Prostate Cancer; Local Anesthesia; Prostate-Specific Antigen/Blood; Biopsy/Methods; Image-guided Biopsy/Methods; Prostatic Neoplasms/Diagnosis; Prostate/Pathology; Prospective Studies; Humans; Male; Ultrasonography, Interventional/Methods

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…

Electronic Cigarettes for Smoking Cessation.

PubMed

Orellana-Barrios, Menfil A; Payne, Drew; Medrano-Juarez, Rita M; Yang, Shengping; Nugent, Kenneth

2016-10-01

The use of electronic cigarettes (e-cigarettes) is increasing, but their use as a smoking-cessation aid is controversial. The reporting of e-cigarette studies on cessation is variable and inconsistent. To date, only 1 randomized clinical trial has included an arm with other cessation methods (nicotine patches). The cessation rates for available clinical trials are difficult to compare given differing follow-up periods and broad ranges (4% at 12 months with non-nicotine e-cigarettes to 68% at 4 weeks with concomitant nicotine e-cigarettes and other cessation methods). The average combined abstinence rate for included prospective studies was 29.1% (combination of 6-18 months׳ rates). There are few comparable clinical trials and prospective studies related to e-cigarettes use for smoking cessation, despite an increasing number of citations. Larger randomized clinical trials are essential to determine whether e-cigarettes are effective smoking-cessation devices. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Effectiveness of the Dader Method for pharmaceutical care in patients with bipolar I disorder: EMDADER-TAB: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Bipolar I disorder (BD-I) is a chronic mental illness characterized by the presence of one or more manic episodes, or both depressive and manic episodes, usually separated by asymptomatic intervals. Pharmacists can contribute to the management of BD-I, mainly with the use of effective and safe drugs, and improve the patient’s life quality through pharmaceutical care. Some studies have shown the effect of pharmaceutical care in the achievement of therapeutic goals in different illnesses; however, to our knowledge, there is a lack of randomized controlled trials designed to assess the effect of pharmacist intervention in patients with BD. The aim of this study is to assess the effectiveness of the Dader Method for pharmaceutical care in patients with BD-I. Methods/design Randomized, controlled, prospective, single-center clinical trial with duration of 12 months will be performed to compare the effect of Dader Method of pharmaceutical care with the usual care process of patients in a psychiatric clinic. Patients diagnosed with BD-I aged between 18 and 65 years who have been discharged or referred from outpatients service of the San Juan de Dios Clinic (Antioquia, Colombia) will be included. Patients will be randomized into the intervention group who will receive pharmaceutical care provided by pharmacists working in collaboration with psychiatrists, or into the control group who will receive usual care and verbal-written counseling regarding BD. Study outcomes will be assessed at baseline and at 3, 6, 9, and 12 months after randomization. The primary outcome will be to measure the number of hospitalizations, emergency service consultations, and unscheduled outpatient visits. Effectiveness, safety, adherence, and quality of life will be assessed as secondary outcomes. Statistical analyses will be performed using two-tailed McNemar tests, Pearson chi-square tests, and Student’s t-tests; a P value <0.05 will be considered as statistically significant. Discussion As far as we know, this is the first randomized controlled trial to assess the effect of the Dader Method for pharmaceutical care in patients with BD-I and it could generate valuable information and recommendations about the role of pharmacists in the improvement of therapeutic goals, solution of drug-related problems, and adherence. Trial registration Registration number NCT01750255 on August 6, 2012. First patient randomized on 24 November 2011. PMID:24885673

Methods for the design of vasomotor symptom trials: the menopausal strategies: finding lasting answers to symptoms and health network.

PubMed

Newton, Katherine M; Carpenter, Janet S; Guthrie, Katherine A; Anderson, Garnet L; Caan, Bette; Cohen, Lee S; Ensrud, Kristine E; Freeman, Ellen W; Joffe, Hadine; Sternfeld, Barbara; Reed, Susan D; Sherman, Sheryl; Sammel, Mary D; Kroenke, Kurt; Larson, Joseph C; Lacroix, Andrea Z

2014-01-01

This report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials. Established in response to a National Institutes of Health request for applications, the network was charged with conducting rapid throughput randomized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms. Included are descriptions of and rationale for criteria used for interventions and study selection, common eligibility and exclusion criteria, common primary and secondary outcome measures, consideration of placebo response, establishment of a biorepository, trial duration, screening and recruitment, statistical methods, and quality control. All trial designs are presented, including the following: (1) a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effectiveness of the selective serotonin reuptake inhibitor escitalopram in reducing vasomotor symptom frequency and severity; (2) a two-by-three factorial design trial to test three different interventions (yoga, exercise, and ω-3 supplementation) for the improvement of vasomotor symptom frequency and bother; and (3) a three-arm comparative efficacy trial of the serotonin-norepinephrine reuptake inhibitor venlafaxine and low-dose oral estradiol versus placebo for reducing vasomotor symptom frequency. The network's structure and governance are also discussed. The methods used in and the lessons learned from the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health trials are shared to encourage and support the conduct of similar trials and to encourage collaborations with other researchers.

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

Correction to: The effectiveness of a life style modification and peer support home blood pressure monitoring in control of hypertension: protocol for a cluster randomized controlled trial.

PubMed

Su, Tin Tin; Majid, Hazreen Abdul; Nahar, Azmi Mohamed; Azizan, Nurul Ain; Hairi, Farizah Mohd; Thangiah, Nithiah; Dahlui, Maznah; Bulgiba, Awang; Murray, Liam J

2017-11-06

After publication of the article [1], it has been brought to our attention that the methodology outlined in the original article was not able to be fully carried out. The article planned a two armed randomized control trial. However, due to a lower response than expected and one housing complex dropping out from the study, the method was changed to pre- and post-intervention with no control group. All other methods were conducted as outlined in the original article.

Design and methods for a pilot randomized clinical trial involving exercise and behavioral activation to treat comorbid type 2 diabetes and major depressive disorder

PubMed Central

Schneider, Kristin L.; Pagoto, Sherry L.; Handschin, Barbara; Panza, Emily; Bakke, Susan; Liu, Qin; Blendea, Mihaela; Ockene, Ira S.; Ma, Yunsheng

2011-01-01

Background The comorbidity of type 2 diabetes mellitus (T2DM) and depression is associated with poor glycemic control. Exercise has been shown to improve mood and glycemic control, but individuals with comorbid T2DM and depression are disproportionately sedentary compared to the general population and report more difficulty with exercise. Behavioral activation, an evidence-based depression psychotherapy, was designed to help people with depression make gradual behavior changes, and may be helpful to build exercise adherence in sedentary populations. This pilot randomized clinical trial will test the feasibility of a group exercise program enhanced with behavioral activation strategies among women with comorbid T2DM and depression. Methods/Design Sedentary women with inadequately controlled T2DM and depression (N=60) will be randomly assigned to one of two conditions: exercise or usual care. Participants randomized to the exercise condition will attend 38 behavioral activation-enhanced group exercise classes over 24 weeks in addition to usual care. Participants randomized to the usual care condition will receive depression treatment referrals and print information on diabetes management via diet and physical activity. Assessments will occur at baseline and 3-, 6-, and 9-months following randomization. The goals of this pilot study are to demonstrate feasibility and intervention acceptability, estimate the resources and costs required to deliver the intervention and to estimate the standard deviation of continuous outcomes (e.g., depressive symptoms and glycosylated hemoglobin) in preparation for a fully-powered randomized clinical trial. Discussion A novel intervention that combines exercise and behavioral activation strategies could potentially improve glycemic control and mood in women with comorbid type 2 diabetes and depression. Trial registration NCT01024790 PMID:21765864

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

Multilevel Analysis Methods for Partially Nested Cluster Randomized Trials

ERIC Educational Resources Information Center

Sanders, Elizabeth A.

2011-01-01

This paper explores multilevel modeling approaches for 2-group randomized experiments in which a treatment condition involving clusters of individuals is compared to a control condition involving only ungrouped individuals, otherwise known as partially nested cluster randomized designs (PNCRTs). Strategies for comparing groups from a PNCRT in the…

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

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

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

The statistical pitfalls of the partially randomized preference design in non-blinded trials of psychological interventions.

PubMed

Gemmell, Isla; Dunn, Graham

2011-03-01

In a partially randomized preference trial (PRPT) patients with no treatment preference are allocated to groups at random, but those who express a preference receive the treatment of their choice. It has been suggested that the design can improve the external and internal validity of trials. We used computer simulation to illustrate the impact that an unmeasured confounder could have on the results and conclusions drawn from a PRPT. We generated 4000 observations ("patients") that reflected the distribution of the Beck Depression Index (DBI) in trials of depression. Half were randomly assigned to a randomized controlled trial (RCT) design and half were assigned to a PRPT design. In the RCT, "patients" were evenly split between treatment and control groups; whereas in the preference arm, to reflect patient choice, 87.5% of patients were allocated to the experimental treatment and 12.5% to the control. Unadjusted analyses of the PRPT data consistently overestimated the treatment effect and its standard error. This lead to Type I errors when the true treatment effect was small and Type II errors when the confounder effect was large. The PRPT design is not recommended as a method of establishing an unbiased estimate of treatment effect due to the potential influence of unmeasured confounders. Copyright © 2011 John Wiley & Sons, Ltd.

High Mortality without ESCAPE: The Registry of Heart Failure Patients Receiving Pulmonary Artery Catheters without Randomization

PubMed Central

Allen, Larry A.; Rogers, Joseph G.; Warnica, J. Wayne; DiSalvo, Thomas G.; Tasissa, Gudaye; Binanay, Cynthia; O’Connor, Christopher M.; Califf, Robert M.; Leier, Carl V.; Shah, Monica R.; Stevenson, Lynne W.

2008-01-01

Background In ESCAPE, there was no difference in days alive and out of the hospital for patients with decompensated heart failure (HF) randomly assigned to therapy guided by pulmonary artery catheter (PAC) plus clinical assessment versus clinical assessment alone. The external validity of these findings is debated. Methods and Results ESCAPE sites enrolled 439 patients receiving PAC without randomization in a prospective registry. Baseline characteristics, pertinent trial exclusion criteria, reasons for PAC use, hemodynamics, and complications were collected. Survival was determined from the National Death Index and the Alberta Registry. On average, registry patients had lower blood pressure, worse renal function, less neurohormonal antagonist therapy, and higher use of intravenous inotropes as compared with trial patients. Although clinical assessment anticipated less volume overload and greater hypoperfusion among the registry population, measured filling pressures were similarly elevated in the registry and trial, while measured perfusion was slightly higher among registry patients. Registry patients had longer hospitalization (13 vs. 6 days, p <0.001) and higher 6-month mortality (34% vs. 20%, p < 0.001) than trial patients. Conclusions The decision to use PAC without randomization identified a population with higher disease severity and risk of mortality. This prospective registry highlights the complex context of patient selection for randomized trials. PMID:18926438

INFERENCES DRAWN FROM A RISK ASSESSMENT COMPARED DIRECTLY TO A RANDOMIZED TRIAL OF A HOME DRINKING WATER INTERVENTION

EPA Science Inventory

Risk assessments and intervention trials have been used to inform the EPA on drinking water risks. Seldom are both methods used concurrently. Between 2001 and 2003, illness data from a trial were collected simultaneously with exposure data, providing a unique opportunity to com...

SMART trial: A randomized clinical trial of self-monitoring in behavioral weight management-design and baseline findings

PubMed Central

Burke, Lora E.; Styn, Mindi A.; Glanz, Karen; Ewing, Linda J.; Elci, Okan U.; Conroy, Margaret B.; Sereika, Susan M.; Acharya, Sushama D.; Music, Edvin; Keating, Alison L.; Sevick, Mary Ann

2009-01-01

Background The primary form of treatment for obesity today is behavioral therapy. Self-monitoring diet and physical activity plays an important role in interventions targeting behavior and weight change. The SMART weight loss trial examined the impact of replacing the standard paper record used for self-monitoring with a personal digital assistant (PDA). This paper describes the design, methods, intervention, and baseline sample characteristics of the SMART trial. Methods The SMART trial used a 3-group design to determine the effects of different modes of self-monitoring on short- and long-term weight loss and on adherence to self-monitoring in a 24-month intervention. Participants were randomized to one of three conditions (1) use of a standard paper record (PR); (2) use of a PDA with dietary and physical activity software (PDA); or (3), use of a PDA with the same software plus a customized feedback program (PDA + FB). Results We screened 704 individuals and randomized 210. There were statistically but not clinically significant differences among the three cohorts in age, education, HDL cholesterol, blood glucose and systolic blood pressure. At 24 months, retention rate for the first of three cohorts was 90%. Conclusions To the best of our knowledge, the SMART trial is the first large study to compare different methods of self-monitoring in a behavioral weight loss intervention and to compare the use of PDAs to conventional paper records. This study has the potential to reveal significant details about self-monitoring patterns and whether technology can improve adherence to this vital intervention component. PMID:19665588

Effects of a Brief Early Start Denver Model (ESDM)-Based Parent Intervention on Toddlers at Risk for Autism Spectrum Disorders: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Rogers, Sally J.; Estes, Annette; Lord, Catherine; Vismara, Laurie; Winter, Jamie; Fitzpatrick, Annette; Guo, Mengye; Dawson, Geraldine

2012-01-01

Objective: This study was carried out to examine the efficacy of a 12-week, low-intensity (1-hour/wk of therapist contact), parent-delivered intervention for toddlers at risk for autism spectrum disorders (ASD) aged 14 to 24 months and their families. Method: A randomized controlled trial involving 98 children and families was carried out in three…

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…

The case for randomized controlled trials to assess the impact of clinical information systems.

PubMed

Liu, Joseph L Y; Wyatt, Jeremy C

2011-01-01

There is a persistent view of a significant minority in the medical informatics community that the randomized controlled trial (RCT) has a limited role to play in evaluating clinical information systems. A common reason voiced by skeptics is that these systems are fundamentally different from drug interventions, so the RCT is irrelevant. There is an urgent need to promote the use of RCTs, given the shift to evidence-based policy and the need to demonstrate cost-effectiveness of these systems. The authors suggest returning to first principles and argue that what is required is clarity about how to match methods to evaluation questions. The authors address common concerns about RCTs, and the extent to which they are fallacious, and also discuss the challenges of conducting RCTs in informatics and alternative study designs when randomized trials are infeasible. While neither a perfect nor universal evaluation method, RCTs form an important part of an evaluator's toolkit.

The case for randomized controlled trials to assess the impact of clinical information systems

PubMed Central

Wyatt, Jeremy C

2011-01-01

There is a persistent view of a significant minority in the medical informatics community that the randomized controlled trial (RCT) has a limited role to play in evaluating clinical information systems. A common reason voiced by skeptics is that these systems are fundamentally different from drug interventions, so the RCT is irrelevant. There is an urgent need to promote the use of RCTs, given the shift to evidence-based policy and the need to demonstrate cost-effectiveness of these systems. The authors suggest returning to first principles and argue that what is required is clarity about how to match methods to evaluation questions. The authors address common concerns about RCTs, and the extent to which they are fallacious, and also discuss the challenges of conducting RCTs in informatics and alternative study designs when randomized trials are infeasible. While neither a perfect nor universal evaluation method, RCTs form an important part of an evaluator's toolkit. PMID:21270132

Do Bayesian adaptive trials offer advantages for comparative effectiveness research? Protocol for the RE-ADAPT study

PubMed Central

Luce, Bryan R; Broglio, Kristine R; Ishak, K Jack; Mullins, C Daniel; Vanness, David J; Fleurence, Rachael; Saunders, Elijah; Davis, Barry R

2013-01-01

Background Randomized clinical trials, particularly for comparative effectiveness research (CER), are frequently criticized for being overly restrictive or untimely for health-care decision making. Purpose Our prospectively designed REsearch in ADAptive methods for Pragmatic Trials (RE-ADAPT) study is a ‘proof of concept’ to stimulate investment in Bayesian adaptive designs for future CER trials. Methods We will assess whether Bayesian adaptive designs offer potential efficiencies in CER by simulating a re-execution of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study using actual data from ALLHAT. Results We prospectively define seven alternate designs consisting of various combinations of arm dropping, adaptive randomization, and early stopping and describe how these designs will be compared to the original ALLHAT design. We identify the one particular design that would have been executed, which incorporates early stopping and information-based adaptive randomization. Limitations While the simulation realistically emulates patient enrollment, interim analyses, and adaptive changes to design, it cannot incorporate key features like the involvement of data monitoring committee in making decisions about adaptive changes. Conclusion This article describes our analytic approach for RE-ADAPT. The next stage of the project is to conduct the re-execution analyses using the seven prespecified designs and the original ALLHAT data. PMID:23983160

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

PubMed Central

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

2010-01-01

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

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

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

PubMed

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

2009-12-01

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

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

Levofloxacin-Based First-Line Therapy versus Standard First-Line Therapy for Helicobacter pylori Eradication: Meta-Analysis of Randomized Controlled Trials

PubMed Central

Peedikayil, Musthafa Chalikandy; AlSohaibani, Fahad Ibrahim; Alkhenizan, Abdullah Hamad

2014-01-01

Background First-line levofloxacin-based treatments eradicate Helicobacter pylori with varying success. We examined the efficacy and safety of first-line levofloxacin-based treatment in comparison to standard first-line therapy for H pylori eradication. Materials and Methods We searched literature databases from Medline, EMBASE, and the Cochrane Register of Randomized Controlled Trials through March 2013 for randomized controlled trials comparing first-line levofloxacin and standard therapy. We included randomized controlled trials conducted only on naïve H pylori infected patients in adults. A systematic review was conducted. Meta-analysis was performed with Review Manager 5.2. Treatment effect was determined by relative risk with a random or fixed model by the Mantel-Haenszel method. Results Seven trials were identified with 888 patients receiving 7 days of first-line levofloxacin and 894 treated with standard therapy (Amoxicillin, Clarithromycin and proton pump inhibitor) for 7 days. The overall crude eradication rate in the Levofloxacin group was 79.05% versus 81.4% in the standard group (risk ratio 0.97; 95% CI; 0.93, 1.02). The overall dropout was 46 (5.2%) in the levofloxacin group and 52 (5.8%) for standard therapy. The dizziness was more common among group who took Levofloxacin based treatment and taste disturbance was more common among group who took standard therapy. Meta-analysis of overall adverse events were similar between the two groups with a relative risk of 1.06 (95% CI 0.72, 1.57). Conclusion Helicobacter pylori eradication with 7 days of Levofloxacin-based first line therapy was safe and equal compared to 7 days of standard first-line therapy. PMID:24465624

A Meta-analysis of Randomized Trials Comparing Surgery versus Endovascular Therapy for Thrombosed Arteriovenous Fistulas and Grafts in Hemodialysis

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

Kuhan, G., E-mail: gkuhan@nhs.net; Antoniou, G. A.; Nikam, M.

Purpose. To carry out a systematic review of randomized trials comparing surgery vs. endovascular therapy for occluded fistulas and grafts. Methods. All randomized trials which compared surgery and endovascular therapy for occluded fistulas and grafts were retrieved from 1990 onwards. The following search terms were used: 'haemodialysis,' 'thrombosis,' 'arteriovenous fistula,' 'arteriovenous shunt,' 'end stage renal failure' on Medline and PubMed. The results of the pooled data were analysed by a fixed-effect model. Results. There were no randomized trials comparing surgery vs. endovascular therapy for native fistulas and vein grafts. Six randomized studies reporting on 573 occluded grafts were identified. Technicalmore » success, need for access line and primary patency at 30 days were similar between the two groups (odds ratio [OR] 1.40, 95 % confidence interval [CI] 0.91-2.14; OR 0.77, 95 % CI 0.44-1.34; and OR 1.15, 95 % CI 0.79-1.68, respectively). There was no significant difference in morbidity at 30 days between groups (OR 1.12, 95 % CI 0.67-1.86). There were no statistical difference between the two groups for 1 year primary patency (OR 2.08, 95 % CI 0.97-4.45). Primary assisted patency at 1 year was better with surgery (OR 3.03, 95 % CI 1.12-8.18) in a single study. Conclusion. Comparable results to surgery have been achieved with endovascular techniques for occluded prosthetic grafts for dialysis access. Long-term data comparing the two groups were lacking. Further trials designed to encompass variation in methods are warranted in order to obtain the best available evidence particularly for native fistulas.« less

Should multiple imputation be the method of choice for handling missing data in randomized trials?

PubMed Central

Sullivan, Thomas R; White, Ian R; Salter, Amy B; Ryan, Philip; Lee, Katherine J

2016-01-01

The use of multiple imputation has increased markedly in recent years, and journal reviewers may expect to see multiple imputation used to handle missing data. However in randomized trials, where treatment group is always observed and independent of baseline covariates, other approaches may be preferable. Using data simulation we evaluated multiple imputation, performed both overall and separately by randomized group, across a range of commonly encountered scenarios. We considered both missing outcome and missing baseline data, with missing outcome data induced under missing at random mechanisms. Provided the analysis model was correctly specified, multiple imputation produced unbiased treatment effect estimates, but alternative unbiased approaches were often more efficient. When the analysis model overlooked an interaction effect involving randomized group, multiple imputation produced biased estimates of the average treatment effect when applied to missing outcome data, unless imputation was performed separately by randomized group. Based on these results, we conclude that multiple imputation should not be seen as the only acceptable way to handle missing data in randomized trials. In settings where multiple imputation is adopted, we recommend that imputation is carried out separately by randomized group. PMID:28034175

Should multiple imputation be the method of choice for handling missing data in randomized trials?

PubMed

Sullivan, Thomas R; White, Ian R; Salter, Amy B; Ryan, Philip; Lee, Katherine J

2016-01-01

The use of multiple imputation has increased markedly in recent years, and journal reviewers may expect to see multiple imputation used to handle missing data. However in randomized trials, where treatment group is always observed and independent of baseline covariates, other approaches may be preferable. Using data simulation we evaluated multiple imputation, performed both overall and separately by randomized group, across a range of commonly encountered scenarios. We considered both missing outcome and missing baseline data, with missing outcome data induced under missing at random mechanisms. Provided the analysis model was correctly specified, multiple imputation produced unbiased treatment effect estimates, but alternative unbiased approaches were often more efficient. When the analysis model overlooked an interaction effect involving randomized group, multiple imputation produced biased estimates of the average treatment effect when applied to missing outcome data, unless imputation was performed separately by randomized group. Based on these results, we conclude that multiple imputation should not be seen as the only acceptable way to handle missing data in randomized trials. In settings where multiple imputation is adopted, we recommend that imputation is carried out separately by randomized group.

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.

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

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial.

PubMed

Nel, Annaléne; Martins, Janine; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides.

“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

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

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.

Effectiveness of workplace weight management interventions: a systematic review

USDA-ARS?s Scientific Manuscript database

Background: A systematic review was conducted of randomized trials of workplace weight management interventions, including trials with dietary, physical activity, environmental, behavioral and incentive based components. Main outcomes were defined as change in weight-related measures. Methods: Key w...

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

PubMed

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

2012-06-01

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

Zhen gan xi feng decoction, a traditional chinese herbal formula, for the treatment of essential hypertension: a systematic review of randomized controlled trials.

PubMed

Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

2013-01-01

Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use.

Sample size calculations for the design of cluster randomized trials: A summary of methodology.

PubMed

Gao, Fei; Earnest, Arul; Matchar, David B; Campbell, Michael J; Machin, David

2015-05-01

Cluster randomized trial designs are growing in popularity in, for example, cardiovascular medicine research and other clinical areas and parallel statistical developments concerned with the design and analysis of these trials have been stimulated. Nevertheless, reviews suggest that design issues associated with cluster randomized trials are often poorly appreciated and there remain inadequacies in, for example, describing how the trial size is determined and the associated results are presented. In this paper, our aim is to provide pragmatic guidance for researchers on the methods of calculating sample sizes. We focus attention on designs with the primary purpose of comparing two interventions with respect to continuous, binary, ordered categorical, incidence rate and time-to-event outcome variables. Issues of aggregate and non-aggregate cluster trials, adjustment for variation in cluster size and the effect size are detailed. The problem of establishing the anticipated magnitude of between- and within-cluster variation to enable planning values of the intra-cluster correlation coefficient and the coefficient of variation are also described. Illustrative examples of calculations of trial sizes for each endpoint type are included. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantifying the impact of fixed effects modeling of clusters in multiple imputation for cluster randomized trials

PubMed Central

Andridge, Rebecca. R.

2011-01-01

In cluster randomized trials (CRTs), identifiable clusters rather than individuals are randomized to study groups. Resulting data often consist of a small number of clusters with correlated observations within a treatment group. Missing data often present a problem in the analysis of such trials, and multiple imputation (MI) has been used to create complete data sets, enabling subsequent analysis with well-established analysis methods for CRTs. We discuss strategies for accounting for clustering when multiply imputing a missing continuous outcome, focusing on estimation of the variance of group means as used in an adjusted t-test or ANOVA. These analysis procedures are congenial to (can be derived from) a mixed effects imputation model; however, this imputation procedure is not yet available in commercial statistical software. An alternative approach that is readily available and has been used in recent studies is to include fixed effects for cluster, but the impact of using this convenient method has not been studied. We show that under this imputation model the MI variance estimator is positively biased and that smaller ICCs lead to larger overestimation of the MI variance. Analytical expressions for the bias of the variance estimator are derived in the case of data missing completely at random (MCAR), and cases in which data are missing at random (MAR) are illustrated through simulation. Finally, various imputation methods are applied to data from the Detroit Middle School Asthma Project, a recent school-based CRT, and differences in inference are compared. PMID:21259309

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

Sleep Promotion Program for Improving Sleep Behaviors in Adolescents: A Randomized Controlled Pilot Study

PubMed Central

John, Bindu; Bellipady, Sumanth Shetty; Bhat, Shrinivasa Undaru

2016-01-01

Aims. The purpose of this pilot trial was to determine the efficacy of sleep promotion program to adapt it for the use of adolescents studying in various schools of Mangalore, India, and evaluate the feasibility issues before conducting a randomized controlled trial in a larger sample of adolescents. Methods. A randomized controlled trial design with stratified random sampling method was used. Fifty-eight adolescents were selected (mean age: 14.02 ± 2.15 years; intervention group, n = 34; control group, n = 24). Self-report questionnaires, including sociodemographic questionnaire with some additional questions on sleep and activities, Sleep Hygiene Index, Pittsburgh Sleep Quality Index, The Cleveland Adolescent Sleepiness Questionnaire, and PedsQL™ Present Functioning Visual Analogue Scale, were used. Results. Insufficient weekday-weekend sleep duration with increasing age of adolescents was observed. The program revealed a significant effect in the experimental group over the control group in overall sleep quality, sleep onset latency, sleep duration, daytime sleepiness, and emotional and overall distress. No significant effect was observed in sleep hygiene and other sleep parameters. All target variables showed significant correlations with each other. Conclusion. The intervention holds a promise for improving the sleep behaviors in healthy adolescents. However, the effect of the sleep promotion program treatment has yet to be proven through a future research. This trial is registered with ISRCTN13083118. PMID:27088040

Randomized Controlled Trial of Teaching Methods: Do Classroom Experiments Improve Economic Education in High Schools?

ERIC Educational Resources Information Center

Eisenkopf, Gerald; Sulser, Pascal A.

2016-01-01

The authors present results from a comprehensive field experiment at Swiss high schools in which they compare the effectiveness of teaching methods in economics. They randomly assigned classes into an experimental and a conventional teaching group, or a control group that received no specific instruction. Both teaching treatments improve economic…

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

PubMed Central

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

2018-01-01

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

Time-Lag Bias in Trials of Pediatric Antidepressants: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Reyes, Magdalena M.; Panza, Kaitlyn E.; Martin, Andres; Bloch, Michael H.

2011-01-01

Objective: To determine whether there is evidence of a time-lag bias in the publication of pediatric antidepressant trials. Method: We conducted a meta-analysis of published and unpublished randomized placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years of age with major depressive disorder. Our main…

2GETHER - The Dual Protection Project: Design and rationale of a randomized controlled trial to increase dual protection strategy selection and adherence among African American adolescent females

PubMed Central

Ewing, Alexander C.; Kottke, Melissa J.; Kraft, Joan Marie; Sales, Jessica M.; Brown, Jennifer L.; Goedken, Peggy; Wiener, Jeffrey; Kourtis, Athena P.

2018-01-01

Background African American adolescent females are at elevated risk for unintended pregnancy and sexually transmitted infections (STIs). Dual protection (DP) is defined as concurrent prevention of pregnancy and STIs. This can be achieved by abstinence, consistent condom use, or the dual methods of condoms plus an effective non-barrier contraceptive. Previous clinic-based interventions showed short-term effects on increasing dual method use, but evidence of sustained effects on dual method use and decreased incident pregnancies and STIs are lacking. Methods/Design This manuscript describes the 2GETHER Project. 2GETHER is a randomized controlled trial of a multi-component intervention to increase dual protection use among sexually active African American females aged 14–19 years not desiring pregnancy at a Title X clinic in Atlanta, GA. The intervention is clinic-based and includes a culturally tailored interactive multimedia component and counseling sessions, both to assist in selection of a DP method and to reinforce use of the DP method. The participants are randomized to the study intervention or the standard of care, and followed for 12 months to evaluate how the intervention influences DP method selection and adherence, pregnancy and STI incidence, and participants’ DP knowledge, intentions, and self-efficacy. Discussion The 2GETHER Project is a novel trial to reduce unintended pregnancies and STIs among African American adolescents. The intervention is unique in the comprehensive and complementary nature of its components and its individual tailoring of provider-patient interaction. If the trial interventions are shown to be effective, then it will be reasonable to assess their scalability and applicability in other populations. PMID:28007634

Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods

PubMed Central

2013-01-01

Background Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain. Methods The design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research. Results The IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8–19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth. Conclusion Antipsychotic-related weight gain is an important public health issue for youth requiring ongoing antipsychotic treatment to maintain psychiatric stability. The IMPACT study provides a model for pediatric research on adverse event management using state-of-the art methods. The results of this study will provide needed data on risks and benefits of two pharmacologic interventions that are already being used in pediatric clinical settings but that have not yet been compared directly in randomized trials. Trial registration Clinical Trials.gov NCT00806234 PMID:23947389

Causal inference from observational data.

PubMed

Listl, Stefan; Jürges, Hendrik; Watt, Richard G

2016-10-01

Randomized controlled trials have long been considered the 'gold standard' for causal inference in clinical research. In the absence of randomized experiments, identification of reliable intervention points to improve oral health is often perceived as a challenge. But other fields of science, such as social science, have always been challenged by ethical constraints to conducting randomized controlled trials. Methods have been established to make causal inference using observational data, and these methods are becoming increasingly relevant in clinical medicine, health policy and public health research. This study provides an overview of state-of-the-art methods specifically designed for causal inference in observational data, including difference-in-differences (DiD) analyses, instrumental variables (IV), regression discontinuity designs (RDD) and fixed-effects panel data analysis. The described methods may be particularly useful in dental research, not least because of the increasing availability of routinely collected administrative data and electronic health records ('big data'). © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Using pilot data to size a two-arm randomized trial to find a nearly optimal personalized treatment strategy.

PubMed

Laber, Eric B; Zhao, Ying-Qi; Regh, Todd; Davidian, Marie; Tsiatis, Anastasios; Stanford, Joseph B; Zeng, Donglin; Song, Rui; Kosorok, Michael R

2016-04-15

A personalized treatment strategy formalizes evidence-based treatment selection by mapping patient information to a recommended treatment. Personalized treatment strategies can produce better patient outcomes while reducing cost and treatment burden. Thus, among clinical and intervention scientists, there is a growing interest in conducting randomized clinical trials when one of the primary aims is estimation of a personalized treatment strategy. However, at present, there are no appropriate sample size formulae to assist in the design of such a trial. Furthermore, because the sampling distribution of the estimated outcome under an estimated optimal treatment strategy can be highly sensitive to small perturbations in the underlying generative model, sample size calculations based on standard (uncorrected) asymptotic approximations or computer simulations may not be reliable. We offer a simple and robust method for powering a single stage, two-armed randomized clinical trial when the primary aim is estimating the optimal single stage personalized treatment strategy. The proposed method is based on inverting a plugin projection confidence interval and is thereby regular and robust to small perturbations of the underlying generative model. The proposed method requires elicitation of two clinically meaningful parameters from clinical scientists and uses data from a small pilot study to estimate nuisance parameters, which are not easily elicited. The method performs well in simulated experiments and is illustrated using data from a pilot study of time to conception and fertility awareness. Copyright © 2015 John Wiley & Sons, Ltd.

The Sexunzipped trial: young people's views of participating in an online randomized controlled trial.

PubMed

Nicholas, Angela; Bailey, Julia V; Stevenson, Fiona; Murray, Elizabeth

2013-12-12

Incidence of sexually transmitted infections (STIs) among young people in the United Kingdom is increasing. The Internet can be a suitable medium for delivery of sexual health information and sexual health promotion, given its high usage among young people, its potential for creating a sense of anonymity, and ease of access. Online randomized controlled trials (RCTs) are increasingly being used to evaluate online interventions, but while there are many advantages to online methodologies, they can be associated with a number of problems, including poor engagement with online interventions, poor trial retention, and concerns about the validity of data collected through self-report online. We conducted an online feasibility trial that tested the effects of the Sexunzipped website for sexual health compared to an information-only website. This study reports on a qualitative evaluation of the trial procedures, describing participants' experiences and views of the Sexunzipped online trial including methods of recruitment, incentives, methods of contact, and sexual health outcome measurement. Our goal was to determine participants' views of the acceptability and validity of the online trial methodology used in the pilot RCT of the Sexunzipped intervention. We used three qualitative data sources to assess the acceptability and validity of the online pilot RCT methodology: (1) individual interviews with 22 participants from the pilot RCT, (2) 133 emails received by the trial coordinator from trial participants, and (3) 217 free-text comments from the baseline and follow-up questionnaires. Interviews were audio-recorded and transcribed verbatim. An iterative, thematic analysis of all three data sources was conducted to identify common themes related to the acceptability and feasibility of the online trial methodology. Interview participants found the trial design, including online recruitment via Facebook, online registration, email communication with the researchers, and online completion of sexual health questionnaires to be highly acceptable and preferable to traditional methods. Incentives might assist in recruiting those who would not otherwise participate. Participants generally enjoyed taking part in sexual health research online and found the questionnaire itself thought-provoking. Completing the sexual health questionnaires online encouraged honesty in responding that might not be achieved with other methods. The majority of interview participants also thought that receiving and returning a urine sample for chlamydia testing via post was acceptable. These findings provide strong support for the use of online research methods for sexual health research, emphasizing the importance of careful planning and execution of all trial procedures including recruitment, respondent validation, trial related communication, and methods to maximize follow-up. Our findings suggest that sexual health outcome measurement might encourage reflection on current behavior, sometimes leading to behavior change. International Standard Randomized Controlled Trial Number (ISRCTN): 55651027; http://www.controlled-trials.com/isrctn/pf/55651027 (Archived by WebCite at http://www.webcitation.org/6LbkxdPKf).

Culturally adaptive storytelling method to improve hypertension control in Vietnam - "We talk about our hypertension": study protocol for a feasibility cluster-randomized controlled trial.

PubMed

Allison, Jeroan J; Nguyen, Hoa L; Ha, Duc A; Chiriboga, Germán; Ly, Ha N; Tran, Hanh T; Phan, Ngoc T; Vu, Nguyen C; Kim, Minjin; Goldberg, Robert J

2016-01-14

Vietnam is experiencing an epidemiologic transition with an increased prevalence of non-communicable diseases. At present, the major risk factors for cardiovascular disease (CVD) are either on the rise or at alarming levels in Vietnam; inasmuch, the burden of CVD will continue to increase in this country unless effective prevention and control measures are put in place. A national survey in 2008 found that the prevalence of hypertension (HTN) was approximately 25 % among Vietnamese adults and it increased with advancing age. Therefore, novel, large-scale, and sustainable interventions for public health education to promote engagement in the process of detecting and treating HTN in Vietnam are urgently needed. A feasibility randomized trial will be conducted in Hung Yen province, Vietnam to evaluate the feasibility and acceptability of a novel community-based intervention using the "storytelling" method to enhance the control of HTN in adults residing in four rural communities. The intervention will center on stories about living with HTN, with patients speaking in their own words. The stories will be obtained from particularly eloquent patients, or "video stars," identified during Story Development Groups. The study will involve two phases: (i) developing a HTN intervention using the storytelling method, which is designed to empower patients to facilitate changes in their lifestyle practices, and (ii) conducting a feasibility cluster-randomized trial to investigate the feasibility, acceptability, and potential efficacy of the intervention compared with usual care in HTN control among rural residents. The trial will be conducted at four communes, and within each commune, 25 individuals 50 years or older with HTN will be enrolled in the trial resulting in a total sample size of 100 patients. This feasibility trial will provide the necessary groundwork for a subsequent large-scale, fully powered, cluster-randomized controlled trial to test the efficacy of our novel community-based intervention. Results from the full-scale trial will provide health policy makers with practical evidence on how to combat a key risk factor for CVD using a feasible, sustainable, and cost-effective intervention that could be used as a national program for controlling HTN in Vietnam and other developing countries. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02483780 (registration date June 22, 2015).

A cluster-randomized, placebo-controlled, maternal vitamin A or beta-carotene supplementation trial in Bangladesh: design and methods.

PubMed

Labrique, Alain B; Christian, Parul; Klemm, Rolf D W; Rashid, Mahbubur; Shamim, Abu Ahmed; Massie, Allan; Schulze, Kerry; Hackman, Andre; West, Keith P

2011-04-21

We present the design, methods and population characteristics of a large community trial that assessed the efficacy of a weekly supplement containing vitamin A or beta-carotene, at recommended dietary levels, in reducing maternal mortality from early gestation through 12 weeks postpartum. We identify challenges faced and report solutions in implementing an intervention trial under low-resource, rural conditions, including the importance of population choice in promoting generalizability, maintaining rigorous data quality control to reduce inter- and intra- worker variation, and optimizing efficiencies in information and resources flow from and to the field. This trial was a double-masked, cluster-randomized, dual intervention, placebo-controlled trial in a contiguous rural area of ~435 sq km with a population of ~650,000 in Gaibandha and Rangpur Districts of Northwestern Bangladesh. Approximately 120,000 married women of reproductive age underwent 5-weekly home surveillance, of whom ~60,000 were detected as pregnant, enrolled into the trial and gave birth to ~44,000 live-born infants. Upon enrollment, at ~ 9 weeks' gestation, pregnant women received a weekly oral supplement containing vitamin A (7000 ug retinol equivalents (RE)), beta-carotene (42 mg, or ~7000 ug RE) or a placebo through 12 weeks postpartum, according to prior randomized allocation of their cluster of residence. Systems described include enlistment and 5-weekly home surveillance for pregnancy based on menstrual history and urine testing, weekly supervised supplementation, periodic risk factor interviews, maternal and infant vital outcome monitoring, birth defect surveillance and clinical/biochemical substudies. The primary outcome was pregnancy-related mortality assessed for 3 months following parturition. Secondary outcomes included fetal loss due to miscarriage or stillbirth, infant mortality under three months of age, maternal obstetric and infectious morbidity, infant infectious morbidity, maternal and infant micronutrient status, fetal and infant growth and prematurity, external birth defects and postnatal infant growth to 3 months of age. Aspects of study site selection and its "resonance" with national and rural qualities of Bangladesh, the trial's design, methods and allocation group comparability achieved by randomization, field procedures and innovative approaches to solving challenges in trial conduct are described and discussed. This trial is registered with http://Clinicaltrials.gov as protocol NCT00198822.

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

PubMed Central

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

2013-01-01

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

Effects of Exercise on Mild-to-Moderate Depressive Symptoms in the Postpartum Period: A Meta-analysis.

PubMed

McCurdy, Ashley P; Boulé, Normand G; Sivak, Allison; Davenport, Margie H

2017-06-01

To examine the influence of exercise on depressive symptoms and the prevalence of depression in the postpartum period. A structured search of MEDLINE, EMBASE, CINAHL, Sport Discus, Ovid's All EBM Reviews, and ClinicalTrials.gov databases was performed with dates from the beginning of the databases until June 16, 2016. The search combined keywords and MeSH-like terms including, but not limited to, "exercise," "postpartum," "depression," and "randomized controlled trial." Randomized controlled trials comparing postpartum exercise (structured, planned, repetitive physical activity) with the standard care for which outcomes assessing depressive symptoms or depressive episodes (as defined by trial authors) were assessed. Trials were identified as prevention trials (women from the general postpartum population) or treatment trials (women were classified as having depression by the trial authors). Effect sizes with 95% confidence intervals (CIs) were calculated using Hedges' g method and standardized mean differences in postintervention depression outcomes were pooled using a random-effects model. Across all 16 trials (1,327 women), the pooled standardized mean difference was -0.34 (95% CI -0.50 to -0.19, I=37%), suggesting a small effect of exercise among all postpartum women on depressive symptoms. Among the 10 treatment trials, a moderate effect size of exercise on depressive symptoms was found (standardized mean difference-0.48, 95% CI -0.73 to -0.22, I=42%). In six prevention trials, a small effect (standardized mean difference-0.22, 95% CI -0.36 to -0.08, I=2%) was found. In women with depression preintervention, exercise increased the odds of resolving depression postintervention by 54% (odds ratio 0.46, Mantel-Haenszel method, 95% CI 0.25-0.84, I=0%). The trials included in this meta-analysis were small and some had methodologic limitations. Light-to-moderate intensity aerobic exercise improves mild-to-moderate depressive symptoms and increases the likelihood that mild-to-moderate depression will resolve.

Extrapolating Survival from Randomized Trials Using External Data: A Review of Methods

PubMed Central

Jackson, Christopher; Stevens, John; Ren, Shijie; Latimer, Nick; Bojke, Laura; Manca, Andrea; Sharples, Linda

2016-01-01

This article describes methods used to estimate parameters governing long-term survival, or times to other events, for health economic models. Specifically, the focus is on methods that combine shorter-term individual-level survival data from randomized trials with longer-term external data, thus using the longer-term data to aid extrapolation of the short-term data. This requires assumptions about how trends in survival for each treatment arm will continue after the follow-up period of the trial. Furthermore, using external data requires assumptions about how survival differs between the populations represented by the trial and external data. Study reports from a national health technology assessment program in the United Kingdom were searched, and the findings were combined with “pearl-growing” searches of the academic literature. We categorized the methods that have been used according to the assumptions they made about how the hazards of death vary between the external and internal data and through time, and we discuss the appropriateness of the assumptions in different circumstances. Modeling choices, parameter estimation, and characterization of uncertainty are discussed, and some suggestions for future research priorities in this area are given. PMID:27005519

Does time-lapse imaging have favorable results for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization? A meta-analysis and systematic review of randomized controlled trials.

PubMed

Chen, Minghao; Wei, Shiyou; Hu, Junyan; Yuan, Jing; Liu, Fenghua

2017-01-01

The present study aimed to undertake a review of available evidence assessing whether time-lapse imaging (TLI) has favorable outcomes for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization (IVF). Using PubMed, EMBASE, Cochrane library and ClinicalTrial.gov up to February 2017 to search for randomized controlled trials (RCTs) comparing TLI versus conventional methods. Both studies randomized women and oocytes were included. For studies randomized women, the primary outcomes were live birth and ongoing pregnancy, the secondary outcomes were clinical pregnancy and miscarriage; for studies randomized oocytes, the primary outcome was blastocyst rate, the secondary outcome was good quality embryo on Day 2/3. Subgroup analysis was conducted based on different incubation and embryo selection between groups. Ten RCTs were included, four randomized oocytes and six randomized women. For oocyte-based review, the pool-analysis observed no significant difference between TLI group and control group for blastocyst rate [relative risk (RR) 1.08, 95% CI 0.94-1.25, I2 = 0%, two studies, including 1154 embryos]. The quality of evidence was moderate for all outcomes in oocyte-based review. For woman-based review, only one study provided live birth rate (RR 1,23, 95% CI 1.06-1.44,I2 N/A, one study, including 842 women), the pooled result showed no significant difference in ongoing pregnancy rate (RR 1.04, 95% CI 0.80-1.36, I2 = 59%, four studies, including 1403 women) between two groups. The quality of the evidence was low or very low for all outcomes in woman-based review. Currently there is insufficient evidence to support that TLI is superior to conventional methods for human embryo incubation and selection. In consideration of the limitations and flaws of included studies, more well designed RCTs are still in need to comprehensively evaluate the effectiveness of clinical TLI use.

Response: Reading between the lines of cancer screening trials: using modeling to understand the evidence.

PubMed

Etzioni, Ruth; Gulati, Roman

2013-04-01

In our article about limitations of basing screening policy on screening trials, we offered several examples of ways in which modeling, using data from large screening trials and population trends, provided insights that differed somewhat from those based only on empirical trial results. In this editorial, we take a step back and consider the general question of whether randomized screening trials provide the strongest evidence for clinical guidelines concerning population screening programs. We argue that randomized trials provide a process that is designed to protect against certain biases but that this process does not guarantee that inferences based on empirical results from screening trials will be unbiased. Appropriate quantitative methods are key to obtaining unbiased inferences from screening trials. We highlight several studies in the statistical literature demonstrating that conventional survival analyses of screening trials can be misleading and list a number of key questions concerning screening harms and benefits that cannot be answered without modeling. Although we acknowledge the centrality of screening trials in the policy process, we maintain that modeling constitutes a powerful tool for screening trial interpretation and screening policy development.

Allowing for uncertainty due to missing continuous outcome data in pairwise and network meta-analysis.

PubMed

Mavridis, Dimitris; White, Ian R; Higgins, Julian P T; Cipriani, Andrea; Salanti, Georgia

2015-02-28

Missing outcome data are commonly encountered in randomized controlled trials and hence may need to be addressed in a meta-analysis of multiple trials. A common and simple approach to deal with missing data is to restrict analysis to individuals for whom the outcome was obtained (complete case analysis). However, estimated treatment effects from complete case analyses are potentially biased if informative missing data are ignored. We develop methods for estimating meta-analytic summary treatment effects for continuous outcomes in the presence of missing data for some of the individuals within the trials. We build on a method previously developed for binary outcomes, which quantifies the degree of departure from a missing at random assumption via the informative missingness odds ratio. Our new model quantifies the degree of departure from missing at random using either an informative missingness difference of means or an informative missingness ratio of means, both of which relate the mean value of the missing outcome data to that of the observed data. We propose estimating the treatment effects, adjusted for informative missingness, and their standard errors by a Taylor series approximation and by a Monte Carlo method. We apply the methodology to examples of both pairwise and network meta-analysis with multi-arm trials. © 2014 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

The Minnesota Green Tea Trial (MGTT), a randomized controlled trial of the efficacy of green tea extract on biomarkers of breast cancer risk: Study rationale, design, methods, and participant characteristics

PubMed Central

Samavat, Hamed; Dostal, Allison M.; Wang, Renwei; Bedell, Sarah; Emory, Tim H.; Ursin, Giske; Torkelson, Carolyn J.; Gross, Myron D.; Le, Chap T.; Yu, Mimi C.; Yang, Chung S.; Yee, Douglas; Wu, Anna H.; Yuan, Jian-Min; Kurzer, Mindy S.

2015-01-01

Purpose The Minnesota Green Tea Trial (MGTT) was a randomized, placebo-controlled, double-blinded trial investigating the effect of daily green tea extract consumption for 12 months on biomarkers of breast cancer risk. Methods Participants were healthy postmenopausal women at high risk of breast cancer due to dense breast tissue with differing catechol-O-methyltransferase (COMT) genotypes. The intervention was a green tea catechin extract containing 843.0 ± 44.0 mg/day epigallocatechin gallate or placebo capsules for one year. Annual digital screening mammograms were obtained at baseline and month 12, and fasting blood and 24-hour urine samples were provided at baseline, months 6, and 12. Primary endpoints included changes in percent mammographic density, circulating endogenous sex hormones and insulin-like growth factor axis proteins; secondary endpoints were changes in urinary estrogens and estrogen metabolites and circulating F2-isoprostanes, a biomarker of oxidative stress. Results The MGTT screened more than 100,000 mammograms and randomized 1075 participants based on treatment (green tea extract vs. placebo), stratified by COMT genotype activity (high COMT vs. low/intermediate COMT genotype activity). 937 women successfully completed the study and 138 dropped out (overall dropout rate= 12.8%). Conclusions In this paper we report the rationale, design, recruitment, participant characteristics, and methods for biomarker and statistical analyses. PMID:26206423

Randomized controlled trial of a computer-based module to improve contraceptive method choice.

PubMed

Garbers, Samantha; Meserve, Allison; Kottke, Melissa; Hatcher, Robert; Ventura, Alicia; Chiasson, Mary Ann

2012-10-01

Unintended pregnancy is common in the United States, and interventions are needed to improve contraceptive use among women at higher risk of unintended pregnancy, including Latinas and women with low educational attainment. A three-arm randomized controlled trial was conducted at two family planning sites serving low-income, predominantly Latina populations. The trial tested the efficacy of a computer-based contraceptive assessment module in increasing the proportion of patients choosing an effective method of contraception (<10 pregnancies/100 women per year, typical use). Participants were randomized to complete the module and receive tailored health materials, to complete the module and receive generic health materials, or to a control condition. In intent-to-treat analyses adjusted for recruitment site (n=2231), family planning patients who used the module were significantly more likely to choose an effective contraceptive method: 75% among those who received tailored materials [odds ratio (OR)=1.56; 95% confidence interval (CI): 1.23-1.98] and 78% among those who received generic materials (OR=1.74; 95% CI: 1.35-2.25), compared to 65% among control arm participants. The findings support prior research suggesting that patient-centered interventions can positively influence contraceptive method choice. Copyright © 2012 Elsevier Inc. All rights reserved.

Physical methods for treating fever in children.

PubMed

Meremikwu, M; Oyo-Ita, A

2003-01-01

Health workers recommend bathing, sponging and other physical methods to treat fever in children and to avoid febrile convulsions. We know little about the most effective methods, or how these methods compare with commonly used drugs. To evaluate the benefits and harms of physical cooling methods used for managing fever in children. We searched the Cochrane Infectious Diseases Group specialized trials register (February 2003), the Cochrane Central Register of Controlled Trials (Issue 1, 2003), MEDLINE (1966 to February 2003), EMBASE (1988 to November 2002), CINHAL (1982 to February 2003), LILACS (February 2003), Science Citation Index (1981 to February 2003), and reference lists of articles. We also contacted researchers in the field. Randomized and quasi-randomized trials comparing physical methods with a drug placebo or no treatment in children with fever of presumed infectious origin. Studies where children in both groups were given an antipyretic drug were included. Two reviewers independently assessed trial methodological quality. One reviewer extracted data and the other checked the data for accuracy. Results were expressed as Relative Risk (RR) with 95% confidence intervals (CI) for discrete variables, and weighted mean differences for continuous outcomes. Seven trials, involving 467 participants, met the inclusion criteria. One small trial (n = 30), comparing physical methods with drug placebo, did not demonstrate a difference in the proportion of children without fever by one hour after treatment in a comparison between physical methods alone and drug placebo. In 2 studies, where all children received an anti-pyretic drug, physical methods resulted in a higher proportion of children without fever at one hour (n=125, RR 11.8, CI 3.39 to 40.8). I; in a third study (n=130), which only reported mean change in temperature, no differences wereas detected. Mild adverse events (shivering and goose pimples) were more common in the physical methods group (3 trials, RR 5.09; CI 1.56 to 16.60). A few small studies demonstrate that tepid sponging helps to reduce fever in children.

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

Enhanced invitation methods to increase uptake of NHS health checks: study protocol for a randomized controlled trial.

PubMed

Forster, Alice S; Burgess, Caroline; McDermott, Lisa; Wright, Alison J; Dodhia, Hiten; Conner, Mark; Miller, Jane; Rudisill, Caroline; Cornelius, Victoria; Gulliford, Martin C

2014-08-30

NHS Health Checks is a new program for primary prevention of heart disease, stroke, diabetes, chronic kidney disease, and vascular dementia in adults aged 40 to 74 years in England. Individuals without existing cardiovascular disease or diabetes are invited for a Health Check every 5 years. Uptake among those invited is lower than anticipated. The project is a three-arm randomized controlled trial to test the hypothesis that enhanced invitation methods, using the Question-Behaviour Effect (QBE), will increase uptake of NHS Health Checks compared with a standard invitation. Participants comprise individuals eligible for an NHS Health Check registered in two London boroughs. Participants are randomized into one of three arms. Group A receives the standard NHS Health Check invitation letter, information sheet, and reminder letter at 12 weeks for nonattenders. Group B receives a QBE questionnaire 1 week before receiving the standard invitation, information sheet, and reminder letter where appropriate. Group C is the same as Group B, but participants are offered a £5 retail voucher if they return the questionnaire. Participants are randomized in equal proportions, stratified by general practice. The primary outcome is uptake of NHS Health Checks 6 months after invitation from electronic health records. We will estimate the incremental health service cost per additional completed Health Check for trial groups B and C versus trial arm A, as well as evaluating the impact of the QBE questionnaire, and questionnaire plus voucher, on the socioeconomic inequality in uptake of Health Checks.The trial includes a nested comparison of two methods for implementing allocation, one implemented manually at general practices and the other implemented automatically through the information systems used to generate invitations for the Health Check. The research will provide evidence on whether asking individuals to complete a preliminary questionnaire, by using the QBE, is effective in increasing uptake of Health Checks and whether an incentive alters questionnaire return rates as well as uptake of Health Checks. The trial interventions can be readily translated into routine service delivery if they are shown to be cost-effective. Current Controlled Trials ISRCTN42856343. Date registered: 21.03.2013.

surrosurv: An R package for the evaluation of failure time surrogate endpoints in individual patient data meta-analyses of randomized clinical trials.

PubMed

Rotolo, Federico; Paoletti, Xavier; Michiels, Stefan

2018-03-01

Surrogate endpoints are attractive for use in clinical trials instead of well-established endpoints because of practical convenience. To validate a surrogate endpoint, two important measures can be estimated in a meta-analytic context when individual patient data are available: the R indiv 2 or the Kendall's τ at the individual level, and the R trial 2 at the trial level. We aimed at providing an R implementation of classical and well-established as well as more recent statistical methods for surrogacy assessment with failure time endpoints. We also intended incorporating utilities for model checking and visualization and data generating methods described in the literature to date. In the case of failure time endpoints, the classical approach is based on two steps. First, a Kendall's τ is estimated as measure of individual level surrogacy using a copula model. Then, the R trial 2 is computed via a linear regression of the estimated treatment effects; at this second step, the estimation uncertainty can be accounted for via measurement-error model or via weights. In addition to the classical approach, we recently developed an approach based on bivariate auxiliary Poisson models with individual random effects to measure the Kendall's τ and treatment-by-trial interactions to measure the R trial 2 . The most common data simulation models described in the literature are based on: copula models, mixed proportional hazard models, and mixture of half-normal and exponential random variables. The R package surrosurv implements the classical two-step method with Clayton, Plackett, and Hougaard copulas. It also allows to optionally adjusting the second-step linear regression for measurement-error. The mixed Poisson approach is implemented with different reduced models in addition to the full model. We present the package functions for estimating the surrogacy models, for checking their convergence, for performing leave-one-trial-out cross-validation, and for plotting the results. We illustrate their use in practice on individual patient data from a meta-analysis of 4069 patients with advanced gastric cancer from 20 trials of chemotherapy. The surrosurv package provides an R implementation of classical and recent statistical methods for surrogacy assessment of failure time endpoints. Flexible simulation functions are available to generate data according to the methods described in the literature. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Open transinguinal preperitoneal mesh repair of inguinal hernia: a targeted systematic review and meta-analysis of published randomized controlled trials

PubMed Central

Sajid, Muhammad S.; Craciunas, L.; Singh, K.K.; Sains, P.; Baig, M.K.

2013-01-01

Objective: The objective of this article is to systematically analyse the randomized, controlled trials comparing transinguinal preperitoneal (TIPP) and Lichtenstein repair (LR) for inguinal hernia. Methods: Randomized, controlled trials comparing TIPP vs LR were analysed systematically using RevMan® and combined outcomes were expressed as risk ratio (RR) and standardized mean difference. Results: Twelve randomized trials evaluating 1437 patients were retrieved from the electronic databases. There were 714 patients in the TIPP repair group and 723 patients in the LR group. There was significant heterogeneity among trials (P < 0.0001). Therefore, in the random effects model, TIPP repair was associated with a reduced risk of developing chronic groin pain (RR, 0.48; 95% CI, 0.26, 0.89; z = 2.33; P < 0.02) without influencing the incidence of inguinal hernia recurrence (RR, 0.18; 95% CI, 0.36, 1.83; z = 0.51; P = 0.61). Risk of developing postoperative complications and moderate-to-severe postoperative pain was similar following TIPP repair and LR. In addition, duration of operation was statistically similar in both groups. Conclusion: TIPP repair for inguinal hernia is associated with lower risk of developing chronic groin pain. It is comparable with LR in terms of risk of hernia recurrence, postoperative complications, duration of operation and intensity of postoperative pain. PMID:24759818

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

PubMed Central

2014-01-01

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

The clinical and cost-effectiveness of the BRinging Information and Guided Help Together (BRIGHT) intervention for the self-management support of people with stage 3 chronic kidney disease in primary care: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Improving the quality of care for people with vascular disease is a key priority. Chronic kidney disease (CKD) has recently been included as a target condition for general practices to add to registers of chronic conditions as part of the Quality and Outcome Framework. This paper outlines the implementation and evaluation of a self-management intervention involving an information guidebook, tailored access to local resources and telephone support for people with stage 3 chronic kidney disease. Methods/Design The study involves a multi-site, longitudinal patient-level randomized controlled trial. The study will evaluate the clinical use and cost-effectiveness of a complex self-management intervention for people with stage 3 chronic kidney disease in terms of self-management capacity, health-related quality of life and blood pressure control compared to care as usual. We describe the methods of the patient-level randomized controlled trial. Discussion The management of chronic kidney disease is a developing area of research. The BRinging Information and Guided Help Together (BRIGHT) trial aims to provide evidence that a complementary package of support for people with vascular disease that targets both clinical and social need broadens the opportunities of self-management support by addressing problems related to social disadvantage. Trial registration Trial registration reference: ISRCTN45433299 PMID:23356861

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

Meta-analysis in clinical trials revisited.

PubMed

DerSimonian, Rebecca; Laird, Nan

2015-11-01

In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effects model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the "DerSimonian and Laird method" is now often referred to as the 'standard approach' or a 'popular' method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. Published by Elsevier Inc.

Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials

PubMed Central

Ha, Vanessa; Sievenpiper, John L.; de Souza, Russell J.; Jayalath, Viranda H.; Mirrahimi, Arash; Agarwal, Arnav; Chiavaroli, Laura; Mejia, Sonia Blanco; Sacks, Frank M.; Di Buono, Marco; Bernstein, Adam M.; Leiter, Lawrence A.; Kris-Etherton, Penny M.; Vuksan, Vladimir; Bazinet, Richard P.; Josse, Robert G.; Beyene, Joseph; Kendall, Cyril W.C.; Jenkins, David J.A.

2014-01-01

Background: Evidence from controlled trials encourages the intake of dietary pulses (beans, chickpeas, lentils and peas) as a method of improving dyslipidemia, but heart health guidelines have stopped short of ascribing specific benefits to this type of intervention or have graded the beneficial evidence as low. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction. Methods: We searched electronic databases and bibliographies of selected trials for relevant articles published through Feb. 5, 2014. We included RCTs of at least 3 weeks’ duration that compared a diet emphasizing dietary pulse intake with an isocaloric diet that did not include dietary pulses. The lipid targets investigated were low-density lipoprotein (LDL) cholesterol, apolipoprotein B and non–high-density lipoprotein (non-HDL) cholesterol. We pooled data using a random-effects model. Results: We identified 26 RCTs (n = 1037) that satisfied the inclusion criteria. Diets emphasizing dietary pulse intake at a median dose of 130 g/d (about 1 serving daily) significantly lowered LDL cholesterol levels compared with the control diets (mean difference −0.17 mmol/L, 95% confidence interval −0.25 to −0.09 mmol/L). Treatment effects on apolipoprotein B and non-HDL cholesterol were not observed. Interpretation: Our findings suggest that dietary pulse intake significantly reduces LDL cholesterol levels. Trials of longer duration and higher quality are needed to verify these results. Trial registration: ClinicalTrials.gov, no. NCT01594567. PMID:24710915

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

Design and methods for a randomized clinical trial treating comorbid obesity and major depressive disorder

PubMed Central

Schneider, Kristin L; Bodenlos, Jamie S; Ma, Yunsheng; Olendzki, Barbara; Oleski, Jessica; Merriam, Philip; Crawford, Sybil; Ockene, Ira S; Pagoto, Sherry L

2008-01-01

Background Obesity is often comorbid with depression and individuals with this comorbidity fare worse in behavioral weight loss treatment. Treating depression directly prior to behavioral weight loss treatment might bolster weight loss outcomes in this population, but this has not yet been tested in a randomized clinical trial. Methods and design This randomized clinical trial will examine whether behavior therapy for depression administered prior to standard weight loss treatment produces greater weight loss than standard weight loss treatment alone. Obese women with major depressive disorder (N = 174) will be recruited from primary care clinics and the community and randomly assigned to one of the two treatment conditions. Treatment will last 2 years, and will include a 6-month intensive treatment phase followed by an 18-month maintenance phase. Follow-up assessment will occur at 6-months and 1- and 2 years following randomization. The primary outcome is weight loss. The study was designed to provide 90% power for detecting a weight change difference between conditions of 3.1 kg (standard deviation of 5.5 kg) at 1-year assuming a 25% rate of loss to follow-up. Secondary outcomes include depression, physical activity, dietary intake, psychosocial variables and cardiovascular risk factors. Potential mediators (e.g., adherence, depression, physical activity and caloric intake) of the intervention effect on weight change will also be examined. Discussion Treating depression before administering intensive health behavior interventions could potentially boost the impact on both mental and physical health outcomes. Trial registration NCT00572520 PMID:18793398

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

2GETHER - The Dual Protection Project: Design and rationale of a randomized controlled trial to increase dual protection strategy selection and adherence among African American adolescent females.

PubMed

Ewing, Alexander C; Kottke, Melissa J; Kraft, Joan Marie; Sales, Jessica M; Brown, Jennifer L; Goedken, Peggy; Wiener, Jeffrey; Kourtis, Athena P

2017-03-01

African American adolescent females are at elevated risk for unintended pregnancy and sexually transmitted infections (STIs). Dual protection (DP) is defined as concurrent prevention of pregnancy and STIs. This can be achieved by abstinence, consistent condom use, or the dual methods of condoms plus an effective non-barrier contraceptive. Previous clinic-based interventions showed short-term effects on increasing dual method use, but evidence of sustained effects on dual method use and decreased incident pregnancies and STIs are lacking. This manuscript describes the 2GETHER Project. 2GETHER is a randomized controlled trial of a multi-component intervention to increase dual protection use among sexually active African American females aged 14-19years not desiring pregnancy at a Title X clinic in Atlanta, GA. The intervention is clinic-based and includes a culturally tailored interactive multimedia component and counseling sessions, both to assist in selection of a DP method and to reinforce use of the DP method. The participants are randomized to the study intervention or the standard of care, and followed for 12months to evaluate how the intervention influences DP method selection and adherence, pregnancy and STI incidence, and participants' DP knowledge, intentions, and self-efficacy. The 2GETHER Project is a novel trial to reduce unintended pregnancies and STIs among African American adolescents. The intervention is unique in the comprehensive and complementary nature of its components and its individual tailoring of provider-patient interaction. If the trial interventions are shown to be effective, then it will be reasonable to assess their scalability and applicability in other populations. Published by Elsevier Inc.

Comparing community and specialty provider-based recruitment in a randomized clinical trial: clinical trial in fecal incontinence.

PubMed

Whitebird, Robin R; Bliss, Donna Zimmaro; Savik, Kay; Lowry, Ann; Jung, Hans-Joachim G

2010-12-01

Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). In the Fiber Study, a randomized controlled trial on symptom management for FI, we successfully enrolled 189 community-living adults through collaborations with specialty-based and community-based settings, each employing methods tailored to the organizational characteristics of their site. Results show that using the two settings increased racial and ethnic diversity of the sample and inclusion of informal caregivers. There were no differential effects on enrollment, final eligibility, or completion of protocol by site. Strategic collaborations with complementary sites can achieve sample recruitment goals for clinical trials on topics that are sensitive or known to be underreported. Copyright © 2010 Wiley Periodicals, Inc.

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.

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.

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

PubMed

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

2012-07-03

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

Meta-analysis of Odds Ratios: Current Good Practices

PubMed Central

Chang, Bei-Hung; Hoaglin, David C.

2016-01-01

Background Many systematic reviews of randomized clinical trials lead to meta-analyses of odds ratios. The customary methods of estimating an overall odds ratio involve weighted averages of the individual trials’ estimates of the logarithm of the odds ratio. That approach, however, has several shortcomings, arising from assumptions and approximations, that render the results unreliable. Although the problems have been documented in the literature for many years, the conventional methods persist in software and applications. A well-developed alternative approach avoids the approximations by working directly with the numbers of subjects and events in the arms of the individual trials. Objective We aim to raise awareness of methods that avoid the conventional approximations, can be applied with widely available software, and produce more-reliable results. Methods We summarize the fixed-effect and random-effects approaches to meta-analysis; describe conventional, approximate methods and alternative methods; apply the methods in a meta-analysis of 19 randomized trials of endoscopic sclerotherapy in patients with cirrhosis and esophagogastric varices; and compare the results. We demonstrate the use of SAS, Stata, and R software for the analysis. Results In the example, point estimates and confidence intervals for the overall log-odds-ratio differ between the conventional and alternative methods, in ways that can affect inferences. Programming is straightforward in the three software packages; an appendix gives the details. Conclusions The modest additional programming required should not be an obstacle to adoption of the alternative methods. Because their results are unreliable, use of the conventional methods for meta-analysis of odds ratios should be discontinued. PMID:28169977

Effects of a novel method for enteral nutrition infusion involving a viscosity-regulating pectin solution: A multicenter randomized controlled trial.

PubMed

Tabei, Isao; Tsuchida, Shigeru; Akashi, Tetsuro; Ookubo, Katsuichiro; Hosoda, Satoru; Furukawa, Yoshiyuki; Tanabe, Yoshiaki; Tamura, Yoshiko

2018-02-01

The initial complications associated with infusion of enteral nutrition (EN) for clinical and nutritional care are vomiting, aspiration pneumonia, and diarrhea. There are many recommendations to prevent these complications. A novel method involving a viscosity-regulating pectin solution has been demonstrated. In Japan, this method along with the other so-called "semi-solid EN" approaches has been widely used in practice. However, there has been no randomized clinical trial to prove the efficiency and safety of a viscosity-regulating pectin solution in EN management. Therefore, we planned and initiated a multicenter randomized controlled trial to determine the efficiency and safety. This study included 34 patients from 7 medical institutions who participated. Institutional review board (IRB) approval was obtained from all participating institutions. Patients who required EN management were enrolled and randomly assigned to the viscosity regulation of enteral feeding (VREF) group and control group. The VREF group (n = 15) was managed with the addition of a viscosity-regulating pectin solution. The control group (n = 12) was managed with conventional EN administration, usually in a gradual step-up method. Daily clinical symptoms of pneumonia, fever, vomiting, and diarrhea; defecation frequency; and stool form were observed in the 2 week trial period. The dose of EN and duration of infusion were also examined. A favorable trend for clinical symptoms was noticed in the VREF group. No significant differences were observed in episodes of pneumonia, fever, vomiting, and diarrhea between the 2 groups. An apparent reduction in infusion duration and hardening of stool form were noted in the VREF group. The novel method involving a viscosity-regulating pectin solution with EN administration can be clinically performed safely and efficiently, similar to the conventional method. Moreover, there were benefits, such as improvement in stool form, a short time for EN infusion, and a reduction in vomiting episodes, with the use of the novel method. This indicates some potential advantages in the quality of life among patients receiving this novel method. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

A New Method for Synthesizing Radiation Dose-Response Data From Multiple Trials Applied to Prostate Cancer

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

Diez, Patricia; Vogelius, Ivan S.; Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792

2010-07-15

Purpose: A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high). Methods and Materials: Nine published prostate cancer dose escalation studies including 6,539 patients were identified in the MEDLINE and CINAHL databases and reviewed to assess the relationship between dose and biochemical control. A novel method of analysis is presented in which the normalized dose-response gradient, {gamma}{sub 50}, is estimated for each study and subsequently synthesized across studies. Our method does not assume that biochemical control rates are directly comparable between studies.more » Results: Nonrandomized studies produced a statistically significantly higher {gamma}{sub 50} than randomized studies for intermediate- to high-risk patients ({gamma}{sub 50} = 1.63 vs. {gamma}{sub 50} = 0.93, p = 0.03) and a borderline significantly higher ({gamma}{sub 50} = 1.78 vs. {gamma}{sub 50} = 0.56, p = 0.08) for low-risk patients. No statistically significant difference in {gamma}{sub 50} was found between low- and intermediate- to high-risk patients (p = 0.31). From the pooled data of low and intermediate- to high-risk patients in randomized trials, we obtain the overall best estimate of {gamma}{sub 50} = 0.84 with 95% confidence interval 0.54-1.15. Conclusions: Nonrandomized studies overestimate the steepness of the dose-response curve as compared with randomized trials. This is probably the result of stage migration, improved treatment techniques, and a shorter follow-up in higher dose patients that were typically entered more recently. This overestimation leads to inflated expectations regarding the benefit from dose-escalation and could lead to underpowered clinical trials. There is no evidence of a steeper dose response for intermediate- to high-risk compared with low-risk patients.« less

Protocol design and current status of CLIVIT: a randomized controlled multicenter relevance trial comparing clips versus ligatures in thyroid surgery

PubMed Central

Seiler, CM; Fröhlich, BE; Veit, JA; Gazyakan, E; Wente, MN; Wollermann, C; Deckert, A; Witte, S; Victor, N; Buchler, MW; Knaebel, HP

2006-01-01

Background Annually, more than 90000 surgical procedures of the thyroid gland are performed in Germany. Strategies aimed at reducing the duration of the surgical procedure are relevant to patients and the health care system especially in the context of reducing costs. However, new techniques for quick and safe hemostasis have to be tested in clinically relevance randomized controlled trials before a general recommendation can be given. The current standard for occlusion of blood vessels in thyroid surgery is ligatures. Vascular clips may be a safe alternative but have not been investigated in a large RCT. Methods/design CLIVIT (Clips versus Ligatures in Thyroid Surgery) is an investigator initiated, multicenter, patient-blinded, two-group parallel relevance randomized controlled trial designed by the Study Center of the German Surgical Society. Patients scheduled for elective resection of at least two third of the gland for benign thyroid disease are eligible for participation. After surgical exploration patients are randomized intraoperatively into either the conventional ligature group, or into the clip group. The primary objective is to test for a relevant reduction in operating time (at least 15 min) when using the clip technique. Since April 2004, 121 of the totally required 420 patients were randomized in five centers. Discussion As in all trials the different forms of bias have to be considered, and as in this case, a surgical trial, the role of surgical expertise plays a key role, and will be documented and analyzed separately. This is the first randomized controlled multicenter relevance trial to compare different vessel occlusion techniques in thyroid surgery with adequate power and other detailed information about the design as well as framework. If significant, the results might be generalized and may change the current surgical practice. PMID:16948853

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.

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

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.

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.

Dose and Fractionation in Radiation Therapy of Curative Intent for Non-Small Cell Lung Cancer: Meta-Analysis of Randomized Trials

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

Ramroth, Johanna; Cutter, David J.; Darby, Sarah C.

Purpose: The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy. Methods and Materials: Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled. Results: 3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, highermore » versus lower corrected dose, was 1.13 (95% confidence interval [CI] 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2). Conclusions: In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no upper dose level was found above which there was no further benefit. These findings support the consideration of further radiation therapy dose escalation trials, making use of modern treatment methods to reduce toxicity.« less

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

PubMed

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

2017-02-24

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

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.

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

PubMed

Dhingra, K

2014-04-01

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

A randomized controlled trial of the different impression methods for the complete denture fabrication: Patient reported outcomes.

PubMed

Jo, Ayami; Kanazawa, Manabu; Sato, Yusuke; Iwaki, Maiko; Akiba, Norihisa; Minakuchi, Shunsuke

2015-08-01

To compare the effect of conventional complete dentures (CD) fabricated using two different impression methods on patient-reported outcomes in a randomized controlled trial (RCT). A cross-over RCT was performed with edentulous patients, required maxillomandibular CDs. Mandibular CDs were fabricated using two different methods. The conventional method used a custom tray border moulded with impression compound and a silicone. The simplified used a stock tray and an alginate. Participants were randomly divided into two groups. The C-S group had the conventional method used first, followed by the simplified. The S-C group was in the reverse order. Adjustment was performed four times. A wash out period was set for 1 month. The primary outcome was general patient satisfaction, measured using visual analogue scales, and the secondary outcome was oral health-related quality of life, measured using the Japanese version of the Oral Health Impact Profile for edentulous (OHIP-EDENT-J) questionnaire scores. Twenty-four participants completed the trial. With regard to general patient satisfaction, the conventional method was significantly more acceptable than the simplified. No significant differences were observed between the two methods in the OHIP-EDENT-J scores. This study showed CDs fabricated with a conventional method were significantly more highly rated for general patient satisfaction than a simplified. CDs, fabricated with the conventional method that included a preliminary impression made using alginate in a stock tray and subsequently a final impression made using silicone in a border moulded custom tray resulted in higher general patient satisfaction. UMIN000009875. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-07-01

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

Does time-lapse imaging have favorable results for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization? A meta-analysis and systematic review of randomized controlled trials

PubMed Central

Yuan, Jing; Liu, Fenghua

2017-01-01

Objective The present study aimed to undertake a review of available evidence assessing whether time-lapse imaging (TLI) has favorable outcomes for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization (IVF). Methods Using PubMed, EMBASE, Cochrane library and ClinicalTrial.gov up to February 2017 to search for randomized controlled trials (RCTs) comparing TLI versus conventional methods. Both studies randomized women and oocytes were included. For studies randomized women, the primary outcomes were live birth and ongoing pregnancy, the secondary outcomes were clinical pregnancy and miscarriage; for studies randomized oocytes, the primary outcome was blastocyst rate, the secondary outcome was good quality embryo on Day 2/3. Subgroup analysis was conducted based on different incubation and embryo selection between groups. Results Ten RCTs were included, four randomized oocytes and six randomized women. For oocyte-based review, the pool-analysis observed no significant difference between TLI group and control group for blastocyst rate [relative risk (RR) 1.08, 95% CI 0.94–1.25, I2 = 0%, two studies, including 1154 embryos]. The quality of evidence was moderate for all outcomes in oocyte-based review. For woman-based review, only one study provided live birth rate (RR 1,23, 95% CI 1.06–1.44,I2 N/A, one study, including 842 women), the pooled result showed no significant difference in ongoing pregnancy rate (RR 1.04, 95% CI 0.80–1.36, I2 = 59%, four studies, including 1403 women) between two groups. The quality of the evidence was low or very low for all outcomes in woman-based review. Conclusions Currently there is insufficient evidence to support that TLI is superior to conventional methods for human embryo incubation and selection. In consideration of the limitations and flaws of included studies, more well designed RCTs are still in need to comprehensively evaluate the effectiveness of clinical TLI use. PMID:28570713

Developing a Reporting Guideline for Social and Psychological Intervention Trials

ERIC Educational Resources Information Center

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

2013-01-01

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

Design and implementation of a dental caries prevention trial in remote Canadian Aboriginal communities

PubMed Central

2010-01-01

Background The goal of this cluster randomized trial is to test the effectiveness of a counseling approach, Motivational Interviewing, to control dental caries in young Aboriginal children. Motivational Interviewing, a client-centred, directive counseling style, has not yet been evaluated as an approach for promotion of behaviour change in indigenous communities in remote settings. Methods/design Aboriginal women were hired from the 9 communities to recruit expectant and new mothers to the trial, administer questionnaires and deliver the counseling to mothers in the test communities. The goal is for mothers to receive the intervention during pregnancy and at their child's immunization visits. Data on children's dental health status and family dental health practices will be collected when children are 30-months of age. The communities were randomly allocated to test or control group by a random "draw" over community radio. Sample size and power were determined based on an anticipated 20% reduction in caries prevalence. Randomization checks were conducted between groups. Discussion In the 5 test and 4 control communities, 272 of the original target sample size of 309 mothers have been recruited over a two-and-a-half year period. A power calculation using the actual attained sample size showed power to be 79% to detect a treatment effect. If an attrition fraction of 4% per year is maintained, power will remain at 80%. Power will still be > 90% to detect a 25% reduction in caries prevalence. The distribution of most baseline variables was similar for the two randomized groups of mothers. However, despite the random assignment of communities to treatment conditions, group differences exist for stage of pregnancy and prior tooth extractions in the family. Because of the group imbalances on certain variables, control of baseline variables will be done in the analyses of treatment effects. This paper explains the challenges of conducting randomized trials in remote settings, the importance of thorough community collaboration, and also illustrates the likelihood that some baseline variables that may be clinically important will be unevenly split in group-randomized trials when the number of groups is small. Trial registration This trial is registered as ISRCTN41467632. PMID:20465831

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

PubMed

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

2010-01-01

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

On the design and analysis of clinical trials with correlated outcomes

PubMed Central

Follmann, Dean; Proschan, Michael

2014-01-01

SUMMARY The convention in clinical trials is to regard outcomes as independently distributed, but in some situations they may be correlated. For example, in infectious diseases, correlation may be induced if participants have contact with a common infectious source, or share hygienic tips that prevent infection. This paper discusses the design and analysis of randomized clinical trials that allow arbitrary correlation among all randomized volunteers. This perspective generalizes the traditional perspective of strata, where patients are exchangeable within strata, and independent across strata. For theoretical work, we focus on the test of no treatment effect μ1 − μ0 = 0 when the n dimensional vector of outcomes follows a Gaussian distribution with known n × n covariance matrix Σ, where the half randomized to treatment (placebo) have mean response μ1 (μ0). We show how the new test corresponds to familiar tests in simple situations for independent, exchangeable, paired, and clustered data. We also discuss the design of trials where Σ is known before or during randomization of patients and evaluate randomization schemes based on such knowledge. We provide two complex examples to illustrate the method, one for a study of 23 family clusters with cardiomyopathy, the other where the malaria attack rates vary within households and clusters of households in a Malian village. PMID:25111420

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

Missing data in trial-based cost-effectiveness analysis: An incomplete journey.

PubMed

Leurent, Baptiste; Gomes, Manuel; Carpenter, James R

2018-06-01

Cost-effectiveness analyses (CEA) conducted alongside randomised trials provide key evidence for informing healthcare decision making, but missing data pose substantive challenges. Recently, there have been a number of developments in methods and guidelines addressing missing data in trials. However, it is unclear whether these developments have permeated CEA practice. This paper critically reviews the extent of and methods used to address missing data in recently published trial-based CEA. Issues of the Health Technology Assessment journal from 2013 to 2015 were searched. Fifty-two eligible studies were identified. Missing data were very common; the median proportion of trial participants with complete cost-effectiveness data was 63% (interquartile range: 47%-81%). The most common approach for the primary analysis was to restrict analysis to those with complete data (43%), followed by multiple imputation (30%). Half of the studies conducted some sort of sensitivity analyses, but only 2 (4%) considered possible departures from the missing-at-random assumption. Further improvements are needed to address missing data in cost-effectiveness analyses conducted alongside randomised trials. These should focus on limiting the extent of missing data, choosing an appropriate method for the primary analysis that is valid under contextually plausible assumptions, and conducting sensitivity analyses to departures from the missing-at-random assumption. © 2018 The Authors Health Economics published by John Wiley & Sons Ltd.

Using Bayesian Adaptive Trial Designs for Comparative Effectiveness Research: A Virtual Trial Execution.

PubMed

Luce, Bryan R; Connor, Jason T; Broglio, Kristine R; Mullins, C Daniel; Ishak, K Jack; Saunders, Elijah; Davis, Barry R

2016-09-20

Bayesian and adaptive clinical trial designs offer the potential for more efficient processes that result in lower sample sizes and shorter trial durations than traditional designs. To explore the use and potential benefits of Bayesian adaptive clinical trial designs in comparative effectiveness research. Virtual execution of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) as if it had been done according to a Bayesian adaptive trial design. Comparative effectiveness trial of antihypertensive medications. Patient data sampled from the more than 42 000 patients enrolled in ALLHAT with publicly available data. Number of patients randomly assigned between groups, trial duration, observed numbers of events, and overall trial results and conclusions. The Bayesian adaptive approach and original design yielded similar overall trial conclusions. The Bayesian adaptive trial randomly assigned more patients to the better-performing group and would probably have ended slightly earlier. This virtual trial execution required limited resampling of ALLHAT patients for inclusion in RE-ADAPT (REsearch in ADAptive methods for Pragmatic Trials). Involvement of a data monitoring committee and other trial logistics were not considered. In a comparative effectiveness research trial, Bayesian adaptive trial designs are a feasible approach and potentially generate earlier results and allocate more patients to better-performing groups. National Heart, Lung, and Blood Institute.

Assessment of Registration Information on Methodological Design of Acupuncture RCTs: A Review of 453 Registration Records Retrieved from WHO International Clinical Trials Registry Platform

PubMed Central

Gu, Jing; Wang, Qi; Wang, Xiaogang; Li, Hailong; Gu, Mei; Ming, Haixia; Dong, Xiaoli; Yang, Kehu; Wu, Hongyan

2014-01-01

Background. This review provides the first methodological information assessment of protocol of acupuncture RCTs registered in WHO International Clinical Trials Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in the ICTRP have been collected. The methodological design assessment involved whether the randomization methods, allocation concealment, and blinding were adequate or not based on the information of registration records (protocols of acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were examined. Methodological details were insufficient in registration records; there were 76.4%, 89.0%, and 21.4% records that did not provide information on randomization methods, allocation concealment, and blinding respectively. The proportions of adequate randomization methods, allocation concealment, and blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The methodological design improved year by year, especially after 2007. Additionally, methodology of RCTs with ethics approval was clearly superior to those without ethics approval and different among registries. Conclusions. The overall methodological design based on registration records of acupuncture RCTs is not very well but improved year by year. The insufficient information on randomization methods, allocation concealment, and blinding maybe due to the relevant description is not taken seriously in acupuncture RCTs' registration. PMID:24688591

Assessment of Registration Information on Methodological Design of Acupuncture RCTs: A Review of 453 Registration Records Retrieved from WHO International Clinical Trials Registry Platform.

PubMed

Gu, Jing; Wang, Qi; Wang, Xiaogang; Li, Hailong; Gu, Mei; Ming, Haixia; Dong, Xiaoli; Yang, Kehu; Wu, Hongyan

2014-01-01

Background. This review provides the first methodological information assessment of protocol of acupuncture RCTs registered in WHO International Clinical Trials Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in the ICTRP have been collected. The methodological design assessment involved whether the randomization methods, allocation concealment, and blinding were adequate or not based on the information of registration records (protocols of acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were examined. Methodological details were insufficient in registration records; there were 76.4%, 89.0%, and 21.4% records that did not provide information on randomization methods, allocation concealment, and blinding respectively. The proportions of adequate randomization methods, allocation concealment, and blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The methodological design improved year by year, especially after 2007. Additionally, methodology of RCTs with ethics approval was clearly superior to those without ethics approval and different among registries. Conclusions. The overall methodological design based on registration records of acupuncture RCTs is not very well but improved year by year. The insufficient information on randomization methods, allocation concealment, and blinding maybe due to the relevant description is not taken seriously in acupuncture RCTs' registration.

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

PubMed Central

Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

2013-01-01

Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use. PMID:23573163

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

PubMed

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

2015-08-01

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

Preventing Cognitive Decline in Older African Americans with Mild Cognitive Impairment: Design and Methods of a Randomized Clinical Trial

PubMed Central

Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Leiby, Benjamin E.

2012-01-01

Mild Cognitive Impairment (MCI) affects 25% of older African Americans and predicts progression to Alzheimer's disease. An extensive epidemiologic literature suggests that cognitive, physical, and/or social activities may prevent cognitive decline. We describe the methods of a randomized clinical trial to test the efficacy of Behavior Activation to prevent cognitive decline in older African Americans with the amnestic multiple domain subtype of MCI. Community Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and then 6 subsequent in-home booster sessions using language, materials, and concepts that are culturally relevant to older African Americans during this 24 month clinical trial. We are randomizing 200 subjects who are recruited from churches, senior centers, and medical clinics to Behavior Activation or Supportive Therapy, which controls for attention. The primary outcome is episodic memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific neuropsychological function, activities of daily living, depression, and quality-of-life. The negative results of recent clinical trials of drug treatments for MCI and Alzheimer's disease suggest that behavioral interventions may provide an alternative treatment approach to preserve cognition in an aging society. PMID:22406101

Preventing Caries in Preschoolers: Successful Initiation of an Innovative Community-Based Clinical Trial in Navajo Nation Head Start

PubMed Central

Quissell, David O.; Bryant, Lucinda L.; Braun, Patricia A.; Cudeii, Diana; Johs, Nikolas; Smith, Vongphone L.; George, Carmen; Henderson, William G.; Albino, Judith

2014-01-01

Navajo Nation children have the greatest prevalence of early childhood caries in the United States. This protocol describes an innovative combination of community-based participatory research and clinical trial methods to rigorously test a lay native Community Oral Health Specialists-delivered oral health intervention, with the goal of reducing the progression of disease and improving family knowledge and behaviors. Methods/Design This cluster-randomized trial designed by researchers at the Center for Native Oral Health Research at the University of Colorado in conjunction with members of the Navajo Nation community compares outcomes between the manualized 2-year oral health fluoride varnish-oral health promotion intervention and usual care in the community (child-caregiver dyads from 26 Head Start classrooms in each study arm; total of 1016 dyads). Outcome assessment includes annual dental screening and an annual caregiver survey of knowledge, attitudes and behaviors; collection of cost data will support cost-benefit analyses. Discussion The study protocol meets all standards required of randomized clinical trials. Aligned with principles of community-based participatory research, extended interaction between members of the Navajo community and researchers preceded study initiation, and collaboration between project staff and a wide variety of community members informed the study design and implementation. We believe the benefits of adding CBPR methods to those of randomized clinical studies outweigh the barriers and constraints, especially in studies of health disparities and in challenging settings. When done well, this innovative mix of methods will increase the likelihood of valid results that communities can use. PMID:24469238

The Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard DerSimonian-Laird method

PubMed Central

2014-01-01

Background The DerSimonian and Laird approach (DL) is widely used for random effects meta-analysis, but this often results in inappropriate type I error rates. The method described by Hartung, Knapp, Sidik and Jonkman (HKSJ) is known to perform better when trials of similar size are combined. However evidence in realistic situations, where one trial might be much larger than the other trials, is lacking. We aimed to evaluate the relative performance of the DL and HKSJ methods when studies of different sizes are combined and to develop a simple method to convert DL results to HKSJ results. Methods We evaluated the performance of the HKSJ versus DL approach in simulated meta-analyses of 2–20 trials with varying sample sizes and between-study heterogeneity, and allowing trials to have various sizes, e.g. 25% of the trials being 10-times larger than the smaller trials. We also compared the number of “positive” (statistically significant at p < 0.05) findings using empirical data of recent meta-analyses with > = 3 studies of interventions from the Cochrane Database of Systematic Reviews. Results The simulations showed that the HKSJ method consistently resulted in more adequate error rates than the DL method. When the significance level was 5%, the HKSJ error rates at most doubled, whereas for DL they could be over 30%. DL, and, far less so, HKSJ had more inflated error rates when the combined studies had unequal sizes and between-study heterogeneity. The empirical data from 689 meta-analyses showed that 25.1% of the significant findings for the DL method were non-significant with the HKSJ method. DL results can be easily converted into HKSJ results. Conclusions Our simulations showed that the HKSJ method consistently results in more adequate error rates than the DL method, especially when the number of studies is small, and can easily be applied routinely in meta-analyses. Even with the HKSJ method, extra caution is needed when there are = <5 studies of very unequal sizes. PMID:24548571

Complementary and Alternative Approaches to Pain Relief During Labor

PubMed Central

Theau-Yonneau, Anne

2007-01-01

This review evaluated the effect of complementary and alternative medicine on pain during labor with conventional scientific methods using electronic data bases through 2006 were used. Only randomized controlled trials with outcome measures for labor pain were kept for the conclusions. Many studies did not meet the scientific inclusion criteria. According to the randomized control trials, we conclude that for the decrease of labor pain and/or reduction of the need for conventional analgesic methods: (i) There is an efficacy found for acupressure and sterile water blocks. (ii) Most results favored some efficacy for acupuncture and hydrotherapy. (iii) Studies for other complementary or alternative therapies for labor pain control have not shown their effectiveness. PMID:18227907

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

Antimicrobial drugs for persistent diarrhoea of unknown or non-specific cause in children under six in low and middle income countries: systematic review of randomized controlled trials

PubMed Central

2009-01-01

Background A high proportion of children with persistent diarrhoea in middle and low income countries die. The best treatment is not clear. We conducted a systematic review to evaluate the effectiveness of antimicrobial drug treatment for persistent diarrhoea of unknown or non-specific cause. Methods We included randomized comparisons of antimicrobial drugs for the treatment of persistent diarrhoea of unknown or non-specific cause in children under the age of six years in low and middle income countries. We searched the electronic databases MEDLINE, EMBASE, LILACS, WEB OF SCIENCE, and the Cochrane Central Register of Controlled Trials (CENTRAL) to May 2008 for relevant randomized or quasi randomized controlled trials. We summarised the characteristics of the eligible trials, assessed their quality using standard criteria, and extracted relevant outcomes data. Where appropriate, we combined the results of different trials. Results Three trials from South East Asia and one from Guatemala were included, all were small, and three had adequate allocation concealment. Two were in patients with diarrhoea of unknown cause, and two were in patients in whom known bacterial or parasitological causes of diarrhoea had been excluded. No difference was demonstrated for oral gentamicin compared with placebo (presence of diarrhoea at 6 or 7 days; 2 trials, n = 151); and for metronidazole compared with placebo (presence of diarrhoea at 3, 5 and 7 days; 1 trial, n = 99). In one small trial, sulphamethoxazole-trimethoprim appeared better than placebo in relation to diarrhoea at seven days and total stool volume (n = 55). Conclusion There is little evidence as to whether or not antimicrobials help treat persistent diarrhoea in young children in low and middle income countries. PMID:19257885

Game-Based Learning as a Vehicle to Teach First Aid Content: A Randomized Experiment

ERIC Educational Resources Information Center

Charlier, Nathalie; De Fraine, Bieke

2013-01-01

Background: Knowledge of first aid (FA), which constitutes lifesaving treatments for injuries or illnesses, is important for every individual. In this study, we have set up a group-randomized controlled trial to assess the effectiveness of a board game for learning FA. Methods: Four class groups (120 students) were randomly assigned to 2…

Effective Strategies to Recruit Young Adults Into the TXT2BFiT mHealth Randomized Controlled Trial for Weight Gain Prevention

PubMed Central

Balestracci, Kate; Wong, Annette TY; Hebden, Lana; McGeechan, Kevin; Denney-Wilson, Elizabeth; Harris, Mark F; Phongsavan, Philayrath; Bauman, Adrian; Allman-Farinelli, Margaret

2015-01-01

Background Younger adults are difficult to engage in preventive health, yet in Australia they are gaining more weight and increasing in waist circumference faster than middle-to-older adults. A further challenge to engaging 18- to 35-year-olds in interventions is the limited reporting of outcomes of recruitment strategies. Objective This paper describes the outcomes of strategies used to recruit young adults to a randomized controlled trial (RCT), healthy lifestyle mHealth program, TXT2BFiT, for prevention of weight gain. The progression from enquiry through eligibility check to randomization into the trial and the costs of recruitment strategies are reported. Factors associated with nonparticipation are explored. Methods Participants were recruited either via letters of invitation from general practitioners (GPs) or via electronic or print advertisements, including Facebook and Google—social media and advertising—university electronic newsletters, printed posters, mailbox drops, and newspapers. Participants recruited from GP invitation letters had an appointment booked with their GP for eligibility screening. Those recruited from other methods were sent an information pack to seek approval to participate from their own GP. The total number and source of enquiries were categorized according to eligibility and subsequent completion of steps to enrolment. Cost data and details of recruitment strategies were recorded. Results From 1181 enquiries in total from all strategies, 250 (21.17%) participants were randomized. A total of 5311 invitation letters were sent from 12 GP practices—16 participating GPs. A total of 131 patients enquired with 68 participants randomized (68/74 of those eligible, 92%). The other recruitment methods yielded the remaining 182 randomized participants. Enrolment from print media was 26% of enquiries, from electronic media was 20%, and from other methods was 3%. Across all strategies the average cost of recruitment was Australian Dollar (AUD) $139 per person. The least expensive modality was electronic (AUD $37), largely due to a free feature story on one university Web home page, despite Facebook advertising costing AUD $945 per enrolment. The most expensive was print media at AUD $213 and GP letters at AUD $145 per enrolment. Conclusions The research indicated that free electronic media was the most cost-effective strategy, with GP letters the least expensive of the paid strategies in comparison to the other strategies. This study is an important contribution for future research into efficacy, translation, and implementation of cost-effective programs for the prevention of weight gain in young adults. Procedural frameworks for recruitment protocols are required, along with systematic reporting of recruitment strategies to reduce unnecessary expenditure and allow for valuable public health prevention programs to go beyond the research setting. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000924853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362872 (Archived by WebCite at http://www.webcitation.org/6YpNfv1gI). PMID:26048581

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

PubMed Central

2013-01-01

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

Meta-Analysis in Clinical Trials Revisited

PubMed Central

Laird, Nan

2015-01-01

In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effect model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the “DerSimonian and Laird method” is now often referred to as the ‘standard approach’ or a ‘popular’ method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. PMID:26343745

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2010-01-01

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

Stress as a seizure precipitant: Identification, associated factors, and treatment options.

PubMed

McKee, Heather R; Privitera, Michael D

2017-01-01

Stress is a common and important seizure precipitant reported by epilepsy patients. Studies to date have used different methodologies to identify relationships between epilepsy and stress. Several studies have identified anxiety, depression, and childhood trauma as being more common in patients with epilepsy who report stress as a seizure precipitant compared to patients with epilepsy who did not identify stress as a seizure precipitant. In one survey study it was found that a majority of patients with stress-triggered seizures had used some type of stress reduction method on their own and, of those who tried this, an even larger majority felt that these methods improved their seizures. Additionally, small to moderate sized prospective trials, including randomized clinical trials, using general stress reduction methods have shown promise in improving outcomes in patients with epilepsy, but results on seizure frequency have been inconsistent. Based on these studies, we recommend that when clinicians encounter patients who report stress as a seizure precipitant, these patients should be screened for a treatable mood disorder. Furthermore, although seizure reduction with stress reduction methods has not been proven in a randomized controlled trial, other important endpoints like quality of life were improved. Therefore, recommending stress reduction methods to patients with epilepsy appears to be a reasonable low risk adjunctive to standard treatments. The current review highlights the need for future research to help further clarify biological mechanisms of the stress-seizure relationship and emphasizes the need for larger randomized controlled trials to help develop evidence based treatment recommendations for our epilepsy patients. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

The RESPECT Approach to Tailored Telephone Education

ERIC Educational Resources Information Center

Brouse, Corey H.; Basch, Charles E.; Wolf, Randi L.

2008-01-01

Objective: The objective of the RESPECT approach to tailored telephone education (TTE) is described. This approach was shown to be highly effective through a randomized intervention trial for increasing the rate of colorectal cancer (CRC) screening. Methods: At the conclusion of the trial, the investigators identified the main principles that…

Dietary Adherence Monitoring Tool for Free-living, Controlled Feeding Studies

USDA-ARS?s Scientific Manuscript database

Objective: To devise a dietary adherence monitoring tool for use in controlled human feeding trials involving free-living study participants. Methods: A scoring tool was devised to measure and track dietary adherence for an 8-wk randomized trial evaluating the effects of two different dietary patter...

The short-term efficacy of vena cava filters for the prevention of pulmonary embolism in patients with venous thromboembolism receiving anticoagulation: Meta-analysis of randomized controlled trials.

PubMed

Jiang, Jun; Jiao, Yuanyong; Zhang, Xiwei

2017-10-01

Objectives To perform a meta-analysis of randomized controlled trials assessing the effectiveness of inferior vena cava filters in patients with deep vein thrombosis for preventing pulmonary embolism. Method Relevant randomized controlled trials of inferior vena cava filters for the prevention of pulmonary embolism were identified by searching electronic databases updated in February 2016. Relative risks of recurrent pulmonary embolism, recurrent deep vein thrombosis, and mortality at three months were analyzed. Results Three published randomized controlled trials were included involving a total of 863 deep vein thrombosis patients. No significant differences were detected with inferior vena cava filters placement with regard to the incidence of recurrent pulmonary embolism or fatal pulmonary embolism. There were also no significant differences in the incidence of recurrent deep vein thrombosis or mortality with inferior vena cava filters placement at three months. Conclusions Inferior vena cava filter in addition to anticoagulation was not associated with a reduction in the incidence of recurrent pulmonary embolism as compared with anticoagulation alone in patients with deep vein thrombosis in the short term.

Effects of pilates on patients with chronic non-specific low back pain: a systematic review

PubMed Central

Lin, Hui-Ting; Hung, Wei-Ching; Hung, Jia-Ling; Wu, Pei-Shan; Liaw, Li-Jin; Chang, Jia-Hao

2016-01-01

[Purpose] To evaluate the effects of Pilates on patients with chronic low back pain through a systematic review of high-quality articles on randomized controlled trials. [Subjects and Methods] Keywords and synonyms for “Pilates” and “Chronic low back pain” were used in database searches. The databases included PubMed, Physiotherapy Evidence Database (PEDro), Medline, and the Cochrane Library. Articles involving randomized controlled trials with higher than 5 points on the PEDro scale were reviewed for suitability and inclusion. The methodological quality of the included randomized controlled trials was evaluated using the PEDro scale. Relevant information was extracted by 3 reviewers. [Results] Eight randomized controlled trial articles were included. Patients with chronic low back pain showed statistically significant improvement in pain relief and functional ability compared to patients who only performed usual or routine health care. However, other forms of exercise were similar to Pilates in the improvement of pain relief and functional capacity. [Conclusion] In patients with chronic low back pain, Pilates showed significant improvement in pain relief and functional enhancement. Other exercises showed effects similar to those of Pilates, if waist or torso movement was included and the exercises were performed for 20 cumulative hours. PMID:27821970

Do health care institutions value research? A mixed methods study of barriers and facilitators to methodological rigor in pediatric randomized trials.

PubMed

Hamm, Michele P; Scott, Shannon D; Klassen, Terry P; Moher, David; Hartling, Lisa

2012-10-18

Pediatric randomized controlled trials (RCTs) are susceptible to a high risk of bias. We examined the barriers and facilitators that pediatric trialists face in the design and conduct of unbiased trials. We used a mixed methods design, with semi-structured interviews building upon the results of a quantitative survey. We surveyed Canadian (n=253) and international (n=600) pediatric trialists regarding their knowledge and awareness of bias and their perceived barriers and facilitators in conducting clinical trials. We then interviewed 13 participants from different subspecialties and geographic locations to gain a more detailed description of how their experiences and attitudes towards research interacted with trial design and conduct. The survey response rate was 23.0% (186/807). 68.1% of respondents agreed that bias is a problem in pediatric RCTs and 72.0% felt that there is sufficient evidence to support changing some aspects of how trials are conducted. Knowledge related to bias was variable, with inconsistent awareness of study design features that may introduce bias into a study. Interview participants highlighted a lack of formal training in research methods, a negative research culture, and the pragmatics of trial conduct as barriers. Facilitators included contact with knowledgeable and supportive colleagues and infrastructure for research. A lack of awareness of bias and negative attitudes towards research present significant barriers in terms of conducting methodologically rigorous pediatric RCTs. Knowledge translation efforts must focus on these issues to ensure the relevance and validity of trial results.

Effectiveness of patient feedback as an educational intervention to improve medical student consultation (PTA Feedback Study): study protocol for a randomized controlled trial.

PubMed

Lai, Michelle Mei Yee; Roberts, Noel; Martin, Jenepher

2014-09-17

Oral feedback from clinical educators is the traditional teaching method for improving clinical consultation skills in medical students. New approaches are needed to enhance this teaching model. Multisource feedback is a commonly used assessment method for learning among practising clinicians, but this assessment has not been explored rigorously in medical student education. This study seeks to evaluate if additional feedback on patient satisfaction improves medical student performance. The Patient Teaching Associate (PTA) Feedback Study is a single site randomized controlled, double-blinded trial with two parallel groups.An after-hours general practitioner clinic in Victoria, Australia, is adapted as a teaching clinic during the day. Medical students from two universities in their first clinical year participate in six simulated clinical consultations with ambulatory patient volunteers living with chronic illness. Eligible students will be randomized in equal proportions to receive patient satisfaction score feedback with the usual multisource feedback and the usual multisource feedback alone as control. Block randomization will be performed. We will assess patient satisfaction and consultation performance outcomes at baseline and after one semester and will compare any change in mean scores at the last session from that at baseline. We will model data using regression analysis to determine any differences between intervention and control groups. Full ethical approval has been obtained for the study. This trial will comply with CONSORT guidelines and we will disseminate data at conferences and in peer-reviewed journals. This is the first proposed trial to determine whether consumer feedback enhances the use of multisource feedback in medical student education, and to assess the value of multisource feedback in teaching and learning about the management of ambulatory patients living with chronic conditions. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613001055796.

Feasibility of a Clinical Trial of Vision Therapy for Treatment of Amblyopia

PubMed Central

Lyon, Don W.; Hopkins, Kristine; Chu, Raymond H.; Tamkins, Susanna M.; Cotter, Susan A.; Melia, B. Michele; Holmes, Jonathan M.; Repka, Michael X.; Wheeler, David T.; Sala, Nicholas A.; Dumas, Janette; Silbert, David I.

2013-01-01

Purpose We conducted a pilot randomized clinical trial of office-based active vision therapy for the treatment of childhood amblyopia to determine the feasibility of conducting a full-scale randomized clinical trial. Methods A training and certification program and manual of procedures were developed to certify therapists to administer a standardized vision therapy program in ophthalmology and optometry offices consisting of weekly visits for 16 weeks. Nineteen children, 7 to less than 13 years of age, with amblyopia (20/40–20/100) were randomly assigned to receive either 2 hours of daily patching with active vision therapy or 2 hours of daily patching with placebo vision therapy. Results Therapists in diverse practice settings were successfully trained and certified to perform standardized vision therapy in strict adherence with protocol. Subjects completed 85% of required weekly in-office vision therapy visits. Eligibility criteria based on age, visual acuity, and stereoacuity, designed to identify children able to complete a standardized vision therapy program and judged likely to benefit from this treatment, led to a high proportion of screened subjects being judged ineligible, resulting in insufficient recruitment. There were difficulties in retrieving adherence data for the computerized home therapy procedures. Conclusions This study demonstrated that a 16-week treatment trial of vision therapy was feasible with respect to maintaining protocol adherence; however, recruitment under the proposed eligibility criteria, necessitated by the standardized approach to vision therapy, was not successful. A randomized clinical trial of in-office vision therapy for the treatment of amblyopia would require broadening of the eligibility criteria and improved methods to gather objective data regarding the home therapy. A more flexible approach that customizes vision therapy based on subject age, visual acuity, and stereopsis, might be required to allow enrollment of a broader group of subjects. PMID:23563444

A multi-level intervention in worksites to increase fruit and vegetable access and intake: Rationale, design and methods of the ‘Good to Go’ cluster randomized trial

PubMed Central

Risica, Patricia M.; Gorham, Gemma; Dionne, Laura; Nardi, William; Ng, Doug; Middler, Reese; Mello, Jennifer; Akpolat, Rahmet; Gettens, Katelyn; Gans, Kim M.

2018-01-01

Background Fruit and vegetable (F&V) consumption is an important contributor to chronic disease prevention. However, most Americans do not eat adequate amounts. The worksite is an advantageous setting to reach large, diverse segments of the population with interventions to increase F&V intake, but research gaps exist. No studies have evaluated the implementation of mobile F&V markets at worksites nor compared the effectiveness of such markets with or without nutrition education. Methods This paper describes the protocol for Good to Go (GTG), a cluster randomized trial to evaluate F&V intake change in employees from worksites randomized into three experimental arms: discount, fresh F&V markets (Access Only arm); markets plus educational components including campaigns, cooking demonstrations, videos, newsletters, and a web site (Access Plus arm); and an attention placebo comparison intervention on physical activity and stress reduction (Comparison). Secondary aims include: 1) Process evaluation to determine costs, reach, fidelity, and dose as well as the relationship of these variables with changes in F&V intake; 2) Applying a mediating variable framework to examine relationships of psychosocial factors/determinants with changes in F&V consumption; and 3) Cost effectiveness analysis of the different intervention arms. Discussion The GTG study will fill important research gaps in the field by implementing a rigorous cluster randomized trial to evaluate the efficacy of an innovative environmental intervention providing access and availability to F&V at the worksite and whether this access intervention is further enhanced by accompanying educational interventions. GTG will provide an important contribution to public health research and practice. Trial registration number NCT02729675, ClinicalTrials.gov PMID:29242108

Design considerations and rationale of a multi-center trial to sustain weight loss: the Weight Loss Maintenance Trial.

PubMed

Brantley, Phillip; Appel, Lawrence; Hollis, Jack; Stevens, Victor; Ard, Jamy; Champagne, Catherine; Elmer, Patricia; Harsha, David; Myers, Valerie; Proschan, Michael; William, Vollmer; Svetkey, Laura

2008-01-01

The Weight Loss Maintenance Trial (WLM) is a multi-center, randomized, controlled trial that compares the effects of two 30-month maintenance interventions, i.e., Personal Contact (PC) and Interactive Technology (IT) to a self-directed usual care control group (SD), in overweight or obese individuals who are at high risk for cardiovascular disease. This paper provides an overview of the design and methods, and design considerations and lessons learned from this trial. All participants received a 6-month behavioral weight loss program consisting of weekly group sessions. Participants who lost 4 kg were randomized to one of three conditions (PC, IT, or SD). The PC condition provided monthly contacts with an interventionist primarily via telephone and quarterly face-to-face visits. The IT condition provided frequent, individualized contact through a tailored, website system. Both the PC and IT maintenance programs encouraged the DASH dietary pattern and employed theory-based behavioral techniques to promote maintenance. Design considerations included choice of study population, frequency and type of intervention visits, and choice of primary outcome. Overweight or obese persons with CVD risk factors were studied. The pros and cons of studying this population while excluding others are presented. We studied intervention contact strategies that made fewer demands on participant time and travel, while providing frequent opportunities for interaction. The primary outcome variable for the trial was change in weight from randomization to end of follow-up (30 months). Limits to generalizability are discussed. Individuals in need of weight loss strategies may have been excluded due to barriers associated with internet use. Other participants may have been excluded secondary to a comorbid condition. This paper highlights the design and methods of WLM and informs readers of discussions of critical issues and lessons learned from the trial.

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.

Commentary on Reconstituting Fibrinogen Concentrate to Maintain Blinding in a Double-blind, Randomized Trial in an Emergency Setting.

PubMed

Bruynseels, Daniel; Solomon, Cristina; Hallam, Angela; Collins, Peter W; Collis, Rachel E; Hamlyn, Vincent; Hall, Judith E

2016-01-01

The gold standard of trial design is the double-blind, placebo-controlled, randomized trial. Intravenous medication, which needs reconstitution by the attending clinician in an emergency situation, can be challenging to incorporate into a suitably blinded study. We have developed a method of blindly reconstituting and administering fibrinogen concentrate (presented as a lyophilized powder), where the placebo is normal saline. Fibrinogen concentrate is increasingly being used early in the treatment of major hemorrhage. Our methodology was designed for a multicenter study investigating the role of fibrinogen concentrate in the treatment of the coagulopathy associated with major obstetric hemorrhage. The method has been verified by a stand-alone pharmaceutical manufacturing unit with an investigational medicinal products license, and to date has successfully been applied 45 times in four study centers. There have been no difficulties in reconstitution and no related adverse events reported. We feel our method is simple to perform and maintains blinding throughout, making it potentially suitable for use in other trials conducted in psychologically high-pressure environments. Although fibrinogen concentrate was the focus of our study, it is likely that the method is applicable to other lyophilized medication with limited shelf life (e.g., antibiotics). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods

PubMed Central

Wiljer, David; Cafazzo, Joseph A

2016-01-01

Background Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Objective Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. Methods We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Results Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=.021, η2=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=.028, η2=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=.030, η2=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<.01, adjusted r2=.33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). Conclusions mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients. PMID:27613084

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

Meta-analysis of two studies in the presence of heterogeneity with applications in rare diseases.

PubMed

Friede, Tim; Röver, Christian; Wandel, Simon; Neuenschwander, Beat

2017-07-01

Random-effects meta-analyses are used to combine evidence of treatment effects from multiple studies. Since treatment effects may vary across trials due to differences in study characteristics, heterogeneity in treatment effects between studies must be accounted for to achieve valid inference. The standard model for random-effects meta-analysis assumes approximately normal effect estimates and a normal random-effects model. However, standard methods based on this model ignore the uncertainty in estimating the between-trial heterogeneity. In the special setting of only two studies and in the presence of heterogeneity, we investigate here alternatives such as the Hartung-Knapp-Sidik-Jonkman method (HKSJ), the modified Knapp-Hartung method (mKH, a variation of the HKSJ method) and Bayesian random-effects meta-analyses with priors covering plausible heterogeneity values; R code to reproduce the examples is presented in an appendix. The properties of these methods are assessed by applying them to five examples from various rare diseases and by a simulation study. Whereas the standard method based on normal quantiles has poor coverage, the HKSJ and mKH generally lead to very long, and therefore inconclusive, confidence intervals. The Bayesian intervals on the whole show satisfying properties and offer a reasonable compromise between these two extremes. © 2016 The Authors. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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

Design of Phase II Non-inferiority Trials.

PubMed

Jung, Sin-Ho

2017-09-01

With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.

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.

Methodological Foundations for the Empirical Evaluation of Non-Experimental Methods in Field Settings

ERIC Educational Resources Information Center

Wong, Vivian C.; Steiner, Peter M.

2015-01-01

Across the disciplines of economics, political science, public policy, and now, education, the randomized controlled trial (RCT) is the preferred methodology for establishing causal inference about program impacts. But randomized experiments are not always feasible because of ethical, political, and/or practical considerations, so non-experimental…

Randomized Trial of Suicide Gatekeeper Training for Social Work Students

ERIC Educational Resources Information Center

Jacobson, Jodi M.; Osteen, Phillip J.; Sharpe, Tanya L.; Pastoor, Jennifer B.

2012-01-01

Problem: Education and research on social work's role in preventing client suicide is limited. Method: Seventy advanced master of social work students were randomly assigned to either the training group (Question, Persuade, and Referral suicide gatekeeper training) or the control group. Outcomes measured over time included suicide knowledge,…

Educational and Skills-Based Interventions to Prevent Relationship Violence in Young People

ERIC Educational Resources Information Center

Fellmeth, Gracia; Heffernan, Catherine; Nurse, Joanna; Habibula, Shakiba; Sethi, Dinesh

2015-01-01

Objectives: To assess the efficacy of educational and skills-based interventions to prevent relationship and dating violence in adolescents and young adults. Methods: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, and other databases for randomized, cluster-randomized, and quasi-randomized…

The impact of loss to follow-up on hypothesis tests of the treatment effect for several statistical methods in substance abuse clinical trials.

PubMed

Hedden, Sarra L; Woolson, Robert F; Carter, Rickey E; Palesch, Yuko; Upadhyaya, Himanshu P; Malcolm, Robert J

2009-07-01

"Loss to follow-up" can be substantial in substance abuse clinical trials. When extensive losses to follow-up occur, one must cautiously analyze and interpret the findings of a research study. Aims of this project were to introduce the types of missing data mechanisms and describe several methods for analyzing data with loss to follow-up. Furthermore, a simulation study compared Type I error and power of several methods when missing data amount and mechanism varies. Methods compared were the following: Last observation carried forward (LOCF), multiple imputation (MI), modified stratified summary statistics (SSS), and mixed effects models. Results demonstrated nominal Type I error for all methods; power was high for all methods except LOCF. Mixed effect model, modified SSS, and MI are generally recommended for use; however, many methods require that the data are missing at random or missing completely at random (i.e., "ignorable"). If the missing data are presumed to be nonignorable, a sensitivity analysis is recommended.

An audit strategy for time-to-event outcomes measured with error: application to five randomized controlled trials in oncology.

PubMed

Dodd, Lori E; Korn, Edward L; Freidlin, Boris; Gu, Wenjuan; Abrams, Jeffrey S; Bushnell, William D; Canetta, Renzo; Doroshow, James H; Gray, Robert J; Sridhara, Rajeshwari

2013-10-01

Measurement error in time-to-event end points complicates interpretation of treatment effects in clinical trials. Non-differential measurement error is unlikely to produce large bias [1]. When error depends on treatment arm, bias is of greater concern. Blinded-independent central review (BICR) of all images from a trial is commonly undertaken to mitigate differential measurement-error bias that may be present in hazard ratios (HRs) based on local evaluations. Similar BICR and local evaluation HRs may provide reassurance about the treatment effect, but BICR adds considerable time and expense to trials. We describe a BICR audit strategy [2] and apply it to five randomized controlled trials to evaluate its use and to provide practical guidelines. The strategy requires BICR on a subset of study subjects, rather than a complete-case BICR, and makes use of an auxiliary-variable estimator. When the effect size is relatively large, the method provides a substantial reduction in the size of the BICRs. In a trial with 722 participants and a HR of 0.48, an average audit of 28% of the data was needed and always confirmed the treatment effect as assessed by local evaluations. More moderate effect sizes and/or smaller trial sizes required larger proportions of audited images, ranging from 57% to 100% for HRs ranging from 0.55 to 0.77 and sample sizes between 209 and 737. The method is developed for a simple random sample of study subjects. In studies with low event rates, more efficient estimation may result from sampling individuals with events at a higher rate. The proposed strategy can greatly decrease the costs and time associated with BICR, by reducing the number of images undergoing review. The savings will depend on the underlying treatment effect and trial size, with larger treatment effects and larger trials requiring smaller proportions of audited data.

Complementary and Alternative Medicine Treatments for Generalized Anxiety Disorder: Systematic Review and Meta-analysis of Randomized Controlled Trials.

PubMed

Barić, Hrvoje; Đorđević, Veljko; Cerovečki, Ivan; Trkulja, Vladimir

2018-03-01

The objective was to evaluate efficacy/safety of complementary and alternative medicine (CAM) methods for generalized anxiety disorder (GAD) based on randomized controlled trials in adults. Data sources. Six electronic databases ("generalized anxiety (disorder)" and "randomized trial") and reference lists of identified publications were searched to March 2017. Eligibility: full-text publications (English, German language); CAM versus conventional treatment, placebo/sham or no treatment; GAD diagnosed according to standard criteria; and a validated scale for disease severity. Of the 6693 screened records, 32 were included (18 on biologically-based therapies, exclusively herbal preparations; eight on manipulative and body-based therapies; and three on alternative medical systems and three on mind-body therapies). Cochrane Collaboration methodology was used for quality assessment and data extraction. Direct comparisons of Kava Kava (Piper methysticum) extracts to placebo (4 quality trials, n = 233) were highly heterogeneous. Network meta-regression reduced heterogeneity and suggested a modest Kava effect [end-of-treatment Hamilton Anxiety scale score difference adjusted for baseline scores and trial duration: - 3.24 (95% CI - 6.65, 0.17; P = 0.059), Kava Kava 4 arms, n = 139; placebo 5 arms, n = 359]. Lavender (Lavandula angustifolia) extract (1 quality trial, 10 weeks, n = 523) and a combination of extracts of C. oxycantha, E. californica and magnesium (1 quality trial, 12 weeks, n = 264) were superior to placebo and balneotherapy was superior to paroxetine (1 quality trial, 8 weeks, n = 237) indicating efficacy. All other trials were small and/or of modest/low quality and/or lacked assay sensitivity. Safety reporting was poor. Evidence about efficacy/safety of most CAM methods in GAD is limited. Apparent efficacy of certain herbal preparations and body-based therapies requires further confirmation.

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

Alternative methods to evaluate trial level surrogacy.

PubMed

Abrahantes, Josè Cortiñas; Shkedy, Ziv; Molenberghs, Geert

2008-01-01

The evaluation and validation of surrogate endpoints have been extensively studied in the last decade. Prentice [1] and Freedman, Graubard and Schatzkin [2] laid the foundations for the evaluation of surrogate endpoints in randomized clinical trials. Later, Buyse et al. [5] proposed a meta-analytic methodology, producing different methods for different settings, which was further studied by Alonso and Molenberghs [9], in their unifying approach based on information theory. In this article, we focus our attention on the trial-level surrogacy and propose alternative procedures to evaluate such surrogacy measure, which do not pre-specify the type of association. A promising correction based on cross-validation is investigated. As well as the construction of confidence intervals for this measure. In order to avoid making assumption about the type of relationship between the treatment effects and its distribution, a collection of alternative methods, based on regression trees, bagging, random forests, and support vector machines, combined with bootstrap-based confidence interval and, should one wish, in conjunction with a cross-validation based correction, will be proposed and applied. We apply the various strategies to data from three clinical studies: in opthalmology, in advanced colorectal cancer, and in schizophrenia. The results obtained for the three case studies are compared; they indicate that using random forest or bagging models produces larger estimated values for the surrogacy measure, which are in general stabler and the confidence interval narrower than linear regression and support vector regression. For the advanced colorectal cancer studies, we even found the trial-level surrogacy is considerably different from what has been reported. In general the alternative methods are more computationally demanding, and specially the calculation of the confidence intervals, require more computational time that the delta-method counterpart. First, more flexible modeling techniques can be used, allowing for other type of association. Second, when no cross-validation-based correction is applied, overly optimistic trial-level surrogacy estimates will be found, thus cross-validation is highly recommendable. Third, the use of the delta method to calculate confidence intervals is not recommendable since it makes assumptions valid only in very large samples. It may also produce range-violating limits. We therefore recommend alternatives: bootstrap methods in general. Also, the information-theoretic approach produces comparable results with the bagging and random forest approaches, when cross-validation correction is applied. It is also important to observe that, even for the case in which the linear model might be a good option too, bagging methods perform well too, and their confidence intervals were more narrow.

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

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

Management of low-grade cervical abnormalities detected at screening: which method do women prefer?

PubMed

Whynes, D K; Woolley, C; Philips, Z

2008-12-01

To establish whether women with low-grade abnormalities detected during screening for cervical cancer prefer to be managed by cytological surveillance or by immediate colposcopy. TOMBOLA (Trial of Management of Borderline and Other Low-grade Abnormal smears) is a randomized controlled trial comparing alternative management strategies following the screen-detection of low-grade cytological abnormalities. At exit, a sample of TOMBOLA women completed a questionnaire eliciting opinions on their management, contingent valuations (CV) of the management methods and preferences. Within-trial quality of life (EQ-5D) data collected for a sample of TOMBOLA women throughout their follow-up enabled the comparison of self-reported health at various time points, by management method. Once management had been initiated, self-reported health in the colposcopy arm rose relative to that in the surveillance arm, although the effect was short-term only. For the majority of women, the satisfaction ratings and the CV indicated approval of the management method to which they had been randomized. Of the minority manifesting a preference for the method which they had not experienced, relatively more would have preferred colposcopy than would have preferred surveillance. The findings must be interpreted in the light of sample bias with respect to preferences, whereby enthusiasm for colposcopy was probably over-represented amongst trial participants. The study suggests that neither of the management methods is preferred unequivocally; rather, individual women have individual preferences, although many would be indifferent between methods.

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

PubMed

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

2008-03-01

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

“Smart” RCTs: Development of a Smartphone App for Fully Automated Nutrition-Labeling Intervention Trials

PubMed Central

Li, Nicole; Dunford, Elizabeth; Eyles, Helen; Crino, Michelle; Michie, Jo; Ni Mhurchu, Cliona

2016-01-01

Background There is substantial interest in the effects of nutrition labels on consumer food-purchasing behavior. However, conducting randomized controlled trials on the impact of nutrition labels in the real world presents a significant challenge. Objective The Food Label Trial (FLT) smartphone app was developed to enable conducting fully automated trials, delivering intervention remotely, and collecting individual-level data on food purchases for two nutrition-labeling randomized controlled trials (RCTs) in New Zealand and Australia. Methods Two versions of the smartphone app were developed: one for a 5-arm trial (Australian) and the other for a 3-arm trial (New Zealand). The RCT protocols guided requirements for app functionality, that is, obtaining informed consent, two-stage eligibility check, questionnaire administration, randomization, intervention delivery, and outcome assessment. Intervention delivery (nutrition labels) and outcome data collection (individual shopping data) used the smartphone camera technology, where a barcode scanner was used to identify a packaged food and link it with its corresponding match in a food composition database. Scanned products were either recorded in an electronic list (data collection mode) or allocated a nutrition label on screen if matched successfully with an existing product in the database (intervention delivery mode). All recorded data were transmitted to the RCT database hosted on a server. Results In total approximately 4000 users have downloaded the FLT app to date; 606 (Australia) and 1470 (New Zealand) users met the eligibility criteria and were randomized. Individual shopping data collected by participants currently comprise more than 96,000 (Australia) and 229,000 (New Zealand) packaged food and beverage products. Conclusions The FLT app is one of the first smartphone apps to enable conducting fully automated RCTs. Preliminary app usage statistics demonstrate large potential of such technology, both for intervention delivery and data collection. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12614000964617. New Zealand trial: Australian New Zealand Clinical Trials Registry ACTRN12614000644662. PMID:26988128

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 ).

The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PubMed Central

Rosenblat, Joshua D; Kakar, Ron

2016-01-01

Background: Cognitive dysfunction is often present in major depressive disorder (MDD). Several clinical trials have noted a pro-cognitive effect of antidepressants in MDD. The objective of the current systematic review and meta-analysis was to assess the pooled efficacy of antidepressants on various domains of cognition in MDD. Methods: Trials published prior to April 15, 2015, were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, Embase, PsychINFO, Clinicaltrials.gov, and relevant review articles. Data from randomized clinical trials assessing the cognitive effects of antidepressants were pooled to determine standard mean differences (SMD) using a random-effects model. Results: Nine placebo-controlled randomized trials (2 550 participants) evaluating the cognitive effects of vortioxetine (n = 728), duloxetine (n = 714), paroxetine (n = 23), citalopram (n = 84), phenelzine (n = 28), nortryptiline (n = 32), and sertraline (n = 49) were identified. Antidepressants had a positive effect on psychomotor speed (SMD 0.16; 95% confidence interval [CI] 0.05–0.27; I2 = 46%) and delayed recall (SMD 0.24; 95% CI 0.15–0.34; I2 = 0%). The effect on cognitive control and executive function did not reach statistical significance. Of note, after removal of vortioxetine from the analysis, statistical significance was lost for psychomotor speed. Eight head-to-head randomized trials comparing the effects of selective serotonin reuptake inhibitors (SSRIs; n = 371), selective serotonin and norepinephrine reuptake inhibitors (SNRIs; n = 25), tricyclic antidepressants (TCAs; n = 138), and norepinephrine and dopamine reuptake inhibitors (NDRIs; n = 46) were identified. No statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs. Significant limitations were the heterogeneity of results, limited number of studies, and small sample sizes. Conclusions: Available evidence suggests that antidepressants have a significant positive effect on psychomotor speed and delayed recall. PMID:26209859

Understanding health economic analysis in critical care: insights from recent randomized controlled trials.

PubMed

Sud, Sachin; Cuthbertson, Brian H

2011-10-01

The article reviews the methods of health economic analysis (HEA) in clinical trials of critically ill patients. Emphasis is placed on the usefulness of HEA in the context of positive and 'no effect' studies, with recent examples. The need to control costs and promote effective spending in caring for the critically ill has garnered considerable attention due to the high cost of critical illness. Many clinical trials focus on short-term mortality, ignoring costs and quality of life, and fail to change clinical practice or promote efficient use of resources. Incorporating HEA into clinical trials is a possible solution. Such studies have shown some interventions, although expensive, provide good value, whereas others should be withdrawn from clinical practice. Incorporating HEA into randomized controlled trials (RCTs) requires careful attention to collect all relevant costs. Decision trees, modeling assumptions and methods for collecting costs and measuring outcomes should be planned and published beforehand to minimize bias. Costs and cost-effectiveness are potentially useful outcomes in RCTs of critically ill patients. Future RCTs should incorporate parallel HEA to provide both economic outcomes, which are important to the community, alongside patient-centered outcomes, which are important to individuals.

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers.

PubMed

Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J; Brown, Powel H; Dannenberg, Andrew J; Szabo, Eva

2012-09-01

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. Published by Elsevier Inc.

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers

PubMed Central

Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J.; Brown, Powel H.; Dannenberg, Andrew J.; Szabo, Eva

2012-01-01

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. PMID:22771576

Is using multiple imputation better than complete case analysis for estimating a prevalence (risk) difference in randomized controlled trials when binary outcome observations are missing?

PubMed

Mukaka, Mavuto; White, Sarah A; Terlouw, Dianne J; Mwapasa, Victor; Kalilani-Phiri, Linda; Faragher, E Brian

2016-07-22

Missing outcomes can seriously impair the ability to make correct inferences from randomized controlled trials (RCTs). Complete case (CC) analysis is commonly used, but it reduces sample size and is perceived to lead to reduced statistical efficiency of estimates while increasing the potential for bias. As multiple imputation (MI) methods preserve sample size, they are generally viewed as the preferred analytical approach. We examined this assumption, comparing the performance of CC and MI methods to determine risk difference (RD) estimates in the presence of missing binary outcomes. We conducted simulation studies of 5000 simulated data sets with 50 imputations of RCTs with one primary follow-up endpoint at different underlying levels of RD (3-25 %) and missing outcomes (5-30 %). For missing at random (MAR) or missing completely at random (MCAR) outcomes, CC method estimates generally remained unbiased and achieved precision similar to or better than MI methods, and high statistical coverage. Missing not at random (MNAR) scenarios yielded invalid inferences with both methods. Effect size estimate bias was reduced in MI methods by always including group membership even if this was unrelated to missingness. Surprisingly, under MAR and MCAR conditions in the assessed scenarios, MI offered no statistical advantage over CC methods. While MI must inherently accompany CC methods for intention-to-treat analyses, these findings endorse CC methods for per protocol risk difference analyses in these conditions. These findings provide an argument for the use of the CC approach to always complement MI analyses, with the usual caveat that the validity of the mechanism for missingness be thoroughly discussed. More importantly, researchers should strive to collect as much data as possible.

The Prevention of Hemorrhagic Stroke

PubMed Central

Raymond, J.; Mohr, JP; the TEAM-ARUBA collaborative groups

2008-01-01

Summary There is currently no evidence that preventive treatment of unruptured aneurysms or AVMs is beneficial and randomized trials have been proposed to address this clinical uncertainty. Participation in a trial may necessitate a shift of point of view compared to a certain habitual clinical mentality. A review of the ethical and rational principles governing the design and realization of a trial may help integrate clinical research into expert clinical practices. The treatment of unruptured aneurysms and AVMs remains controversial, and data from observational studies cannot provide a normative basis for clinical decisions. Prevention targets healthy individuals and hence has an obligation of results. There is no opposition between the search for objective facts using scientific methods and the ethics of medical practice since a good practice cannot forbid physicians the means to define what could be beneficial to patients. Perhaps the most difficult task is to recognize the uncertainty that is crucial to allow resorting to trial methodology. The reasoning that is used in research and analysis differs from the casuistic methods typical of clinical work, but clinical judgement remains the dominant factor that decides both who enters the trial and to whom the results of the trial will apply. Randomization is still perceived as a difficult and strange method to integrate into normal practice, but in the face of uncertainty it assures the best chances for the best outcome to each participant. Some tension exists between scientific methods and normal practice, but they need to coexist if we are to progress at the same time we care for patients. PMID:20557736

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

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

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

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

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

PubMed

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

2018-06-01

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

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

The face of equipoise - delivering a structured education programme within a randomized controlled trial: qualitative study

PubMed Central

2014-01-01

Background In trials of behavioural interventions, the individuals who deliver the intervention are in a position of key influence on the success of the trial. Their fidelity to the intervention is crucial. Yet little is understood about the experiences of this group of trial personnel. This study aimed to investigate the views and experiences of educators who delivered a structured education intervention to people with type 2 diabetes, which incorporated training in self-monitoring of either blood glucose (SMBG) or urine glucose (SMUG) as part of a randomized controlled trial (RCT). Methods Educators’ views were explored through focus groups before and after training (N = 18) and approximately 1 year into the trial (N = 14), and semi-structured telephone interviews at approximately 2 years (N = 7). Analysis was based on the constant comparative method. Results Educators held preferences regarding the intervention variants; thus, they were not in individual equipoise. Training raised awareness of preferences and their potential to impact on delivery. Educators were confident in their unbiased delivery, but acknowledged the challenges involved. Concealing their preferences was helped by a sense of professionalism, the patient-centred nature of the intervention, and concessions in the trial protocol (enabling participants to swap monitoring methods if needed). Commitment to unbiased delivery was explained through a desire for evidence-based knowledge in the contentious area of SMBG. Conclusions The findings provide insight into a previously unexplored group of trial personnel - intervention deliverers in trials of behavioural interventions - which will be useful to those designing and running similar trials. Rather than individual equipoise, it is intervention deliverers’ awareness of personal preferences and their potential impact on the trial outcome that facilitates unbiased delivery. Further, awareness of community equipoise, the need for evidence, and relevance to the individual enhance commitment to the RCT. Trial registration ISRCTN95696668 PMID:24405854

Reduced Mortality With Partial-Breast Irradiation for Early Breast Cancer: A Meta-Analysis of Randomized Trials

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

Vaidya, Jayant S., E-mail: jayant.vaidya@ucl.ac.uk; Department of Surgery, Royal Free Hospital, London; Department of Surgery, Whittington Health, London

Purpose: With earlier detection and more effective treatment, mortality from breast cancer continues to fall and it has become increasingly important to reduce the toxicity of treatments. Partial-breast radiation therapy, which focuses radiation to the tumor bed, may achieve this aim. We analyzed mortality differences in randomized trials of partial-breast irradiation (PBI). Methods and Materials: We included data from published randomized trials of PBI (alone or as part of a risk-adapted approach) versus whole-breast irradiation (WBI) for invasive breast cancer suitable for breast-conserving therapy. We identified trials using PubMed and Google searches with the terms “partial breast irradiation” OR “intraoperativemore » radiotherapy” OR “IMRT” OR (“accelerated” AND “radiation”) AND “randomised/randomized,” as well as through discussion with colleagues in the field. We calculated the proportion of patients who had events in each randomized arm at 5 years' follow-up and created a forest plot using Stata, version 14.1. Results: We identified 9 randomized trials of PBI versus WBI in invasive breast cancer; 5-year outcomes were available for non–breast cancer mortality in 5 trials (n=4489) and for breast cancer mortality in 4 trials (n=4231). The overall mortality was 4.9%. There was no detectable heterogeneity between the trials for any of the outcomes. There was no difference in the proportion of patients dying of breast cancer (difference, 0.000% [95% confidence interval (CI), −0.7 to +0.7]; P=.999). Non–breast cancer mortality with PBI was lower than with WBI (difference, 1.1% [95% CI, −2.1% to −0.2%]; P=.023). Total mortality with PBI was also lower than with WBI (difference, 1.3% [95% CI, −2.5% to 0.0%]; P=.05). Conclusions: Use of PBI instead of WBI in selected patients results in a lower 5-year non–breast cancer and overall mortality, amounting to a 25% reduction in relative terms. This information should be included when breast-conserving therapy is proposed to a patient.« less

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.

Echocardiographic Methods, Quality Review, and Measurement Accuracy in a Randomized Multicenter Clinical Trial of Marfan Syndrome

PubMed Central

Selamet Tierney, Elif Seda; Levine, Jami C.; Chen, Shan; Bradley, Timothy J.; Pearson, Gail D.; Colan, Steven D.; Sleeper, Lynn A.; Campbell, M. Jay; Cohen, Meryl S.; Backer, Julie De; Guey, Lin T.; Heydarian, Haleh; Lai, Wyman W.; Lewin, Mark B.; Marcus, Edward; Mart, Christopher R.; Pignatelli, Ricardo H.; Printz, Beth F.; Sharkey, Angela M.; Shirali, Girish S.; Srivastava, Shubhika; Lacro, Ronald V.

2013-01-01

Background The Pediatric Heart Network is conducting a large international randomized trial to compare aortic root growth and other cardiovascular outcomes in 608 subjects with Marfan syndrome randomized to receive atenolol or losartan for 3 years. The authors report here the echocardiographic methods and baseline echocardiographic characteristics of the randomized subjects, describe the interobserver agreement of aortic measurements, and identify factors influencing agreement. Methods Individuals aged 6 months to 25 years who met the original Ghent criteria and had body surface area–adjusted maximum aortic root diameter (ROOTmax) Z scores > 3 were eligible for inclusion. The primary outcome measure for the trial is the change over time in ROOTmax Z score. A detailed echocardiographic protocol was established and implemented across 22 centers, with an extensive training and quality review process. Results Interobserver agreement for the aortic measurements was excellent, with intraclass correlation coefficients ranging from 0.921 to 0.989. Lower interobserver percentage error in ROOTmax measurements was independently associated (model R2 = 0.15) with better image quality (P = .002) and later study reading date (P < .001). Echocardiographic characteristics of the randomized subjects did not differ by treatment arm. Subjects with ROOTmax Z scores ≥ 4.5 (36%) were more likely to have mitral valve prolapse and dilation of the main pulmonary artery and left ventricle, but there were no differences in aortic regurgitation, aortic stiffness indices, mitral regurgitation, or left ventricular function compared with subjects with ROOTmax Z scores < 4.5. Conclusions The echocardiographic methodology, training, and quality review process resulted in a robust evaluation of aortic root dimensions, with excellent reproducibility. PMID:23582510

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

ERIC Educational Resources Information Center

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

2012-01-01

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

Assessment of contamination and misclassification biases in a randomized controlled trial of a social network peer education intervention to reduce HIV risk behaviors among drug users and risk partners in Philadelphia, PA and Chiang Mai, Thailand

PubMed Central

Simmons, Nicole; Donnell, Deborah; Ou, San-san; Celentano, David D.; Aramrattana, Apinun; Davis-Vogel, Annet; Metzger, David; Latkin, Carl

2015-01-01

Context Controlled trials of educational interventions are susceptible to contamination. Objectives To test a contamination measure based on recall of terms. Main study A randomized controlled trial of a social network peer education intervention among 1,123 injection drug users and risk partners in Philadelphia, PA and Chiang Mai, Thailand. Methods We assessed the recall of test, negative and positive control terms by intervention and control arm participants and compared the relative odds (OR) of recall of test vs. negative control terms between study arms. Results The contamination measure showed good discriminant ability only among participants from Chiang Mai. In Philadelphia there was no evidence of contamination and little evidence of diffusion. In Chiang Mai there was evidence of diffusion and contamination of 4 of 5 terms tested. Conclusions Network structure and peer education in Chiang Mai likely led to contamination. Recall of intervention materials can be a useful method to detect contamination in trials of educational interventions. PMID:25935214

Design issues in a randomized controlled trial of a pre-emptive versus empiric antifungal strategy for invasive aspergillosis in patients with high-risk hematologic malignancies.

PubMed

Morrissey, C Orla; Chen, Sharon C-A; Sorrell, Tania C; Bradstock, Kenneth F; Szer, Jeffrey; Halliday, Catriona L; Gilroy, Nicole M; Schwarer, Anthony P; Slavin, Monica A

2011-02-01

Invasive aspergillosis (IA) is a major cause of mortality in patients with hematological malignancies, due largely to the inability of traditional culture and biopsy methods to make an early or accurate diagnosis. Diagnostic accuracy studies suggest that Aspergillus galactomannan (GM) enzyme immunoassay (ELISA) and Aspergillus PCR-based methods may overcome these limitations, but their impact on patient outcomes should be evaluated in a diagnostic randomized controlled trial (D-RCT). This article describes the methodology of a D-RCT which compares a new pre-emptive strategy (GM-ELISA- and Aspergillus PCR-driven antifungal therapy) with the standard fever-driven empiric antifungal treatment strategy. Issues including primary end-point and patient selection, duration of screening, choice of tests for the pre-emptive strategy, antifungal prophylaxis and bias control, which were considered in the design of the trial, are discussed. We suggest that the template presented herein is considered by researchers when evaluating the utility of new diagnostic tests (ClinicalTrials.gov number, NCT00163722).

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

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 Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face

PubMed Central

Goldman, Mitchel P.

2017-01-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality. PMID:28670356

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face.

PubMed

Wu, Douglas C; Goldman, Mitchel P

2017-05-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality.

Whose data set is it anyway? Sharing raw data from randomized trials.

PubMed

Vickers, Andrew J

2006-05-16

Sharing of raw research data is common in many areas of medical research, genomics being perhaps the most well-known example. In the clinical trial community investigators routinely refuse to share raw data from a randomized trial without giving a reason. Data sharing benefits numerous research-related activities: reproducing analyses; testing secondary hypotheses; developing and evaluating novel statistical methods; teaching; aiding design of future trials; meta-analysis; and, possibly, preventing error, fraud and selective reporting. Clinical trialists, however, sometimes appear overly concerned with being scooped and with misrepresentation of their work. Both possibilities can be avoided with simple measures such as inclusion of the original trialists as co-authors on any publication resulting from data sharing. Moreover, if we treat any data set as belonging to the patients who comprise it, rather than the investigators, such concerns fall away. Technological developments, particularly the Internet, have made data sharing generally a trivial logistical problem. Data sharing should come to be seen as an inherent part of conducting a randomized trial, similar to the way in which we consider ethical review and publication of study results. Journals and funding bodies should insist that trialists make raw data available, for example, by publishing data on the Web. If the clinical trial community continues to fail with respect to data sharing, we will only strengthen the public perception that we do clinical trials to benefit ourselves, not our patients.

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

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

PubMed Central

Irvin, Veronica L.; Kaplan, Robert M.

2015-01-01

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

The effects of probiotic and synbiotic supplementation on metabolic syndrome indices in adults at risk of type 2 diabetes: study protocol for a randomized controlled trial.

PubMed

Kassaian, Nazila; Aminorroaya, Ashraf; Feizi, Awat; Jafari, Parvaneh; Amini, Masoud

2017-03-29

The incidence of type 2 diabetes, cardiovascular diseases, and obesity has been rising dramatically; however, their pathogenesis is particularly intriguing. Recently, dysbiosis of the intestinal microbiota has emerged as a new candidate that may be linked to metabolic diseases. We hypothesize that selective modulation of the intestinal microbiota by probiotic or synbiotic supplementation may improve metabolic dysfunction and prevent diabetes in prediabetics. In this study, a synthesis and study of synbiotics will be carried out for the first time in Iran. In a randomized triple-blind controlled clinical trial, 120 adults with impaired glucose tolerance based on the inclusion criteria will be selected by a simple random sampling method and will be randomly allocated to 6 months of 6 g/d probiotic, synbiotic or placebo. The fecal abundance of bacteria, blood pressure, height, weight, and waist and hip circumferences will be measured at baseline and following treatment. Also, plasma lipid profiles, HbA1C, fasting plasma glucose, and insulin levels, will be measured and insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) will be calculated at baseline and will be repeated at months 3, 6, 12, and 18. The data will be compared within and between groups using statistical methods. The results of this trial could contribute to the evidence-based clinical guidelines that address gut microbiota manipulation to maximize health benefits in prevention and management of metabolic syndrome in prediabetes. Iranian Registry of Clinical Trials: IRCT201511032321N2 . Registered on 27 February 2016.

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.

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

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

PubMed

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

2010-01-01

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

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

PubMed

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

2010-03-01

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

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

PubMed

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

2010-01-01

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

Recruitment, screening, and baseline participant characteristics in the WALK 2.0 study: A randomized controlled trial using web 2.0 applications to promote physical activity.

PubMed

Caperchione, Cristina M; Duncan, Mitch J; Rosenkranz, Richard R; Vandelanotte, Corneel; Van Itallie, Anetta K; Savage, Trevor N; Hooker, Cindy; Maeder, Anthony J; Mummery, W Kerry; Kolt, Gregory S

2016-04-15

To describe in detail the recruitment methods and enrollment rates, the screening methods, and the baseline characteristics of a sample of adults participating in the Walk 2.0 Study, an 18 month, 3-arm randomized controlled trial of a Web 2.0 based physical activity intervention. A two-fold recruitment plan was developed and implemented, including a direct mail-out to an extract from the Australian Electoral Commission electoral roll, and other supplementary methods including email and telephone. Physical activity screening involved two steps: a validated single-item self-report instrument and the follow-up Active Australia Questionnaire. Readiness for physical activity participation was also based on a two-step process of administering the Physical Activity Readiness Questionnaire and, where needed, further clearance from a medical practitioner. Across all recruitment methods, a total of 1244 participants expressed interest in participating, of which 656 were deemed eligible. Of these, 504 were later enrolled in the Walk 2.0 trial (77% enrollment rate) and randomized to the Walk 1.0 group (n = 165), the Walk 2.0 group (n = 168), or the Logbook group (n = 171). Mean age of the total sample was 50.8 years, with 65.2% female and 79.1% born in Australia. The results of this recruitment process demonstrate the successful use of multiple strategies to obtain a diverse sample of adults eligible to take part in a web-based physical activity promotion intervention. The use of dual screening processes ensured safe participation in the intervention. This approach to recruitment and physical activity screening can be used as a model for further trials in this area.

Acute cholecystitis in high risk surgical patients: percutaneous cholecystostomy versus laparoscopic cholecystectomy (CHOCOLATE trial): Study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice. Methods/Design The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs. Discussion The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients. Trial Registration Netherlands Trial Register (NTR): NTR2666 PMID:22236534

Effects of a Brief Multimedia Psychoeducational Intervention on the Attitudes and Interest of Patients With Cancer Regarding Clinical Trial Participation: A Multicenter Randomized Controlled Trial

PubMed Central

Jacobsen, Paul B.; Wells, Kristen J.; Meade, Cathy D.; Quinn, Gwendolyn P.; Lee, Ji-Hyun; Fulp, William J.; Gray, Jhanelle E.; Baz, Rachid C.; Springett, Gregory M.; Levine, Richard M.; Markham, Merry-Jennifer; Schreiber, Fred J.; Cartwright, Thomas H.; Burke, James M.; Siegel, Robert D.; Malafa, Mokenge P.; Sullivan, Daniel

2012-01-01

Purpose The negative attitudes of patients with cancer regarding clinical trials are an important contributor to low participation rates. This study evaluated whether a brief psychoeducational intervention was effective in improving patients' attitudes as well as their knowledge, self-efficacy for decision making, receptivity to receiving more information, and general willingness to participate in clinical trials. Patients and Methods A total of 472 adults with cancer who had not been asked previously to participate in a clinical trial were randomly assigned to receive printed educational information about clinical trials or a psychoeducational intervention that provided similar information and also addressed misperceptions and concerns about clinical trials. The primary (attitudes) and secondary outcomes (knowledge, self-efficacy, receptivity, and willingness) were assessed via patient self-report before random assignment and 7 to 28 days later. Results Patients who received the psychoeducational intervention showed more positive attitudes toward clinical trials (P = .016) and greater willingness to participate (P = .011) at follow-up than patients who received printed educational information. Evidence of an indirect effect of intervention assignment on willingness to participate (estimated at 0.168; 95% CI, 0.088 to 0.248) suggested that the benefits of psychoeducation on willingness to participate were explained by the positive impact of psychoeducation on attitudes toward clinical trials. Conclusion A brief psychoeducational intervention can improve the attitudes of patients with cancer toward clinical trials and thereby increase their willingness to participate in clinical trials. Findings support conducting additional research to evaluate effects of this intervention on quality of decision making and rates of participation among patients asked to enroll onto therapeutic clinical trials. PMID:22614993

Maternal Opioid Treatment: Human Experimental Research (MOTHER) – Approach, Issues, and Lessons Learned

PubMed Central

Jones, Hendrée E.; Fischer, Gabriele; Heil, Sarah H.; Kaltenbach, Karol; Martin, Peter R.; Coyle, Mara G.; Selby, Peter; Stine, Susan M.; O’Grady, Kevin E.; Arria, Amelia M.

2015-01-01

Aims The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current – and single most comprehensive – research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine. Methods The MOTHER study design is outlined, and its basic features are presented. Conclusions At least seven important lessons have been learned from the MOTHER study: (1) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (2) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment goals, patient populations, and hospital practices that in turn differentially impact recruitment rates, treatment compliance, and attrition; (3) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (4) staff turnover needs to be addressed with a proactive focus on both hiring and training; (5) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (6) timely tracking of data in a multi-site trial is both demanding and unforgiving; and, (7) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results. PMID:23106924

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

PubMed

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

2013-01-01

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

Inference in randomized trials with death and missingness.

PubMed

Wang, Chenguang; Scharfstein, Daniel O; Colantuoni, Elizabeth; Girard, Timothy D; Yan, Ying

2017-06-01

In randomized studies involving severely ill patients, functional outcomes are often unobserved due to missed clinic visits, premature withdrawal, or death. It is well known that if these unobserved functional outcomes are not handled properly, biased treatment comparisons can be produced. In this article, we propose a procedure for comparing treatments that is based on a composite endpoint that combines information on both the functional outcome and survival. We further propose a missing data imputation scheme and sensitivity analysis strategy to handle the unobserved functional outcomes not due to death. Illustrations of the proposed method are given by analyzing data from a recent non-small cell lung cancer clinical trial and a recent trial of sedation interruption among mechanically ventilated patients. © 2016, The International Biometric Society.

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

PubMed

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

2015-09-01

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

SPECT Analysis of Cardiac Perfusion Changes After Whole-Breast/Chest Wall Radiation Therapy With or Without Active Breathing Coordinator: Results of a Randomized Phase 3 Trial

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

Zellars, Richard, E-mail: zellari@jhmi.edu; Bravo, Paco E.; Tryggestad, Erik

2014-03-15

Purpose: Cardiac muscle perfusion, as determined by single-photon emission computed tomography (SPECT), decreases after breast and/or chest wall (BCW) irradiation. The active breathing coordinator (ABC) enables radiation delivery when the BCW is farther from the heart, thereby decreasing cardiac exposure. We hypothesized that ABC would prevent radiation-induced cardiac toxicity and conducted a randomized controlled trial evaluating myocardial perfusion changes after radiation for left-sided breast cancer with or without ABC. Methods and Materials: Stages I to III left breast cancer patients requiring adjuvant radiation therapy (XRT) were randomized to ABC or No-ABC. Myocardial perfusion was evaluated by SPECT scans (before andmore » 6 months after BCW radiation) using 2 methods: (1) fully automated quantitative polar mapping; and (2) semiquantitative visual assessment. The left ventricle was divided into 20 segments for the polar map and 17 segments for the visual method. Segments were grouped by anatomical rings (apical, mid, basal) or by coronary artery distribution. For the visual method, 2 nuclear medicine physicians, blinded to treatment groups, scored each segment's perfusion. Scores were analyzed with nonparametric tests and linear regression. Results: Between 2006 and 2010, 57 patients were enrolled and 43 were available for analysis. The cohorts were well matched. The apical and left anterior descending coronary artery segments had significant decreases in perfusion on SPECT scans in both ABC and No-ABC cohorts. In unadjusted and adjusted analyses, controlling for pretreatment perfusion score, age, and chemotherapy, ABC was not significantly associated with prevention of perfusion deficits. Conclusions: In this randomized controlled trial, ABC does not appear to prevent radiation-induced cardiac perfusion deficits.« less

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.

Should in-line filters be used in peripheral intravenous catheters to prevent infusion-related phlebitis? A systematic review of randomized controlled trials.

PubMed

Niël-Weise, Barbara S; Stijnen, Theo; van den Broek, Peterhans J

2010-06-01

In this systematic review, we assessed the effect of in-line filters on infusion-related phlebitis associated with peripheral IV catheters. The study was designed as a systematic review and meta-analysis of randomized controlled trials. We used MEDLINE and the Cochrane Controlled Trial Register up to August 10, 2009. Two reviewers independently assessed trial quality and extracted data. Data on phlebitis were combined when appropriate, using a random-effects model. The impact of the risk of phlebitis in the control group (baseline risk) on the effect of in-line filters was studied by using meta-regression based on the bivariate meta-analysis model. The quality of the evidence was determined by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method. Eleven trials (1633 peripheral catheters) were included in this review to compare the effect of in-line filters on the incidence of phlebitis in hospitalized patients. Baseline risks across trials ranged from 23% to 96%. Meta-analysis of all trials showed that in-line filters reduced the risk of infusion-related phlebitis (relative risk, 0.66; 95% confidence interval, 0.43-1.00). This benefit, however, is very uncertain, because the trials had serious methodological shortcomings and meta-analysis revealed marked unexplained statistical heterogeneity (P < 0.0000, I(2) = 90.4%). The estimated benefit did not depend on baseline risk. In-line filters in peripheral IV catheters cannot be recommended routinely, because evidence of their benefit is uncertain.

COACH trial: A randomized controlled trial of nurse practitioner/community health worker cardiovascular disease risk reduction in urban community health centers: Rationale and design

PubMed Central

Allen, Jerilyn K; Himmelfarb, Cheryl R Dennison; Szanton, Sarah L; Bone, Lee; Hill, Martha N; Levine, David M

2011-01-01

Background Despite well-publicized guidelines on the appropriate management of cardiovascular disease (CVD) and type 2 diabetes, implementation of risk-reducing practices remains poor. This paper describes the rationale and design of a randomized controlled clinical trial evaluating the effectiveness of a comprehensive program of CVD risk reduction delivered by nurse practitioner (NP)/community health worker (CHW) teams versus enhanced usual care in improving the proportion of patients in urban community health centers who achieve goal levels recommended by national guidelines for lipids, blood pressure, HbA1c and prescription of appropriate medications. Methods The COACH (Community Outreach and Cardiovascular Health) trial is a randomized controlled trial in which patients at federally-qualified community health centers were randomly assigned to one of two groups: comprehensive intensive management of CVD risk factors for one year by a NP/CHW team or an enhanced usual care control group. Results A total of 3899 patients were assessed for eligibility and 525 were randomized. Groups were comparable at baseline on sociodemographic and clinical characteristics with the exception of statistically significant differences in total cholesterol and hemoglobin A1c. Conclusions This study is a novel amalgam of multilevel interdisciplinary strategies to translate highly efficacious therapies to low-income federally-funded health centers that care for patients who carry a disproportionate burden of CVD, type 2 diabetes and uncontrolled CVD risk factors. The impact of such a community clinic-based intervention is potentially enormous. PMID:21241828

Predicting Outcome in Computerized Cognitive Behavioral Therapy for Depression in Primary Care: A Randomized Trial

ERIC Educational Resources Information Center

de Graaf, L. Esther; Hollon, Steven D.; Huibers, Marcus J. H.

2010-01-01

Objective: To explore pretreatment and short-term improvement variables as potential moderators and predictors of 12-month follow-up outcome of unsupported online computerized cognitive behavioral therapy (CCBT), usual care, and CCBT combined with usual care for depression. Method: Three hundred and three depressed patients were randomly allocated…

Tic Reduction with Risperidone Versus Pimozide in a Randomized, Double-Blind, Crossover Trial

ERIC Educational Resources Information Center

Gilbert, Donald L.; Batterson, J. Robert; Sethuraman, Gopalan; Sallee, Floyd R.

2004-01-01

Objective: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. Method: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic…

Medical Students' Comfort with Pregnant Women with Substance-Use Disorders: A Randomized Educational Study

ERIC Educational Resources Information Center

Albright, Brittany; Skipper, Betty; Riley, Shawne; Wilhelm, Peggy; Rayburn, William F.

2012-01-01

Objective: The study objective was to determine whether medical students' attendance at a rehabilitation residence for pregnant women with substance-use disorders yielded changes in their attitudes and comfort levels in providing care to this population. Methods: This randomized educational trial involved 96 consecutive medical students during…

Hybrid Implementation Model of Community-Partnered Early Intervention for Toddlers with Autism: A Randomized Trial

ERIC Educational Resources Information Center

Shire, Stephanie Y.; Chang, Ya-Chih; Shih, Wendy; Bracaglia, Suzanne; Kodjoe, Maria; Kasari, Connie

2017-01-01

Background: Interventions found to be effective in research settings are often not as effective when implemented in community settings. Considering children with autism, studies have rarely examined the efficacy of laboratory-tested interventions on child outcomes in community settings using randomized controlled designs. Methods: One hundred and…

Entre Dos Mundos/Between Two Worlds: Youth Violence Prevention for Acculturating Latino Families

ERIC Educational Resources Information Center

Smokowski, Paul R.; Bacallao, Martica

2009-01-01

Objective: This study evaluated the efficacy of Entre Dos Mundos/Between Two Worlds (EDM) prevention for Latino adolescents. Method: In an experimental trial to compare implementation formats, 41 Latino families were randomly assigned to EDM action-oriented skills training groups, and 47 families were randomly assigned to unstructured EDM support…

The Efficacy of Incentives to Motivate Continued Fitness-Center Attendance in College First-Year Students: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Pope, Lizzy; Harvey, Jean

2014-01-01

Objective: To determine whether fitness-center attendance established with the provision of weekly monetary incentives persisted after the discontinuation, or decreased frequency, of incentives. Participants: One hundred seventeen first-year college students participated during the 2011-2012 academic year. Methods: A randomized controlled trial…

Melatonin Treatment in Individuals with Intellectual Disability and Chronic Insomnia: A Randomized Placebo-Controlled Study

ERIC Educational Resources Information Center

Braam, W.; Didden, R.; Smits, M.; Curfs, L.

2008-01-01

Background: While several small-number or open-label studies suggest that melatonin improves sleep in individuals with intellectual disabilities (ID) with chronic sleep disturbance, a larger randomized control trial is necessary to validate these promising results. Methods: The effectiveness of melatonin for the treatment of chronic sleep…

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.

Treatment of Subacromial Impingement Syndrome: Platelet-Rich Plasma or Exercise Therapy? A Randomized Controlled Trial

PubMed Central

Nejati, Parisa; Ghahremaninia, Armita; Naderi, Farrokh; Gharibzadeh, Safoora; Mazaherinezhad, Ali

2017-01-01

Background: Subacromial impingement syndrome (SAIS) is the most common disorder of the shoulder. The evidence for the effectiveness of treatment options is inconclusive and limited. Therefore, there is a need for more evidence in this regard, particularly for long-term outcomes. Hypothesis: Platelet-rich plasma (PRP) would be an effective method in treating subacromial impingement. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This was a single-blinded randomized clinical trial with 1-, 3-, and 6-month follow-up. Sixty-two patients were randomly placed into 2 groups, receiving either PRP or exercise therapy. The outcome parameters were pain, shoulder range of motion (ROM), muscle force, functionality, and magnetic resonance imaging findings. Results: Both treatment options significantly reduced pain and increased shoulder ROM compared with baseline measurements. Both treatments also significantly improved functionality. However, the treatment choices were not significantly effective in improving muscle force. Trend analysis revealed that in the first and third months, exercise therapy was superior to PRP in pain, shoulder flexion and abduction, and functionality. However, in the sixth month, only shoulder abduction and total Western Ontario Rotator Cuff score were significantly different between the 2 groups. Conclusion: Both PRP injection and exercise therapy were effective in reducing pain and disability in patients with SAIS, with exercise therapy proving more effective. PMID:28567426

Reconciling research and implementation in micro health insurance experiments in India: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Microinsurance or Community-Based Health Insurance is a promising healthcare financing mechanism, which is increasingly applied to aid rural poor persons in low-income countries. Robust empirical evidence on the causal relations between Community-Based Health Insurance and healthcare utilisation, financial protection and other areas is scarce and necessary. This paper contains a discussion of the research design of three Cluster Randomised Controlled Trials in India to measure the impact of Community-Based Health Insurance on several outcomes. Methods/Design Each trial sets up a Community-Based Health Insurance scheme among a group of micro-finance affiliate families. Villages are grouped into clusters which are congruous with pre-existing social groupings. These clusters are randomly assigned to one of three waves of implementation, ensuring the entire population is offered Community-Based Health Insurance by the end of the experiment. Each wave of treatment is preceded by a round of mixed methods evaluation, with quantitative, qualitative and spatial evidence on impact collected. Improving upon practices in published Cluster Randomised Controlled Trial literature, we detail how research design decisions have ensured that both the households offered insurance and the implementers of the Community-Based Health Insurance scheme operate in an environment replicating a non-experimental implementation. Discussion When a Cluster Randomised Controlled Trial involves randomizing within a community, generating adequate and valid conclusions requires that the research design must be made congruous with social structures within the target population, to ensure that such trials are conducted in an implementing environment which is a suitable analogue to that of a non-experimental implementing environment. PMID:21988774

Convergence Insufficiency Treatment Trial – Attention and Reading Trial (CITT-ART): Design and Methods

PubMed Central

Scheiman, Mitchell; Mitchell, G. Lynn; Cotter, Susan A.; Kulp, Marjean; Chase, Christopher; Borsting, Eric; Arnold, Eugene; Denton, Carolyn; Hertle, Richard

2016-01-01

Objective To describe the design and methodology of the Convergence Insufficiency Treatment Trial: Attention and Reading Trial (CITT-ART), the first randomized clinical trial evaluating the effect of vision therapy on reading and attention in school-age children with symptomatic convergence insufficiency (CI). Methods CITT-ART is a multicenter, placebo-controlled, randomized clinical trial of 324 children ages 9 to 14 years in grades 3 to 8 with symptomatic CI. Participants are randomized to 16 weeks of office-based vergence/accommodative therapy (OBVAT) or placebo therapy (OBPT), both supplemented with home therapy. The primary outcome measure is the change in the Wechsler Individual Achievement Test-Version 3 (WIAT-III) reading comprehension subtest score. Secondary outcome measures are changes in attention as measured by the Strengths and Weaknesses of Attention (SWAN) as reported by parents and teachers, tests of binocular visual function, and other measures of reading and attention. The long-term effects of treatment are assessed 1 year after treatment completion. All analyses will test the null hypothesis of no difference in outcomes between the two treatment groups. The study is entering its second year of recruitment. The final results will contribute to a better understanding of the relationship between the treatment of symptomatic CI and its effect on reading and attention. Conclusion The study will provide an evidence base to help parents, eye professionals, educators, and other health care providers make informed decisions as they care for children with CI and reading and attention problems. Results may also generate additional hypothesis and guide the development of other scientific investigations of the relationships between visual disorders and other developmental disorders in children. PMID:26942226

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.

The DiaS trial: dialectical behavior therapy versus collaborative assessment and management of suicidality on self-harm in patients with a recent suicide attempt and borderline personality disorder traits - study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background In Denmark 8,000 to 10,000 people will attempt suicide each year. The Centre of Excellence in Suicide Prevention in the Capital Region of Denmark is treating patients with suicidal behavior, and a recent survey has shown that 30% of the patients are suffering from borderline personality disorder. The majority of patients (70% to 75%) with borderline personality disorder have a history of deliberate self-harm and 10% have a lifetime risk to die by suicide. The DiaS trial is comparing dialectical behavior therapy with collaborative assessment and management of suicidality-informed supportive psychotherapy, for the risk of repetition of deliberate self-harm in patients with a recent suicide attempt and personality traits within the spectrum of borderline personality disorder. Both treatments have previously shown effects in this group of patients on suicide ideation and self-harm compared with treatment as usual. Methods/Design The trial is designed as a single-center, two-armed, parallel-group observer-blinded randomized clinical superiority trial. We will recruit 160 participants with a recent suicide attempt and at least two traits of the borderline personality disorder from the Centre of Excellence in Suicide Prevention, Capital Region of Denmark. Randomization will be performed though a centralized and computer-generated approach that conceals the randomization sequence. The interventions that are offered are a modified version of a dialectical behavior therapy program lasting 16 weeks versus collaborative assessment and management of suicidality-informed supportive psychotherapy, where the duration treatment will vary in accordance with established methods up to 16 weeks. The primary outcome measure is the ratio of deliberate self-harming acts including suicide attempts measured at week 28. Other exploratory outcomes are included such as severity of symptoms, suicide intention and ideation, depression, hopelessness, self-esteem, impulsivity, anger, and duration of respective treatments. Trial registration Clinical Trial.gov: NCT01512602. PMID:24885904

Hand washing for preventing diarrhoea.

PubMed

Ejemot, R I; Ehiri, J E; Meremikwu, M M; Critchley, J A

2008-01-23

Diarrhoea is a common cause of morbidity and a leading cause of death among children aged less than five years, particularly in low- and middle-income countries. It is transmitted by ingesting contaminated food or drink, by direct person-to-person contact, or from contaminated hands. Hand washing is one of a range of hygiene promotion interventions that can interrupt the transmission of diarrhoea-causing pathogens. To evaluate the effects of interventions to promote hand washing on diarrhoeal episodes in children and adults. In May 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 2), MEDLINE, EMBASE, LILACS, PsycINFO, Science Citation Index and Social Science Citation Index, ERIC (1966 to May 2007), SPECTR, Bibliomap, RoRe, The Grey Literature, and reference lists of articles. We also contacted researchers and organizations in the field. Randomized controlled trials, where the unit of randomization is an institution (eg day-care centre), household, or community, that compared interventions to promote hand washing or a hygiene promotion that included hand washing with no intervention to promote hand washing. Two authors independently assessed trial eligibility and methodological quality. Where appropriate, incidence rate ratios (IRR) were pooled using the generic inverse variance method and random-effects model with 95% confidence intervals (CI). Fourteen randomized controlled trials met the inclusion criteria. Eight trials were institution-based, five were community-based, and one was in a high-risk group (AIDS patients). Interventions promoting hand washing resulted in a 29% reduction in diarrhoea episodes in institutions in high-income countries (IRR 0.71, 95% CI 0.60 to 0.84; 7 trials) and a 31% reduction in such episodes in communities in low- or middle-income countries (IRR 0.69, 95% CI 0.55 to 0.87; 5 trials). Hand washing can reduce diarrhoea episodes by about 30%. This significant reduction is comparable to the effect of providing clean water in low-income areas. However, trials with longer follow up and that test different methods of promoting hand washing are needed.

Self-Management and Clinical Decision Support for Patients With Complex Chronic Conditions Through the Use of Smartphone-Based Telemonitoring: Randomized Controlled Trial Protocol

PubMed Central

Ware, Patrick; Logan, Alexander G; Cafazzo, Joseph A; Chapman, Kenneth R; Segal, Phillip; Ross, Heather J

2017-01-01

Background The rising prevalence of chronic illnesses hinders the sustainability of the health care system because of the high cost of frequent hospitalizations of patients with complex chronic conditions. Clinical trials have demonstrated that telemonitoring can improve health outcomes, but they have generally been limited to single conditions such as diabetes, hypertension, or heart failure. Few studies have examined the impact of telemonitoring on complex patients with multiple chronic conditions, although these patients may benefit the most from this technology. Objective The aim of this study is to investigate the impact of a smartphone-based telemonitoring system on the clinical care and health outcomes of complex patients across several chronic conditions. Methods A mixed-methods, 6-month randomized controlled trial (RCT) of a smartphone-based telemonitoring system is being conducted in specialty clinics. The study will include patients who have been diagnosed with one or more of any of the following conditions: heart failure, chronic obstructive pulmonary disease, chronic kidney disease, uncontrolled hypertension, or insulin-requiring diabetes. The primary outcome will be the health status of patients as measured with SF-36. Patients will be randomly assigned to either the control group receiving usual care (n=73) or the group using the smartphone-based telemonitoring system in addition to usual care (n=73). Results Participants are currently being recruited for the trial. Data collection is anticipated to be completed by the fall of 2018. Conclusions This RCT will be among the first trials to provide evidence of the impact of telemonitoring on costs and health outcomes of complex patients who may have multiple chronic conditions. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 41238563; http://www.isrctn.com/ISRCTN41238563 (Archived by WebCite at http://www.webcitation.org/6ug2Sk0af) and Clinicaltrials.gov NCT03127852; https://clinicaltrials.gov/ct2/show/NCT03127852 (Archived by WebCite at http://www.webcitation.org/6uvjNosBC) PMID:29162557

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

PubMed

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

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

Costs of revascularization over eight years in the randomized and eligible patients in the Emory Angioplasty versus Surgery Trial (EAST).

PubMed

Weintraub, W S; Becker, E R; Mauldin, P D; Culler, S; Kosinski, A S; King, S B

2000-10-01

The Emory Angioplasty versus Surgery Trial (EAST) was a randomized trial that compared, by intention to treat, the clinical outcome and costs of percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass grafting (CABG) for multivessel coronary artery disease. We present the findings of the economic analysis of EAST through 8 years of follow-up and compare the cost and outcomes of patients randomized in EAST versus patients eligible but not randomized (registry patients). Charges were assessed from hospital UB82 and UB92 bills and professional charges from the Emory Clinic. Hospital charges were reduced to cost through step-down accounting methods. All costs and charges were inflated to 1997 dollars. Costs were assessed for initial hospitalization and for cumulative costs of the initial hospitalization and additional revascularization procedures up to 8 years. Total 8-year costs were $46,548 for CABG and $44,491 for PTCA (p = 0.37). Cost of CABG in the eligible registry group showed a pattern similar to that for randomized patients, but total cost of PTCA was lower for registry patients than for randomized patients. Thus, the primary procedural costs of CABG are more than those for PTCA; this cost advantage, given the limits of measurement, is largely or even completely lost for randomized patients over the course of 8 years because of additional procedures after a first revascularization by PTCA.

Practical considerations for estimating clinical trial accrual periods: application to a multi-center effectiveness study

PubMed Central

Carter, Rickey E; Sonne, Susan C; Brady, Kathleen T

2005-01-01

Background Adequate participant recruitment is vital to the conduct of a clinical trial. Projected recruitment rates are often over-estimated, and the time to recruit the target population (accrual period) is often under-estimated. Methods This report illustrates three approaches to estimating the accrual period and applies the methods to a multi-center, randomized, placebo controlled trial undergoing development. Results Incorporating known sources of accrual variation can yield a more justified estimate of the accrual period. Simulation studies can be incorporated into a clinical trial's planning phase to provide estimates for key accrual summaries including the mean and standard deviation of the accrual period. Conclusion The accrual period of a clinical trial should be carefully considered, and the allocation of sufficient time for participant recruitment is a fundamental aspect of planning a clinical trial. PMID:15796782

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.

A novel complete-case analysis to determine statistical significance between treatments in an intention-to-treat population of randomized clinical trials involving missing data.

PubMed

Liu, Wei; Ding, Jinhui

2018-04-01

The application of the principle of the intention-to-treat (ITT) to the analysis of clinical trials is challenged in the presence of missing outcome data. The consequences of stopping an assigned treatment in a withdrawn subject are unknown. It is difficult to make a single assumption about missing mechanisms for all clinical trials because there are complicated reactions in the human body to drugs due to the presence of complex biological networks, leading to data missing randomly or non-randomly. Currently there is no statistical method that can tell whether a difference between two treatments in the ITT population of a randomized clinical trial with missing data is significant at a pre-specified level. Making no assumptions about the missing mechanisms, we propose a generalized complete-case (GCC) analysis based on the data of completers. An evaluation of the impact of missing data on the ITT analysis reveals that a statistically significant GCC result implies a significant treatment effect in the ITT population at a pre-specified significance level unless, relative to the comparator, the test drug is poisonous to the non-completers as documented in their medical records. Applications of the GCC analysis are illustrated using literature data, and its properties and limits are discussed.

Designing clinical trials to test disease-modifying agents: application to the treatment trials of Alzheimer's disease.

PubMed

Xiong, Chengjie; van Belle, Gerald; Miller, J Philip; Morris, John C

2011-02-01

Therapeutic trials of disease-modifying agents on Alzheimer's disease (AD) require novel designs and analyses involving switch of treatments for at least a portion of subjects enrolled. Randomized start and randomized withdrawal designs are two examples of such designs. Crucial design parameters such as sample size and the time of treatment switch are important to understand in designing such clinical trials. The purpose of this article is to provide methods to determine sample sizes and time of treatment switch as well as optimum statistical tests of treatment efficacy for clinical trials of disease-modifying agents on AD. A general linear mixed effects model is proposed to test the disease-modifying efficacy of novel therapeutic agents on AD. This model links the longitudinal growth from both the placebo arm and the treatment arm at the time of treatment switch for these in the delayed treatment arm or early withdrawal arm and incorporates the potential correlation on the rate of cognitive change before and after the treatment switch. Sample sizes and the optimum time for treatment switch of such trials as well as optimum test statistic for the treatment efficacy are determined according to the model. Assuming an evenly spaced longitudinal design over a fixed duration, the optimum treatment switching time in a randomized start or a randomized withdrawal trial is half way through the trial. With the optimum test statistic for the treatment efficacy and over a wide spectrum of model parameters, the optimum sample size allocations are fairly close to the simplest design with a sample size ratio of 1:1:1 among the treatment arm, the delayed treatment or early withdrawal arm, and the placebo arm. The application of the proposed methodology to AD provides evidence that much larger sample sizes are required to adequately power disease-modifying trials when compared with those for symptomatic agents, even when the treatment switch time and efficacy test are optimally chosen. The proposed method assumes that the only and immediate effect of treatment switch is on the rate of cognitive change. Crucial design parameters for the clinical trials of disease-modifying agents on AD can be optimally chosen. Government and industry officials as well as academia researchers should consider the optimum use of the clinical trials design for disease-modifying agents on AD in their effort to search for the treatments with the potential to modify the underlying pathophysiology of AD.

Design of the multicenter standardized supervised exercise training intervention for the claudication: exercise vs endoluminal revascularization (CLEVER) study.

PubMed

Bronas, Ulf G; Hirsch, Alan T; Murphy, Timothy; Badenhop, Dalynn; Collins, Tracie C; Ehrman, Jonathan K; Ershow, Abby G; Lewis, Beth; Treat-Jacobson, Diane J; Walsh, M Eileen; Oldenburg, Niki; Regensteiner, Judith G

2009-11-01

The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

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.

The Recruitment Experience of a Randomized Clinical Trial to Aid Young Adult Smokers to Stop Smoking without Weight Gain with Interactive Technology.

PubMed

Coday, Mace; Richey, Phyllis; Thomas, Fridtjof; Tran, Quynh T; Terrell, Sarah B; Tylavsky, Fran; Miro, Danielle; Caufield, Margaret; Johnson, Karen C

2016-04-15

Multiple recruitment strategies are often needed to recruit an adequate number of participants, especially hard to reach groups. Technology-based recruitment methods hold promise as a more robust form of reaching and enrolling historically hard to reach young adults. The TARGIT study is a randomized two-arm clinical trial in young adults using interactive technology testing an efficacious proactive telephone Quitline versus the Quitline plus a behavioral weight management intervention focusing on smoking cessation and weight change. All randomized participants in the TARGIT study were required to be a young adult smoker (18-35 years), who reported smoking at least 10 cigarettes per day, had a BMI < 40 kg/m 2, and were willing to stop smoking and not gain weight. Traditional recruitment methods were compared to technology-based strategies using standard descriptive statistics based on counts and proportions to describe the recruitment process from initial pre-screening (PS) to randomization into TARGIT. Participants at PS were majority Black (59.80%), female (52.66%), normal or over weight (combined 62.42%), 29.5 years old, and smoked 18.4 cigarettes per day. There were differences in men and women with respect to reasons for ineligibility during PS (p < 0.001; ignoring gender specific pregnancy-related ineligibility). TARGIT experienced a disproportionate loss of minorities during recruitment as well as a prolonged recruitment period due to either study ineligibility or not completing screening activities. Recruitment into longer term behavioral change intervention trials can be challenging and multiple methods are often required to recruit hard to reach groups.

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.

Estimating the optimal dynamic antipsychotic treatment regime: Evidence from the sequential multiple assignment randomized CATIE Schizophrenia Study

PubMed Central

Shortreed, Susan M.; Moodie, Erica E. M.

2012-01-01

Summary Treatment of schizophrenia is notoriously difficult and typically requires personalized adaption of treatment due to lack of efficacy of treatment, poor adherence, or intolerable side effects. The Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) Schizophrenia Study is a sequential multiple assignment randomized trial comparing the typical antipsychotic medication, perphenazine, to several newer atypical antipsychotics. This paper describes the marginal structural modeling method for estimating optimal dynamic treatment regimes and applies the approach to the CATIE Schizophrenia Study. Missing data and valid estimation of confidence intervals are also addressed. PMID:23087488

Non-surgical treatment of hip osteoarthritis. Hip school, with or without the addition of manual therapy, in comparison to a minimal control intervention: Protocol for a three-armed randomized clinical trial

PubMed Central

2011-01-01

Background Hip osteoarthritis is a common and chronic condition resulting in pain, functional disability and reduced quality of life. In the early stages of the disease, a combination of non-pharmacological and pharmacological treatment is recommended. There is evidence from several trials that exercise therapy is effective. In addition, single trials suggest that patient education in the form of a hip school is a promising intervention and that manual therapy is superior to exercise. Methods/Design This is a randomized clinical trial. Patients with clinical and radiological hip osteoarthritis, 40-80 years of age, and without indication for hip surgery were randomized into 3 groups. The active intervention groups A and B received six weeks of hip school, taught by a physiotherapist, for a total of 5 sessions. In addition, group B received manual therapy consisting of joint manipulation and soft-tissue therapy twice a week for six weeks. Group C received a self-care information leaflet containing advice on "live as usual" and stretching exercises from the hip school. The primary time point for assessing relative effectiveness is at the end of the six weeks intervention period with follow-ups after three and 12 months. Primary outcome measure is pain measured on an eleven-point numeric rating scale. Secondary outcome measures are the hip dysfunction and osteoarthritis outcome score, patient's global perceived effect, patient specific functional scale, general quality of life and hip range of motion. Discussion To our knowledge this is the first randomized clinical trial comparing a patient education program with or without the addition of manual therapy to a minimal intervention for patients with hip osteoarthritis. Trial registration ClinicalTrials NCT01039337 PMID:21542914

Power Calculations for Moderators in Multi-Site Cluster Randomized Trials

ERIC Educational Resources Information Center

Spybrook, Jessaca; Kelcey, Ben; Dong, Nianbo

2016-01-01

Cluster randomized trials (CRTs), or studies in which intact groups of individuals are randomly assigned to a condition, are becoming more common in evaluation studies of educational programs. A specific type of CRT in which clusters are randomly assigned to treatment within blocks or sites, known as multisite cluster randomized trials (MSCRTs),…

Alcohol Prevention and School Students: Findings from an Australian 2-Year Trial of Integrated Harm Minimization School Drug Education

ERIC Educational Resources Information Center

Midford, Richard; Ramsden, Robyn; Lester, Leanne; Cahill, Helen; Mitchell, Johanna; Foxcroft, David R.; Venning, Lynne

2014-01-01

The Drug Education in Victorian Schools program provided integrated education about licit and illicit drugs, employed a harm minimization approach that incorporated participatory, critical thinking and skill-based teaching methods, and engaged parental influence through home activities. A cluster-randomized, controlled trial of the program was…

A Pocock Approach to Sequential Meta-Analysis of Clinical Trials

ERIC Educational Resources Information Center

Shuster, Jonathan J.; Neu, Josef

2013-01-01

Three recent papers have provided sequential methods for meta-analysis of two-treatment randomized clinical trials. This paper provides an alternate approach that has three desirable features. First, when carried out prospectively (i.e., we only have the results up to the time of our current analysis), we do not require knowledge of the…

Differential Benefits of Memory Training for Minority Older Adults in the SeniorWISE Study

ERIC Educational Resources Information Center

McDougall, Graham J., Jr.; Becker, Heather; Pituch, Keenan; Acee, Taylor W.; Vaughan, Phillip W.; Delville, Carol L.

2010-01-01

Purpose: Cognitive training improves mental abilities in older adults, but the benefit to minority elders is unclear. We conducted a subgroup analysis of subjects in the SeniorWISE (Wisdom Is Simply Exploration) trial to examine this issue. Design and Methods: SeniorWISE was a Phase 3 randomized trial that enrolled 265 nondemented…

Venlafaxine ER for the Treatment of Pediatric Subjects with Depression: Results of Two Placebo-Controlled Trials

ERIC Educational Resources Information Center

Emslie, Graham J.; Findling, Robert L.; Yeung, Paul P.; Kunz, Nadia R.; Li, Yunfeng

2007-01-01

Objective: The safety, efficacy, and tolerability of venlafaxine extended release (ER) in subjects ages 7 to 17 years with major depressive disorder were evaluated in two multicenter, randomized, double-blind, placebo-controlled trials conducted between October 1997 and August 2001. Method: Participants received venlafaxine ER (flexible dose,…

Impact of a Parenting Program in a High-Risk, Multi-Ethnic Community: The PALS Trial

ERIC Educational Resources Information Center

Scott, Stephen; O'Connor, Thomas G.; Futh, Annabel; Matias, Carla; Price, Jenny; Doolan, Moira

2010-01-01

Background: Parenting programs have been shown to work when delivered to motivated ethnic majority parents in demonstration projects, but comparatively little is known about their impact when delivered to high-risk, multi-ethnic populations by routine local services. Methods: The Primary Age Learning Skills (PALS) trial was a randomized controlled…

Missing data in trial‐based cost‐effectiveness analysis: An incomplete journey

PubMed Central

Gomes, Manuel; Carpenter, James R.

2018-01-01

SUMMARY Cost‐effectiveness analyses (CEA) conducted alongside randomised trials provide key evidence for informing healthcare decision making, but missing data pose substantive challenges. Recently, there have been a number of developments in methods and guidelines addressing missing data in trials. However, it is unclear whether these developments have permeated CEA practice. This paper critically reviews the extent of and methods used to address missing data in recently published trial‐based CEA. Issues of the Health Technology Assessment journal from 2013 to 2015 were searched. Fifty‐two eligible studies were identified. Missing data were very common; the median proportion of trial participants with complete cost‐effectiveness data was 63% (interquartile range: 47%–81%). The most common approach for the primary analysis was to restrict analysis to those with complete data (43%), followed by multiple imputation (30%). Half of the studies conducted some sort of sensitivity analyses, but only 2 (4%) considered possible departures from the missing‐at‐random assumption. Further improvements are needed to address missing data in cost‐effectiveness analyses conducted alongside randomised trials. These should focus on limiting the extent of missing data, choosing an appropriate method for the primary analysis that is valid under contextually plausible assumptions, and conducting sensitivity analyses to departures from the missing‐at‐random assumption. PMID:29573044

Strategies for dealing with missing data in clinical trials: from design to analysis.

PubMed

Dziura, James D; Post, Lori A; Zhao, Qing; Fu, Zhixuan; Peduzzi, Peter

2013-09-01

Randomized clinical trials are the gold standard for evaluating interventions as randomized assignment equalizes known and unknown characteristics between intervention groups. However, when participants miss visits, the ability to conduct an intent-to-treat analysis and draw conclusions about a causal link is compromised. As guidance to those performing clinical trials, this review is a non-technical overview of the consequences of missing data and a prescription for its treatment beyond the typical analytic approaches to the entire research process. Examples of bias from incorrect analysis with missing data and discussion of the advantages/disadvantages of analytic methods are given. As no single analysis is definitive when missing data occurs, strategies for its prevention throughout the course of a trial are presented. We aim to convey an appreciation for how missing data influences results and an understanding of the need for careful consideration of missing data during the design, planning, conduct, and analytic stages.

Randomized Placebo-Controlled Double-Blind Clinical Trial of Cannabis-Based Medicinal Product (Sativex) in Painful Diabetic Neuropathy

PubMed Central

Selvarajah, Dinesh; Gandhi, Rajiv; Emery, Celia J.; Tesfaye, Solomon

2010-01-01

OBJECTIVE To assess the efficacy of Sativex, a cannabis-based medicinal extract, as adjuvant treatment in painful diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS In this randomized controlled trial, 30 subjects with painful DPN received daily Sativex or placebo. The primary outcome measure was change in mean daily pain scores, and secondary outcome measures included quality-of-life assessments. RESULTS There was significant improvement in pain scores in both groups, but mean change between groups was not significant. There were no significant differences in secondary outcome measures. Patients with depression had significantly greater baseline pain scores that improved regardless of intervention. CONCLUSIONS This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN. Depression was a major confounder and may have important implications for future trials on painful DPN. PMID:19808912

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

Immigrant family skills-building to prevent tobacco use in Latino youth: study protocol for a community-based participatory randomized controlled trial

PubMed Central

2012-01-01

Background Despite declines over recent years, youth tobacco and other substance use rates remain high. Latino youth are at equal or increased risk for lifetime tobacco, alcohol, marijuana, and other illicit drug use compared with their white peers. Family plays an important and influential role in the lives of youth, and longitudinal research suggests that improving parenting skills may reduce youth substance use. However, few interventions are oriented towards immigrant Latino families, and none have been developed and evaluated using a community-based participatory research (CBPR) process that may increase the effectiveness and sustainability of such projects. Therefore, using CBPR principles, we developed a randomized clinical trial to assess the efficacy of a family-skills training intervention to prevent tobacco and other substance use intentions in Latino youth. Methods/Design In collaboration with seven Latino community-serving agencies, we will recruit and randomize 336 immigrant families, into intervention or delayed treatment conditions. The primary outcome is youth intention to smoke 6 months post intervention. The intervention consists of eight parent and four youth sessions targeting parenting skills and parent–youth relational factors associated with lower smoking and other substance use in youth. Discussion We present the study protocol for a family intervention using a CBPR randomized clinical trial to prevent smoking among Latino youth. The results of this trial will contribute to the limited information on effective and sustainable primary prevention programs for tobacco and other substance use directed at the growing US Latino communities. Trial registration ClinicalTrials.gov: NCT01442753 PMID:23253201

Asthma randomized trial of indoor wood smoke (ARTIS): Rationale and Methods

PubMed Central

Noonan, Curtis W.; Ward, Tony J.

2012-01-01

Background Particulate matter (PM) exposures have been linked with poor respiratory health outcomes, especially among susceptible populations such as asthmatic children. Smoke from biomass combustion for residential home heating is an important source of PM in many rural or peri-urban areas in the United States. Aim To assess the efficacy of residential interventions that reduce indoor PM exposure from wood stoves and to quantify the corresponding improvements in quality of life and health outcomes for asthmatic children. Design The Asthma Randomized Trial of Indoor wood Smoke (ARTIS) study is an in-home intervention study of susceptible children exposed to biomass combustion smoke. Children, ages 7 to 17, with persistent asthma and living in homes that heat with wood stoves were recruited for this three arm randomized placebo-controlled trial. Two household-level intervention strategies, wood stove replacement and air filters, were compared to a sham air filter placebo. Improvement in quality of life of asthmatic children was the primary outcomes. Secondary asthma-related health outcomes included peak expiratory flow (PEF) and forced expiratory volume in first second (FEV1), biomarkers in exhaled breath condensate, and frequency of asthma symptoms, medication usage, and healthcare utilization. Exposure outcomes included indoor and outdoor PM2.5 mass, particle counts of several size fractions, and carbon monoxide. Discussion To our knowledge, this was the first randomized trial in the US to utilize interventions targeting residential wood stoves to assess the impact on indoor PM and health outcomes in a susceptible population. Trial registration ClincialTrials.gov NCT00807183. PMID:22735495

A joint sparse representation-based method for double-trial evoked potentials estimation.

PubMed

Yu, Nannan; Liu, Haikuan; Wang, Xiaoyan; Lu, Hanbing

2013-12-01

In this paper, we present a novel approach to solving an evoked potentials estimating problem. Generally, the evoked potentials in two consecutive trials obtained by repeated identical stimuli of the nerves are extremely similar. In order to trace evoked potentials, we propose a joint sparse representation-based double-trial evoked potentials estimation method, taking full advantage of this similarity. The estimation process is performed in three stages: first, according to the similarity of evoked potentials and the randomness of a spontaneous electroencephalogram, the two consecutive observations of evoked potentials are considered as superpositions of the common component and the unique components; second, making use of their characteristics, the two sparse dictionaries are constructed; and finally, we apply the joint sparse representation method in order to extract the common component of double-trial observations, instead of the evoked potential in each trial. A series of experiments carried out on simulated and human test responses confirmed the superior performance of our method. © 2013 Elsevier Ltd. Published by Elsevier Ltd. All rights reserved.

Fallibility: a new perspective on the ethics of clinical trial enrollment.

PubMed

Shamy, Michel C F; Stahnisch, Frank W; Hill, Michael D

2015-01-01

The ethical principle of 'equipoise', introduced in 1974, represents the most widely influential justification for the enrollment of patients into randomized clinical trials. However, definitions of equipoise vary, and its terms are not universally accepted. In this paper, we suggest a new way of approaching the ethics of clinical trial enrollment, which we call fallibility. The principle of fallibility argues that all physician opinions are sufficiently uncertain to warrant investigation, and that the ethical justification for any trial becomes a question of its epistemic validity, by which we mean the strength of its hypotheses and methods. The principle of fallibility can be translated into practice through the virtues of humility, skepticism and caring. While we cite recent examples from stroke medicine to demonstrate the limitations of equipoise, we propose that fallibility may offer a more general means of addressing the controversies that arise surrounding randomized controlled trials in many disciplines of medicine. © 2014 World Stroke Organization.

A pragmatic randomized comparative effectiveness trial of transitional care for a socioeconomically diverse population: Design, rationale and baseline characteristics.

PubMed

Schaeffer, Christine; Teter, Caroline; Finch, Emily A; Hurt, Courtney; Keeter, Mary Kate; Liss, David T; Rogers, Angela; Sheth, Avani; Ackermann, Ronald

2018-02-01

Transitional care programs have been widely used to reduce readmissions and improve the quality and safety of the handoff process between hospital and outpatient providers. Very little is known about effective transitional care interventions among patients who are uninsured or with Medicaid. This paper describes the design and baseline characteristics of a pragmatic randomized comparative effectiveness trial of transitional care. Northwestern Medical Group- Transitional Care (NMG-TC) care model was developed to address the needs of patients with multiple medical problems that required lifestyle changes and were amenable to office-based management. We present the design, evaluation methods and baseline characteristics of NMG-TC trial patients. Baseline demographic characteristics indicate that our patient population is predominantly male, Medicaid insured and non-white. This study will evaluate two methods for implementing an effective transitional care model in a medically complex and socioeconomically diverse population. Copyright © 2017 Elsevier Inc. All rights reserved.

Recruiting Community-Based Dementia Patients and Caregivers in a Nonpharmacologic Randomized Trial: What Works and How Much Does It Cost?

PubMed

Morrison, Karen; Winter, Laraine; Gitlin, Laura N

2016-07-01

The aim of this study was to evaluate the yield and cost of three recruitment strategies-direct mail, newspaper advertisements, and community outreach-for identifying and enrolling dementia caregivers into a randomized trial testing a nonpharmacologic approach to enhancing quality of life of patients and caregivers (dyads). Enrollment occurred between 2006 and 2008. The number of recruitment inquiries, number and race of enrollees, and costs for each recruitment strategy were recorded. Of 284 inquiries, 237 (83%) dyads enrolled. Total cost for recruitment across methodologies was US$154 per dyad. Direct mailings resulted in the most enrollees (n = 135, 57%) and was the least costly method (US$63 per dyad) compared with newspaper ads (US$224 per dyad) and community outreach (US$350 per dyad). Although enrollees were predominately White, mailings yielded the highest number of non-Whites (n = 37). Direct mailings was the most effective and least costly method for enrolling dyads in a nonpharmacologic dementia trial. © The Author(s) 2014.

Effect of Tree Nuts on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Dietary Trials

PubMed Central

Viguiliouk, Effie; Kendall, Cyril W. C.; Blanco Mejia, Sonia; Cozma, Adrian I.; Ha, Vanessa; Mirrahimi, Arash; Jayalath, Viranda H.; Augustin, Livia S. A.; Chiavaroli, Laura; Leiter, Lawrence A.; de Souza, Russell J.; Jenkins, David J. A.; Sievenpiper, John L.

2014-01-01

Background Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent. Objective To provide better evidence for diabetes guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes. Data Sources MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014. Study Selection Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR. Data Extraction and Synthesis Two independent reviewer’s extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI’s. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2). Results Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = −0.07% [95% CI:−0.10, −0.03%]; P = 0.0003) and fasting glucose (MD = −0.15 mmol/L [95% CI: −0.27, −0.02 mmol/L]; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts. Limitations Majority of trials were of short duration and poor quality. Conclusions Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates. Trial Registration ClinicalTrials.gov NCT01630980 PMID:25076495

Effects of calcium on the incidence of recurrent colorectal adenomas

PubMed Central

Veettil, Sajesh K.; Ching, Siew Mooi; Lim, Kean Ghee; Saokaew, Surasak; Phisalprapa, Pochamana; Chaiyakunapruk, Nathorn

2017-01-01

Abstract Background: Protective effects of calcium supplementation against colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Our objective was to update and systematically evaluate the evidence for calcium supplementation taking into consideration the risks of systematic and random error and to GRADE the evidence. Methods: The study comprised a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCTs). We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. Primary outcome measures were the incidences of any recurrent adenomas and of advanced adenomas. Meta-analytic estimates were calculated with the random-effects model and random errors were evaluated with trial sequential analyses (TSAs). Results: Five randomized trials (2234 patients with a history of adenomas) were included. Two of the 5 trials showed either unclear or high risks of bias in most criteria. Meta-analysis of good quality RCTs suggest a moderate protective effect of calcium supplementation on recurrence of adenomas (relative risk [RR], 0.88 [95% CI 0.79–0.99]); however, its effects on advanced adenomas did not show statistical significance (RR, 1.02 [95% CI 0.67–1.55]). Subgroup analyses demonstrated a greater protective effect on recurrence of adenomas with elemental calcium dose ≥1600 mg/day (RR, 0.74 [95% CI 0.56–0.97]) compared to ≤1200 mg/day (RR, 0.84 [95% CI 0.73–0.97]). No major serious adverse events were associated with the use of calcium, but there was an increase in the incidence of hypercalcemia (P = .0095). TSA indicated a lack of firm evidence for a beneficial effect. Concerns with directness and imprecision rated down the quality of the evidence to “low.” Conclusion: The available good quality RCTs suggests a possible beneficial effect of calcium supplementation on the recurrence of adenomas; however, TSA indicated that the accumulated evidence is still inconclusive. Using GRADE-methodology, we conclude that the quality of evidence is low. Large well-designed randomized trials with low risk of bias are needed. PMID:28796047

The effects and costs of the universal parent group program – all children in focus: a study protocol for a randomized wait-list controlled trial

PubMed Central

2013-01-01

Background In recent decades, parents have been involved in programs that aim to improve parenting style and reduce child behavior problems. Research of preventive parenting programs has shown that these interventions generally have a positive influence on both parents and children. However, to our knowledge there is a gap in the scientific literature when it comes to randomized controlled trials of brief, manual-based structured programs which address general parenting among the population, and focus on promoting health. A four-session universal health promotion parent group program named All Children in Focus was developed. It aims at promoting parental competence and children’s positive development with the parent–child relationship as the target. There is currently no randomized controlled trial existing of the program. Methods/Design A prospective multicenter randomized wait-list controlled trial is being conducted. Approximately 600 parents with children ranging in age from 3–12 years have been recruited in eleven municipalities and city districts in the County of Stockholm, Sweden. Parents are randomized at baseline to an intervention group, which receives the program directly, or to a waiting-list control group, which participates in the program six months later. Changes in parenting and child health and development are assessed with measures immediately post-intervention and six months after the baseline. Observations of a minor group of parents and children are conducted to explore possible relations between parental reports and observed behaviors, as well as changes in the interaction between parent and child. Further, data collected within the evaluation will also be applied to evaluate the possible cost-effectiveness of the program. Discussion This paper describes a study protocol of a randomized controlled trial. Except for the quantitative outcome measures to evaluate the effectiveness of All Children in Focus, this protocol also describes health economic and qualitative analyses to deepen the knowledge of the program. We further discuss some issues regarding the implementation of the program in municipalities and city districts. Trial registration Current Controlled Trials ISRCTN70202532 PMID:23890316

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

PubMed Central

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

2013-01-01

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

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

Patient Satisfaction with Different Interpreting Methods: A Randomized Controlled Trial

PubMed Central

Leng, Jennifer; Shapiro, Ephraim; Abramson, David; Motola, Ivette; Shield, David C.; Changrani, Jyotsna

2007-01-01

Background Growth of the foreign-born population in the U.S. has led to increasing numbers of limited-English-proficient (LEP) patients. Innovative medical interpreting strategies, including remote simultaneous medical interpreting (RSMI), have arisen to address the language barrier. This study evaluates the impact of interpreting method on patient satisfaction. Methods 1,276 English-, Spanish-, Mandarin-, and Cantonese-speaking patients attending the primary care clinic and emergency department of a large New York City municipal hospital were screened for enrollment in a randomized controlled trial. Language-discordant patients were randomized to RSMI or usual and customary (U&C) interpreting. Patients with language-concordant providers received usual care. Demographic and patient satisfaction questionnaires were administered to all participants. Results 541 patients were language-concordant with their providers and not randomized; 371 were randomized to RSMI, 167 of whom were exposed to RSMI; and 364 were randomized to U&C, 198 of whom were exposed to U&C. Patients randomized to RSMI were more likely than those with U&C to think doctors treated them with respect (RSMI 71%, U&C 64%, p < 0.05), but they did not differ in other measures of physician communication/care. In a linear regression analysis, exposure to RSMI was significantly associated with an increase in overall satisfaction with physician communication/care (β 0.10, 95% CI 0.02–0.18, scale 0–1.0). Patients randomized to RSMI were more likely to think the interpreting method protected their privacy (RSMI 51%, U&C 38%, p < 0.05). Patients randomized to either arm of interpretation reported less comprehension and satisfaction than patients in language-concordant encounters. Conclusions While not a substitute for language-concordant providers, RSMI can improve patient satisfaction and privacy among LEP patients. Implementing RSMI should be considered an important component of a multipronged approach to addressing language barriers in health care. PMID:17957417

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

The Method of Randomization for Cluster-Randomized Trials: Challenges of Including Patients with Multiple Chronic Conditions

PubMed Central

Esserman, Denise; Allore, Heather G.; Travison, Thomas G.

2016-01-01

Cluster-randomized clinical trials (CRT) are trials in which the unit of randomization is not a participant but a group (e.g. healthcare systems or community centers). They are suitable when the intervention applies naturally to the cluster (e.g. healthcare policy); when lack of independence among participants may occur (e.g. nursing home hygiene); or when it is most ethical to apply an intervention to all within a group (e.g. school-level immunization). Because participants in the same cluster receive the same intervention, CRT may approximate clinical practice, and may produce generalizable findings. However, when not properly designed or interpreted, CRT may induce biased results. CRT designs have features that add complexity to statistical estimation and inference. Chief among these is the cluster-level correlation in response measurements induced by the randomization. A critical consideration is the experimental unit of inference; often it is desirable to consider intervention effects at the level of the individual rather than the cluster. Finally, given that the number of clusters available may be limited, simple forms of randomization may not achieve balance between intervention and control arms at either the cluster- or participant-level. In non-clustered clinical trials, balance of key factors may be easier to achieve because the sample can be homogenous by exclusion of participants with multiple chronic conditions (MCC). CRTs, which are often pragmatic, may eschew such restrictions. Failure to account for imbalance may induce bias and reducing validity. This article focuses on the complexities of randomization in the design of CRTs, such as the inclusion of patients with MCC, and imbalances in covariate factors across clusters. PMID:27478520

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

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

PubMed

Gowri, S; Kannan, Sridharan

2017-01-01

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

Using Non-experimental Data to Estimate Treatment Effects

PubMed Central

Stuart, Elizabeth A.; Marcus, Sue M.; Horvitz-Lennon, Marcela V.; Gibbons, Robert D.; Normand, Sharon-Lise T.

2009-01-01

While much psychiatric research is based on randomized controlled trials (RCTs), where patients are randomly assigned to treatments, sometimes RCTs are not feasible. This paper describes propensity score approaches, which are increasingly used for estimating treatment effects in non-experimental settings. The primary goal of propensity score methods is to create sets of treated and comparison subjects who look as similar as possible, in essence replicating a randomized experiment, at least with respect to observed patient characteristics. A study to estimate the metabolic effects of antipsychotic medication in a sample of Florida Medicaid beneficiaries with schizophrenia illustrates methods. PMID:20563313

Social network targeting to maximise population behaviour change: a cluster randomised controlled trial.

PubMed

Kim, David A; Hwong, Alison R; Stafford, Derek; Hughes, D Alex; O'Malley, A James; Fowler, James H; Christakis, Nicholas A

2015-07-11

Information and behaviour can spread through interpersonal ties. By targeting influential individuals, health interventions that harness the distributive properties of social networks could be made more effective and efficient than those that do not. Our aim was to assess which targeting methods produce the greatest cascades or spillover effects and hence maximise population-level behaviour change. In this cluster randomised trial, participants were recruited from villages of the Department of Lempira, Honduras. We blocked villages on the basis of network size, socioeconomic status, and baseline rates of water purification, for delivery of two public health interventions: chlorine for water purification and multivitamins for micronutrient deficiencies. We then randomised villages, separately for each intervention, to one of three targeting methods, introducing the interventions to 5% samples composed of either: randomly selected villagers (n=9 villages for each intervention); villagers with the most social ties (n=9); or nominated friends of random villagers (n=9; the last strategy exploiting the so-called friendship paradox of social networks). Participants and data collectors were not aware of the targeting methods. Primary endpoints were the proportions of available products redeemed by the entire population under each targeting method. This trial is registered with ClinicalTrials.gov, number NCT01672580. Between Aug 4, and Aug 14, 2012, 32 villages in rural Honduras (25-541 participants each; total study population of 5773) received public health interventions. For each intervention, nine villages (each with 1-20 initial target individuals) were randomised, using a blocked design, to each of the three targeting methods. In nomination-targeted villages, 951 (74·3%) of 1280 available multivitamin tickets were redeemed compared with 940 (66·2%) of 1420 in randomly targeted villages and 744 (61·0%) of 1220 in indegree-targeted villages. All pairwise differences in redemption rates were significant (p<0·01) after correction for multiple comparisons. Targeting nominated friends increased adoption of the nutritional intervention by 12·2% compared with random targeting (95% CI 6·9-17·9). Targeting the most highly connected individuals, by contrast, produced no greater adoption of either intervention, compared with random targeting. Introduction of a health intervention to the nominated friends of random individuals can enhance that intervention's diffusion by exploiting intrinsic properties of human social networks. This method has the additional advantage of scalability because it can be implemented without mapping the network. Deployment of certain types of health interventions via network targeting, without increasing the number of individuals targeted or the resources used, could enhance the adoption and efficiency of those interventions, thereby improving population health. National Institutes of Health, The Bill & Melinda Gates Foundation, Star Family Foundation, and the Canadian Institutes of Health Research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Assessments of the quality of randomized controlled trials published in International Journal of Urology from 1994 to 2011.

PubMed

Cho, Hee Ju; Chung, Jae Hoon; Jo, Jung Ki; Kang, Dong Hyuk; Cho, Jeong Man; Yoo, Tag Keun; Lee, Seung Wook

2013-12-01

Randomized controlled trials are one of the most reliable resources for assessing the effectiveness and safety of medical treatments. Low quality randomized controlled trials carry a large bias that can ultimately impair the reliability of their conclusions. The present study aimed to evaluate the quality of randomized controlled trials published in International Journal of Urology by using multiple quality assessment tools. Randomized controlled trials articles published in International Journal of Urology were found using the PubMed MEDLINE database, and qualitative analysis was carried out with three distinct assessment tools: the Jadad scale, the van Tulder scale and the Cochrane Collaboration Risk of Bias Tool. The quality of randomized controlled trials was analyzed by publication year, type of subjects, intervention, presence of funding and whether an institutional review board reviewed the study. A total of 68 randomized controlled trial articles were published among a total of 1399 original articles in International Journal of Urology. Among these randomized controlled trials, 10 (2.70%) were from 1994 to 1999, 23 (4.10%) were from 2000 to 2005 and 35 (4.00%) were from 2006 to 2011 (P = 0.494). On the assessment with the Jadad and van Tulder scale, the numbers and percentage of high quality randomized controlled trials increased over time. The studies that had institutional review board reviews, funding resources or that were carried out in multiple institutions had an increased percentage of high quality articles. The numbers and percentage of high-quality randomized controlled trials published in International Journal of Urology have increased over time. Furthermore, randomized controlled trials with funding resources, institutional review board reviews or carried out in multiple institutions have been found to be of higher quality compared with others not presenting these features. © 2013 The Japanese Urological Association.

Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods.

PubMed

Pham, Quynh; Wiljer, David; Cafazzo, Joseph A

2016-09-09

Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=.021, η(2)=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=.028, η(2)=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=.030, η(2)=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<.01, adjusted r(2)=.33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients.

Optimizing the Primary Prevention of Type-2 Diabetes in Primary Health Care

ClinicalTrials.gov

2017-08-18

Interprofessional Relations; Primary Health Care/Organization & Administration; Diabetes Mellitus, Type 2/Prevention & Control; Primary Prevention/Methods; Risk Reduction Behavior; Randomized Controlled Trial; Life Style

Guidelines for randomized clinical trial protocol content: a systematic review

PubMed Central

2012-01-01

Background All randomized clinical trials (RCTs) require a protocol; however, numerous studies have highlighted protocol deficiencies. Reporting guidelines may improve the content of research reports and, if developed using robust methods, may increase the utility of reports to stakeholders. The objective of this study was to systematically identify and review RCT protocol guidelines, to assess their characteristics and methods of development, and to compare recommendations. Methods We conducted a systematic review of indexed literature (MEDLINE, EMBASE and the Cochrane Methodology Register from inception to September 2010; reference lists; related article features; forward citation searching) and a targeted search of supplementary sources, including a survey of major trial funding agencies in six countries. Records were eligible if they described a content guideline in English or French relevant to RCT protocols. Guidelines were excluded if they specified content for protocols for trials of specific procedures or conditions or were intended to assess trial quality. We extracted guideline characteristics and methods. Content was mapped for a subset of guidelines that described development methods or had institutional endorsement. Results Forty guidelines published in journals, books and institutional reports were included in the review; seven were specific to RCT protocols. Only eight (20%) described development methods which included informal consensus methods, pilot testing and formal validation; no guideline described all of these methods. No guideline described formal consensus methods or a systematic retrieval of empirical evidence to inform its development. The guidelines included a median of 23 concepts per guideline (interquartile range (IQR) = 14 to 34; range = 7 to 109). Among the subset of guidelines (n = 23) for which content was mapped, approximately 380 concepts were explicitly addressed (median concepts per guideline IQR = 31 (24,80); range = 16 to 150); most concepts were addressed in a minority of guidelines. Conclusions Existing guidelines for RCT protocol content varied substantially in their recommendations. Few reports described the methods of guideline development, limiting comparisons of guideline validity. Given the importance of protocols to diverse stakeholders, we believe a systematically developed, evidence-informed guideline for clinical trial protocols is needed. PMID:23006870

Effect of paricalcitol on renin and albuminuria in non-diabetic stage III-IV chronic kidney disease: a randomized placebo-controlled trial

PubMed Central

2013-01-01

Background Vitamin D receptor activators reduce albuminuria, and may improve survival in chronic kidney disease (CKD). Animal studies suggest that these pleiotropic effects of vitamin D may be mediated by suppression of renin. However, randomized trials in humans have yet to establish this relationship. Methods In a randomized, placebo-controlled, double-blinded crossover study, the effect of oral paricalcitol (2 μg/day) was investigated in 26 patients with non-diabetic, albuminuric stage III-IV CKD. After treatment, plasma concentrations of renin (PRC), angiotensin II (AngII) and aldosterone (Aldo) were measured. GFR was determined by 51Cr-EDTA clearance. Assessment of renal NO dependency was performed by infusion of NG-monomethyl-L-arginine (L-NMMA). Albumin excretion rate (AER) was analyzed in 24-h urine and during 51Cr-EDTA clearance. Results Paricalcitol did not alter plasma levels of renin, AngII, Aldo, or urinary excretion of sodium and potassium. A modest reduction of borderline significance was observed in AER, and paricalcitol abrogated the albuminuric response to L-NMMA. Conclusions In this randomized, placebo-controlled trial paricalcitol only marginally decreased AER and did not alter circulating levels of renin, AngII or Aldo. The abrogation of the rise in albumin excretion by paricalcitol during NOS blockade may indicate that favourable modulation of renal NO dependency could be involved in mediating reno-protection and survival benefits in CKD. Trial registration ClinicalTrials.gov identifier: NCT01136564 PMID:23889806

Safety and Efficacy of the ACE-Inhibitor Ramipril in Alport Syndrome: The Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase III EARLY PRO-TECT Alport Trial in Pediatric Patients.

PubMed

Gross, Oliver; Friede, Tim; Hilgers, Reinhard; Görlitz, Anke; Gavénis, Karsten; Ahmed, Raees; Dürr, Ulrike

2012-01-01

Introduction. Retrospective observational data show that ACE-inhibitor therapy delays renal failure and improves life expectancy in Alport patients with proteinuria. The EARLY PRO-TECT Alport trial assesses the safety and efficacy of early therapy onset with ramipril in pediatric Alport patients. Methods and analysis. This double-blind, randomized, placebo-controlled, multicenter phase III trial (NCT01485978; EudraCT-number 2010-024300-10) includes 120 pediatric patients aged 24 months to 18 years with early stages of Alport syndrome (isolated hematuria or microalbuminuria). From March 2012, up to 80 patients will be randomized 1:1 to ramipril or placebo. In the event of disease progression during 3-year treatment, patients are unblinded and ramipril is initiated, if applicable. Approximately 40 patients receive open-label ramipril contributing to the safety database. Primary end-points are "time to progression to next disease level" and "incidence of adverse drug events before disease progression." Treatment effect estimates from the randomized comparison and Alport registry data will be combined in supportive analyses to maximize evidence. Conclusion. Without this trial, ACE inhibitors may become standard off-label treatment in Alport syndrome without satisfactory evidence base. The results are expected to be of relevance for therapy of all pediatric patients with kidney disease, and the trial protocol might serve as a model for other rare pediatric glomerulopathies.

Acupuncture as prophylaxis for menstrual-related migraine: study protocol for a multicenter randomized controlled trial

PubMed Central

2013-01-01

Background Menstrual-related migraine is a common form of migraine affecting >50% of female migraineurs. Acupuncture may be a choice for menstrual-related migraine, when pharmacological prophylaxis is not suitable. However, the efficacy of acupuncture has not been confirmed. We design and perform a randomized controlled clinical trial to evaluate the efficacy of acupuncture compared with naproxen in menstrual-related migraine patients. Methods/Design This is a multicenter, single blind, randomized controlled clinical trial. A total of 184 participants will be randomly assigned to two different groups. Participants will receive verum acupuncture and placebo medicine in the treatment group, while participants in the control group will be treated with sham acupuncture and medicine (Naproxen Sustained Release Tablets). All treatments will be given for 3 months (menstrual cycles). The primary outcome measures are the change of migraine days inside the menstrual cycle and the proportion of responders (defined as the proportion of patients with at least a 50% reduction in the number of menstrual migraine days). The secondary outcome measures are the change of migraine days outside the menstrual cycle, duration of migraine attack, the Visual Analogue Scale (VAS), and intake of acute medication. The assessment will be made at baseline (before treatment), 3 months (menstrual cycles), and 4 months (menstrual cycles) after the first acupuncture session. Discussion The results of this trial will be helpful to supply the efficacy of acupuncture for menstrual-related migraine prophylaxis. Trial registration ISRCTN: ISRCTN57133712 PMID:24195839

Leveraging prognostic baseline variables to gain precision in randomized trials

PubMed Central

Colantuoni, Elizabeth; Rosenblum, Michael

2015-01-01

We focus on estimating the average treatment effect in a randomized trial. If baseline variables are correlated with the outcome, then appropriately adjusting for these variables can improve precision. An example is the analysis of covariance (ANCOVA) estimator, which applies when the outcome is continuous, the quantity of interest is the difference in mean outcomes comparing treatment versus control, and a linear model with only main effects is used. ANCOVA is guaranteed to be at least as precise as the standard unadjusted estimator, asymptotically, under no parametric model assumptions and also is locally semiparametric efficient. Recently, several estimators have been developed that extend these desirable properties to more general settings that allow any real-valued outcome (e.g., binary or count), contrasts other than the difference in mean outcomes (such as the relative risk), and estimators based on a large class of generalized linear models (including logistic regression). To the best of our knowledge, we give the first simulation study in the context of randomized trials that compares these estimators. Furthermore, our simulations are not based on parametric models; instead, our simulations are based on resampling data from completed randomized trials in stroke and HIV in order to assess estimator performance in realistic scenarios. We provide practical guidance on when these estimators are likely to provide substantial precision gains and describe a quick assessment method that allows clinical investigators to determine whether these estimators could be useful in their specific trial contexts. PMID:25872751

High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials

PubMed Central

Berry, Donald A.; Ueno, Naoto T.; Johnson, Marcella M.; Lei, Xiudong; Caputo, Jean; Smith, Dori A.; Yancey, Linda J.; Crump, Michael; Stadtmauer, Edward A.; Biron, Pierre; Crown, John P.; Schmid, Peter; Lotz, Jean-Pierre; Rosti, Giovanni; Bregni, Marco; Demirer, Taner

2011-01-01

Purpose High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer. Methods We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients. Results The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support. Conclusion Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy. PMID:21768454

Impact of a mHealth intervention for peer health workers on AIDS care in rural Uganda: a mixed methods evaluation of a cluster-randomized trial.

PubMed

Chang, Larry W; Kagaayi, Joseph; Arem, Hannah; Nakigozi, Gertrude; Ssempijja, Victor; Serwadda, David; Quinn, Thomas C; Gray, Ronald H; Bollinger, Robert C; Reynolds, Steven J

2011-11-01

Mobile phone access in low and middle-income countries is rapidly expanding and offers an opportunity to leverage limited human resources for health. We conducted a mixed methods evaluation of a cluster-randomized trial exploratory substudy on the impact of a mHealth (mobile phone) support intervention used by community-based peer health workers (PHW) on AIDS care in rural Uganda. 29 PHWs at 10 clinics were randomized by clinic to receive the intervention or not. PHWs used phones to call and text higher level providers with patient-specific clinical information. 970 patients cared for by the PHWs were followed over a 26 month period. No significant differences were found in patients' risk of virologic failure. Qualitative analyses found improvements in patient care and logistics and broad support for the mHealth intervention among patients, clinic staff, and PHWs. Key challenges identified included variable patient phone access, privacy concerns, and phone maintenance.

The CardiAMP Heart Failure trial: A randomized controlled pivotal trial of high-dose autologous bone marrow mononuclear cells using the CardiAMP cell therapy system in patients with post-myocardial infarction heart failure: Trial rationale and study design.

PubMed

Raval, Amish N; Cook, Thomas D; Duckers, Henricus J; Johnston, Peter V; Traverse, Jay H; Abraham, William T; Altman, Peter A; Pepine, Carl J

2018-07-01

Heart failure following myocardial infarction is a common, disabling, and deadly condition. Direct injection of autologous bone marrow mononuclear cells into the myocardium may result in improved functional recovery, relieve symptoms, and improve other cardiovascular outcomes. CardiAMP-HF is a randomized, double-blind, sham-controlled, pivotal trial designed to investigate the safety and efficacy of autologous bone marrow mononuclear cells treatment for patients with medically refractory and symptomatic ischemic cardiomyopathy. The primary end point is change in 6-minute walk distance adjusted for major adverse cardiovascular events at 12 months following treatment. Particularly novel aspects of this trial include a cell potency assay to screen subjects who have bone marrow cell characteristics that suggest a favorable response to treatment, a point-of-care treatment method, a high target dose of 200 million cells, and an efficient transcatheter intramyocardial delivery method that is associated with high cell retention. This novel approach may lead to a new treatment for those with ischemic heart disease suffering from medically refractory heart failure. Copyright © 2018 Elsevier Inc. All rights reserved.

Promoting state health department evidence-based cancer and chronic disease prevention: a multi-phase dissemination study with a cluster randomized trial component

PubMed Central

2013-01-01

Background Cancer and other chronic diseases reduce quality and length of life and productivity, and represent a significant financial burden to society. Evidence-based public health approaches to prevent cancer and other chronic diseases have been identified in recent decades and have the potential for high impact. Yet, barriers to implement prevention approaches persist as a result of multiple factors including lack of organizational support, limited resources, competing emerging priorities and crises, and limited skill among the public health workforce. The purpose of this study is to learn how best to promote the adoption of evidence based public health practice related to chronic disease prevention. Methods/design This paper describes the methods for a multi-phase dissemination study with a cluster randomized trial component that will evaluate the dissemination of public health knowledge about evidence-based prevention of cancer and other chronic diseases. Phase one involves development of measures of practitioner views on and organizational supports for evidence-based public health and data collection using a national online survey involving state health department chronic disease practitioners. In phase two, a cluster randomized trial design will be conducted to test receptivity and usefulness of dissemination strategies directed toward state health department chronic disease practitioners to enhance capacity and organizational support for evidence-based chronic disease prevention. Twelve state health department chronic disease units will be randomly selected and assigned to intervention or control. State health department staff and the university-based study team will jointly identify, refine, and select dissemination strategies within intervention units. Intervention (dissemination) strategies may include multi-day in-person training workshops, electronic information exchange modalities, and remote technical assistance. Evaluation methods include pre-post surveys, structured qualitative phone interviews, and abstraction of state-level chronic disease prevention program plans and progress reports. Trial registration clinicaltrials.gov: NCT01978054. PMID:24330729

Design and challenges for a randomized, multi-site clinical trial comparing the use of service dogs and emotional support dogs in Veterans with post-traumatic stress disorder (PTSD).

PubMed

Saunders, Gabrielle H; Biswas, Kousick; Serpi, Tracey; McGovern, Stephanie; Groer, Shirley; Stock, Eileen M; Magruder, Kathryn M; Storzbach, Daniel; Skelton, Kelly; Abrams, Thad; McCranie, Mark; Richerson, Joan; Dorn, Patricia A; Huang, Grant D; Fallon, Michael T

2017-11-01

Posttraumatic stress disorder (PTSD) is a leading cause of impairments in quality of life and functioning among Veterans. Service dogs have been promoted as an effective adjunctive intervention for PTSD, however published research is limited and design and implementation flaws in published studies limit validated conclusions. This paper describes the rationale for the study design, a detailed methodological description, and implementation challenges of a multisite randomized clinical trial examining the impact of service dogs on the on the functioning and quality of life of Veterans with PTSD. Trial design considerations prioritized participant and intervention (dog) safety, selection of an intervention comparison group that would optimize enrollment in all treatment arms, pragmatic methods to ensure healthy well-trained dogs, and the selection of outcomes for achieving scientific and clinical validity in a Veteran PTSD population. Since there is no blueprint for conducting a randomized clinical trial examining the impact of dogs on PTSD of this size and scope, it is our primary intent that the successful completion of this trial will set a benchmark for future trial design and scientific rigor, as well as guiding researchers aiming to better understand the role that dogs can have in the management of Veterans experiencing mental health conditions such as PTSD. Published by Elsevier Inc.

Traumeel S® for pain relief following hallux valgus surgery: a randomized controlled trial

PubMed Central

2010-01-01

Background In spite of recent advances in post-operative pain relief, pain following orthopedic surgery remains an ongoing challenge for clinicians. We examined whether a well known and frequently prescribed homeopathic preparation could mitigate post-operative pain. Method We performed a randomized, double blind, placebo-controlled trial to evaluate the efficacy of the homeopathic preparation Traumeel S® in minimizing post-operative pain and analgesic consumption following surgical correction of hallux valgus. Eighty consecutive patients were randomized to receive either Traumeel tablets or an indistinguishable placebo, and took primary and rescue oral analgesics as needed. Maximum numerical pain scores at rest and consumption of oral analgesics were recorded on day of surgery and for 13 days following surgery. Results Traumeel was not found superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial, however a transient reduction in the daily maximum post-operative pain score favoring the Traumeel arm was observed on the day of surgery, a finding supported by a treatment-time interaction test (p = 0.04). Conclusions Traumeel was not superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial. A transient reduction in the daily maximum post-operative pain score on the day of surgery is of questionable clinical importance. Trial Registration This study was registered at ClinicalTrials.gov. # NCT00279513 PMID:20380750

Structuring communication relationships for interprofessional teamwork (SCRIPT): a cluster randomized controlled trial

PubMed Central

Zwarenstein, Merrick; Reeves, Scott; Russell, Ann; Kenaszchuk, Chris; Conn, Lesley Gotlib; Miller, Karen-Lee; Lingard, Lorelei; Thorpe, Kevin E

2007-01-01

Background Despite a burgeoning interest in using interprofessional approaches to promote effective collaboration in health care, systematic reviews find scant evidence of benefit. This protocol describes the first cluster randomized controlled trial (RCT) to design and evaluate an intervention intended to improve interprofessional collaborative communication and patient-centred care. Objectives The objective is to evaluate the effects of a four-component, hospital-based staff communication protocol designed to promote collaborative communication between healthcare professionals and enhance patient-centred care. Methods The study is a multi-centre mixed-methods cluster randomized controlled trial involving twenty clinical teaching teams (CTTs) in general internal medicine (GIM) divisions of five Toronto tertiary-care hospitals. CTTs will be randomly assigned either to receive an intervention designed to improve interprofessional collaborative communication, or to continue usual communication practices. Non-participant naturalistic observation, shadowing, and semi-structured, qualitative interviews were conducted to explore existing patterns of interprofessional collaboration in the CTTs, and to support intervention development. Interviews and shadowing will continue during intervention delivery in order to document interactions between the intervention settings and adopters, and changes in interprofessional communication. The primary outcome is the rate of unplanned hospital readmission. Secondary outcomes are length of stay (LOS); adherence to evidence-based prescription drug therapy; patients' satisfaction with care; self-report surveys of CTT staff perceptions of interprofessional collaboration; and frequency of calls to paging devices. Outcomes will be compared on an intention-to-treat basis using adjustment methods appropriate for data from a cluster randomized design. Discussion Pre-intervention qualitative analysis revealed that a substantial amount of interprofessional interaction lacks key core elements of collaborative communication such as self-introduction, description of professional role, and solicitation of other professional perspectives. Incorporating these findings, a four-component intervention was designed with a goal of creating a culture of communication in which the fundamentals of collaboration become a routine part of interprofessional interactions during unstructured work periods on GIM wards. Trial registration Registered with National Institutes of Health as NCT00466297. PMID:17877830

Methodological and Ethical Challenges in a Web-Based Randomized Controlled Trial of a Domestic Violence Intervention

PubMed Central

Valpied, Jodie; Koziol-McLain, Jane; Glass, Nancy; Hegarty, Kelsey

2017-01-01

The use of Web-based methods to deliver and evaluate interventions is growing in popularity, particularly in a health care context. They have shown particular promise in responding to sensitive or stigmatized issues such as mental health and sexually transmitted infections. In the field of domestic violence (DV), however, the idea of delivering and evaluating interventions via the Web is still relatively new. Little is known about how to successfully navigate several challenges encountered by the researchers while working in this area. This paper uses the case study of I-DECIDE, a Web-based healthy relationship tool and safety decision aid for women experiencing DV, developed in Australia. The I-DECIDE website has recently been evaluated through a randomized controlled trial, and we outline some of the methodological and ethical challenges encountered during recruitment, retention, and evaluation. We suggest that with careful consideration of these issues, randomized controlled trials can be safely conducted via the Web in this sensitive area. PMID:28351830

A randomized controlled trial on the efficacy of thoracic CT screening for lung cancer in non-smokers and smokers of <30 pack-years aged 50-64 years (JECS study): research design.

PubMed

Sagawa, Motoyasu; Nakayama, Tomio; Tanaka, Makoto; Sakuma, Tsutomu; Sobue, Tomotaka

2012-12-01

In order to assess the efficacy of lung cancer screening using low-dose thoracic computed tomography, compared with chest roentgenography, in people aged 50-64 years with a smoking history of <30 pack-years, a randomized controlled trial is being conducted in Japan. The screening methods are randomly assigned individually. The duration of this trial is 10 years. In the intervention arm, low-dose thoracic computed tomography is performed for each participant in the first and the sixth years. In the control arm, chest roentgenography is performed for each participant in the first year. The participants in both arms are also encouraged to receive routine lung cancer screening using chest roentgenography annually. The interpretation of radiological findings and the follow-up of undiagnosed nodules are to be carried out according to the guidelines published in Japan. The required sample size is calculated to be 17 500 subjects for each arm.

Emotion Regulation Training for Adolescents with Borderline Personality Disorder Traits: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Schuppert, H. Marieke; Timmerman, Marieke E.; Bloo, Josephine; van Gemert, Tonny G.; Wiersema, Herman M.; Minderaa, Ruud B.; Emmelkamp, Paul M. G.; Nauta, Maaike H.

2012-01-01

Objective: To evaluate the effectiveness of Emotion Regulation Training (ERT), a 17-session weekly group training for adolescents with borderline personality disorder (BPD) symptoms. Method: One hundred nine adolescents with borderline traits (73% meeting the full criteria for BPD) were randomized to treatment as usual only (TAU) or ERT + TAU.…

Mentalization-Based Treatment for Self-Harm in Adolescents: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Rossouw, Trudie I.; Fonagy, Peter

2012-01-01

Objective: We examined whether mentalization-based treatment for adolescents (MBT-A) is more effective than treatment as usual (TAU) for adolescents who self-harm. Method: A total of 80 adolescents (85% female) consecutively presenting to mental health services with self-harm and comorbid depression were randomly allocated to either MBT-A or TAU.…

A Randomized, Controlled Trial of Integrated Home-School Behavioral Treatment for ADHD, Predominantly Inattentive Type

ERIC Educational Resources Information Center

Pfiffner, Linda J.; Mikami, Amori Yee; Huang-Pollock, Cynthia; Easterlin, Barbara; Zalecki, Christine; McBurnett, Keith

2007-01-01

Objective: To evaluate the efficacy of a behavioral psychosocial treatment integrated across home and school (Child Life and Attention Skills Program) with attention-deficit/hyperactivity disorder (ADHD) predominantly inattentive type (ADHD-I). Method: Sixty-nine children ages 7 to 11 years were randomized to the Child Life and Attention Skills…

Randomized Clinical Trial of Cognitive Behavioral Therapy (CBT) versus Acceptance and Commitment Therapy (ACT) for Mixed Anxiety Disorders

ERIC Educational Resources Information Center

Arch, Joanna J.; Eifert, Georg H.; Davies, Carolyn; Vilardaga, Jennifer C. Plumb; Rose, Raphael D.; Craske, Michelle G.

2012-01-01

Objective: Randomized comparisons of acceptance-based treatments with traditional cognitive behavioral therapy (CBT) for anxiety disorders are lacking. To address this gap, we compared acceptance and commitment therapy (ACT) to CBT for heterogeneous anxiety disorders. Method: One hundred twenty-eight individuals (52% female, mean age = 38, 33%…

A Randomized Trial of Brief Interventions for Problem and Pathological Gamblers

ERIC Educational Resources Information Center

Petry, Nancy M.; Weinstock, Jeremiah; Ledgerwood, David M.; Morasco, Benjamin

2008-01-01

Limited research exists regarding methods for reducing problem gambling. Problem gamblers (N = 180) were randomly assigned to assessment only control, 10 min of brief advice, 1 session of motivational enhancement therapy (MET), or 1 session of MET plus 3 sessions of cognitive-behavioral therapy. Gambling was assessed at baseline, at 6 weeks, and…

A Randomized Placebo-Controlled Trial of a School-Based Depression Prevention Program.

ERIC Educational Resources Information Center

Merry, Sally; McDowell, Heather; Wild, Chris J.; Bir, Julliet; Cunliffe, Rachel

2004-01-01

Objective: To conduct a placebo-controlled study of the effectiveness of a universal school-based depression prevention program. Method: Three hundred ninety-two students age 13 to 15 from two schools were randomized to intervention (RAP-Kiwi) and placebo programs run by teachers. RAP-Kiwi was an 11-session manual-based program derived from…

Bereaved Adults with Intellectual Disabilities: A Combined Randomized Controlled Trial and Qualitative Study of Two Community-Based Interventions

ERIC Educational Resources Information Center

Dowling, S.; Hubert, J.; White, S.; Hollins, S.

2006-01-01

Background: Bereaved adults with intellectual disabilities are known to experience prolonged and atypical grief which is often unrecognized. The aim of this project was to find an effective way to improve mental health and behavioural outcomes. Methods: Subjects were randomized to two different therapeutic interventions: traditional counselling by…

The Efficacy of Early Language Intervention in Mainstream School Settings: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Fricke, Silke; Burgoyne, Kelly; Bowyer-Crane, Claudine; Kyriacou, Maria; Zosimidou, Alexandra; Maxwell, Liam; Lervåg, Arne; Snowling, Margaret J.; Hulme, Charles

2017-01-01

Background: Oral language skills are a critical foundation for literacy and more generally for educational success. The current study shows that oral language skills can be improved by providing suitable additional help to children with language difficulties in the early stages of formal education. Methods: We conducted a randomized controlled…

Gender Differences in the Maintenance of Response to Cognitive Behavior Therapy for Posttraumatic Stress Disorder

ERIC Educational Resources Information Center

Felmingham, Kim L.; Bryant, Richard A.

2012-01-01

Objective: To examine potential differential responses in men and women to cognitive behavior therapy for posttraumatic stress disorder (PTSD). Method: Fifty-two men and 56 women diagnosed with PTSD participated in randomized controlled trials of cognitive behavior therapy for PTSD. Participants were randomly allocated to either (a) exposure-only…

Vestibular Stimulation for ADHD: Randomized Controlled Trial of Comprehensive Motion Apparatus

ERIC Educational Resources Information Center

Clark, David L.; Arnold, L. Eugene; Crowl, Lindsay; Bozzolo, Hernan; Peruggia, Mario; Ramadan, Yaser; Bornstein, Robert; Hollway, Jill A.; Thompson, Susan; Malone, Krista; Hall, Kristy L.; Shelton, Sara B.; Bozzolo, Dawn R.; Cook, Amy

2008-01-01

Objective: This research evaluates effects of vestibular stimulation by Comprehensive Motion Apparatus (CMA) in ADHD. Method: Children ages 6 to 12 (48 boys, 5 girls) with ADHD were randomized to thrice-weekly 30-min treatments for 12 weeks with CMA, stimulating otoliths and semicircular canals, or a single-blind control of equal duration and…

A Randomized Trial of Longitudinal Effects of Low-Intensity Responsivity Education/Prelinguistic Milieu Teaching

ERIC Educational Resources Information Center

Warren, Steven F.; Fey, Marc E.; Finestack, Lizbeth, H.; Brady, Nancy C.; Bredin-Oja, Shelley L.; Fleming, Kandace K.

2008-01-01

Purpose: To evaluate the longitudinal effects of a 6-month course of responsivity education (RE)/prelinguistic milieu teaching (PMT) for young children with developmental delay. Method: Fifty-one children, age 24-33 months, with fewer than 10 expressive words were randomly assigned to early-treatment/no-treatment groups. All treatment was added as…

Weight Management in Adults with Intellectual and Developmental Disabilities: A Randomized Controlled Trial of Two Dietary Approaches

ERIC Educational Resources Information Center

Ptomey, Lauren T.; Saunders, Richard R.; Saunders, Muriel; Washburn, Richard A.; Mayo, Matthew S.; Sullivan, Debra K.; Gibson, Cheryl A.; Goetz, Jeannine R.; Honas, Jeff J.; Willis, Erik A.; Danon, Jessica C.; Krebill, Ron; Donnelly, Joseph E.

2018-01-01

Background: The prevalence of obesity among individuals with intellectual and developmental disabilities (IDD) is equal to or greater than the general population. Methods: Overweight/obese adults (BMI =25 kg/m2) with mild-to-moderate intellectual and developmental disabilities were randomized to an enhanced stop light diet…

Reducing Sexual Risk Behaviors for HIV/STDs in Women with Alcohol Use Disorders

ERIC Educational Resources Information Center

Langhorst, Diane M.; Choi, Y. Joon; Keyser-Marcus, Lori; Svikis, Dace S.

2012-01-01

Objective: A pilot randomized clinical trial (RCT) examined effectiveness of HIV/STD Safer Sex Skills Building + Alcohol (SSB+A) intervention for women with Alcohol Use Disorders (AUDs) in a residential treatment setting. Method: After randomizing thirty-six women with AUDs and reporting having intercourse with a male partner in the past 180 days…

A critical appraisal of the reporting quality of published randomized controlled trials in the fall injuries.

PubMed

Asghari Jafarabadi, Mohammad; Sadeghi-Bazrgani, Homayoun; Dianat, Iman

2018-06-01

To evaluate the quality of reporting in published randomized controlled trials (RTCs) in the field of fall injuries. The 188 RTCs published between 2001 and 2011, indexed in EMBASE and Medline databases were extracted through searching by appropriate keywords and EMTree classification terms. The evaluation trustworthiness was assured through parallel evaluations of two experts in epidemiology and biostatistics. About 40%-75% of papers had problems in reporting random allocation method, allocation concealment, random allocation implementation, blinding and similarity among groups, intention to treat and balancing benefits and harms. Moreover, at least 10% of papers inappropriately/not reported the design, protocol violations, sample size justification, subgroup/adjusted analyses, presenting flow diagram, drop outs, recruitment time, baseline data, suitable effect size on outcome, ancillary analyses, limitations and generalizability. Considering the shortcomings found and due to the importance of the RCTs for fall injury prevention programmes, their reporting quality should be improved.

Collaborative Care for Older Adults with low back pain by family medicine physicians and doctors of chiropractic (COCOA): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Low back pain is a prevalent and debilitating condition that affects the health and quality of life of older adults. Older people often consult primary care physicians about back pain, with many also receiving concurrent care from complementary and alternative medicine providers, most commonly doctors of chiropractic. However, a collaborative model of treatment coordination between these two provider groups has yet to be tested. The primary aim of the Collaborative Care for Older Adults Clinical Trial is to develop and evaluate the clinical effectiveness and feasibility of a patient-centered, collaborative care model with family medicine physicians and doctors of chiropractic for the treatment of low back pain in older adults. Methods/design This pragmatic, pilot randomized controlled trial will enroll 120 participants, age 65 years or older with subacute or chronic low back pain lasting at least one month, from a community-based sample in the Quad-Cities, Iowa/Illinois, USA. Eligible participants are allocated in a 1:1:1 ratio to receive 12 weeks of medical care, concurrent medical and chiropractic care, or collaborative medical and chiropractic care. Primary outcomes are self-rated back pain and disability. Secondary outcomes include general and functional health status, symptom bothersomeness, expectations for treatment effectiveness and improvement, fear avoidance behaviors, depression, anxiety, satisfaction, medication use and health care utilization. Treatment safety and adverse events also are monitored. Participant-rated outcome measures are collected via self-reported questionnaires and computer-assisted telephone interviews at baseline, and at 4, 8, 12, 24, 36 and 52 weeks post-randomization. Provider-rated expectations for treatment effectiveness and participant improvement also are evaluated. Process outcomes are assessed through qualitative interviews with study participants and research clinicians, chart audits of progress notes and content analysis of clinical trial notes. Discussion This pragmatic, pilot randomized controlled trial uses a mixed method approach to evaluate the clinical effectiveness, feasibility, and participant and provider perceptions of collaborative care between medical doctors and doctors of chiropractic in the treatment of older adults with low back pain. Trial registration This trial registered in ClinicalTrials.gov on 04 March 2011 with the ID number of NCT01312233. PMID:23324133

Endovascular therapy for acute ischemic stroke.

PubMed

Broderick, Joseph P

2009-03-01

To review advances in endovascular therapy for acute ischemic stroke. Data from primate studies, randomized studies of intravenous recombinant tissue-type plasminogen activator, and nonrandomized and randomized studies of endovascular therapy were reviewed. Clinical trial data demonstrate the superiority of endovascular treatment with thrombolytic medication or mechanical methods to reopen arteries compared with control patients from the PROACT II Trial treated with heparin alone. However, these same clinical trials, as well as preclinical primate models, indicate that recanalization, whether by endovascular approaches or standard-dose recombinant tissue-type plasminogen activator, is unlikely to improve clinical outcome after a certain time point. Although the threshold beyond which reperfusion has no or little benefit has yet to be conclusively defined, accumulated data to this point indicate an overall threshold of approximately 6 to 7 hours. In addition, although the risk of symptomatic intracerebral hemorrhage is similar in trials of intravenous lytics and endovascular approaches, endovascular approaches have distinctive risk profiles that can impact outcome. The treatment of acute ischemic stroke is evolving with new tools to reopen arteries and salvage the ischemic brain. Ongoing randomized trials of these new approaches are prerequisite next steps to demonstrate whether reperfusion translates into clinical effectiveness. Physiologic time to reperfusion will remain critical no matter which tools prove most effective and safest.

Insufflation with Humidified and Heated Carbon Dioxide in Short-Term Laparoscopy: A Double-Blinded Randomized Controlled Trial

PubMed Central

Herrmann, Anja; De Wilde, Rudy Leon

2015-01-01

Background. We tested the hypothesis that warm-humidified carbon dioxide (CO2) insufflation would reduce postoperative pain and morphine requirement compared to cold-dry CO2 insufflation. Methods. A double-blinded, randomized, controlled trial was conducted to compare warm, humidified CO2 and cold-dry CO2. Patients with benign uterine diseases were randomized to either treatment (n = 48) or control (n = 49) group during laparoscopically assisted vaginal hysterectomy. Primary endpoints of the study were rest pain, movement pain, shoulder-tip pain, and cough pain at 2, 4, 6, 24, and 48 hours postoperatively, measured by visual analogue scale. Secondary outcomes were morphine consumption, rejected boli, temperature change, recovery room stay, and length of hospital stay. Results. There were no significant differences in all baseline characteristics. Shoulder-tip pain at 6 h postoperatively was significantly reduced in the intervention group. Pain at rest, movement pain, and cough pain did not differ. Total morphine consumption and rejected boli at 24 h postoperatively were significantly higher in the control group. Temperature change, recovery room stay, and length of hospital were similar. Conclusions. Warm, humidified insufflation gas significantly reduces postoperative shoulder-tip pain as well as morphine demand. This trial is registered with Clinical Trial Registration Number   DRKS00003853 (German Clinical Trials Register (DRKS)). PMID:25722977

Recruitment of participants to a clinical trial of botanical therapy for benign prostatic hyperplasia.

PubMed

Lee, Jeannette Y; Foster, Harris E; McVary, Kevin T; Meleth, Sreelatha; Stavris, Karen; Downey, Joe; Kusek, John W

2011-05-01

The timely recruitment of study participants is a critical component of successful trials. Benign prostatic hyperplasia (BPH), a common nonmalignant urologic condition among older men, is characterized by lower urinary tract symptoms (LUTS). Successful recruitment methods for a trial of medical therapy for BPH, Medical Therapy of Prostate Symptoms (MTOPS), were mass mailing and advertising. The Complementary and Alternative Medicines Trial for Urological Symptoms (CAMUS) was designed to evaluate a botanical therapy, saw palmetto, for the treatment of BPH. The objective of this study was to evaluate recruitment strategies for CAMUS and to contrast the baseline characteristics of CAMUS participants with those recruited to a similar trial using conventional medical therapy. CAMUS is a randomized, double-blind, placebo-controlled trial designed to evaluate the effects of saw palmetto given at escalating doses over an 18-month period on relief from LUTS. The target enrollment goal was 350 men with LUTS from 11 clinical centers over a 12-month period. The recruitment techniques used and participants contacted, screened, and randomized through each technique were obtained from the clinical centers. Baseline characteristics of the CAMUS participants were compared with participants in the MTOPS trial who met the CAMUS eligibility criteria for LUTS. The target enrollment goal was achieved in 11 months. The overall monthly recruitment rate per site was 3.7 and ranged from 2.4 to 8.0. The most successful recruitment methods were mass mailing and advertising, which accounted for 39% and 35% of the study participants, respectively. In comparison to MTOPS participants, CAMUS participants were younger, more highly educated, more diverse, and had less severe urinary symptoms. Successful recruitment methods for CAMUS were similar to those in MTOPS. The use of botanical therapy attracted a less symptomatic and more educated study population.

Selecting promising treatments in randomized Phase II cancer trials with an active control.

PubMed

Cheung, Ying Kuen

2009-01-01

The primary objective of Phase II cancer trials is to evaluate the potential efficacy of a new regimen in terms of its antitumor activity in a given type of cancer. Due to advances in oncology therapeutics and heterogeneity in the patient population, such evaluation can be interpreted objectively only in the presence of a prospective control group of an active standard treatment. This paper deals with the design problem of Phase II selection trials in which several experimental regimens are compared to an active control, with an objective to identify an experimental arm that is more effective than the control or to declare futility if no such treatment exists. Conducting a multi-arm randomized selection trial is a useful strategy to prioritize experimental treatments for further testing when many candidates are available, but the sample size required in such a trial with an active control could raise feasibility concerns. In this study, we extend the sequential probability ratio test for normal observations to the multi-arm selection setting. The proposed methods, allowing frequent interim monitoring, offer high likelihood of early trial termination, and as such enhance enrollment feasibility. The termination and selection criteria have closed form solutions and are easy to compute with respect to any given set of error constraints. The proposed methods are applied to design a selection trial in which combinations of sorafenib and erlotinib are compared to a control group in patients with non-small-cell lung cancer using a continuous endpoint of change in tumor size. The operating characteristics of the proposed methods are compared to that of a single-stage design via simulations: The sample size requirement is reduced substantially and is feasible at an early stage of drug development.

Bias, precision and statistical power of analysis of covariance in the analysis of randomized trials with baseline imbalance: a simulation study

PubMed Central

2014-01-01

Background Analysis of variance (ANOVA), change-score analysis (CSA) and analysis of covariance (ANCOVA) respond differently to baseline imbalance in randomized controlled trials. However, no empirical studies appear to have quantified the differential bias and precision of estimates derived from these methods of analysis, and their relative statistical power, in relation to combinations of levels of key trial characteristics. This simulation study therefore examined the relative bias, precision and statistical power of these three analyses using simulated trial data. Methods 126 hypothetical trial scenarios were evaluated (126 000 datasets), each with continuous data simulated by using a combination of levels of: treatment effect; pretest-posttest correlation; direction and magnitude of baseline imbalance. The bias, precision and power of each method of analysis were calculated for each scenario. Results Compared to the unbiased estimates produced by ANCOVA, both ANOVA and CSA are subject to bias, in relation to pretest-posttest correlation and the direction of baseline imbalance. Additionally, ANOVA and CSA are less precise than ANCOVA, especially when pretest-posttest correlation ≥ 0.3. When groups are balanced at baseline, ANCOVA is at least as powerful as the other analyses. Apparently greater power of ANOVA and CSA at certain imbalances is achieved in respect of a biased treatment effect. Conclusions Across a range of correlations between pre- and post-treatment scores and at varying levels and direction of baseline imbalance, ANCOVA remains the optimum statistical method for the analysis of continuous outcomes in RCTs, in terms of bias, precision and statistical power. PMID:24712304

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.

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