Controlled clinical trials
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Control Clin Trials · Dec 2004
ReviewMeasuring treatment impact: a review of patient-reported outcomes and other efficacy endpoints in approved product labels.
The term "patient-reported outcomes" (PROs) has evolved to include any endpoint derived from patient reports, whether collected in the clinic, in a diary, or by other means, including single-item outcome measures, event logs, symptom reports, formal instruments to measure health-related quality of life (HRQL), health status, adherence, and satisfaction with treatment. This term coincides with the explicit interest from drug development researchers and regulatory authorities in the appropriate utilization and reporting of treatment impact measures. ⋯ PROs, although quite variable as a class of study endpoints, were found to have a significant role in the development and evaluation of new medicines. More formal guidance from the FDA about use of such measures along with continued collaboration by PRO researchers to develop and disseminate standards will enhance the appropriate use of PROs in future drug development and labeling.
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Control Clin Trials · Dec 2004
ReviewAn analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia.
The effect of funding source on the outcome of randomized controlled trials has been investigated in several medical disciplines; however, psychiatry has been largely excluded from such analyses. In this article, randomized controlled trials of second generation antipsychotics in schizophrenia are reviewed and analyzed with respect to funding source (industry vs. non-industry funding). ⋯ While the retrospective design of the study limits the strength of the findings, the data suggest that industry bias may occur in randomized controlled trials in schizophrenia. There appears to be several sources by which bias may enter clinical research, including trial design, control of data analysis and multiplicity/redundancy of trials.
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Control Clin Trials · Oct 2003
ReviewA group sequential, response-adaptive design for randomized clinical trials.
There has been considerable methodological research on response-adaptive designs for clinical trials but they have seldom been used in practice. The many reasons for this are summarized in an article by Rosenberger and Lachin, but the two main reasons generally cited are logistical difficulties and the potential for bias due to selection effects, "drift" in patient characteristics or risk factors over time, and other sources. Jennison and Turnbull consider a group sequential, response-adaptive design for continuous outcome variables that partially addresses these concerns while at the same time allowing for early stopping. ⋯ Limitations, such as the impact of delays in observing outcomes, are discussed, as well as areas for further research. We conclude that responsive adaptive designs may be useful for some purposes, particularly in the presence of large treatment effects, although allowing early stopping minimizes the benefits. If such a design is undertaken, the randomization and analysis should be stratified in order to avoid bias due to time trends.
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Control Clin Trials · Dec 1997
ReviewClinical trials with multiple outcomes: a statistical perspective on their design, analysis, and interpretation.
This article tackles both practical and statistical issues in the handling of multiple outcomes in clinical trials, with relevance to trial design, analysis, and reporting. Specific topics illustrated by examples include: the advantage of prespecifying priorities amongst outcomes and analyses, corrections for multiple significance testing and their limited value, problems with adverse event data, the use of a single global test of significance for clinically related outcomes, the use of a combined outcome for clinical event data, and the value of exploring interrelationships amongst outcomes. The problems in handling multiple outcomes are enhanced by trials being too small, dichotomous attitudes (is the trial "positive" or not?), obsession with p-values, and the manipulative instincts of human nature. While predeclarations of priorities in analysis and reporting of multiple outcomes are important in suppressing distortive claims, it would be unfortunate if too inflexible an approach suppressed unpredictable findings from being seriously considered.
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Control Clin Trials · Dec 1997
Review Comparative StudyMeta-analysis of randomized trials: looking back and looking ahead.
Meta-analyses as currently practiced are usually retrospective. They can be made more rigorous by developing a protocol that incorporates prospectively the elements that are usually necessary in a well-designed trial. ⋯ Once the large trials have been completed, they could be brought together within the framework of a meta-analysis to estimate the overall treatment effect with greater confidence and to explore the effects in various subgroups. This article explores the value and limitations of meta-analyses and suggests ways of improving their conduct and interpretation.