Clinical trials : journal of the Society for Clinical Trials
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The decision to terminate a controlled clinical trial at the time of an interim analysis is perhaps best made by weighing the value of the likely additional information to be gained if further subjects are enrolled against the various costs of that further enrollment. The most commonly used statistical plans for interim analysis (eg, O'Brien-Fleming), however, are based on a frequentist approach that makes no such comparison. A two-armed Bayesian decision-theoretic clinical trial design is developed for a disease with two possible outcomes, incorporating a quadratic decision loss function and using backward induction to quantify the cost of future enrollment. ⋯ Our Bayesian designs allow interpretation of the final results along either Bayesian or frequentist lines. For the Bayesian, they minimize the total cost and allow the direct calculation of the probability density function for the difference in efficacy. For the frequentist, they have well-characterized type I and II error rates and in some cases lead to a reduction in the mean sample size.
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The Women's Health Initiative (WHI) randomized trial of estrogen plus progestin (E + P) was terminated early based on an assessment of harms exceeding benefits for disease prevention. The results contravened prevailing wisdom and a large body of literature regarding benefits of menopausal hormone therapy. The results and their interpretation have been the subject of considerable debate. ⋯ Developing a formal trial monitoring plan with a view towards influencing clinical practice is useful for creating consensus among DSMB members regarding the evidence that would justify stopping a trial and the framework to be used to address statistical complexities. Departures from design assumptions typically occur. These reinforce the role of the DSMB in exercising their judgment, and the judicious adaptation of these statistical guidelines in monitoring and reporting trials. In communicating the results in such circumstances, priority should be given to presenting as fair, accurate and transparent a view of the data and findings as current methods and technology allow.
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Randomized Controlled Trial
Quality assurance questionnaire for professionals fails to improve the quality of informed consent.
The informed consent process for research warrants improvement but approaches designed to enhance informed consent need testing in the context of actual clinical research. ⋯ Despite prior beliefs, a standardized quality assurance tool do not enhance informed consent in actual clinical trials. Future research is needed to rigorously evaluate proposed methods to enhance informed consent prior to widespread introduction.
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Sample size decisions for clinical trials should be taken in such a way as to maximize informed choice by reducing scientific uncertainty about the consequences of an intervention. ⋯ The approach is a pragmatic aid to trial design in settings where patient preference drives the choice between alternative treatments.
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The analysis of clinical trials with dropout usually assumes the missing data are ;missing at random', i.e. given an individual's past observed data, their probability of dropout does not depend on their present outcome. However, in many settings this assumption is implausible, so it is sensible to assess the robustness of conclusions to departures from missing at random. ⋯ Our proposed approach allows for the greater uncertainty introduced by missing data that are potentially informatively missing. It can therefore claim to be a truly conservative method, unlike methods such as ;last observation carried forward'. It is practical and accessible to non-statisticians. It should be considered as part of the design and analysis of future clinical trials.