Clinical trials : journal of the Society for Clinical Trials
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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 Multicenter Study
A study design to assess the safety and efficacy of on-pump versus off-pump coronary bypass grafting: the ROOBY trial.
Since the late 1960s, coronary artery bypass graft (CABG-only) procedures were traditionally performed using a heart-lung machine on an arrested heart (on-pump). Over the past decade, an increasing number CABG-only procedures were performed on a beating heart (off-pump). Advocates of the off-pump approach expect to reduce many of the adverse side effects related to using the heart-lung machine, while advocates for the on-pump procedure raise concerns related to graft patency rates and long-term event-free survival for the off-pump technique. ⋯ The study design presented allows for a balanced and fair assessment of the on-pump and off-pump CABG procedures across a diversity of clinical outcomes and resource use metrics. Its results have the potential to influence clinical cardiac surgical practice in the future.
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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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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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Traditionally, phase I clinical trial designs are based upon one predefined course of treatment while varying among patients the dose given at each administration. In actual medical practice, patients receive a schedule comprised of several courses of treatment, and some patients may receive one or more dose reductions or delays during treatment. Consequently, the overall risk of toxicity for each patient is a function of both actual schedule of treatment and the differing doses used at each adminstration. ⋯ Our design is the first for phase I clinical trials that is sufficiently flexible and practical to truly reflect clinical practice by varying both dose and the timing and number of administrations given to each patient.