Taking the long view: how to design a series of Phase III trials to maximize cumulative therapeutic benefit.

Clinical Trials : Journal of the Society for Clinical Trials
Marie-Cécile Le DeleyDaniel Sargent

Abstract

Traditional clinical trial designs strive to definitively establish the superiority of an experimental treatment, which results in risk-adverse criteria and large sample sizes. Increasingly, common cancers are recognized as consisting of small subsets with specific aberrations for targeted therapy, making large trials infeasible. To compare the performance of different trial design strategies over a long-term research horizon. We simulated a series of two-treatment superiority trials over 15 years using different design parameters. Trial parameters examined included the number of positive trials to establish superiority (one-trial vs. two-trial rule), α level (2.5%-50%), and the number of trials in the 15-year period, K (thus, trial sample size). The design parameters were evaluated for different disease scenarios, accrual rates, and distributions of treatment effect. Metrics used included the overall survival gain at a 15-year horizon measured by the hazard ratio (HR), year 15 versus year 0. We also computed the expected total survival benefit and the risk of selecting as new standard of care at year 15 a treatment inferior to the initial control treatment, P(detrimental effect). Expected survival benefits over the 15-year hor...Continue Reading

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Citations

Feb 2, 2015·The Lancet Oncology·Michelle K WilsonAmit M Oza
Apr 17, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Stefan SleijferLillian L Siu
Jul 3, 2016·Reproductive Sciences·Peter A W RogersUNKNOWN WES/WERF Consortium for Research Priorities in Endometriosis
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Feb 1, 2017·Reproductive Sciences·A W PeterUNKNOWN WES/WERF Consortium for Research Priorities in Endometriosis

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