Using simulation to optimize adaptive trial designs: applications in learning and confirmatory phase trials

Failures in Phase III clinical trials have a major impact on escalating drug development costs. Clinical trial simulation can improve decisions made in learning Phase I and Phase II studies, leading to better designs and reduced chance of failure in high-cost, confirmatory Phase III trials. In adaptive design trials – which use early findings to modify the trial toward the most promising dose, sample size or patient population – simulation is instrumental in guiding selection of optimal design modifications. In this article, the authors present case studies demonstrating the benefits of simulations to identify maximum tolerated dose in Phase I, define dose–response relationships in Phase II, and determine the best type and timing of interim analyses in Phase III.