Abstract

For the past few decades, there has been considerable interest among pharmaceutical and other medical product developers in adaptive design clinical trials, in which knowledge learned from data of an ongoing trial affects design features or analysis of the study. Following the initial release of the FDA Draft Guidance “Adaptive Design Clinical Trials for Drugs and Biologics” in early 2010, there have been high expectations of an increase in regulatory submissions involving adaptive design features, particularly for trials that are intended to provide substantial evidence for product registration. More recently, the finalized FDA Guidance on Adaptive Designs for Medical Device Clinical Studies lays out the principles of conducting adaptive design clinical trials. The passed 21st Century Cures Act encourages a broader use of adaptive design in clinical studies. Despite all these, there remain some concerns and questions regarding statistical analyses and operational challenges in conducting adaptive design clinical trials. In this article, we provide some case studies reviewed at the FDA and general considerations for developing proposals for adaptive design clinical trials.