Interpreting the Regulatory Perspective on Adaptive Designs

Abstract

ABSTRACTThe Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) released a draft guidance (DG) on adaptive clinical trials (ACT) for drugs and biologics in February, 2010. In May, 2016, FDA Center for Devices and Radiological Heath (CDRH) and CBER issued the final guidance (FG) on adaptive medical device trials. The purpose of the FG is to provide clarity on how to plan and implement adaptive designs (AD) for clinical studies used in medical device development and to further encourage companies to use AD.While both the device FG and drug and biologics DG provided positive review of ACT, the FG position was stronger, stating that the FDA centers “further encourage companies to consider the use of AD in their clinical trials.” Both guidances emphasize the importance of preplanning to avoid Type I error inflation, strict following of the plan to minimize operational bias, and frequent and early interactions with the FDA to ensure the success of the planned ACT. Both guidances emphasize the utilities of clinical trial simulations in design of ACT and in analysis of adaptive trial data. In this article, we present our understanding the guidances.