Adaptive designs: The Swiss Army knife among clinical trial designs?

Abstract

There has been considerable progress in the development and implementation of adaptive designs over the past 30 years. A major driver for this class of novel designs is the possibility to increase the information value of clinical trial data to enable better decisions, leading to more efficient drug development processes and improved late-stage success rates. In the first part of this article, we review the development of adaptive designs from different perspectives. We trace back key historical papers, report on landmark adaptive design clinical trials, review major cross-industry collaborations, and highlight key regulatory guidance documents. In the second, more technical part of this article, we address the question of whether it is possible to define factors which guide the choice between a fixed or an adaptive design for a given trial. We show that in non-linear regression models with a moderate variance of the responses, the first-stage sample size of an adaptive design should be chosen sufficiently large in order to address variability in the interim parameter estimate. In conclusion, the choice between an adaptive and a fixed design depends in a sensitive manner on the specific statistical problem under investigation.