Adding flexibility to clinical trial designs: an example-based guide to the practical use of adaptive designs

摘要

In a traditional clinical trial, the design is fixed in advance, the study is carried out, and the data analysed after completion [1]. In contrast, adaptive designs pre-plan possible modifications on the basis of the data accumulating over the course of the trial as part of the trial protocol [2]. We consider designs that allow for modifications of the trial such as the sample size, the number of treatments, or the allocation ratio to different arms. We do not consider options such as stopping early due to failure to meet operational criteria or excessive safety events, although adaptive designs for some of these do also exist [3]. Adaptive design methodology has been around for more than 25 years [4], with some methods such as group sequential designs being even older [5].