Adaptive designs in clinical trials: why use them, and how to run and report them

Adaptive designs can make clinical trials more flexible by utilising results accumulating in the trial to modify the trial’scourse in accordance with pre-specified rules. Trials with an adaptive design are often more efficient, informative andethical than trials with a traditional fixed design since they often make better use of resources such as time andmoney, and might require fewer participants. Adaptive designs can be applied across all phases of clinical research,from early-phase dose escalation to confirmatory trials. The pace of the uptake of adaptive designs in clinical research,however, has remained well behind that of the statistical literature introducing new methods and highlighting theirpotential advantages. We speculate that one factor contributing to this is that the full range of adaptations availableto trial designs, as well as their goals, advantages and limitations, remains unfamiliar to many parts of the clinicalcommunity. Additionally, the term adaptive design has been misleadingly used as an all-encompassing label to referto certain methods that could be deemed controversial or that have been inadequately implemented.We believe that even if the planning and analysis of a trial is undertaken by an expert statistician, it is essential that theinvestigators understand the implications of using an adaptive design, for example, what the practical challenges are,what can (and cannot) be inferred from the results of such a trial, and how to report and communicate the results.This tutorial paper provides guidance on key aspects of adaptive designs that are relevant to clinical triallists. Weexplain the basic rationale behind adaptive designs, clarify ambiguous terminology and summarise the utility andpitfalls of adaptive designs. We discuss practical aspects around funding, ethical approval, treatment supply andcommunication with stakeholders and trial participants. Our focus, however, is on the interpretation and reporting ofresults from adaptive design trials, which we consider vital for anyone involved in medical research. We emphasise thegeneral principles of transparency and reproducibility and suggest how best to put them into practice.