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Adaptive trial designs: what are multiarm, multistage trials?
  1. Gerard Cathal Millen1,
  2. Christina Yap2,3
  1. 1Paediatric Oncology, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, UK
  2. 2Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, University of Birmingham College of Medical and Dental Sciences, Birmingham, Birmingham, UK
  3. 3Clinical Trials and Statistics Unit, Institute of Cancer Research, London, UK
  1. Correspondence to Dr Gerard Cathal Millen, Paediatric Oncology, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, B4 6NH, UK; g.millen{at}nhs.net

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Introduction

Clinical trials can be separated into phase I (dose finding and safety), phase II (activity or early efficacy), phase III (efficacy compared with current standard of care) and occasionally phase IV (postmarketing studies). A new compound would usually have to go through phase I–III studies sequentially with all of the financial and regulatory hurdles this poses. A recent study has estimated that only 13.8% of compounds tested will be successful in achieving a marketing license.1

Adaptive designs are an extensive class of flexible tools which use accumulated data in the trial to make preplanned adaptations to the trial’s course. They can be used in all trial phases. The adaptations can include stopping an arm early for futility or safety, closing recruitment to an arm early if there is strong evidence of efficacy, changing of target sample size or allocation ratios. They are usually more efficient, informative and ethical than traditional fixed designs (where no interim adaptations are permitted). They can often offer savings in resources and even number of patients (figure 1).2

Figure 1

Benefits of adaptive trial designs. Adapted from: adaptive designs in clinical trials: why use them, and how to run and report them.

A novel paradigm for conducting adaptive trials, which allows several treatments to be assessed concurrently with preplanned interim adaptations, is the so-called multiarm, …

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