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

Research output: Contribution to journalArticle

Authors

  • Philip Pallmann
  • Alun W. Bedding
  • Babak Choodari-Oskooei
  • Munyaradzi Dimairo
  • Laura Flight
  • Lisa V. Hampson
  • Jane Holmes
  • Adrian P. Mander
  • Lang'o Odondi
  • Matthew R. Sydes
  • Sofía S. Villar
  • James M. S. Wason
  • Christopher J. Weir
  • Graham M. Wheeler
  • Thomas Jaki

Colleges, School and Institutes

External organisations

  • Lancaster University
  • Roche Products Ltd
  • Institute of Clinical Trials and Methodology, University College London
  • Clinical Trials Research Unit, University of Sheffield
  • Medical Statistics Group, University of Sheffield
  • Statistical Innovation Group, Advanced Analytics Centre, AstraZeneca
  • Centre for Statistics in Medicine, University of Oxford
  • University of Cambridge
  • Newcastle University
  • Usher Institute of Population Health Sciences and Informatics, University of Edinburgh
  • Cancer Research UK & UCL Cancer Trials Centre, University College London

Abstract

Adaptive designs can make clinical trials more flexible by utilising results accumulating in the trial to modify the trial's course in accordance with pre-specified rules. Trials with an adaptive design are often more efficient, informative and ethical than trials with a traditional fixed design since they often make better use of resources such as time and money, 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 their potential advantages. We speculate that one factor contributing to this is that the full range of adaptations available to trial designs, as well as their goals, advantages and limitations, remains unfamiliar to many parts of the clinical community. Additionally, the term adaptive design has been misleadingly used as an all-encompassing label to refer to 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 the investigators 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. We explain the basic rationale behind adaptive designs, clarify ambiguous terminology and summarise the utility and pitfalls of adaptive designs. We discuss practical aspects around funding, ethical approval, treatment supply and communication with stakeholders and trial participants. Our focus, however, is on the interpretation and reporting of results from adaptive design trials, which we consider vital for anyone involved in medical research. We emphasise the general principles of transparency and reproducibility and suggest how best to put them into practice.

Details

Original languageEnglish
Article number29
JournalBMC medicine
Volume16
Issue number1
Publication statusPublished - 28 Feb 2018

Keywords

  • statistical methods , adaptive design , flexible design, interim analysis , design modification , seamless design