Adaptive designs in clinical trials: why use them, and how to run and report them.
Date
2018-02-28ICR Author
Author
Pallmann, P
Bedding, AW
Choodari-Oskooei, B
Dimairo, M
Flight, L
Hampson, LV
Holmes, J
Mander, AP
Odondi, L
Sydes, MR
Villar, SS
Wason, JMS
Weir, CJ
Wheeler, GM
Yap, C
Jaki, T
Type
Journal Article
Metadata
Show full item recordAbstract
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.
xmlui.dri2xhtml.METS-1.0.item-oa-location
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1017-7Collections
Subject
Humans
Reproducibility of Results
Research Design
Clinical Trials as Topic
Research team
Clinical Trials & Statistics Unit
Language
eng
Date accepted
2018-01-30
License start date
2018-02-28
Citation
BMC medicine, 2018, 16 (1), pp. 29 - ?