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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’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 sin...

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Autores principales: Pallmann, Philip, Bedding, Alun W., Choodari-Oskooei, Babak, Dimairo, Munyaradzi, Flight, Laura, Hampson, Lisa V., Holmes, Jane, Mander, Adrian P., Odondi, Lang’o, Sydes, Matthew R., Villar, Sofía S., Wason, James M. S., Weir, Christopher J., Wheeler, Graham M., Yap, Christina, Jaki, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830330/
https://www.ncbi.nlm.nih.gov/pubmed/29490655
http://dx.doi.org/10.1186/s12916-018-1017-7
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author Pallmann, Philip
Bedding, Alun W.
Choodari-Oskooei, Babak
Dimairo, Munyaradzi
Flight, Laura
Hampson, Lisa V.
Holmes, Jane
Mander, Adrian P.
Odondi, Lang’o
Sydes, Matthew R.
Villar, Sofía S.
Wason, James M. S.
Weir, Christopher J.
Wheeler, Graham M.
Yap, Christina
Jaki, Thomas
author_facet Pallmann, Philip
Bedding, Alun W.
Choodari-Oskooei, Babak
Dimairo, Munyaradzi
Flight, Laura
Hampson, Lisa V.
Holmes, Jane
Mander, Adrian P.
Odondi, Lang’o
Sydes, Matthew R.
Villar, Sofía S.
Wason, James M. S.
Weir, Christopher J.
Wheeler, Graham M.
Yap, Christina
Jaki, Thomas
author_sort Pallmann, Philip
collection PubMed
description 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.
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spelling pubmed-58303302018-03-05 Adaptive designs in clinical trials: why use them, and how to run and report them Pallmann, Philip Bedding, Alun W. Choodari-Oskooei, Babak Dimairo, Munyaradzi Flight, Laura Hampson, Lisa V. Holmes, Jane Mander, Adrian P. Odondi, Lang’o Sydes, Matthew R. Villar, Sofía S. Wason, James M. S. Weir, Christopher J. Wheeler, Graham M. Yap, Christina Jaki, Thomas BMC Med Correspondence 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. BioMed Central 2018-02-28 /pmc/articles/PMC5830330/ /pubmed/29490655 http://dx.doi.org/10.1186/s12916-018-1017-7 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Correspondence
Pallmann, Philip
Bedding, Alun W.
Choodari-Oskooei, Babak
Dimairo, Munyaradzi
Flight, Laura
Hampson, Lisa V.
Holmes, Jane
Mander, Adrian P.
Odondi, Lang’o
Sydes, Matthew R.
Villar, Sofía S.
Wason, James M. S.
Weir, Christopher J.
Wheeler, Graham M.
Yap, Christina
Jaki, Thomas
Adaptive designs in clinical trials: why use them, and how to run and report them
title Adaptive designs in clinical trials: why use them, and how to run and report them
title_full Adaptive designs in clinical trials: why use them, and how to run and report them
title_fullStr Adaptive designs in clinical trials: why use them, and how to run and report them
title_full_unstemmed Adaptive designs in clinical trials: why use them, and how to run and report them
title_short Adaptive designs in clinical trials: why use them, and how to run and report them
title_sort adaptive designs in clinical trials: why use them, and how to run and report them
topic Correspondence
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830330/
https://www.ncbi.nlm.nih.gov/pubmed/29490655
http://dx.doi.org/10.1186/s12916-018-1017-7
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