Parmar, MKB;
Sydes, MR;
Morris, TP;
(2016)
How do you design randomised trials for smaller populations? A framework.
BMC Medicine
, 14
, Article 183. 10.1186/s12916-016-0722-3.
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Abstract
How should we approach trial design when we can get some, but not all, of the way to the numbers required for a randomised phase III trial? We present an ordered framework for designing randomised trials to address the problem when the ideal sample size is considered larger than the number of participants that can be recruited in a reasonable time frame. Staying with the frequentist approach that is well accepted and understood in large trials, we propose a framework that includes small alterations to the design parameters. These aim to increase the numbers achievable and also potentially reduce the sample size target. The first step should always be to attempt to extend collaborations, consider broadening eligibility criteria and increase the accrual time or follow-up time. The second set of ordered considerations are the choice of research arm, outcome measures, power and target effect. If the revised design is still not feasible, in the third step we propose moving from two- to one-sided significance tests, changing the type I error rate, using covariate information at the design stage, re-randomising patients and borrowing external information. We discuss the benefits of some of these possible changes and warn against others. We illustrate, with a worked example based on the Euramos-1 trial, the application of this framework in designing a trial that is feasible, while still providing a good evidence base to evaluate a research treatment. This framework would allow appropriate evaluation of treatments when large-scale phase III trials are not possible, but where the need for high-quality randomised data is as pressing as it is for common diseases.
| Type: | Article |
|---|---|
| Title: | How do you design randomised trials for smaller populations? A framework |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s12916-016-0722-3 |
| Publisher version: | http://dx.doi.org/10.1186/s12916-016-0722-3 |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2016. 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. |
| Keywords: | Randomised trials, Trial design, Smaller populations, Uncommon diseases |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1529853 |
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