Edwards, J.M. orcid.org/0000-0001-8337-8962, Walters, S.J. and Julious, S.A. (2023) A retrospective analysis of conditional power assumptions in clinical trials with continuous or binary endpoints. Trials, 24. 215. ISSN 1745-6215
Abstract
Background Adaptive clinical trials may use conditional power (CP) to make decisions at interim analyses, requiring assumptions about the treatment effect for remaining patients. It is critical that these assumptions are understood by those using CP in decision-making, as well as timings of these decisions.
Methods Data for 21 outcomes from 14 published clinical trials were made available for re-analysis. CP curves for accruing outcome information were calculated using and compared with a pre-specified objective criteria for original and transformed versions of the trial data using four future treatment effect assumptions: (i) observed current trend, (ii) hypothesised effect, (iii) 80% optimistic confidence limit, (iv) 90% optimistic confidence limit.
Results The hypothesised effect assumption met objective criteria when the true effect was close to that planned, but not when smaller than planned. The opposite was seen using the current trend assumption. Optimistic confidence limit assumptions appeared to offer a compromise between the two, performing well against objective criteria when the end observed effect was as planned or smaller.
Conclusion The current trend assumption could be the preferable assumption when there is a wish to stop early for futility. Interim analyses could be undertaken as early as 30% of patients have data available. Optimistic confidence limit assumptions should be considered when using CP to make trial decisions, although later interim timings should be considered where logistically feasible.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data. |
Keywords: | Conditional power; Adaptive designs; Futility; Sample size re-estimation; Clinical trials |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield) > ScHARR - Sheffield Centre for Health and Related Research |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 27 Mar 2023 15:12 |
Last Modified: | 27 Mar 2023 15:12 |
Published Version: | http://dx.doi.org/10.1186/s13063-023-07202-6 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1186/s13063-023-07202-6 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:197743 |