Gorrod, H.B. orcid.org/0000-0001-8054-8073, Mt-Isa, S., Xuan, J. orcid.org/0000-0002-5721-4857 et al. (5 more authors) (2025) Adjusting for switches to multiple treatments: Should switches be handled separately or combined? Statistical Methods in Medical Research, 34 (2). pp. 322-335. ISSN 0962-2802
Abstract
Treatment switching is common in randomised controlled trials (RCTs). Participants may switch onto a variety of different treatments, all of which may have different treatment effects. Adjustment analyses that target hypothetical estimands – estimating outcomes that would have been observed in the absence of treatment switching – have focused primarily on a single type of switch. In this study, we assess the performance of applications of inverse probability of censoring weights (IPCW) and two-stage estimation (TSE) which adjust for multiple switches by either (i) adjusting for each type of switching separately (‘treatments separate’) or (ii) adjusting for switches combined without differentiating between switched-to treatments (‘treatments combined’). We simulate 48 scenarios in which RCT participants may switch to multiple treatments. Switch proportions, treatment effects, number of switched-to treatments and censoring proportions were varied. Method performance measures included mean percentage bias in restricted mean survival time and the frequency of model convergence. Similar levels of bias were produced by treatments combined and treatments separate in both TSE and IPCW applications. In the scenarios examined, there was no demonstrable advantage associated with adjusting for each type of switch separately, compared with adjusting for all switches together.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
Keywords: | Treatment switching; multiple treatments; counterfactual; health technology assessment; oncology; overall survival; survival analysis; time-dependent confounding; time-to-event outcomes |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 21 Jan 2025 11:35 |
Last Modified: | 12 Mar 2025 08:55 |
Status: | Published |
Publisher: | SAGE Publications |
Refereed: | Yes |
Identification Number: | 10.1177/09622802241300049 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:222044 |