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Estimating interactions and subgroup-specific treatment effects in meta-analysis without aggregation bias: A within-trial framework

Godolphin, Peter J; White, Ian R; Tierney, Jayne F; Fisher, David J; (2022) Estimating interactions and subgroup-specific treatment effects in meta-analysis without aggregation bias: A within-trial framework. Research Synthesis Methods 10.1002/jrsm.1590. (In press). Green open access

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Abstract

Estimation of within-trial interactions in meta-analysis is crucial for reliable assessment of how treatment effects vary across participant subgroups. However, current methods have various limitations. Patients, clinicians and policy-makers need reliable estimates of treatment effects within specific covariate subgroups, on relative and absolute scales, in order to target treatments appropriately - which estimation of an interaction effect does not in itself provide. Also, the focus has been on covariates with only two subgroups, and may exclude relevant data if only a single subgroup is reported. Therefore, in this article we further develop the "within-trial" framework by providing practical methods to (1) estimate within-trial interactions across two or more subgroups; (2) estimate subgroup-specific ("floating") treatment effects that are compatible with the within-trial interactions and make maximum use of available data; and (3) clearly present this data using novel implementation of forest plots. We described the steps involved and apply the methods to two examples taken from previously published meta-analyses, and demonstrate a straightforward implementation in Stata based upon existing code for multivariate meta-analysis. We discuss how the within-trial framework and plots can be utilised with aggregate (or "published") source data, as well as with individual participant data, to effectively demonstrate how treatment effects differ across participant subgroups.

Type: Article
Title: Estimating interactions and subgroup-specific treatment effects in meta-analysis without aggregation bias: A within-trial framework
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/jrsm.1590
Publisher version: https://doi.org/10.1002/jrsm.1590
Language: English
Additional information: Copyright © 2022 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Covariate interaction, effect modifier, floating subgroup, meta-analysis, subgroup analysis, within-trial
UCL classification: UCL
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
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
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10152223
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