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Inclusive designs that allow the inclusion of a broader population in randomized controlled trials: An evaluation of randomization ratio and analysis strategy.

Created on 21 Aug 2026

Authors

Kim May Lee, Ziyan Wang, Richard Emsley, Nigel Stallard

Published in

Statistical methods in medical research. Pages 9622802261475687. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

In most multi-arm randomized controlled trials, all participants need to be eligible to be randomized to all the arms. This means some participants are excluded from participating in multi-arm studies. We propose to relax this by considering a 'differential randomization' approach that allows the inclusion of participants who are eligible for some but not all arms, as in some innovative trial approaches. We refer to a multi-arm design that employs differential randomization as an 'inclusive design' because it maximizes participant inclusion. Considering superiority comparisons for a normal endpoint, we evaluate the performance of some analysis methods for a three-arm inclusive design by simulation studies. Methods include pairwise or overall regression analysis, an averaging approach that pools summary statistics using prevalence rate, and a meta-analysis type framework. We compare the statistical power when the inclusive design employs different treatment allocation schemes. We find that using equal allocation ratio within each subpopulation leads to a higher disjunctive power than using equal allocation across arms, when the many-to-one comparisons are analysed using the corresponding pairwise data separately as opposed to using all data in a single regression analysis. We find that differential covariate-outcome relations among patients can affect the property of the inference.

PMID:
42627367
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

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