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WATCH: A Workflow to Assess Treatment Effect Heterogeneity in Drug Development for Clinical Trial Sponsors

1 May 2024arXiv:2405.00859links table onlyarchive 2025-07-28

Konstantinos Sechidis, Sophie Sun, Yao Chen, Jiarui Lu, Cong Zhang, Mark Baillie, David Ohlssen, Marc Vandemeulebroecke, Rob Hemmings, Stephen Ruberg, Björn Bornkamp

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This paper proposes a Workflow for Assessing Treatment effeCt Heterogeneity (WATCH) in clinical drug development targeted at clinical trial sponsors. WATCH is designed to address the challenges of investigating treatment effect heterogeneity (TEH) in randomized clinical trials, where sample size and multiplicity limit the reliability of findings. The proposed workflow includes four steps: Analysis Planning, Initial Data Analysis and Analysis Dataset Creation, TEH Exploration, and Multidisciplinary Assessment. The workflow offers a general overview of how treatment effects vary by baseline covariates in the observed data, and guides interpretation of the observed findings based on external evidence and best scientific understanding. The workflow is exploratory and not inferential/confirmatory in nature, but should be pre-planned before data-base lock and analysis start. It is focused on providing a general overview rather than a single specific finding or subgroup with differential effect.

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