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

TL;DR

WATCH is a structured workflow designed to help clinical trial sponsors explore and interpret treatment effect heterogeneity in drug development, addressing challenges of sample size and multiplicity in randomized trials.

Contribution

The paper introduces a novel, generalizable workflow for assessing treatment effect heterogeneity that is pre-planned and exploratory, aiding interpretation in clinical trials.

Findings

Provides a four-step workflow for TEH assessment

Guides interpretation based on external evidence

Focuses on exploratory analysis rather than confirmatory results

Abstract

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.