Using Individualized Treatment Effects to Assess Treatment Effect Heterogeneity

• DOI: 10.48550/arxiv.2502.00713
• Publication Date: 2025-01-01
• Authors: Sechidis, Konstan...; Zhang, Cong; Sun, Sophie; Chen, Yao; Spector, Asher; Bornkamp, Björn
• Keywords: Methodology (stat.ME); FOS: Computer and information sciences; Applications (stat.AP); Statistics - Applications; Statistics - Methodology

Assessing treatment effect heterogeneity (TEH) in clinical trials is crucial, as it provides insights into the variability of treatment responses among patients, influencing important decisions related to drug development. Furthermore, it can lead to personalized medicine by tailoring treatments to individual patient characteristics. This paper introduces novel methodologies for assessing treatment effects using the individual treatment effect as a basis. To estimate this effect, we use a Double Robust (DR) learner to infer a pseudo-outcome that reflects the causal contrast. This pseudo-outcome is then used to perform three objectives: (1) a global test for heterogeneity, (2) ranking covariates based on their influence on effect modification, and (3) providing estimates of the individualized treatment effect. We compare our DR-learner with various alternatives and competing methods in a simulation study, and also use it to assess heterogeneity in a pooled analysis of five Phase III trials in psoriatic arthritis. By integrating these methods with the recently proposed WATCH workflow (Workflow to Assess Treatment Effect Heterogeneity in Drug Development for Clinical Trial Sponsors), we provide a robust framework for analyzing TEH, offering insights that enable more informed decision-making in this challenging area.