Identifying Treatment Effect Heterogeneity with Bayesian Hierarchical Adjustable Random Partition in Adaptive Enrichment Trials

TL;DR

This paper introduces the BHARP model, a Bayesian approach for identifying treatment effect heterogeneity in clinical trials, which jointly estimates subgroup effects and adapts borrowing strength without manual calibration.

Contribution

The paper presents a novel Bayesian hierarchical model with a reversible-jump MCMC sampler for flexible, uncertainty-aware partitioning in adaptive enrichment trials.

Findings

BHARP outperforms existing methods in simulation studies.

It effectively estimates subgroup-specific effects and heterogeneity patterns.

Application to a diabetes trial demonstrates practical utility.

Abstract

Treatment effect heterogeneity refers to the systematic variation in treatment effects across subgroups. There is an increasing need for clinical trials that aim to investigate treatment effect heterogeneity and estimate subgroup-specific responses. While several statistical methods have been proposed to address this problem, existing partitioning-based methods often depend on auxiliary analysis, overlook model uncertainty, or impose inflexible borrowing strength. We propose the Bayesian Hierarchical Adjustable Random Partition (BHARP) model, a self-contained framework that applies a finite mixture model with an unknown number of components to explore the partition space accounting for model uncertainty. The BHARP model jointly estimates subgroup-specific effects and the heterogeneity patterns, and adjusts the borrowing strengths based on within-cluster cohesion without requiring manual calibration. Posterior sampling is performed via a custom reversible-jump Markov chain Monte Carlo sampler tailored to partitioning-based information borrowing in clinical trials. Simulation studies across a range of treatment effect heterogeneity patterns show that the BHARP model achieves better accuracy and precision compared to conventional and advanced methods. We showcase the utilities of the BHARP model in the context of a multi-arm adaptive enrichment trial investigating physical activity interventions in patients with type 2 diabetes.