Incorporating external data into the analysis of clinical trials via Bayesian additive regression trees

Abstract

Most clinical trials involve the comparison of a new treatment to a control arm (eg, the standard of care) and the estimation of a treatment effect. External data, including historical clinical trial data and real-world observational data, are commonly available for the control arm. With proper statistical adjustments, borrowing information from external data can potentially reduce the mean squared errors of treatment effect estimates and increase the power of detecting a meaningful treatment effect. In this article, we propose to use Bayesian additive regression trees (BART) for incorporating external data into the analysis of clinical trials, with a specific goal of estimating the conditional or population average treatment effect. BART naturally adjusts for patient-level covariates and captures potentially heterogeneous treatment effects across different data sources, achieving flexible borrowing. Simulation studies demonstrate that BART maintains desirable and robust performance across a variety of scenarios and compares favorably to alternatives. We illustrate the proposed method with an acupuncture trial and a colorectal cancer trial.