Bayesian Additive Regression Trees (BART) with covariate adjusted borrowing in subgroup analyses

摘要

It is crucial in clinical trials to investigate treatment effect consistency across subgroups defined by patient baseline characteristics. However, there may be treatment effect variability across subgroups due to small subgroup sample size. Various Bayesian models have been proposed to incorporate this variability when borrowing information across subgroups. These models rely on the underlying assumption that patients with similar characteristics will have similar outcomes to the same treatment. Patient populations within each subgroup must subjectively be deemed similar enough Pocock (1976) to borrow response information across subgroups. We propose utilizing the machine learning method of Bayesian Additive Regression Trees (BART) to provide a method for subgroup borrowing that does not rely on an underlying assumption of homogeneity between subgroups. BART is a data-driven approach that utilizes patient-level observations. The amount of borrowing between subgroups automatically adjusts as BART learns the covariate- response relationships. Modeling patient-level data rather than treating the subgroup as a single unit minimizes assumptions regarding homogeneity across subgroups. We illustrate the use of BART in this context by comparing performance from existing subgroup borrowing methods in a simulation study and a case study in non-small cell lung cancer. The application of BART in the context of subgroup analyses alleviates the need to subjectively choose how much information to borrow based on subgroup similarity. Having the amount of borrowing be analytically determined and controlled for based on the similarity of individual patient-level characteristics allows for more objective decision making in the drug development process with many other applications including basket trials.