Nonparametric machine learning for precision medicine with longitudinal clinical trials and Bayesian additive regression trees with mixed models
Charles Spanbauer, Rodney Sparapani
Abstract
Precision medicine is an active area of research that could offer an analytic paradigm shift for clinical trials and the subsequent treatment decisions based on them. Clinical trials are typically analyzed with the intent of discovering beneficial treatments if the same treatment is applied to the entire population under study. But, such a treatment strategy could be suboptimal if subsets of the population exhibit varying treatment effects. Identifying subsets of the population experiencing differential treatment effect and forming individualized treatment rules is a task well-suited to modern machine learning methods such as tree-based ensemble predictive models. Specifically, Bayesian additive regression trees (BART) has shown promise in this regard because of its exceptional performance in out-of-sample prediction. Due to the unique inferential needs of precision medicine for clinical trials, we have proposed the BART extensions explicated here. We incorporate random effects for longitudinal repeated measures and subject clustering within medical centers. The addition of a novel interaction detection prior to identify treatment heterogeneity among clinical trial patients and its association with patient characteristics. These extensions are unified under a framework that we call mixedBART. Simulation studies and applications of precision medicine based on real randomized clinical trials data examples are presented.