Central to personalized medicine and tailored therapies is discovering the subpopulations that account for treatment effect heterogeneity and are likely to benefit more from given interventions. In this article, we introduce a change plane model averaging method to identify subgroups characterized by linear combinations of predictive variables and multiple cut-offs. We first fit a sequence of statistical models, each incorporating the thresholding effect of one particular covariate. The estimation of submodels is accomplished through an iterative integration of a change point detection method and numerical optimization algorithms. A frequentist model averaging approach is then employed to linearly combine the submodels with optimal weights. Our approach can deal with high-dimensional settings involving enormous potential grouping variables by adopting the sparsity-inducing penalties. Simulation studies are conducted to investigate the prediction and subgrouping performance of the proposed method, with a comparison to various competing subgroup detection methods. Our method is applied to a dataset from a warfarin pharmacogenetics study, producing some new findings.
Keywords: Change plane analysis; model averaging; personalized medicine; subgroup identification; warfarin pharmacogenetics study.