Sequential estimation for mixture of regression models for heterogeneous population

Abstract

Heterogeneity among patients commonly exists in clinical studies and leads to challenges in medical research. It is widely accepted that there exist various sub-types in the population and they are distinct from each other. The approach of identifying the sub-types and thus tailoring disease prevention and treatment is known as precision medicine. The mixture model is a classical statistical model to cluster the heterogeneous population into homogeneous sub-populations. However, for the highly heterogeneous population with multiple components, its parameter estimation and clustering results may be ambiguous due to the dependence of the EM algorithm on the initial values. For sub-typing purposes, the finite mixture of regression models with concomitant variables is considered and a novel statistical method is proposed to identify the main components with large proportions in the mixture sequentially. Compared to existing typical statistical inferences, the new method not only requires no pre-specification on the number of components for model fitting, but also provides more reliable parameter estimation and clustering results. Simulation studies demonstrated the superiority of the proposed method. Real data analysis on the drug response prediction illustrated its reliability in the parameter estimation and capability to identify the important subgroup.