Multi-threshold proportional hazards model and subgroup identification

Stat Med. 2022 Dec 20;41(29):5715-5737. doi: 10.1002/sim.9589. Epub 2022 Oct 5.

Abstract

We propose a novel two-stage procedure for change point detection and parameter estimation in a multi-threshold proportional hazards model. In the first stage, we estimate the number of thresholds by formulating the threshold detection problem as a variable selection problem and applying the penalized partial likelihood approach. In the second stage, the change point locations are refined by a grid search and the standard inference for segment regression can then follow. The proposed model and estimation procedure could lend support to subgroup identification and personalized treatment recommendation in medical research. We establish the consistency of the threshold estimators and regression coefficient estimators under technical conditions. The finite sample performance of the method is demonstrated via simulation studies and two cancer data examples.

Keywords: Cox proportional hazards regression; multiple change point detection; non-concave penalty; personalized medicine; subgroup identification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Humans
  • Likelihood Functions
  • Neoplasms* / therapy
  • Proportional Hazards Models
  • Research Design*