Bayesian additive decision trees of biomarker by treatment interactions for predictive biomarker detection and subgroup identification

J Biopharm Stat. 2018;28(3):534-549. doi: 10.1080/10543406.2017.1372770. Epub 2017 Nov 27.

Abstract

Personalized medicine, or tailored therapy, has been an active and important topic in recent medical research. Many methods have been proposed in the literature for predictive biomarker detection and subgroup identification. In this article, we propose a novel decision tree-based approach applicable in randomized clinical trials. We model the prognostic effects of the biomarkers using additive regression trees and the biomarker-by-treatment effect using a single regression tree. Bayesian approach is utilized to periodically revise the split variables and the split rules of the decision trees, which provides a better overall fitting. Gibbs sampler is implemented in the MCMC procedure, which updates the prognostic trees and the interaction tree separately. We use the posterior distribution of the interaction tree to construct the predictive scores of the biomarkers and to identify the subgroup where the treatment is superior to the control. Numerical simulations show that our proposed method performs well under various settings comparing to existing methods. We also demonstrate an application of our method in a real clinical trial.

Keywords: Bayesian decision tree; predictive biomarker; predictive value; randomized clinical trial.

MeSH terms

  • Bayes Theorem
  • Biomarkers / blood
  • Decision Trees*
  • Humans
  • Neoplasms / blood*
  • Neoplasms / diagnosis*
  • Neoplasms / therapy
  • Predictive Value of Tests
  • Randomized Controlled Trials as Topic / methods*
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Treatment Outcome

Substances

  • Biomarkers