Bayesian credible subgroup identification for treatment effectiveness in time-to-event data

PLoS One. 2020 Feb 26;15(2):e0229336. doi: 10.1371/journal.pone.0229336. eCollection 2020.

Abstract

Due to differential treatment responses of patients to pharmacotherapy, drug development and practice in medicine are concerned with personalized medicine, which includes identifying subgroups of population that exhibit differential treatment effect. For time-to-event data, available methods only focus on detecting and testing treatment-by-covariate interactions and may not consider multiplicity. In this work, we introduce the Bayesian credible subgroups approach for time-to-event endpoints. It provides two bounding subgroups for the true benefiting subgroup: one which is likely to be contained by the benefiting subgroup and one which is likely to contain the benefiting subgroup. A personalized treatment effect is estimated by two common measures of survival time: the hazard ratio and restricted mean survival time. We apply the method to identify benefiting subgroups in a case study of prostate carcinoma patients and a simulated large clinical dataset.

MeSH terms

  • Aged
  • Bayes Theorem*
  • Cardiovascular Diseases / mortality*
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / therapy
  • Computer Simulation
  • Data Interpretation, Statistical*
  • Dyslipidemias / mortality*
  • Dyslipidemias / pathology
  • Dyslipidemias / therapy
  • Humans
  • Male
  • Middle Aged
  • Models, Statistical*
  • Precision Medicine
  • Prognosis
  • Prostatic Neoplasms / mortality*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • Survival Rate
  • Treatment Outcome

Grants and funding

This study was funded from a commercial source: Merck & Company. The funder provided support in the form of salaries for authors Duy Ngo, Richard Baumgartner, Shahrul Mt-Isa, Jie Chen and Dai Feng. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.