A comparative study of subgroup identification methods for differential treatment effect: Performance metrics and recommendations

Stat Methods Med Res. 2018 Dec;27(12):3658-3678. doi: 10.1177/0962280217710570. Epub 2017 Jun 20.


Subgroup identification with differential treatment effects serves as an important step towards precision medicine, as it provides evidence regarding how individuals with specific characteristics respond to a given treatment. This knowledge not only supports the tailoring of treatment strategies but also prompts the development of new treatments. This manuscript provides a brief overview of the issues associated with the methodologies aimed at identifying subgroups with differential treatment effects, and studies in depth the operational characteristics of five data-driven methods that have appeared recently in the literature. The performance of the methods under study to identify correctly the covariates affecting treatment effects is evaluated via simulation and under various conditions. Two clinical trial data sets are also used to illustrate the application of these methods. Discussion and recommendations pertaining to the use of these methods are provided, with emphasis on the relative performance of the methods under the conditions studied.

Keywords: Data-driven methods; differential treatment effects; predictive covariates; prognostic covariates; subgroup identification methods.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Data Interpretation, Statistical
  • Humans
  • Models, Statistical*
  • Outcome Assessment, Health Care / methods*
  • Precision Medicine*
  • Research Design