Generalized Pairwise Comparisons to Assess Treatment Effects: JACC Review Topic of the Week

J Am Coll Cardiol. 2023 Sep 26;82(13):1360-1372. doi: 10.1016/j.jacc.2023.06.047.


A time-to-first-event composite endpoint analysis has well-known shortcomings in evaluating a treatment effect in cardiovascular clinical trials. It does not fully describe the clinical benefit of therapy because the severity of the events, events repeated over time, and clinically relevant nonsurvival outcomes cannot be considered. The generalized pairwise comparisons (GPC) method adds flexibility in defining the primary endpoint by including any number and type of outcomes that best capture the clinical benefit of a therapy as compared with standard of care. Clinically important outcomes, including bleeding severity, number of interventions, and quality of life, can easily be integrated in a single analysis. The treatment effect in GPC can be expressed by the net treatment benefit, the success odds, or the win ratio. This review provides guidance on the use of GPC and the choice of treatment effect measures for the analysis and reporting of cardiovascular trials.

Keywords: absolute treatment effect; biostatistics; clinical trials; composite endpoints; endpoint determinations; generalized pairwise comparisons; net treatment benefit; randomized controlled trials as topic; relative treatment effect; success odds; survival analysis; win ratio.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases* / therapy
  • Endpoint Determination
  • Humans
  • Outcome and Process Assessment, Health Care*
  • Quality of Life