biostudies-literatureHanlon PMedical Research CouncilWellcome Truste1004176https://www.ebi.ac.uk/biostudies/studies/S-EPMC10243630biostudies-literatureUnknown20(6)<h4>Background</h4>People with comorbidities are underrepresented in clinical trials. Empirical estimates of treatment effect modification by comorbidity are lacking, leading to uncertainty in treatment recommendations. We aimed to produce estimates of treatment effect modification by comorbidity using individual participant data (IPD).<h4>Methods and findings</h4>We obtained IPD for 120 industry-sponsored phase 3/4 trials across 22 index conditions (n = 128,331). Trials had to be registered between 1990 and 2017 and have recruited ≥300 people. Included trials were multicentre and international. For each index condition, we analysed the outcome most frequently reported in the included trials. We performed a two-stage IPD meta-analysis to estimate modification of treatment effect by comorbiPLoS medicineTreatment effect modification due to comorbidity: Individual participant data meta-analyses of 120 randomised controlled trials.PMC10243630MR/S021949/1201492/Z/16/ZLewsey JMair FSWild SHHannigan LJDias SMcAllister DAShah ASGuthrie BKent DMHanlon PButterly EWWelton NJfalseTreatment effect modification due to comorbidity: Individual participant data meta-analyses of 120 randomised controlled trials.<h4>Background</h4>People with comorbidities are underrepresented in clinical trials. Empirical estimates of treatment effect modification by comorbidity are lacking, leading to uncertainty in treatment recommendations. We aimed to produce estimates of treatment effect modification by comorbidity using individual participant data (IPD).<h4>Methods and findings</h4>We obtained IPD for 120 industry-sponsored phase 3/4 trials across 22 index conditions (n = 128,331). Trials had to be registered between 1990 and 2017 and have recruited ≥300 people. Included trials were multicentre and international. For each index condition, we analysed the outcome most frequently reported in the included trials. We performed a two-stage IPD meta-analysis to estimate modification of treatment effect by comorbi2023-01-01T00:00:00Z2023 Jun2026-05-05T02:51:11.548Z2025-04-19T14:14:03.683ZS-EPMC102436303727919910.1371/journal.pmed.1004176