biostudies-literatureKaizer AMNIDA NIH HHSCase Comprehensive Cancer Center, Case Western Reserve UniversityNCI NIH HHSNational Institute on Drug Abuse785-798https://www.ebi.ac.uk/biostudies/studies/S-EPMC9907719biostudies-literatureUnknown30(3)Breakthroughs in cancer biology have defined new research programs emphasizing the development of therapies that target specific pathways in tumor cells. Innovations in clinical trial design have followed with master protocols defined by inclusive eligibility criteria and evaluations of multiple therapies and/or histologies. Consequently, characterization of subpopulation heterogeneity has become central to the formulation and selection of a study design. However, this transition to master protocols has led to challenges in identifying the optimal trial design and proper calibration of hyperparameters. We often evaluate a range of null and alternative scenarios; however, there has been little guidance on how to synthesize the potentially disparate recommendations for what may be optimal. TStatistical methods in medical researchStatistical design considerations for trials that study multiple indications.PMC9907719R01 DA046320P30 CA043703NIH R01-DA046320Chen NKoopmeiners JSKaizer AMHobbs BPfalseStatistical design considerations for trials that study multiple indications.Breakthroughs in cancer biology have defined new research programs emphasizing the development of therapies that target specific pathways in tumor cells. Innovations in clinical trial design have followed with master protocols defined by inclusive eligibility criteria and evaluations of multiple therapies and/or histologies. Consequently, characterization of subpopulation heterogeneity has become central to the formulation and selection of a study design. However, this transition to master protocols has led to challenges in identifying the optimal trial design and proper calibration of hyperparameters. We often evaluate a range of null and alternative scenarios; however, there has been little guidance on how to synthesize the potentially disparate recommendations for what may be optimal. T2021-01-01T00:00:00Z2021 Mar2026-03-15T14:00:16.364Z2025-04-04T23:52:30.181ZS-EPMC99077193326774610.1177/0962280220975187