Zhao, SaijunThall, Peter F.Yuan, YingLee, JuheeMsaouel, PavlosZang, Yong2025-08-122025-08-122025Zhao S, Thall PF, Yuan Y, Lee J, Msaouel P, Zang Y. Precision generalized phase I-II designs. Biometrics. 2025;81(3):ujaf043. doi:10.1093/biomtc/ujaf043https://hdl.handle.net/1805/50215A new family of precision Bayesian dose optimization designs, PGen I-II, based on early efficacy, early toxicity, and long-term time to treatment failure is proposed. A PGen I-II design refines a Gen I-II design by accounting for patient heterogeneity characterized by subgroups that may be defined by prognostic levels, disease subtypes, or biomarker categories. The design makes subgroup-specific decisions, which may be to drop an unacceptably toxic or inefficacious dose, randomize patients among acceptable doses, or identify a best dose in terms of treatment success defined in terms of time to failure over long-term follow-up. A piecewise exponential distribution for failure time is assumed, including subgroup-specific effects of dose, response, and toxicity. Latent variables are used to adaptively cluster subgroups found to have similar dose-outcome distributions, with the model simplified to borrow strength between subgroups in the same cluster. Guidelines and user-friendly computer software for implementing the design are provided. A simulation study is reported that shows the PGen I-II design is superior to similarly structured designs that either assume patient homogeneity or conduct separate trials within subgroups.en-USPublisher PolicyBayesian adaptive designCell therapyDose optimizationPhase I-II clinical trialsPrecision medicineArticle