A Phase I-II Basket Trial Design to Optimize Dose-Schedule Regimes Based on Delayed Outcomes.

ABSTRACT: This paper proposes a Bayesian adaptive basket trial design to optimize the dose-schedule regimes of an experimental agent within disease subtypes, called "baskets", for phase I-II clinical trials based on late-onset efficacy and toxicity. To characterize the association among the baskets and regimes, a Bayesian hierarchical model is assumed that includes a heterogeneity parameter, adaptively updated during the trial, that quantifies information shared across baskets. To account for late-onset outcomes when doing sequential decision making, unobserved outcomes are treated as missing values and imputed by exploiting early biomarker and low-grade toxicity information. Elicited joint utilities of efficacy and toxicity are used for decision making. Patients are randomized adaptively to regimes

SUBMITTER: Lin R 

PROVIDER: S-EPMC8277108 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature