A phase I-II design based on periodic and continuous monitoring of disease status and the times to toxicity and death.

ABSTRACT: A Bayesian phase I-II dose-finding design is presented for a clinical trial with four coprimary outcomes that reflect the actual clinical observation process. During a prespecified fixed follow-up period, the times to disease progression, toxicity, and death are monitored continuously, and an ordinal disease status variable, including progressive disease (PD) as one level, is evaluated repeatedly by scheduled imaging. We assume a proportional hazards model with piecewise constant baseline hazard for each continuous variable and a longitudinal multinomial probit model for the ordinal disease status process and include multivariate patient frailties to induce association among the outcomes. A finite partition of the nonfatal outcome combinations during the follow-up period is constructed, an

SUBMITTER: Lee J 

PROVIDER: S-EPMC9133492 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature