Using joint utilities of the times to response and toxicity to adaptively optimize schedule-dose regimes.

ABSTRACT: A Bayesian two-stage phase I-II design is proposed for optimizing administration schedule and dose of an experimental agent based on the times to response and toxicity in the case where schedules are non-nested and qualitatively different. Sequentially adaptive decisions are based on the joint utility of the two event times. A utility function is constructed by partitioning the two-dimensional positive real quadrant of possible event time pairs into rectangles, eliciting a numerical utility for each rectangle, and fitting a smooth parametric function to the elicited values. We assume that each event time follows a gamma distribution with shape and scale parameters both modeled as functions of schedule and dose. A copula is assumed to obtain a bivariate distribution. To ensure an ethical tr

SUBMITTER: Thall PF 

PROVIDER: S-EPMC3963428 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature