Parametric Dose Standardization for Optimizing Two-Agent Combinations in a Phase I-II Trial with Ordinal Outcomes.

ABSTRACT: A Bayesian model and design are described for a phase I-II trial to jointly optimise the doses of a targeted agent and a chemotherapy agent for solid tumors. A challenge in designing the trial was that both the efficacy and toxicity outcomes were defined as four-level ordinal variables. To reflect possibly complex joint effects of the two doses on each of the two outcomes, for each marginal distribution a generalised continuation ratio model was assumed, with each agent's dose parametrically standardised in the linear term. A copula was assumed to obtain a bivariate distribution. Elicited outcome probabilities were used to construct a prior, with variances calibrated to obtain small prior effective sample size. Elicited numerical utilities of the 16 elementary outcomes were used to compute

SUBMITTER: Thall PF 

PROVIDER: S-EPMC5328131 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature