Utility-based designs for randomized comparative trials with categorical outcomes

A general utility-based testing methodology for design and conduct of randomized comparative clinical trials with categorical outcomes is presented. Numerical utilities of all elementary events are elicited to quantify their desirabilities. These numerical values are used to map the categorical outcome probability vector of each treatment to a mean utility, which is used as a one-dimensional criterion for constructing comparative tests. Bayesian tests are presented, including fixed sample and group sequential procedures, assuming Dirichlet-multinomial models for the priors and likelihoods. Guidelines are provided for establishing priors, eliciting utilities, and specifying hypotheses. Efficient posterior computation is discussed, and algorithms are provided for jointly calibrating test cutoffs and sample size to control overall type I error and achieve specified power. Asymptotic approximations for the power curve are used to initialize the algorithms. The methodology is applied to re-design a completed trial that compared two chemotherapy regimens for chronic lymphocytic leukemia, in which an ordinal efficacy outcome was dichotomized, and toxicity was ignored to construct the trial's design. The Bayesian tests also are illustrated by several types of categorical outcomes arising in common clinical settings. Freely available computer software for implementation is provided. Copyright (c) 2016 John Wiley & Sons, Ltd.