Decision theoretic designs for phase II clinical trials with multiple outcomes

In many phase II clinical trials, it is essential to assess both efficacy a nd safety. Although several phase II designs that accommodate multiple outc omes have been proposed recently, none are derived using decision theory. T his paper describes a Bayesian decision theoretic strategy for constructing phase II designs based on both efficacy and adverse events. The gain funct ion includes utilities assigned to patient outcomes, a reward for declaring the new treatment promising, and costs associated with the conduct of the phase II trial and future phase III testing. A method for eliciting gain fu nction parameters from medical collaborators and for evaluating the design' s frequentist operating characteristics is described. The strategy is illus trated by application to a clinical trial of peripheral blood stem cell tra nsplantation for multiple myeloma.