Bayesian Utility-Based Designs for Subgroup-Specific Treatment Comparison and Early-Phase Dose Optimization in Oncology Clinical Trials

PURPOSEDespite the fact that almost any sample of patients with a particular disease is heterogeneous, most clinical trial designs ignore the possibility that treatment or dose effects may differ between prognostic or biologically defined subgroups. This article reviews two clinical trial designs that make subgroup-specific decisions and compares each to a simpler design that ignores patient heterogeneity. The purpose is to illustrate the benefits of accounting prospectively for treatment-subgroup interactions and how utilities may be used to quantify risk-benefit trade-offs.METHODSTwo Bayesian clinical trial designs that perform subgroup-specific decision making and inference based on elicited utilities of patient outcomes are reviewed. The first is a randomized comparative trial of nutritional prehabilitation for patients undergoing esophageal resection that has two prognostic subgroups and is based on postoperative morbidity score. The second is a sequentially adaptive trial of natural killer cells for treating hematologic malignancies that is based on five time-to-event outcomes and that performs safety monitoring and optimizes cell dose within six disease subgroups. Computer s