Comparison of clinical development plans for a confirmatory trial with subpopulation selection


Given ever increasing costs to develop a new drug and intense competition, population enrichment designs should be considered during the planning phase of a pivotal trial with potential subgroup defined by a binary biomarker. Population enrichment designs explicitly factor in the possibility that the new drug might differentially benefit distinct biomarker subgroups. We have compared three clinical development plans for a time-to-event endpoint, such as overall survival, that all lead to a final decision in a pivotal trial either in allcomers only, in allcomers and biomarker positive, in the biomarker positive only, or to declare the drug futile. The decision about which hypothesis to test at the final analysis is made based on a quick time-to-event endpoint, such as progression-free survival, at an interim analysis. We quantify the time gain when using a seamless Phase II/III adaptive design versus alternative development approaches and we outline what type of biomarker needs to be available prior to Phase II in each scenario.

Joint Meeting of the International Biometric Society Austro-Swiss and Italian Regions (invited talk)
Milan, Italy