Designs and adaptive analysis plans for pivotal clinical trials of therapeutics and companion diagnostics

Abstract

Background: Developments in genomics and biotechnology provide unprecedented opportunities for the development of effective therapeutics and companion diagnostics for matching the right drug to the right patient. Effective co-development involves many new challenges with increased opportunity for success as well as delay and failure. Objective: Clinical trial designs and adaptive analysis plans for the prospective design of pivotal trials of new therapeutics and companion diagnostics are reviewed. Conclusions: Effective co-development requires careful prospective planning of the design and analysis strategy for pivotal clinical trials. Randomized clinical trials continue to be important for evaluating the effectiveness of new treatments, but the target populations for analysis should be prospectively specified based on the companion diagnostic. Post hoc analyses of traditionally designed randomized clinical trials are often deeply problematic. Clear separation is generally required of the data used for de...