A New Clinical Trial Design Combining Phases 2 and 3: Sequential Designs with Treatment Selection and a Change of Endpoint

Abstract

This paper describes a method for designing a clinical trial to combine aspects of Phases 2 and 3 of the clinical development program. Specifically, a group sequential design is presented, which incorporates treatment selection based upon a short-term “provisional” endpoint, as is often undertaken in Phase 2 trials, followed by a comparison of the selected treatment with control in terms of a longer-term primary endpoint. An example is given illustrating the methodology and we discuss how this approach may reduce the total number of patients required in the evaluation process without compromising its integrity, leading to more ethical and efficient clinical studies.