A proof-of-concept clinical trial design combined with dose-ranging exploration.

In recent years, the pharmaceutical industry has experienced many challenges in discovering and developing new drugs, including long clinical development timelines with significant investment risks. In response, many sponsors are working to speed up the clinical development process. One strategy is to combine the proof-of-concept (PoC) and the dose-ranging clinical studies into a single trial. This manuscript proposes approaches to help address both PoC and dose-ranging objectives in such a combined design. One proposal is to use a linear trend test for PoC, together with a serial gatekeeping method (TGK) to identify individual doses; the other is to use the dose-response curve estimated from a three-parameter Emax model to establish PoC and explore activities of various doses. Simulations were performed to evaluate the performance of both proposals with recommendations based on the simulation results.