Can a multiple ascending dose study serve as an informative proof‐of‐concept study?

Drug development is a long, complex, and costly process. The majority of the cost arises from Phase 2 and Phase 3 clinical development. Reducing Phase 2 and Phase 3 failure rates would greatly reduce the average drug development cost. Obtaining more informative data on a candidate drug's efficacy and safety prior to moving to Phase 2 will improve Phase 2 success and, hence, reduce the overall development cost. While, typically, multiple ascending dose (MAD) study focuses on safety, this article proposes a model‐based MAD design that not only can provide the desired safety information but also can provide informative efficacy data for certain endpoints in certain therapeutic areas where the parametric models for the longitudinal dose response and the impact of dose titration on a response variable are utilized. This type of MAD design allows relatively informative efficacy data available prior to Phase 2 development and, hence, can serve as a proof‐of‐concept study. This approach may greatly reduce the drug development cycle time without increasing the risk of Phase 2 development.