Statistics in Medicine

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

Journal Article

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.

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Published features on are checked for statistical accuracy by a panel from the European Network for Business and Industrial Statistics (ENBIS)   to whom Wiley and express their gratitude. This panel are: Ron Kenett, David Steinberg, Shirley Coleman, Irena Ograjenšek, Fabrizio Ruggeri, Rainer Göb, Philippe Castagliola, Xavier Tort-Martorell, Bart De Ketelaere, Antonio Pievatolo, Martina Vandebroek, Lance Mitchell, Gilbert Saporta, Helmut Waldl and Stelios Psarakis.