Adaptive Dose-Response Studies

Insufficient exploration of the dose-response is a shortcoming of clinical drug development, and failure to characterize dosing early is often cited as a key contributor to the high late-stage attrition rate currently faced by the industry. Adaptive methods, for example, make it feasible to design a proof-of-concept study as an adaptive dose-response trial. Efficient learning about the dose response earlier in development will ultimately reduce overall costs and provide better information on dose in the filing package. This article presents the Pharmaceutical Research and Manufacturers of America working group’s main recommendations regarding adaptive dose-response studies. As background, traditional fixed and adaptive dose-response designs are briefly reviewed. Information on developing a Bayesian adaptive dose design and some monitoring and processing issues are also discussed.