Keywords: adaptive design, clinical trials, regulatory perspective,
I will provide a regulatory perspective on key principles for adaptive designs. In general, the design, conduct, and analysis of a proposed adaptive clinical trial intended to provide substantial evidence of effectiveness should satisfy four key principles: the chance of erroneous conclusions should be adequately controlled, estimation of treatment effects should be sufficiently reliable, details of the design should be completely pre-specified, and trial integrity should be appropriately maintained. It is also good practice for sponsors to compare a variety of adaptive and non-adaptive designs with respect to a range of important operating characteristics at the trial planning stage to ensure that the most appropriate design is selected. These concepts will be illustrated in a setting in which a design with adaptive modifications to the sample size based on interim comparative results is being considered.