In designing a Phase III randomized trial, care must be taken in selecting the target population. Advantages of enrolling from a larger population include wider generalizability of results and faster recruitment. However, since earlier trials (e.g. Phase II trials) may only have enrolled participants from a relatively narrow population, little data may be available on the larger population. This makes a Phase III trial that enrolls from the larger population more risky. We propose new adaptive, group sequential designs aimed at gaining the advantages of wider generalizability and faster recruitment, while mitigating the risks of including a population for which there is little prior data. These designs use preplanned rules for changing the enrollment criteria if the participants from predefined subpopulations are not benefiting from the new treatment. We demonstrate these adaptive designs in the context of a Phase III trial of a new treatment for stroke, and compare them to standard designs in terms of expected sample size and trial duration. In this context, we investigate the tradeoff between sample size and trial duration that arises in designs with preplanned rules for changing the enrollment criteria.
Rosenblum, Michael; Thompson, Richard E.; Luber, Brandon S.; and Hanley, Daniel F., "Adaptive Group Sequential Designs that Balance the Benefits and Risks of Expanding Inclusion Criteria" (December 2012). Johns Hopkins University, Dept. of Biostatistics Working Papers. Working Paper 250.