Abstract

Prior work has shown that certain types of adaptive designs can always be dominated by a suitably chosen, standard, group sequential design. This applies to adaptive designs with rules for modifying the total sample size. A natural question is whether analogous results hold for other types of adaptive designs. We focus on adaptive enrichment designs, which involve preplanned rules for modifying enrollment criteria based on accrued data in a randomized trial. Such designs often involve multiple hypotheses, e.g., one for the total population and one for a predefined subpopulation, such as those with high disease severity at baseline. We fix the total sample size, and consider overall power, defined as the probability of rejecting at least one false null hypothesis. We present adaptive enrichment designs whose overall power at two alternatives cannot simultaneously be matched by any standard design. In some scenarios there is a substantial gap between the overall power achieved by these adaptive designs and that of any standard design. We also prove that such gains in overall power come at a cost. To attain overall power above what is achievable by certain standard designs, it is necessary to increase power to reject some hypotheses and reduce power to reject others. We conclude by showing the class of adaptive enrichment designs allows certain power tradeoffs that are not available when restricting to standard designs. We illustrate our results in the context of planning a hypothetical, randomized trial of a new antidepressant, using data distributions from (Kirsch et al., 2008).

Disciplines

Statistical Methodology | Statistical Theory

Media Format

flash_audio