Phase 2 Design Considerations from a Program Perspective

One of the key objectives of Phase 2 trials in drug development is de-risking the investment into costly Phase 3 trials. This de-risking introduces added costs, an extended drug-development duration, as well as the likelihood of discontinuing truly efficacious interventions based on chance findings. The choice of Phase 2 sample size and decision rules have, as such, large impact on the value of development programs. Still, Phase 2 designs are frequently guided by rather qualitative discussions on Type 1 error and power only, instead of discussing more directly the financial impact. In this paper, we introduce a model, which allows for the rapid assessment of the expected net present value (eNPV) and allows to optimize Phase 2 sample size and decision rules. Using a limited number of additional assumptions, the model generates helpful insights to ease understanding of program design operating characteristics. We discuss key limitations of designs, which are driven solely by the eNPV optimization, and propose an alternative using constrained optimization to optimize candidate Phase 2 study designs.