Design considerations for noninferiority trials in phase II: Use of optimal design, quantitative decision criteria and trial success simulations to increase the probability of making the correct decision at the end of the trial

Objectives: Increasingly noninferiority designs are being used for Phase II trials to compare new drugs to standard treatment (i.e. a well proven standard therapy which has been shown to be superior to placebo, and has an established, predictable and quantifiable effect). It is often of interest to know early in the drug development process whether the new drug is equi-efficacious to standard treatment. In particular where the benefits of the new drug may be a better safety profile or an improved administration schedule. The large sample sizes required for noninferiority trials means they can be more costly and take longer to run, so it is important that the design is optimised to keep the impact on costs and timelines to a minimum. This poster outlines simulation methodology used to optimise trial design for a Phase II PoC study where the primary objective is to assess noninferiority against the standard treatment, and the secondary objective is to define the dose-response of the new drug in patients.