Success and Futility Criteria for Accelerated Approval of Oncology Drugs.

Project FrontRunner encourages development of cancer drugs for advanced or metastatic disease in an earlier clinical setting by promoting regulatory approaches such as the accelerated approval pathway. The FDA draft guideline proposes a one-trial approach to combine accelerated approval and regular approval in a single trial to maintain efficiency. This article describes our idea of controlling Type I error for accelerated and regular approvals in the one-trial approach. We introduce success and futility boundaries on p-values for accelerated approval to create three outcomes: success, RA, and futility. If success, accelerated approval can be claimed for; for RA, only regular approval (RA) is considered; if futility, we stop the trial early for futility. For both success and RA, the endpoint for regular approval can be tested with no penalty on its significance level. The proposed approach is robust to all possible values of correlation between test statistics of the endpoints for accelerated and regular approvals. This framework is flexible to allow clinical trial teams to tailor success and futility boundaries to meet clinical and regulatory needs, while maintaining the overall Type I error control in the strong sense.