Trial Design and Efficacy Thresholds for Granting Breakthrough Therapy Designation in Oncology.

Breakthrough therapy designation (BTD) is a new approach created by the US Congress and the US Food and Drug Administration (FDA) as part of the FDA Innovation and Safety Act of 2012 to expedite the drug development process for serious illness, including cancer. By law, to qualify for BTD, a new molecular entity must demonstrate substantial clinical improvement over existing therapies. Although the administrative requirements for granting BTD have been made available by the FDA, the actual trial designs, end points, and quantitative therapeutic thresholds involved in the granting process have not been made public. This literature review evaluates nine oncology new molecular entities granted BTD involved in 10 accelerated approvals and summarizes the key factors in clinical trial design leading to successful BTD applications. This information can be used by oncology research teams to set goals for BTD when developing clinical trial designs and thresholds in expedited drug development programs.