Why do so Many Phase III Fail?
Randomized controlled trials (RCTs), particularly in phase 3, are the preferred sources of evidence for drug approval and reimbursement decisions. Moreover, phase 3 trials are at the top of the evidence-based medicine pyramid, thus representing the gold-standard for judgements about the efficacy and safety of new treatments and their worth in clinical practice. Nevertheless, regulatory and clinical decisions sometimes need to be made on evidence of lower level, such as that provided by phase 2 trials, particularly in oncology. As a matter of fact, nearly one-third of anticancer drug approvals by the US Food and Drug Administration (FDA) between 1992 and 2017 were accelerated approvals, one of the four types of expedited programs offered by that Agency.1,2
Marc Buyse, ScD, and Everardo Saad, MD