The US Food and Drug Administration’s expedited approval programs: addressing premarket flexibility with enhanced postmarket evidence generation

When the editors of Clinical Trials solicited our review on the U.S. Food and Drug Administration’s (FDA) expedited development and review programs, we anticipated there would be accompanying commentaries from other academics with differing opinions, or perhaps from the perspectives of industry or venture capital. We hardly expected to initiate a discussion among the former Commissioner of the FDA, the current Director of the Center for Drug Evaluation and Research (CDER), and the Chief Medical Officer of the American Society of Clinical Oncology on the advantages and disadvantages to patients and clinicians of FDA’s expedited approval programs. But we appreciate the opportunity to have done so. To be clear, the goal of our review was to engage in constructive dialogue, discussing the implications of expedited approval programs on premarket and postmarket evidence generation, highlighting some specific concerns, and offering our recommendations for robust medical product evaluations that ensure high-quality clinical evidence is available to inform patient care and clinical decision-making. The FDA faces the challenging task of striking the right balance between ensuring that novel therapeutics are safe and effective and allowing promising new drugs to enter the market as quickly as possible. We agree with Dr. Califf that FDA’s regulatory approach should not ‘revert back to the strategy of the 1970s’.2 Likely in response to the desires frequently expressed by patients and clinicians, the U.S. Congress has enacted laws requiring the FDA to develop expedited development and review pathways to accelerate the availability of novel therapeutics. Some of these pathways necessarily offer potential flexibility with respect to the evidentiary standards that are required to demonstrate medical product safety and effectiveness and secure approval. Accordingly, we believe there is a need for corresponding efforts to strengthen the clinical evidence that is generated after market approval.