Managing the Risks of Medicines: An Examination of FDA's Application of Criteria for Requiring a REMS.

Background: In September 2016, the Food and Drug Administration (FDA) published a draft guidance for industry, , that detailed the factors the Agency considers in determining when a Risk Evaluation and Mitigation Strategy (REMS) is necessary. The objective of this study was to determine how the FDA has applied these criteria for newly approved drugs.

Methods: For the 3-year period, 2015-2017, which included a full year of FDA approvals both before and after the issuance of the draft guidance, publicly available FDA reviews were analyzed for all 113 approved products using the criteria outlined in the guidance.

Risk Evaluation and Mitigation Strategies With Elements to Assure Safe Use: Alignment of the Goals With the Tools to Manage Risk.

The Food and Drug Administration Amendments Act of 2007 gave the FDA the authority to require drug sponsors to submit a risk evaluation and mitigation strategies (REMS) program for those medicines with serious risks such that failure to effectively manage these risks would tip the benefit-risk balance. As of August 8, 2013, the 34 distinct individual and shared REMS programs that have specific elements to assure safe use (ETASU) were reviewed to ascertain the types of risks managed, the goals of the REMS, and the tools that were employed targeting prescribers, health care facilities, pharmacists, and particular conditions for safe use. Most REMS (65%) have a combination of risk mitigation and educational goals, but 4 REMS programs (12%) have exclusively educational goals.

Using controlled clinical trials to learn more about acute drug-induced liver injury.

Drug-induced liver injury (DILI) is of major interest to hepatologists and clinicians in general, patients, government regulators, and the pharmaceutical industry. Understanding why this form of injury occurs only in certain individuals has major implications for the development and availability of drug therapies and in the prevention of these events. A single controlled clinical trial may be unlikely to show cases of such rare events, but in the aggregate, clinical trials offer a unique resource for learning more about individual susceptibility and developing truly predictive new biomarkers for DILI.