Risk evaluation and mitigation strategies: Who is responsible for drug safety in the US?

BACKGROUND: The Food and Drug Administration Amendment Act of 2007 enabled the FDA to require risk evaluation and mitigation strategies (REMS) for any drug or biologic to ensure that benefits of the product outweigh its risks. We assessed the characteristics of REMS approved by the FDA in the period 2008-2011, and evaluated when REMS were approved during the lifecycle of drugs. DATA AND METHODS: Data were collected from the following FDA databases: Approved Drug Products with Therapeutic Equivalence Evaluations, Approved REMS and Drugs@FDA. Information extracted included: generic availability, application type, application approval date, therapeutic class, FDA review class, orphan designation, and market discontinuations. REMS information included: components, and date of approval, modification and release. Data were updated through December 31, 2011. REMS characteristics were assessed to determine trends in FDA selection of drugs that require REMS. The approval, modification and release of REMS were incorporated into the drug lifecycle. RESULTS: The FDA approved 199 REMS (NDA=164; ANDA=5; BLA=30) in the period of analysis. There were 26 REMS approved in 2008, 75 in 2009, 64 in 2010 and 34 in 2011. The FDA released 47.7% of the drugs from REMS requirements in 2011. The FDA granted Orphan designation to 16 products with REMS (8.7% of products that qualified for Orphan status). The FDA granted priority review to 32.3% of the NDAs with REMS. A total of 85 companies -incorporated in 14 countries- hold REMS for their products. FDA required the largest number of REMS for drugs in the classes nervous system (31.7% of REMS), alimentary tract and metabolism (15.1%), and antineoplastic and immunomodulating agents (13.1%). Medication guide (90.5%) and communication plan (29.6%) were the most commonly approved REMS components. The average number of years from 1st drug application approval to REMS approval was 7.8±11.8 years, from REMS approval to 1st REMS modification was 5.2 ±5.4 years, and from REMS approval to REM release was 1.7±0.8. There were 76 REMS (38.2% of REMS approved in the study period) approved the same day that the 1st drug application. CONCLUSIONS: The majority of REMS were approved for drugs without priority review or orphan designation. Earlier REMS were approved mostly for drugs that were already in the market. In 2011, the FDA changed its policy and released almost half of the products from REMS requirements. The REMS represents a transfer of the responsibility for drug safety from the FDA to patients and health care providers.