Abstract
The decision to approve a drug for clinical use is based on an understanding of its benefits versus the risks. Although efficacy is generally understood at the time of submission to the FDA for approval, the risks are more difficult to assess. Both PubMed (from 2000 to 2012) and the FDA website (www.fda.gov) were searched using the search terms “risk evaluation and mitigation strategy” (REMS). Articles for review were selected by relevance to topic, and their references were searched as well for additional relevant resources. Since the search results were not expected to contain research studies, formal quality assessment and inclusion and exclusion criteria were not utilized resulting in a narrative review. Few directly relevant research studies exist, although supporting documents such as government reports were available. For effective drugs with unclear or concerning safety records, the FDA has the option of requiring a risk evaluation and mitigation strategy, which allows a systematic approach to track and assure safe medication use. Over 100 different medications are currently covered by REMS, and each REMS is developed individually based on the needs of the specific drug or class. Although likely associated with improvements in medication safety, the potential benefit, limitations, and consequences of REMS are not yet fully understood.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Avorn J (2011) Learning about the safety of drugs—a half-century of evolution. N Engl J Med 365:2151–2153. doi:10.1056/NEJMp1110327
Food and Drug Administration (2005) Guidance for industry development and use of risk minimization action plans
HHS Office of Inspector General (2006) FDA’s monitoring of postmarketing study commitments
United States Government Accountability Office (2010) Drug safety: FDA has begun efforts to enhance postmarket safety, but additional actions are needed
Food and Drug Administration Drug Safety Oversight Board. In: fda.gov. http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm082129.htm. Accessed 4 Mar 2012
Baciu A, Stratton K, Burke S (2007) The future of drug safety: promoting and protecting the health of the public. The National Academy Press, Washington, DC
United States Congress (2010) Food and Drug Administration Amendments Act of 2007
Leiderman DB (2009) Risk management of drug products and the U.S. Food and Drug Administration: evolution and context. Drug Alcohol Depend 105:S9–S13. doi:10.1016/j.drugalcdep.2009.02.007
American Pharmacists Association (2011) APhA 2011 REMS white paper: summary of the REMS stakeholder meeting on improving program design and implementation. J Am Pharm Assoc 51:340–358. doi:10.1331/JAPhA.2011.11519
Food and Drug Administration. Approved risk evaluation and mitigation strategies (REMS). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm. Accessed 4 Mar 2012
Enger C, Younus M, Petronis KR et al (2013) The effectiveness of varenicline medication guide for conveying safety information to patients: a REMS assessment survey. Pharmacoepidemiol Drug Saf 22:705–715. doi:10.1002/pds.3400
Food and Drug Administration (2011) Medication guides—distribution requirements and inclusion in risk evaluation and mitigation strategies (REMS).
Wolf MS, King J, Wilson EAH et al (2012) Usability of FDA-approved medication guides. J Gen Intern Med 27:1714–1720. doi:10.1007/s11606-012-2068-7
Dal Pan GJ (2013) Commentary on “The effectiveness of varenicline medication guide for conveying safety information to patients: a REMS assessment survey” by Enger et al. Pharmacoepidemiol Drug Saf 22:716–718. doi:10.1002/pds.3450
Lee LY, Kortepeter CM, Willy ME, Nourjah P (2008) Drug-risk communication to pharmacists: assessing the impact of risk-minimization strategies on the practice of pharmacy. J Am Pharm Assoc 48:494–500. doi:10.1331/JAPhA.2008.07045
Food and Drug Administration (2010) Drug administration. Guidance for industry: format and content of proposed risk evaluation and mitigation strategies (REMS), REMS assessments, and proposed REMS modifications
Food and Drug Administration (2007) Briefing document for iPLEDGE year one update. http://www.fda.gov/downloads/AdvisoryCommittees/…/UCM281376.pdf. Accessed 4 Mar 2012
Wedin GP, Hornfeldt CS, Ylitalo LM (2006) The clinical development of gamma-hydroxybutyrate (GHB). Curr Drug Saf 1:99–106
Food and Drug Administration. Warning letter to Jazz Pharmaceuticals, Inc. 10/11/11. http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm275565.htm. Accessed 4 Mar 2012
Centers for Disease Control and Prevention (CDC) (2012) CDC grand rounds: prescription drug overdoses—a U.S. epidemic. MMWR Morb Mortal Wkly Rep 61:10–13
Office of National Drug Control Policy (2011) Epidemic: responding to America’s Prescription drug abuse crisis. http://www.whitehouse.gov/sites/default/files/ondcp/…/rx_abuse_plan.pdf. Accessed 10 Feb 2012
Food and Drug Administration (2013) FDA blueprint for prescriber education for extended-release and long-acting opioid analgesics. 1–13
Food and Drug Administration (2010) Minutes for the July 22–23, 2010 joint meeting of the Anesthetic and Life Support Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee. 1–10
Nelson LS, Perrone J (2012) Curbing the opioid epidemic in the United States: the risk evaluation and mitigation strategy (REMS). JAMA 308:457–458. doi:10.1001/jama.2012.8165
Food and Drug Administration. Information by drug class—risk evaluation and mitigation strategy (REMS) for extended-release and long-acting opioids. In: fda.gov. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm163647.htm. Accessed 25 Aug 2013
Perrone J, Nelson LS (2012) Medication reconciliation for controlled substances—an “ideal” prescription-drug monitoring program. N Engl J Med 366:2341–2343. doi:10.1056/NEJMp1204493
Slevin KA, Ashburn MA (2011) Primary care physician opinion survey on FDA opioid risk evaluation and mitigation strategies. J Opioid Manag 7:109–115
Salinas GD, Robinson CO, Abdolrasulnia M (2012) Primary care physician attitudes and perceptions of the impact of FDA-proposed REMS policy on prescription of extended-release and long-acting opioids. J Pain Res 5:363–369. doi:10.2147/JPR.S35798
HHS Office of Inspector General (2013) FDA lacks comprehensive data to determine whether risk evaluation and mitigation strategies improve, drug safety (OEI-04–11–00510; 02/13). 1–38
Center for Drug Evaluation, Research Prescription Drug User Fee Act (PDUFA). REMS integration initiative. http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm350852.htm. Accessed 6 Oct 2013
Schwartz LM, Woloshin S (2011) Communicating uncertainties about prescription drugs to the public: a national randomized trial. Arch Intern Med 171:1463–1468. doi:10.1001/archinternmed.2011.396
Conflict of Interest
None
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nelson, L.S., Loh, M. & Perrone, J. Assuring Safety of Inherently Unsafe Medications: the FDA Risk Evaluation and Mitigation Strategies. J. Med. Toxicol. 10, 165–172 (2014). https://doi.org/10.1007/s13181-013-0374-z
Published:
Issue date:
DOI: https://doi.org/10.1007/s13181-013-0374-z