Assuring safety of inherently unsafe medications: the FDA risk evaluation and mitigation strategies

J Med Toxicol. 2014 Jun;10(2):165-72. doi: 10.1007/s13181-013-0374-z.


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 ( 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.

Publication types

  • Historical Article
  • Review

MeSH terms

  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Inappropriate Prescribing / prevention & control
  • Practice Guidelines as Topic
  • Prescription Drugs / adverse effects*
  • Prescription Drugs / therapeutic use
  • Product Surveillance, Postmarketing / methods*
  • Registries
  • Risk Assessment
  • United States
  • United States Food and Drug Administration / history*


  • Analgesics, Opioid
  • Prescription Drugs