Benefit-risk reassessment of medicines: a retrospective analysis of all safety-related referral procedures in Europe during 2001-2012

Pharmacoepidemiol Drug Saf. 2016 Sep;25(9):1004-14. doi: 10.1002/pds.4011. Epub 2016 May 4.


Purpose: The aim of this study was to determine the outcomes and timing within the product life cycle of all benefit-risk reassessment procedures for marketed products that were completed by the committee for medicinal product for human use during 2001-2012.

Methods: A cohort of all referral procedures for benefit-risk reassessment (Article 20, Article 31, Article 36, Article 107 procedures) for which committee for medicinal product for human use issued an opinion between 1 January 2001 and 31 December 2012 was created. The European Medicines Agency website and the Dutch Medicines Evaluation Board website were used to collect all data.

Results: There were a total of 73 benefit-risk reassessments during the study period; 61 reassessments for a single product and 12 reassessments for multiple products or an entire product class. Nineteen reassessments resulted in the recommendation to remove the product from the market. On average, a benefit-risk reassessment was performed 18.7 years after the product was first marketed. Seventeen products were marketed 5 years or less when the reassessment procedure was completed; six of these products were subsequently removed from the market.

Conclusions: The majority of all benefit-risk reassessments that were performed during the study period did not result in removing the product from the market, but rather, in confirming the positive benefit-risk of the product, conditional to changes to the product's marketing authorisation. About half of all products that were removed from the market during the 2000s had been marketed for more than 20 years. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: benefit-risk assessment; drug regulation; pharmacoepidemiology; pharmacovigilance; referrals; regulatory science.

MeSH terms

  • Drug Approval*
  • Europe
  • Humans
  • Netherlands
  • Product Surveillance, Postmarketing / methods
  • Product Surveillance, Postmarketing / statistics & numerical data*
  • Retrospective Studies
  • Risk Assessment / methods*
  • Safety-Based Drug Withdrawals / statistics & numerical data*
  • Time Factors