Approvals of drugs with uncertain benefit-risk profiles in Europe

Eur J Intern Med. 2015 Oct;26(8):572-84. doi: 10.1016/j.ejim.2015.08.008. Epub 2015 Sep 3.


Purpose: This paper examines conditional approvals that allow the marketing of medicines with unsettled benefit-risk profiles in the European Union.

Methods: We identified medicines that had received conditional approval from the European Medicines Agency in the period January 2006-June 2015. We searched the reasons and bases for approvals, the median time to address the specific obligations imposed in order to cover the information gap and allow regular authorisations, and their extent of fulfilment.

Results: Of the 26 products conditionally authorised two were withdrawn for commercial reasons, ten were switched to regular approval, and 14 are still under conditional approval. Conditional approval was granted mainly to medicinal products intended for seriously debilitating disease or life-threatening disease. The median time to address the specific obligations was four years (range 0.2 to 7.7). There were delays or discrepancies in the fulfilment of these obligations in more than one third of the authorisation procedures.

Conclusions: In most cases there was limited evidence supporting the positive benefit-risk balance at the time of approval. Delays or discrepancies in the fulfilment of obligations allow medicinal products with unsettled benefit-risk profiles onto the market for several years. This should be taken into account when further early or step-wise licensing strategies are considered.

Keywords: Clinical trials; Drug regulation; Marketing authorisation; Orphan drugs; Post-market measure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Approval* / methods
  • Drug Approval* / organization & administration
  • European Union
  • Humans
  • Risk Assessment
  • Uncertainty