Postauthorization Changes to Specific Obligations of Conditionally Authorized Medicines in the European Union: A Retrospective Cohort Study

Clin Pharmacol Ther. 2019 Feb;105(2):426-435. doi: 10.1002/cpt.1169. Epub 2018 Aug 12.


When medicines are granted a Conditional Marketing Authorisation (CMA) in Europe, specific obligations are requested to obtain comprehensive data on benefits and risks. We performed a retrospective cohort study to characterize obligations, examine changes to their description and due dates after initial authorization, determine timing of data submission relative to due dates, and identify drug-related, procedure-related, and obligation-related factors associated with change. We identified 69 obligations for 26 medicines conditionally authorized between 2006 and 2016. We found 39 changes to 27 obligations (39% of obligations), of which four substantially changed the obligation. For 55% of obligations, data submission was delayed. Eleven factors were associated with change, including the use of CMA as a rescue option. The results are potentially indicative of a continuous search by regulators to reduce uncertainties. Submission delays impact public health negatively by prolonging exposure of patients to unknown risks, particularly when the level of uncertainty is high.

MeSH terms

  • Clinical Trials as Topic
  • Cohort Studies
  • Drug Approval / methods*
  • Drug Labeling
  • European Union
  • Humans
  • Research Design
  • Retrospective Studies