The Role of Regulator-Imposed Post-Approval Studies in Health Technology Assessments for Conditionally Approved Drugs

Rick A Vreman, Lourens T Bloem, Stijn van Oirschot, Jarno Hoekman, Menno E van der Elst, Hubert Gm Leufkens, Olaf H Klungel, Wim G Goettsch, Aukje K Mantel-Teeuwisse

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BACKGROUND: The European Medicines Agency (EMA) aims to resolve uncertainties associated with conditionally approved drugs by imposing post-approval studies. Results from these studies may be relevant for health technology assessment (HTA) organizations. This study investigated the role of regulator-imposed post-approval studies within HTA.

METHODS: For all conditionally approved drugs up to December 2018, regulator-imposed post-approval studies were identified from EMA's public assessment reports. The availability for and inclusion of study results in relative effectiveness (re)assessments were analyzed for 4 European HTA organizations: NICE (National Institute for Health and Care Excellence, England/Wales), HAS (Haute Autorité de Santé, France), ZIN (Zorginstituut Nederland, the Netherlands) and the European Network for Health Technology Assessment (EUnetHTA, Europe). When study results became available between an HTA organization's initial assessment and reassessment, it was evaluated whether and how they affected the assessment and its outcome.

RESULTS: For 36 conditionally approved drugs, 98 post-approval studies were imposed. In total, 81 initial relative effectiveness assessments (REAs) and 13 reassessments were available, with numbers of drugs (re)assessed varying greatly between jurisdictions. Study results were available for 16 initial REAs (20%) and included in 14 (88%), and available for 10 reassessments (77%) and included in all (100%). Five reassessments had an outcome different from the initial REA, with 4 (2 positive and 2 negative changes) relating directly to the new study results. Reassessments often cited the inability of post-approval studies to resolve the concerns reported in the initial REA.

CONCLUSION: Results from regulator-imposed post-approval studies for conditionally approved drugs were not often used in REAs by HTA organizations, because they were often not yet available at the time of initial assessment and because reassessments were scarce. When available, results from post-approval studies were almost always used within HTA, and they have led to changes in conclusions about drugs' relative effectiveness. Post-approval studies can be relevant within HTA but the current lack of alignment between regulators and HTA organizations limits their potential.

Original languageEnglish
Pages (from-to)642-650
Number of pages9
JournalInternational Journal of Health Policy and Management
Issue number5
Early online date2020
Publication statusPublished - May 2022


  • Authorization
  • Conditional
  • Evidence
  • Health Technology Assessment
  • Post-approval
  • Relative Effectiveness


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