Decision Making Under Uncertainty: Comparing Regulatory and Health Technology Assessment Reviews of Medicines in the United States and Europe

Clin Pharmacol Ther. 2020 Aug;108(2):350-357. doi: 10.1002/cpt.1835. Epub 2020 Apr 20.


Assessments of clinical evidence vary between regulators and health technology assessment bodies, but precise differences remain unclear. To compare uncertainties raised on the clinical evidence of approved drugs, we analyzed assessments of regulators and health technology assessment (HTA) bodies in the United States and Europe. We found that US and European regulators report uncertainties related to safety for almost all drugs (85-94%), whereas HTA bodies reported these less (53-59%). By contrast, HTA bodies raised uncertainties related to effects against relevant comparators for almost all drugs (88-100%), whereas this was infrequently addressed by regulators (12-32%). Regulators as well as HTA bodies reported uncertainties related to the patient population for 60-95% of drugs. The patterns of regulator-HTA misalignment were comparable between the United States and Europe. Our results indicate that increased coordination between these complementary organizations is necessary to facilitate the collection of necessary evidence in an efficient and timely manner.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Decision Making*
  • Drug Approval*
  • Europe
  • Humans
  • Patient Safety
  • Risk Assessment
  • Technology Assessment, Biomedical*
  • Uncertainty
  • United States
  • United States Food and Drug Administration*