OBJECTIVES: The European Medicines Agency (EMA) evaluates drugs’ benefit/risk, while Health Technology Assessment (HTA) bodies assess added value for reimbursement. EMA may grant marketing authorization (MA) under “exceptional circumstances” when there is insufficient data on efficacy and safety due to disease rarity or ethical reasons. This study analyzes HTA outcomes in Germany, Italy, France, and England for medicines approved under exceptional circumstances.

METHODS: All products granted MA by EMA under exceptional circumstances between 2016-2020 were identified and assessed regarding inclusion criteria. The EMA website and publicly available HTA resources in Germany, Italy, France, and England were searched to extract regulatory and HTA outcomes.

RESULTS: Of twelve identified products, eight were included, all with orphan designation. Four did not meet the inclusion criteria (withdrawal, specific vaccinations/uses). Five of the included products were reimbursed in France, six in Italy, five in Germany, and three in England. Two in France and one in England were denied reimbursement. One in France, two in Italy and Germany, and four in England were not assessed. One was exempt from assessment in Germany. Average time to decision on reimbursement in years for these products was longer compared to all drugs: France (4.1 vs. 1.4), Italy (2.7 vs. 1.2), England (2.1 vs. 0.9), and Germany (1.7 vs. 0.4).

For all products in France, Germany, and all except one in Italy, the reimbursed population was unrestricted versus the EMA-approved label. France required additional data, aligned with EMA requests, and Italy required a prescription registry for reimbursed products. In England, reimbursed products underwent multiple review rounds, with two recommended for a subset of the population. All appraisals acknowledged caregiver/family burden's significance.

CONCLUSIONS: Contrary to expectations, expedited regulatory approval under the exceptional circumstances pathway paradoxically slows down pricing and reimbursement decisions, even for products with small patient populations and orphan status.