Luísa Bouwman, Diogo Almeida, Carla Jonker, Hubert Leufkens, Bruno Sepodes, Carla Torre
Our findings confirm that RWD/RWE have become an essential component of the regulatory evaluation of orphan medicinal products. In the period studied, more than 80% of the marketing authorisation approvals of OMPs contained RWD/RWE. The prevalence of RWD/RWE was higher in the post-authorisation phase (72%) than in the pre-authorisation phase (66%). In the pre-authorisation phase, the role of RWD was mainly (68%) supportive. The RWE studies in the post-authorisation phase intended to investigate specific safety concerns, including collecting long-term safety data, and evaluate effectiveness in real-world conditions.
PURPOSE: We aimed to assess the role of real-world data (RWD)/real-world evidence (RWE) for regulatory decision-making of the marketing authorisation approvals of orphan medicinal products (OMPs) in the European Union (EU) between 2000 and 2025.
METHODS: All European public assessment reports (EPAR) of the OMPs approved in the EU between 1 January 2000 and 31 December 2025 were screened for RWD/RWE submitted by the applicant in the initial application (pre-authorisation phase) and classified as 'main', 'supportive' or 'not known'. Post-authorisation measures foreseen, described in Annex II conditions or additional pharmacovigilance activities required to address specific safety concerns were checked and were included if RWD/RWE was present.
RESULTS: RWD/RWE were present in about 80% of the marketing authorisation applications analysed. RWD had a supportive role in the benefit-risk assessment in 68% of cases and contributed to the main evidence in 21% of the cases. The RWE in the pre-authorisation phase comes from data from early access programs (36%), case reports and natural history studies used as historical controls (24%), clinical data from electronic health records (17%), and safety data from post-marketing experience in other geographic regions (11%). RWD sources in the post-authorisation phase were most commonly registries (67%), followed by electronic health records (19%).
CONCLUSIONS: Our findings confirm that RWD/RWE have become an essential component of the regulatory evaluation of orphan medicinal products. In the period studied, more than 80% of the marketing authorisation approvals of OMPs contained RWD/RWE. The prevalence of RWD/RWE was higher in the post-authorisation phase (72%) than in the pre-authorisation phase (66%). In the pre-authorisation phase, the role of RWD was mainly (68%) supportive. The RWE studies in the post-authorisation phase intended to investigate specific safety concerns, including collecting long-term safety data, and evaluate effectiveness in real-world conditions.