Director, Safety Evidence for Regulators IQVIA, Netherlands
Background: The EU Risk Management Plan (RMP) lists all Post-authorization safety studies (PASS) that are commitments to the European Medicines Agency (EMA) to further characterize the benefit risk profile of products following marketing authorization. To support transparency and scientific rigor, the EMA requires studies to be registered. Per EMA guidance, the marketing authorization holders should record all observational PASS, both imposed Category I and II and required Category III, in the new HMA-EMA Catalogues of real-world data sources and studies (RW catalogue); this catalogue was reviewed to understand progress of required post-marketing evidence.
Objectives: To describe design and status of 2022 PASS requirements by EMA per the RMP.
Methods: For all human medicinal products approved by the EMA in 2022 the publicly available RMP was reviewed. PASS were described using a standardised form. For all observational studies in Categories I to III the RW Catalogue was checked whether it was registered and if so, available key data including progress status were extracted. For all interventional studies status was determined using clinicaltrials.gov.
Results: There were 82 medicinal products approved by EMA in 2022 and half with PASS (n=41). The EU RMP included a total of 104 PASS for 41 products; 89 for 35 new active substance (NAS). Due to product withdrawal, 6 PASS are excluded from further analysis. From the 53 (54%) observational studies, 34 (64%) will perform primary data collection, 29 will use existing data. There were 35 PASS with an interventional design. For 10 studies the design could not be determined from RMP and were not registered in either the RW catalogue or on ClinicalTrials.gov. Most (N=18/21) imposed Category I and II PASS were registered in the RW catalogue or on clinicaltrials.gov. Among the 26 interventional Category III PASS, one was not on clinicaltrials.gov. Of the 41 observational Category III PASS 25 (61%) were recorded in the RW Catalogue. In summary, of the 98 Category I to III PASS, 27 (28%) were not found.
Conclusions: For half the products approved by EMA in 2022, post-marketing evidence was required. Most PASS were for products that contain a NAS. Observational studies were the most common type of studies in the RMP, with majority performing primary data collection. Several years of data should be reviewed to understand a trend in study design. Few Category I and II studies were not found; for the category III studies however, 36% were not found. This is a relatively large number of studies missing after a considerable amount of time; planning and protocol endorsement may take more than 2 years and for category III studies, there may be lower adherence to the EMA guideline. This indicates a transparency gap in post-authorization evidence generation.
