Identifying regulatory outcomes of non-interventional Post Authorisation Safety Studies in the European repository of studies using publicly available information

Mariana Ferreira Almas^1*Anna Girardi²Salvatore Crisafulli³Katarina Gvozdanovic^4,5Katja Hakkarainen⁶Giulia Hyeraci²Wilhelmina Hoogendoorn⁷Bettina Rillmann⁸Giuseppe Roberto²Giacomo Vitturi³Gianluca Trifirò³

• ¹IQVIA (Portugal), Porto Salvo, Portugal
• ²Agenzia Regionale di Sanità Toscana, Tuscany, Italy
• ³University of Verona, Verona, Veneto, Italy
• ⁴Agency for Medicinal Products and Medical Devices, Zagreb, Croatia
• ⁵Andrija Stampar Teaching Institute of Public Health, Zagreb, Croatia
• ⁶Epidemiology and Real-World Science, Parexel, Gothenburg, Sweden
• ⁷IQVIA Epidemiology and Database Studies, Amsterdam, Netherlands
• ⁸Late Phase and Real World Evidence ICON Plc, Frankfurt, Germany

Post Authorisation Safety Studies (PASS) generate evidence that may support regulators to evaluate the medicinal products and to take regulatory actions when needed. The European Medicine Agency (EMA) promoted decision-making transparency by publishing regulatory guidelines and endorsing the registration of PASS in the European Post-Authorisation Study (EU PAS) Register. A recent analysis of the EU PAS Register showed a marked increase of PASS conducted as multidatabase studies (MDS) during the last decade. This study aimed to assess the feasibility of using public information from the EMA website to identify regulatory outcomes of PASS and, to describe those outcomes by MDS and non-MDS. An equal number of MDS and non-MDS PASS, were selected from the EU PAS Register if: completed between 07/2012 and 12/2020, part of the Risk Management Plan (RMP), required by a European regulator, and conducted in ≥1 EU/UK country. Mentions of the PASS were searched in the Pharmacovigilance Risk Assessment Committee (PRAC) meeting minutes, the European Public Assessment Report (EPAR), and other EMA webpages using study title, acronym, protocol, or regulatory number. Whenever identified, the regulatory outcome information was retrieved. A total of 84 PASS (42 MDS and 42 non-MDS) were analysed., of which, 77% were found in at least one of the sources but the information available was scarce. Regulatory outcomes were identified for 46% of all 84 PASS, with no differences between MDS and non-MDS. Outcomes were more frequently identified for imposed (78%) than non-imposed PASS (34%). The availability of regulatory outcomes increased from 25% for PASS completed in the years 2012-2014 to 56% for those completed in 2018-2020. The regulatory outcome information was unspecific for two thirds of the PASS with outcomes, limiting our description of outcome types.The attempt to identify and describe the regulatory outcomes of MDS and compare them to non-MDS, was impaired by difficulties in identifying PASS, lack of information, granularity, standardisation and consistency across sources. We advocate for an increased transparency of the regulatory outcomes of PASS through the use of a unique PASS identifier and for a complete regulatory outcome publication to understand the regulatory impact of the PASS.