(004) Challenges of multi-country post-authorisation safety studies for surveillance of new medical products

Background: Post-authorisation safety studies (PASS) are an essential part of pharmacovigilance plans for newly marketed drugs. Given the complexities of real-world data, there are common challenges to be dealt with during study set-up. However, there are also unforeseen challenges that may arise during the execution of the study, particularly for newer drug classes where there are fewer historical PASS to reference.

Objectives: To describe challenges and learnings from the development and execution of a drug utilisation and long-term safety PASS for galcanezumab, a biologic for use in migraine prevention which received central marketing authorisation approval in the EU in 2018, across seven European real-world databases.

Methods: This analysis was conducted as part of the ongoing galcanezumab EU PASS (2019-2026; EU PAS Register Number EUPAS27594) in seven European countries (France, Germany, Italy, the Netherlands, Spain, Sweden and the United Kingdom). To assess feasibility of study objectives, the number of countries in which the product had actually been launched to date was assessed, as well as the accrued person-time exposure in comparison to the targeted exposure time for reaching analytical power. Furthermore, a qualitative examination was undertaken to identify the main challenges during study development and execution, focusing on unforeseen challenges that impacted the ability to meet the study objectives in a timely manner.

Results: By the 2023 EU interim analysis, galcanezumab had been launched in 6 out of 7 selected countries initially planned to be included in the PASS. Time of country-specific reimbursed launch ranged from April 2019 to September 2021. Total person-time exposure accrued ranged between the countries from 0 to 6% of the targeted exposure time, with the data cut ending in December 2021 at maximum. Besides this lagging drug uptake, another challenge identified was the access to data as planned, which was mainly compromised by the COVID-19 pandemic, by regulatory changes for data access and by the channels of drug distribution.

Conclusions: The uncertain timing of the country-specific galcanezumab reimbursed launch after marketing approval was identified as an important challenge in being able to reach the targeted sample size on time. Altogether, conducting a long-term PASS of new medical products proves to be a dynamic endeavour, underscoring the critical need for proactive anticipation of unforeseen challenges, continuous monitoring of drug uptake, and agile adjustments throughout the process. Balancing this adaptive approach with committed study milestones requires ensuring both timeliness and the quality needed for valuable study outcomes.