Background: Enhanced Safety Surveillance is required by the European Medicines Agency (EMA) for seasonal influenza vaccines. EPSS, one of the recommended designs, aims to rapidly detect potential new safety concerns early in the season by facilitating voluntary reporting of adverse drug reactions (ADRs).
Objectives: To review challenges and strengths of influenza vaccine EPSS.
Methods: Sanofi carried out 8 EPSS in Finland, United Kingdom, Ireland, Denmark, and Germany between seasons 2015/16 and 2022/23. Country selection was mainly based on availability of Sanofi flu vaccines, timing of the vaccination campaign, and national recommendations. Vaccine exposure was collected by healthcare professionals (HCPs) through vaccination cards entered in an electronic system. HCPs encouraged vaccinees to report ADRs, particularly those occurring in the 7 days following vaccination. In each season, approximately 1000 subjects per vaccine brand were enrolled. From 2015/16 to 2019/20, vaccinees reported ADRs by telephone (structured interview), email, or mail. From 2020/21 to 2022/23, a structured electronic data reporting form was implemented with telephone remaining as a backup option.
Results: Recurrent challenges included finding sites where HCPs were willing to participate and ensuring adequate representation of all age groups covered by the indications, especially pediatric and elderly populations. A key strength was the use of an electronic system to collect exposure data, allowing the study team to monitor the number of enrolled vaccinees on a real-time basis. Various methods were applied to collect ADRs over the years. Email reports led to poor data quality and returning ADR forms via mail required additional work for the vaccinees, especially in the case of multiple events at different time points. The use of an electronic ADR form in the past 3 seasons simplified data collection and management. It enabled safety concerns to be rapidly processed by local pharmacovigilance staff through automatic notifications once a new ADR was reported. From 2015/16 to 2019/20, the vaccinee reporting rate ranged from 1.2% to 6.0%. From 2020/21 to 2022/23, the range was 1.0% to 5.1%. Over the past 3 seasons, among vaccinees that reported at least one ADR, 80.0% to 98.0% used the electronic system. Although the electronic reporting system may not have increased the reporting rates, it was generally well accepted by vaccinees and facilitated the study from an operational perspective.
Conclusions: Sanofi has successfully implemented EPSS in Europe. For future seasons, collaboration between influenza vaccine manufacturers in Europe and an update of the EMA guideline could create strategies for a sustainable ADR collection system in EPSS and strengthen the true value of this initiative.
