Enhanced passive safety surveillance (EPSS) of a seasonal intranasal influenza vaccine (Fluenz® Tetra) in children in England: methodology, results and lessons learned from eight influenza seasons (2015/2016 to 2022/2023)

INTRODUCTION: Fluenz® Tetra, an intranasal influenza vaccine, was recommended for children aged 2-17 years as part of the UK influenza vaccination campaign. Following regulatory guidance issued by the European Medicines Agency (EMA), enhanced passive safety surveillance (EPSS) was conducted annually for Fluenz® Tetra to monitor its safety in real-time. OBJECTIVE: To evaluate the methodological approach implemented for EPSS of Fluenz® Tetra in England. METHODS: The EPSS used a prospective, non-interventional design to enhance spontaneous reporting of adverse drug reaction (ADRs). Over eight influenza seasons (2015/2016-2022/2023), GP practices/school immunisation teams handed out a safety report card (SRC) to vaccinees or their representatives following vaccination. Recipients were asked to return the SRC only if an ADR occurred. Sites recorded the number of SRCs distributed, which served as the denominator for risk estimates. Descriptive analyses were performed. RESULTS: Each season, between 38 and 49 GP practices and 25-50 schools participated. A total of 8753-17,922 SRCs were issued annually. Return rates for eligible SRCs were highest in 2015/2016 (1.9%), declining to 0.4% in 2022/2023. In all seasons, most reports received were for 2-4-year-olds (41.3%-64.4%). Rhinorrhoea was most frequently reported across all seasons (0.1%-0.6%). Serious ADRs were rare. CONCLUSIONS: The EPSS served as a valuable extension to routine pharmacovigilance, by facilitating near real-time collection of patient-reported outcomes, alongside denominator data for risk estimates. ADR frequencies reported across seasons were low. Whilst some degree of underreporting may have remained despite the enhanced methodology, findings supported the positive benefit-risk profile of Fluenz® Tetra in children over eight seasons.