Vaccines and EU HTA: Exploring Misalignments Between Joint Clinical Assessment Requirements and a Hypothetical Vaccine Evidence Package

OBJECTIVES: EU HTAR (Health Technology Assessment Regulation) on the Joint Clinical Assessment (JCA) of new health technologies includes prophylactic vaccines, confirmed in article 4 of the regulation; however, there is a concerning lack of information on how the process will apply to vaccines specifically. Given significant differences between drug HTA and vaccine NITAG frameworks, this research aims to explore the challenges of subjecting a vaccine to JCA.

METHODS: A hypothetical prophylactic vaccine profile was created, based on a typical evidence package at the time of EMA marketing authorisation (e.g., vaccine efficacy, safety, tolerability, duration of protection). Evidence was compared to Member State data request expectations using all publicly available guidelines/templates/methodologies on the JCA process, following the PICO framework approach. Areas of alignment/misalignment were outlined and implications for vaccine Health Technology Developers (HTD) identified.

RESULTS: This analysis suggests that vaccine evidence packages may not meet JCA requirements across 3 main PICO parameters (population, comparator, and outcomes) unless exceptions are made. Key findings include 1) lack of confirmation that immunogenicity is sufficiently validated for JCA as a surrogate for protection; 2) risk of variable sub-population expectations from MS based on inclusion on National Immunization Programs; 3) rigid JCA safety definitions do not account for the nuances between reactogenicity and safety for vaccines; 4) lack of clarity on use of placebo control, as is standard for first-in-disease vaccines.

CONCLUSIONS: There are critical misalignments between vaccine RCT standard practices today and evidence expectations for JCA, which have been shaped by value frameworks for drugs and with insufficient input from vaccine specific stakeholders (e.g., NITAGs). Formal clarification from the HTACG is needed on how HTDs for vaccines should approach the JCA. Additionally, HTDs for vaccines should seek all opportunities for early advice – including JSC from 2025, where eligible – prior to pivotal study finalization.