Presentation (CTI)

OBJECTIVES: Comparing the efficacy/effectiveness of vaccines using network meta-analysis (NMA) presents challenges that can impact the relevance and validity of findings. Although established frameworks to guide NMA feasibility assessments exist, they do not address factors that are unique to comparisons of vaccines.
METHODS: A novel framework for assessing the feasibility of NMAs of seasonal vaccines (i.e., influenza, respiratory syncytial virus, severe acute respiratory syndrome coronavirus 2) was developed.
RESULTS: Network connectivity and the selection of common comparators pose a critical challenge; particularly, since brand-specific comparisons are often infeasible, and therefore, grouping vaccines by platform or valence may be required. When assessing evidence of effect modification (EM), variables beyond population characteristics require careful consideration, such as geography, study period, vaccine mismatch, prior vaccination, and prior infection. Special target populations for vaccination (i.e., elderly or high-risk individuals) are often evaluated as subgroups lacking available characteristics to effectively evaluate evidence of EM. Importantly, the likelihood of EM may be compounded with placebo or unvaccinated comparators, requiring unique considerations unlike with head-to-head active vaccine comparisons. Furthermore, many individual studies do not report circulating variants/strains, requiring assumptions which must be vetted with clinical experts and/or virus specialists to appropriately group studies. Other challenges relate to variability in outcome definitions and follow-up durations. Clinical trials of vaccines are also often small and lack the power to detect differences in key efficacy outcomes, which typically occur as rare events (i.e., severe infection or death). While event rates are frequently reported, robust NMAs often require adjusted relative effects from real-world evidence studies; however, adjustment factors may vary across studies which further complicate study comparability.
CONCLUSIONS: Addressing these challenges in a clear and transparent manner is essential for generating relevant, reliable, and valid conclusions from NMAs of vaccines. Such analyses are crucial for informing public health decisions and guiding vaccine policy and implementation.