Considerations for assessing the feasibility of network meta-analysis of seasonal vaccines

Aim: Network meta-analyses (NMAs) of seasonal vaccines face distinct challenges that can compromise the validity and relevance of findings. While established frameworks offer guidance for evaluating the feasibility of NMAs, they do not address factors specific to seasonal vaccines. This study aims to highlight unique methodological challenges related to conducting NMA feasibility assessments of seasonal vaccines. The considerations are framed to be compatible with existing guidance and recommendations for the conduct and reporting of NMAs. Materials & methods: We developed a set of key considerations that should be applied when assessing the feasibility and/or validity of NMAs comparing seasonal vaccines. The considerations were based on systematic reviews and critical appraisals of published NMAs of seasonal vaccines, hands-on experience performing feasibility assessments of seasonal vaccines, and input from consultations with vaccine experts. Results: Unique considerations for evaluating comparability across seasonal vaccine studies include: whether vaccines should be compared by platform, formulation, dose, and/or valence; the impact of seasonality, strain evolution and definitions of placebo/unvaccinated controls on network connectivity; target population characteristics including history and recency of prior vaccination and/or infection(s), and baseline infection/severe disease risk; antigenic match (i.e., the degree of concordance between vaccine composition and circulating viral strains), which directly influences effectiveness and outcome measurement approaches that consider time varying epidemiology and assay and measure discrepancy. Comprehensively integrating these elements into existing guidance frameworks ensures transparent assessment of the key assumptions underlying NMA (i.e., transitivity and homogeneity) within the context of unique study design and methodological features of seasonal vaccine studies. Conclusion: The concepts highlighted in this paper address important gaps in the feasibility assessment process for NMAs of seasonal vaccines, which are crucial for informing public health decisions and guiding vaccine policy and implementation.