A systematic literature review of methodologies used in economic evaluations of combination vaccines

Combination vaccines offer simultaneous protection against different diseases or strains of the same pathogen. They could improve vaccine coverage and health outcomes while reducing healthcare visits and injection costs. This systematic literature review (CRD420251135227) aimed to characterise methodologies employed in full economic evaluations of combination vaccines targeting multiple diseases. Searches were performed in August 2025 in MEDLINE, Embase, Web of Science, CEA Registry, International HTA Database, and the NHS Economic Evaluation Database. Studies included cost-utility (CUA), cost-effectiveness (CEA) or cost-benefit analyses (CBA) evaluating all the diseases covered by combination vaccines. Given the qualitative research question, findings were narratively synthesised. Quality assessment used CHEERS and the WHO framework for Immunisation Programmes. Seven studies (3 CUAs; 4 CEAs) were included. They targeted five different combination vaccines across four countries and ∼20 years (1999–2019). All employed static models and compared with single vaccines (n = 3) or no vaccination (n = 5). Two studies adopted a societal perspective, three a healthcare perspective, and two adopted both. Four targeted paediatrics, three targeted adults. The efficacy of combination vaccines was assumed to be equivalent to single vaccines, and value was modelled as the incremental reduction in burden and costs of the additional disease covered, or due to higher coverage and fewer visits. There was variation in assessment of severe and long-term outcomes, adverse events, and productivity loss. Cross-disease data integration (e.g. co-infection, interference) was not considered. All studies generally supported cost-effectiveness of the assessed combination vaccines, but these results largely reflected the choice of comparator and modelling assumptions. Methodological and reporting quality varied widely. Economic evaluations of combination vaccines targeting multiple diseases remain scarce, outdated, and simplistic, highlighting opportunities to explore dynamic transmission models, broader societal perspectives, comparisons to single vaccines and extensive sensitivity analyses.