Methodological Gaps in Economic Evaluations of Vaccines: A Systematic Review

Economic evaluations of vaccines targeting multi-disease combinations, such as hepatitis A/B or measles-mumps-rubella (MMR), reveal critical methodological shortcomings in this systematic literature review. Synthesizing seven full economic evaluations published across four countries from 1999 to 2019, these studies mostly used static cohort models and deemed combination vaccines cost-effective or cost-saving compared to single vaccines or no vaccination. Benefits stemmed from assumptions like equivalent efficacy, fewer visits, or better coverage, yet persistent issues like absent dynamic modeling and inconsistent inputs highlight the need for rigorous Health Economics and Outcomes Research (HEOR).

Static Models Miss Transmission Dynamics

The studies leaned on static, deterministic models—decision trees in three, Markov models in four—that ignored transmission dynamics, herd immunity, or cross-disease interactions like co-infections. None factored in infectiousness duration or contact rates, and none justified skipping dynamic models, likely underestimating gains for diseases like MMR. Only three compared combinations to single vaccines (e.g., Hib-HepB vs. separate Hib and hepatitis B), while four used no-vaccination baselines, straying from WHO guidance on real-world benchmarks. This setup yielded favorable incremental cost-effectiveness ratios (ICERs) under $50,000–$200,000 per quality-adjusted life-year (QALY) in U.S. contexts, but hinged on optimistic assumptions, signaling needs for better validation and comparators in economic evaluations vaccines.

Rigorous Review Protocol Exposes Quality Shortfalls

Registered in PROSPERO (CRD420251135227) and following PRISMA 2020 and Cochrane Handbook, the review screened 5,878 records from MEDLINE, Embase, and CEA Registry up to August 2025, selecting seven cost-utility analyses (CUAs; three) or cost-effectiveness analyses (CEAs; four) on multi-disease combinations. Exclusions covered monovalent vaccines, with dual-reviewer checks extracting 75+ fields on perspectives (societal in two, payer in three, both in two), time horizons (six months to lifetime), and inputs like national epidemiology. Quality via WHO Immunization Framework rated CUAs high and CEAs moderate/low; CHEERS 2022 scored 15–24/28, with narrative synthesis per Popay et al. flagging transparency issues like unreported funding in three studies.

Upgrading HEOR for Vaccine Market Access

Findings demand HEOR advances in vaccine pricing, reimbursement, and access amid emerging combinations. Sparse sensitivity analyses—mostly one-/two-way deterministic, probabilistic in one—undervalue societal gains like productivity (in three studies) or logistics savings (e.g., MMR wastage), per WHO 2019 guidance. Inconsistent adverse events and omitted costs (syringes, cold-chain) could raise ICERs; dynamic models tackling interference may prove superior value against thresholds like €10,000–€52,500/QALY in Europe. Implementing upgrades in economic evaluations of vaccines can solidify evidence for reducing disease burden and costs, promoting improved access against infectious threats.