Cost-Effectiveness Analyses of Hepatitis A Vaccine: A Systematic Review to Explore the Effect of Methodological Quality on the Economic Attractiveness of Vaccination Strategies

Hepatitis A vaccines have been available for more than a decade. Because the burden of hepatitis A virus has fallen in developed countries, the appropriate role of vaccination programmes, especially universal vaccination strategies, remains unclear. Cost-effectiveness analysis is a useful method of relating the costs of vaccination to its benefits, and may inform policy. This article systematically reviews the evidence on the cost effectiveness of hepatitis A vaccination in varying populations, and explores the effects of methodological quality and key modelling issues on the cost-effectiveness ratios. Cost-effectiveness/cost-utility studies of hepatitis A vaccine were identified via a series of literature searches (MEDLINE, EMBASE, HSTAR and SSCI). Citations and full-text articles were reviewed independently by two reviewers. Reference searching, author searches and expert consultation ensured literature saturation. Incremental cost-effectiveness ratios (ICERs) were abstracted for base-case analyses, converted to $US, year 2005 values, and categorised to reflect various levels of cost effectiveness. Quality of reporting, methodological issues and key modelling issues were assessed using frameworks published in the literature. Thirty-one cost-effectiveness studies (including 12 cost-utility analyses) were included from full-text article review (n = 58) and citation screening (n = 570). These studies evaluated universal mass vaccination (n = 14), targeted vaccination (n = 17) and vaccination of susceptibles (i.e. individuals initially screened for antibody and, if susceptible, vaccinated) [n = 13]. For universal vaccination, 50% of the ICERs were <$US20_000 per QALY or life-year gained. Analyses evaluating vaccination in children, particularly in high incidence areas, produced the most attractive ICERs. For targeted vaccination, cost effectiveness was highly dependent on the risk of infection. Incidence, vaccine cost and discount rate were the most influential parameters in sensitivity analyses. Overall, analyses that evaluated the combined hepatitis A/hepatitis B vaccine, adjusted incidence for under-reporting, included societal costs and that came from studies of higher methodological quality tended to have more attractive cost-effectiveness ratios. Methodological quality varied across studies. Major methodological flaws included inappropriate model type, comparator, incidence estimate and inclusion/exclusion of costs.