title: Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis.
abstract: BACKGROUND
  Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited.
  
  
  METHODS
  We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries.
  
  
  RESULTS
  We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the adoption of the target vaccination strategy depended on the inclusion of the herd protection effect.
  
  
  CONCLUSIONS
  Inclusion of herd-protection effects in CEAs had a substantial impact in the estimated ICERs and made target-vaccination strategies more attractive options in almost half of the cases where ICERs were above the societal-willingness to pay threshold without herd-protection. More empirical epidemiologic data are needed to determine the size of herd-protection effects across diverse settings and also the size of negative vaccine effects, e.g. from serotype substitution.
authors.affiliation: Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Marisa
authors.initials: M
authors.lastname: Holubar
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai/ Elmhurst Hospital Center, New York, New York, United States of America.
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Stavroulakis
authors.affiliation: Department of Pediatrics, Division of Pediatric Infectious Diseases and Department of Health Research and Policy, Senior Associate Dean for Faculty Development and Diversity, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Maldonado
authors.affiliation: Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, United States of America.|Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, United States of America.
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
authors.affiliation: Department of Pediatrics, Division of Pediatric Infectious Diseases and Department of Health Research and Policy, Senior Associate Dean for Faculty Development and Diversity, Stanford University School of Medicine, Stanford, California, United States of America.|Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, United States of America.
authors.forename: Despina
authors.initials: D
authors.lastname: Contopoulos-Ioannidis
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003365:Costs and Cost Analysis; D005260:Female; D006801:Humans; D032521:Immunity, Herd; D007223:Infant; D008297:Male; D018803:Models, Economic; D014611:Vaccination / Q000191:economics*; D014612:Vaccines / Q000191:economics*
chemical_list: D014612:Vaccines