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      Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis

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          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.

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          Most cited references67

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          Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance.

          In 2000, seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the USA and resulted in dramatic reductions in invasive pneumococcal disease (IPD) and moderate increases in non-PCV7 type IPD. In 2010, PCV13 replaced PCV7 in the US immunisation schedule. We aimed to assess the effect of use of PCV13 in children on IPD in children and adults in the USA.
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            Herd immunity and serotype replacement 4 years after seven-valent pneumococcal conjugate vaccination in England and Wales: an observational cohort study.

            The seven-valent pneumococcal conjugate vaccine (PCV7) has reduced vaccine-type (VT) invasive pneumococcal disease but increases in non-vaccine-type (NVT) disease have varied between countries. We assess the effect of the PCV7 vaccination on VT and NVT disease in England and Wales. The study cohort was the population of England and Wales from July, 2000, to June, 2010. We calculated incidence rate ratios (IRRs) to compare incidences of VT and NVT disease before (2000-06) and after (2009-10) the introduction of PCV7. We used data from the national surveillance database. Cases included in our analysis were restricted to those confirmed by culture linked with isolates referred for serotyping at the national reference centre by laboratories in England and Wales. We adjusted for potential bias from missing data (serotype and age of patient) and changes in case ascertainment rates during the study period. 5809 cases of invasive pneumococcal disease were reported in 2009-10, giving an incidence of 10·6 per 100,000 population in 2009-10, which, when compared with the adjusted average annual incidence of 16·1 in 2000-06, gives an overall reduction of 34% (95% CI 28-39). VT disease decreased in all age groups, with reductions of 98% in individuals younger than 2 years and 81% in those aged 65 years or older. NVT disease increased by 68% in individuals younger than 2 years and 48% in those aged 65 years or older, giving an overall reduction in invasive pneumococcal disease of 56% in those younger than 2 years and 19% in those aged 65 years or older. After vaccine introduction, more NVT serotypes increased in frequency than decreased, which is consistent with vaccine-induced replacement. Key serotypes showing replacement were 7F, 19A, and 22F. Increases in NVT invasive pneumococcal disease were not associated with antimicrobial resistance. Despite much serotype replacement, a substantial reduction in invasive pneumococcal disease in young children can be achieved with PCV7 vaccination, with some indirect benefit in older age groups. Further reductions should be achievable by use of higher valency vaccines. Robust surveillance data are needed to properly assess the epidemiological effect of multivalent pneumococcal disease vaccines. Health Protection Agency. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Assessing cost-effectiveness in healthcare: history of the $50,000 per QALY threshold.

              Cost-effectiveness analyses, particularly in the USA, commonly use a figure of $50,000 per life-year or quality-adjusted life-year gained as a threshold for assessing the cost-effectiveness of an intervention. The history of this practice is ill defined, although it has been linked to the end-stage renal disease kidney dialysis cost-effectiveness literature from the 1980s. The use of $50,000 as a benchmark for assessing the cost-effectiveness of an intervention first emerged in 1992 and became widely used after 1996. The appeal of the $50,000 figure appears to lie in the convenience of a round number rather than in the value of renal dialysis. Rather than arbitrary thresholds, estimates of willingness to pay and the opportunity cost of healthcare resources are needed.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 March 2017
                2017
                : 12
                : 3
                : e0172414
                Affiliations
                [1 ]Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California, United States of America
                [2 ]Department of Pediatrics, Icahn School of Medicine at Mount Sinai/ Elmhurst Hospital Center, New York, New York, United States of America
                [3 ]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
                [4 ]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
                [5 ]Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, United States of America
                University of Louisville School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: DCI JPAI YM.

                • Data curation: MH MCS DCI.

                • Formal analysis: MH MCS DCI.

                • Investigation: MH MCS DCI JPAI YM.

                • Methodology: MH MCS DCI JPAI YM.

                • Project administration: MH MCS DCI.

                • Software: DCI MCS.

                • Supervision: DCI.

                • Validation: MH MCS DCI.

                • Visualization: MH MCS DCI JPAI YM.

                • Writing – original draft: DCI MH MCS.

                • Writing – review & editing: MH MCS DCI JPAI YM.

                Article
                PONE-D-16-38929
                10.1371/journal.pone.0172414
                5332092
                28249046
                d5e28218-67e4-4972-a477-e2763df8c3c8
                © 2017 Holubar et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 September 2016
                : 20 January 2017
                Page count
                Figures: 3, Tables: 2, Pages: 22
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Vaccines
                Biology and Life Sciences
                Immunology
                Vaccination and Immunization
                Medicine and Health Sciences
                Immunology
                Vaccination and Immunization
                Medicine and Health Sciences
                Public and Occupational Health
                Preventive Medicine
                Vaccination and Immunization
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Vaccines
                Conjugate Vaccines
                Social Sciences
                Economics
                Economic Analysis
                Cost-Effectiveness Analysis
                Medicine and Health Sciences
                Infectious Diseases
                Viral Diseases
                Influenza
                Biology and life sciences
                Organisms
                Viruses
                RNA viruses
                Reoviruses
                Rotavirus
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Viral Pathogens
                Reoviruses
                Rotavirus
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Viral Pathogens
                Reoviruses
                Rotavirus
                Biology and Life Sciences
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                Viruses
                Viral Pathogens
                Reoviruses
                Rotavirus
                People and Places
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                Europe
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                Engineering and Technology
                Electronics
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