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      Estimating the cost-effectiveness of an infant 13-valent pneumococcal conjugate vaccine national immunization program in China

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          Abstract

          Background

          The burden of pneumococcal disease in China is high, and a 13-valent pneumococcal conjugate vaccine (PCV13) recently received regulatory approval and is available to Chinese infants. PCV13 protects against the most prevalent serotypes causing invasive pneumococcal disease (IPD) in China, but will not provide full societal benefits until made broadly available through a national immunization program (NIP).

          Objective

          To estimate clinical and economic benefits of introducing PCV13 into a NIP in China using local cost estimates and accounting for variability in vaccine uptake and indirect (herd protection) effects.

          Methods

          We developed a population model to estimate the effect of PCV13 introduction in China. Modeled health states included meningitis, bacteremia, pneumonia (PNE), acute otitis media, death and sequelae, and no disease. Direct healthcare costs and disease incidence data for IPD and PNE were derived from the China Health Insurance and Research Association database; all other parameters were derived from published literature. We estimated total disease cases and associated costs, quality-adjusted life years (QALYs), and deaths for three scenarios from a Chinese Payer Perspective: (1) direct effects only, (2) direct+indirect effects for IPD only, and (3) direct+indirect effects for IPD and inpatient PNE.

          Results

          Scenario (1) resulted in 370.3 thousand QALYs gained and 12.8 thousand deaths avoided versus no vaccination. In scenarios (2) and (3), the PCV13 NIP gained 383.2 thousand and 3,580 thousand QALYs, and avoided 13.1 thousand and 147.5 thousand deaths versus no vaccination, respectively. In all three scenarios, the vaccination cost was offset by cost reductions from prevented disease yielding net costs of ¥29,362.32 million, ¥29,334.29 million, and ¥13,524.72 million, respectively. All resulting incremental cost-effectiveness ratios fell below a 2x China GDP cost-effectiveness threshold across a range of potential vaccine prices.

          Discussion

          Initiation of a PCV13 NIP in China incurs large upfront costs but is good value for money, and is likely to prevent substantial cases of disease among children and non-vaccinated individuals.

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          Most cited references35

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          Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine.

          Changes in invasive pneumococcal disease (IPD) incidence were evaluated after 7 years of 7-valent pneumococcal conjugate vaccine (PCV7) use in US children. Laboratory-confirmed IPD cases were identified during 1998-2007 by 8 active population-based surveillance sites. We compared overall, age group-specific, syndrome-specific, and serotype group-specific IPD incidence in 2007 with that in 1998-1999 (before PCV7) and assessed potential serotype coverage of new conjugate vaccine formulations. Overall and PCV7-type IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100,000 population), respectively (P< .01 all age groups). The incidence of IPD caused by serotype 19A and other non-PCV7 types increased from 0.8 to 2.7 cases per 100,000 population and from 6.1 to 7.9 cases per 100,000 population, respectively (P< .01 for all age groups). The rates of meningitis and invasive pneumonia caused by non-PCV7 types increased for all age groups (P< .05), whereas the rates of primary bacteremia caused by these serotypes did not change. In 2006-2007, PCV7 types caused 2% of IPD cases, and the 6 additional serotypes included in an investigational 13-valent conjugate vaccine caused 63% of IPD cases among children <5 years-old. Dramatic reductions in IPD after PCV7 introduction in the United States remain evident 7 years later. IPD rates caused by serotype 19A and other non-PCV7 types have increased but remain low relative to decreases in PCV7-type IPD.
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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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              Trends in acute otitis media-related health care utilization by privately insured young children in the United States, 1997-2004.

              The goal was to estimate the population effect of 7-valent pneumococcal conjugate vaccine on rates of acute otitis media-related ambulatory visits and antibiotic prescriptions for 500,000 person-years of observations for children <2 years of age. Trends in rates of International Classification of Diseases, Ninth Revision-coded ambulatory visits and antibiotic prescriptions attributable to acute otitis media were evaluated, and the national direct medical expenditures for these outcomes were estimated. In a comparison of 2004 with 1997-1999 (baseline period), rates of ambulatory visits and antibiotic prescriptions attributable to acute otitis media decreased from 2173 to 1244 visits per 1000 person-years (42.7% reduction) and from 1244 to 722 prescriptions per 1000 person-years (41.9% reduction), respectively. Total, estimated, national direct medical expenditures for acute otitis media-related ambulatory visits and antibiotic prescriptions for children <2 years of age decreased from an average of $1.41 billion during 1997 to 1999 to $0.95 billion in 2004 (32.3% reduction). Acute otitis media-related health care utilization and associated antibiotic prescriptions for privately insured young children decreased more than expected (on the basis of efficacy estimates in prelicensure clinical trials) after the introduction of routine 7-valent pneumococcal conjugate vaccine immunization. Although other factors, such as clinical practice guidelines to reduce antibiotic use, might have contributed to the observed trend, 7-valent pneumococcal conjugate vaccine may play an important role in reducing the burden of acute otitis media, resulting in substantial savings in medical care costs.
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                Author and article information

                Contributors
                Role: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 July 2018
                2018
                : 13
                : 7
                : e0201245
                Affiliations
                [1 ] Department of Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
                [2 ] Pfizer Inc. New York, NY, United States of America
                [3 ] Pfizer Inc., Beijing, China
                [4 ] Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, National Clinical Research Centre for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Laboratory of Microbiology, Beijing Children's Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
                [5 ] Elysia Group, LLC., New York, NY, United States of America
                [6 ] Pfizer Inc. Collegeville, PA, United States of America
                Universidad Nacional de la Plata, ARGENTINA
                Author notes

                Competing Interests: MW, DL, JY, BH, and RF are employees of Pfizer Inc. BW and GG are employees of Elysia Group LLC, who were paid consultants to Pfizer in connection with the development of this manuscript. KS and YHY do not have any financial or nonfinancial competing interests to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0003-3300-2742
                Article
                PONE-D-17-41868
                10.1371/journal.pone.0201245
                6059448
                30044865
                246b8dc3-6731-425c-ae53-f238cb5fe373
                © 2018 Shen 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
                : 11 December 2017
                : 11 July 2018
                Page count
                Figures: 1, Tables: 4, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100004319, Pfizer;
                This work was sponsored by Pfizer Inc. MW, DL, JY, BH, and RF are employees of Pfizer Inc. The specific roles of these authors are articulated in the ‘author contributions’ section. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Vaccines
                People and Places
                Geographical Locations
                Asia
                China
                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
                Social Sciences
                Economics
                Economic Analysis
                Cost-Effectiveness Analysis
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Diseases of the Nervous System
                Meningitis
                Medicine and Health Sciences
                Neurology
                Infectious Diseases of the Nervous System
                Meningitis
                Medicine and Health Sciences
                Inflammatory Diseases
                Meningitis
                Medicine and Health Sciences
                Otorhinolaryngology
                Otology
                Otitis Media
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Bacteremia
                Medicine and Health Sciences
                Health Care
                Patients
                Inpatients
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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