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The addition of pneumococcal conjugate vaccines (PCVs) to the United States (US) national immunization program led to significant reductions in incidence, mortality, and associated sequelae caused by pneumococcal disease (PD) in children and adults through direct and indirect protection. However, there remains clinical and economic burden due to PD caused by serotypes not included in the current 13-valent PCV (PCV13) formulation. To address this unmet need, 15-valent PCV (PCV15) and 20-valent PCV (PCV20), containing additional serotypes to PCV13, were recently approved in the US for adults and are anticipated for pediatrics in the near future. The study objective was to estimate the annual number of cases, deaths, and economic burden of PD due to serotypes included in PCV13, PCV15, and PCV20 for both US pediatric and adult populations. An Excel-based model was developed to calculate clinical and economic outcomes using published age-group specific serotype coverage; incidence of invasive PD, community-acquired pneumonia, and acute otitis media; case fatality rates; and disease-related costs. The results showed that across all age groups, the estimated annual PD cases and associated deaths covered by PCV13 serotypes were 914,199 and 4320, respectively. Compared with PCV13 serotypes, the additional 2 and 7 serotypes covered by PCV15 and PCV20 were attributed with 550,475 and 991,220 annual PD cases, as well as 1425 and 3226 annual deaths, respectively. This clinical burden translates into considerable economic costs ranging from $903 to $1,928 million USD that could be potentially addressed by PCV15 and PCV20. The additional serotypes included in PCV20 contribute substantially to the clinical and economic PD burden in the US pediatric and adult populations. Despite the success of the PCV13 pediatric national immunization program and increased adult uptake of PCV13 and 23-valent polysaccharide vaccine, broader PCV serotype coverage is needed across all ages to further reduce pneumococcal disease burden.

Introduction The widespread implementation of pneumococcal conjugate vaccines (PCVs) has significantly reduced the burden of pneumococcal disease around the world. Although licensed 10-valent (PCV10) and 13-valent (PCV13) vaccines have considerably reduced mortality and morbidity, a sizeable disease burden attributable to serotypes not contained in these PCVs remains. This study aimed to estimate the annual clinical and economic burden of pneumococcal disease attributable to licensed (PCV10 and PCV13) and investigational PCVs, notably 15-valent (PCV15) and 20-valent (PCV20) vaccines, in 13 countries in children under 5 years of age. Methods A decision-analytic model was created to aggregate total cases [inclusive of invasive pneumococcal disease (IPD), pneumonia, and otitis media (OM)], deaths, and direct costs in each country of interest [stratified by PCV10/PCV13 countries, depending on national immunization programs (NIPs)] over 1 year, using up to the three most recent years of available serotype coverage data. Data inputs were sourced from local databases, surveillance reports, and published literature. Results In 5 PCV10 NIPs (Austria, Finland, Netherlands, New Zealand, Sweden), most remaining PCV20-type disease was due to PCV13-unique serotypes (30–85%), followed by PCV20-unique (9–50%), PCV15-unique (4–15%), and PCV10-unique (2–14%) serotypes. In 8 PCV13 NIPs (Australia, Canada, France, Germany, Italy, South Korea, Spain, United Kingdom), most remaining PCV20-type disease was caused by PCV20-unique serotypes (16–69%), followed by PCV13-unique (11–54%), PCV15-unique (2–33%), and PCV10-unique serotypes (3–19%). Across all countries, PCV20 serotypes caused 3000 to 345,000 cases of disease and cost between $1.3 and $44.9 million USD annually with variability driven by population size, NIP status, and epidemiologic inputs. In aggregate, PCV20 serotypes caused 1,234,000 cases and $213.5 million in annual direct medical costs in children under 5 years of age. Conclusion Despite the success of PCV10 and PCV13 in reducing pneumococcal disease, a substantial clinical and economic burden remains due to serotypes contained in investigational vaccines. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00544-1.

Introduction Although the pneumococcal conjugate vaccine (PCV) has been introduced into select state immunization programs (SIPs) in India, many children remain unvaccinated. Recently, India’s Advisory Committee on Vaccines & Immunization Practices recommended PCV on the pediatric immunization schedule nationally. This study estimates the public health and economic impact of introducing either Pfizer’s 13-valent PCV (PCV13-PFE), GlaxoSmithKline’s 10-valent PCV (PCV10-GSK), or Serum Institute of India’s 10-valent PCV (PCV10-SII) into every pediatric SIP. Methods A model was developed to predict the disease cases, deaths, and costs associated with implementing PCV13-PFE, PCV10-GSK, or PCV10-SII in SIPs compared to no vaccination program across a 5-year period (2021–2025). State and national-level uptake rate and clinical and economic input parameters were collected from published literature. Disease outcomes included invasive pneumococcal disease, inpatient and outpatient pneumonia, and otitis media. Costs were estimated as vaccine-related costs and direct medical costs incurred to the healthcare system. Results were reported by individual state and aggregated nationally. Results Estimated over 5 years, implementing PCV13-PFE in SIPs could avert 12.1 million cases and save 626,512 lives among children under 5 years old compared to no vaccination. This corresponds to net national cost savings of over $1.0 billion. Both lower-valent PCVs are estimated to provide less economic savings than PCV13-PFE inclusive of vaccine-related costs. Compared with PCV13-PFE, implementing PCV10-GSK or PCV10-SII nationally is estimated to have a smaller public health impact, with PCV10-GSK averting 8.4 million cases (436,577 deaths) and PCV10-SII preventing 10.3 million cases (531,545 deaths) in India compared to no vaccination, respectively. Conclusion Implementation of PCV13-PFE throughout India is estimated to provide greater public health and economic benefits than PCV10-GSK or PCV10-SII SIPs. Our analysis highlights the substantial disease cases, deaths, and health system cost savings that may be realized from implementing PCV programs throughout India. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00498-4.

Introduction Since 2010, 10-valent (PCV10) and 13-valent pneumococcal conjugate vaccines (PCV13) have been available as part of infant national immunization programs. Belgium is as one of the few countries that implemented PCV13 (2007–2015), switched to PCV10 (2015–2018) and then switched back to PCV13 (2018–present) after observing increases in disease. We assessed the impacts of both historical and prospective PCV choice in the context of the Belgian health care system and used this experience to validate previously developed economic models. Methods Using historical incidence (2007–2018) of pneumococcal disease for Belgian children aged

Pneumococcal conjugate vaccines (PCVs) have been used in the United States since 2000. To assess the cumulative 20-year effect of PCVs on invasive pneumococcal disease (IPD) incidence among children 282,000 cases of IPD, including ≈16,000 meningitis, ≈172,000 bacteremia, and ≈55,000 bacteremic pneumonia cases. In addition, vaccination has prevented 97 million healthcare visits for otitis media, 438,914–706,345 hospitalizations for pneumonia, and 2,780 total deaths. IPD cases declined 91%, from 15,707 in 1997 to 1,382 in 2019. Average annual visits for otitis media declined 41%, from 78 visits/100 children before PCV introduction to 46 visits/100 children after PCV13 introduction. Annual pneumonia hospitalizations declined 66%–79%, from 110,000–175,000 in 1997 to 37,000 in 2019. These findings confirm the substantial benefits of PCVs for preventing IPD in children.

Gomez and colleagues [1] recently published a budget impact analysis (BIA) evaluating pneumococcal conjugate vaccines (PCVs) use over 5 years (2020 to 2024) in the National Immunization Program (NI...

Pneumococcal disease is a substantial contributor to illness and death in young children globally. The introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 had a significant impact in preventing pneumococcal disease in both vaccinated children and unvaccinated individuals (through herd effect). A higher valent PCV13 replaced PCV7 in late 2009. This analysis was undertaken to assess how many cases and deaths have been averted over the last decade since PCV13 introduction. A model estimated the number of infants vaccinated annually with PCV13, as well as the number of cases and deaths of invasive pneumococcal disease, pneumococcal pneumonia, and acute otitis media cases averted. PCV13 vaccination was estimated to have prevented 175.2 million cases of all pneumococcal diseases and 624,904 deaths globally between 2010 and 2019. These results demonstrate the substantial public health impact of PCV13 and highlight the importance of increasing the global reach of PCV programs.

Brazil currently has a 10-valent pneumococcal conjugate vaccine (PCV10) pediatric national immunization program (NIP). However, in recent years, there has been significant progressive increases in pneumococcal disease attributed to serotypes 3, 6A, and 19A, which are covered by the 13-valent PCV (PCV13). We sought to evaluate the cost-effectiveness and budget impact of switching from PCV10 to PCV13 for Brazilian infants from a payer perspective. A decision-analytic model was adapted to evaluate the clinical and economic outcomes of continuing PCV10 or switching to PCV13. The analysis estimated future costs ($BRL), quality-adjusted life-years (QALYs), and health outcomes for PCV10 and PCV13 over 5 y. Input parameters were from published sources. Future serotype dynamics were predicted using Brazilian and global historical trends. Over 5 y, PCV13 could prevent 12,342 bacteremia, 15,330 meningitis, 170,191 hospitalized pneumonia, and 25,872 otitis media cases, avert 13,709 pneumococcal disease deaths, gain 20,317 QALYs, and save 172 million direct costs compared with PCV10. The use of PCV13 in the Brazilian NIP could reduce pneumococcal disease, improve population health, and save substantial health-care costs. Results are reliable even when considering uncertainty for possible serotype dynamics with different underlying assumptions.

Introduction Globally, pneumococcal disease represents a significant burden. South Korea implemented the 7-valent pneumococcal conjugate vaccine (PCV7) in 2003, replaced with the 10-valent (PCV10) and 13-valent (PCV13) vaccine in 2010. In 2014, both vaccines were introduced in the national immunization program (NIP) for infants with 3 primary doses and one booster dose We performed a cost-effectiveness evaluation to elucidate which vaccine may be expected to provide greater impact if included in a NIP. Methodology Using an established model, we estimated the impact of introducing either PCV13 or PCV10 into the South Korean NIP in 2015. Vaccine impact was based on historic observed impact of PCV13 from 2010 to 2015 in Korea given high uptake of PCV13, and PCV10 impact was estimated based on experiences in countries using PCV10. Incidence and costs for all ages and including invasive pneumococcal disease, pneumonia, and acute otitis media were derived from the literature and Health Insurance Review and Assessment database. Results In the base-case, over 5-years PCV13 was estimated to avert 550,000 more cases of pneumococcal disease compared to PCV10, driven by broader serotype coverage and less replacement due to serotypes 3 and 19A. This translated to a cost-savings of $47.4 million USD despite PCV13’s higher cost. Sensitivity analysis found incremental cost-effectiveness ratios (ICERs) ranged from cost-saving to $7,300 USD per quality-adjusted life year (QALY). Conclusion A NIP using PCV13 was estimated to have a more substantial public health impact and be cost-saving compared to a program with PCV10 due to broader serotype coverage.

Objective A model was developed to estimate the historical impact (including total societal health and economic benefit) of pneumococcal conjugate vaccine (PCV) programs in the overall Canadian population between 2005 and 2015, inclusively. Methods Historical incidence of invasive pneumococcal disease (IPD), pneumonia, and acute otitis media (AOM) were obtained from epidemiologic databases supplemented with published and unpublished data. Two scenarios were considered: (1) the observed historical incidence from 2005 to 2015 in the setting of PCV use; (2) a hypothetical scenario in which we estimated the number of disease cases assuming no PCV use. Disease cases averted as a result of PCV programs were calculated by subtracting the number of observed historical cases from the number of estimated cases expected in the absence of PCV use. Results PCV programs were estimated to have saved 6631 lives and averted 14,990 IPD cases, 735,700 pneumonia episodes, and 3,697,993 AOM episodes. Positive clinical outcomes resulted in total cost savings of CAD $1.76 billion over 11 years. Vaccination costs were offset by the direct medical cost savings from fewer cases of IPD, pneumonia, and AOM. Conclusions Canadian PCV programs have provided significant health benefits and resulted in a substantial value for money. Net savings achieved over the reviewed period would have provided funding for $1.76 billion in other health care costs or public health initiatives. These findings highlight the importance of considering the total value of a vaccination program, rather than vaccine acquisition costs only, when assessing the value of immunization programs. Electronic supplementary material The online version of this article (10.1007/s40121-020-00294-6) contains supplementary material, which is available to authorized users.

Introduction Widespread use of ten-valent (Synflorix™, GSK) or 13-valent (Prevenar 13™; Pfizer) conjugate vaccination programs has effectively reduced invasive pneumococcal disease (IPD) globally. However, IPD caused by serotypes not contained within the respective vaccines continues to increase, notably serotypes 3, 6A, and 19A in countries using lower-valent vaccines. Our objective was to estimate the clinical and economic benefit of replacing PCV10 with PCV13 in Colombia, Finland, and The Netherlands. Methods Country-specific databases, supplemented with published and unpublished data, informed the historical incidence of pneumococcal disease as well as direct and indirect medical costs. A decision-analytic forecasting model was applied, and both costs and outcomes were discounted. The observed invasive pneumococcal disease (IPD) trends from each country were used to forecast the future number of IPD cases given a PCV13 or PCV10 program. Results Over a 5-year time horizon, a switch to a PCV13 program was estimated to reduce overall IPD among 0–2 year olds by an incremental − 37.6% in Colombia, − 32.9% in Finland, and − 26% in The Netherlands, respectively, over PCV10. Adults > 65 years experienced a comparable incremental decrease in overall IPD in Colombia (− 32.2%), Finland (− 15%), and The Netherlands (− 3.7%). Serotypes 3, 6A, and 19A drove the incremental decrease in disease for PCV13 over PCV10 in both age groups. A PCV13 program was dominant in Colombia and Finland and cost-effective in The Netherlands at 1 × GDP per capita (€34,054/QALY). Conclusion In Colombia, Finland, and The Netherlands, countries with diverse epidemiologic and population distributions, switching from a PCV10 to PCV13 program would significantly reduce the burden of IPD in all three countries in as few as 5 years. Electronic supplementary material The online version of this article (10.1007/s40121-020-00287-5) contains supplementary material, which is available to authorized users.

Pneumococcal conjugate vaccines (PCVs) have significantly reduced disease burden caused by Streptococcus pneumoniae, a leading cause of childhood morbidity and mortality globally. This systematic review and meta-analysis aimed to assess the incremental net benefit (INB) of the 13-valent PCV (PCV13) and 10-valent PCV (PCV10) in children.We performed a comprehensive search in several databases published before May 2022. Studies were included if they were cost-effectiveness or cost-utility analyses of PCV13 or PCV10 compared with no vaccination or with each other in children. Various monetary units were converted to purchasing power parity, adjusted to 2021 US dollars. The INBs were calculated and then pooled across studies stratified by country income level, perspective, and consideration of herd effects, using a random-effect model.Seventy studies were included. When herd effects were considered, PCV13 was cost-effective compared with PCV10 from the payer perspective in both high-income countries (HICs) (INB, $103.94; 95% confidence interval, $75.28-$132.60) and low- and middle-income countries (LMICs) (INB, $53.49; 95% confidence interval, $30.42-$76.55) with statistical significance. These findings were robust across a series of sensitivity analyses. PCV13 was cost-effective compared with no vaccination across perspectives and consideration of herd effects in both HICs and LMICs, whereas findings were less consistent for PCV10.PCVs were generally cost-effective compared with no vaccination in HICs and LMICs. Our study found that PCV13 was cost-effective compared with PCV10 when herd effects were considered from the payer perspective in both HICs and LMICs. The results are sensitive to the consideration of herd effects.

Modeling analyses have attempted to quantify the global impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal disease (PD), however these pediatric models face several challenges in obtaining comprehensive impact measurements. We present several measurement challenges and discuss examples from recently published pediatric modeling evaluations. Challenges include estimating the number of infants fully or partially vaccinated with PCVs, inclusion of indirect effects of vaccination, accounting for various dosing schedules, capturing effect of PCVs on nonspecific, noninvasive PD, and inclusion of adult PCV use. The true impact of PCVs has been consistently underestimated in published analyses due to multiple measurement challenges. Nearly 100 million adults are estimated to have received PCV13 over the last decade globally, potentially preventing up to 662 thousand cases of PD. Approximately 4.1 million cases of invasive PD alone may have been averted through indirect protection. Estimates of PCV impact on noninvasive PD remain a challenge due to altered epidemiology. Program switches, incomplete vaccination, and private market uptake among children also confound PD impact estimates. Taken together, the number of averted PD cases from PCV use in the last ten years may be up to three times higher than estimated in previous studies.

Background Pneumonia in infancy has been linked to long-term consequences for the rapidly developing lung. We examined the impact of hospitalized community-acquired pneumonia (CAP) on subsequent respiratory health. Methods We conducted a retrospective matched-cohort study using the Optum® de-identified Electronic Health Record Dataset (2009-2018). Study population comprised healthy infants hospitalized for CAP (“CAP patients”), and matched comparators without pneumonia (“comparison patients”), before age 2 years. Study outcomes included any chronic respiratory disorder, reactive airway disease (asthma, hyperactive airway disease, recurrent wheezing), and CAP hospitalization occurring between age 2 to 5 years, and were evaluated overall as well as by age and etiology at first CAP hospitalization. Results Study population totaled 1,343 CAP patients and 6,715 comparison patients. Rates per 100 patient-years and relative rates (RR) of study outcomes from age 2 to 5 years for CAP patients versus comparison patients were: any chronic respiratory disorder, 11.6 vs. 4.9 (RR=2.4 [95% CI: 2.1-2.6]); reactive airway disease, 6.1 vs 1.9 (RR=3.2 [2.6-3.8]); and CAP hospitalization, 1.0 vs 0.2 (RR=6.3 [3.6-10.9]). Rates of study outcomes were highest among CAP patients who had their initial hospitalization in the second year of life. Conclusions Infant CAP foreshadows an increased risk of subsequent chronic respiratory disorders, which may be elevated when CAP occurs closer to pre-school age (i.e., age 2 to 5 years). These findings are most consistent with the hypothesis that inflammation persists beyond the acute stage of pneumonia and plays a role in the development of chronic respiratory sequelae.

Pneumococcal infections can lead to serious invasive diseases such as meningitis, septicemia and pneumonia, as well as milder but more common illnesses such as sinusitis and otitis media. The World Health Organization (WHO) recommends the inclusion of pneumococcal conjugate vaccines (PCVs) in infant National Immunization Program (NIP) programs worldwide. Decision-makers in Asian countries planning to introduce PCVs in their respective NIP will need a comprehensive evidence of effectiveness of PCVs at the population level and economic evidence including cost-effectiveness.A systematic literature review (from 1/1/2016 to 10/11/2019) of PCVs in East and Southeast Asia to understand (1) the contributing factors to cost-effectiveness results of PCVs and (2) whether gaps in evidence exist suggesting why the region may have yet to implement full NIPs.In East and Southeast Asia, vaccination with PCVs was found to significantly reduce the mortality and morbidity of pneumococcal diseases and was cost-effective compared to no vaccination. Study assumptions, specifically vaccine local acquisition, the inclusion or exclusion of indirect effects (serotype replacement and herd effect), cross-protection, and protection against nontypeable

Australia introduced the 7-valent pneumococcal conjugate vaccine (7vPCV) on the universal infant National Immunisation Program (NIP) in 2005 and replaced it with the 13-valent pneumococcal conjugate vaccine (13vPCV) in 2011, both under a 3 + 0 schedule. The objective of this analysis was to quantify the clinical and economic impact of the universal infant PCV program in Australia from its introduction. A decision-analytic model was developed to estimate the historical impact of pneumococcal conjugate vaccine (PCV) programs in Australia from a direct health care perspective. Historical incidence of invasive pneumococcal disease (IPD), pneumonia, and otitis media (OM) were obtained from available Australian epidemiologic databases supplemented with published data. Costs were from Medicare Benefits Schedule in 2018 Australian dollars and utility weights from published sources. Historical observed changes in disease for the universal PCV NIP era (2005–2017) were compared against a “no-vaccine” scenario. The expected incidence for the no-vaccine scenario in years 2005–2017 was calculated using pre-universal PCV NIP era (2001–2004) data. Averted cases, deaths, incremental costs, and quality-adjusted life years (QALYs) were obtained by subtracting the vaccine scenario totals from the no-vaccine scenario totals. From the inclusion in the universal infant NIP, 7vPCV and 13vPCV are estimated to have prevented 1,770,024 cases of pneumococcal disease (IPD = 16,392; OM = 1,575,491; pneumonia = 102,059) and 1195 associated deaths. Over this period, there was a total 24,335 QALYs gained. Costs for the universal infant NIP were offset by $733 million direct costs saved, resulting in an incremental cost-effectiveness ratio of $3347 per QALY gained. PCVs have provided substantial public health and economic value from sustained use in Australia. Results are conservative, since long-term pneumococcal disease consequences and broader socioeconomic benefits were not considered. Maintaining 13vPCV on the Australian infant NIP under the newly implemented 2 + 1 schedule will likely provide more return on investment and sustained reductions in pneumococcal disease.

Introduction Limited changes in serotype 3 invasive pneumococcal disease (IPD) incidence rates after a decade of 13-valent pneumococcal conjugate vaccine (PCV13) introduction into several national immunization programs (NIP) have raised questions about PCV13's effectiveness against this serotype. Methods We analyzed the impact of pediatric PCV programs on serotype 3 IPD with two approaches. First, we reviewed the publicly available surveillance data from countries identified in two recently published reviews to describe the population impact of pediatric PCV13 or PCV10 vaccination programs on serotype 3 IPD. We then compared the observed trends in PCV10 and PCV13 countries to a previously described dynamic transmission model that simulates the spread of pneumococcal carriage and development of IPD in a population over time. Results When serotype 3 disease rates are compared from countries that have introduced either a 10-valent (PCV10) vaccine that does not contain serotype 3 in its formulation or PCV13 in their pediatric NIP, over time, serotype 3 incidence rate trends are markedly different. Countries with a PCV10 NIP showed a substantial linear increase in serotype 3 pneumococcal disease among all age groups since the time of PCV10 introduction, whereas countries with a PCV13 NIP experienced a modest decline during the 3–4 years after vaccine introduction followed by an inflection upward in subsequent years. Conclusion These data suggest that PCV13 provides a certain degree of direct and indirect protection against serotype 3 at the population level and direct adult vaccination with a serotype 3-containing vaccine is likely to provide substantial benefit in the context of a pediatric PCV NIP. Further research around serotype 3 transmission patterns and epidemiology is nonetheless warranted. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00406-w.

Introduction Pneumococcal conjugate vaccines (PCVs) have been available in Canada since 2001, with 13-valent PCV (PCV13) added to the infant routine immunization program throughout all Canadian provinces by 2011. The use of PCVs has dramatically reduced the burden of pneumococcal disease in Canada. As a result, decision-makers may consider switching from a more costly, higher-valent vaccine to a lower-cost, lower-valent vaccine in an attempt to allocate funds for other vaccine programs. We assessed the health and economic impact of switching the infant vaccination program from PCV13 to 10-valent PCV (PCV10) in the context of the Canadian health care system. Methods We performed a review of Canadian databases supplemented with published and unpublished data to obtain the historical incidence of pneumococcal disease and direct and indirect medical costs. Observed invasive pneumococcal disease (IPD) trends from surveillance data were used as a basis to forecast the future number of cases of IPD, pneumococcal pneumonia, and acute otitis media given a PCV13- or PCV10-based program. Costs and outcomes over 10 years were then estimated and presented in 2017 Canadian dollars discounted at 3% per year. Results Switching from PCV13 to PCV10 would result in an additional 762,531 cases of pneumococcal disease over 10 years. Although PCV13 has a higher acquisition cost, switching to PCV10 would increase overall costs by over $500 million. Forecasted overall disease incidence was estimated substantially higher with PCV10 than with PCV13 primarily because of the potential reemergence of serotypes 3 and 19A. PCV13 was also cost saving compared with PCV10, even within a 5-year time horizon. Probabilistic sensitivity analysis showed that a PCV13-based program remained cost saving in all simulations. Conclusion Although switching to a PCV10-based infant vaccination program in Canada might result in lower acquisition costs, it would also result in higher public health cost and burden because of serotype reemergence. Funding Pfizer Inc. Electronic supplementary material The online version of this article (10.1007/s40121-018-0206-1) contains supplementary material, which is available to authorized users.

Introduction: Pneumococcal diseases caused by Streptococcus pneumoniae represent a significant health and economic burden. Mexico has benefited from the inclusion of the 7-valent (PCV7) and 13-valent pneumococcal conjugate vaccines (PCV13) since their inclusion in the National Immunization Program (NIP) in 2006 and 2010, respectively. The objective of this study is to estimate the impact of the existing program and predict future implications of a change in the current program. Methods: A previously published model was updated to estimate the historic impact of the PCV programs relative to pre-PCV implementation. Future disease trends were forecasted based on historical serotype behaviors for each PCV13 serotype and non-vaccine serotypes across different age groups. Costs and outcomes were estimated over a 10-year period based on continued use of PCV13 compared to a switch to PCV10. Results: The PCV7 and subsequent PCV13 NIP were estimated to prevent over 1.5 million cases of pneumococcal disease and 1,854 deaths, corresponding to a net savings of $34.50 Billion MXN. Continued use of PCV13 was estimated to save over 300 thousand cases of pneumococcal disease and 373 deaths compared to switching to PCV10 over a 10-year period. Despite a higher vaccine cost, maintaining PCV13 was cost-saving compared to PCV10, saving $6.71 billion MXN over 10 years. Conclusion: The PCV program in Mexico has provided a significant return on investment. Sustained PCV13 use was estimated to provide the greatest healthcare and economic impact in Mexico. Changes to the pneumococcal vaccination program could result in serotype replacement and reduction in herd effects.

Pneumococcal diseases caused by Streptococcus pneumoniae represent a significant health and economic burden. Mexico has benefited from the inclusion of the 7-valent (PCV7) and 13-valent pneumococcal conjugate vaccines (PCV13) since their inclusion in the National Immunization Program (NIP) in 2006 and 2010, respectively. The objective of this study is to estimate the impact of the existing program and predict future implications of a change in the current program.A previously published model was updated to estimate the historic impact of the PCV programs relative to pre-PCV implementation. Future disease trends were forecasted based on historical serotype behaviors for each PCV13 serotype and non-vaccine serotypes across different age groups. Costs and outcomes were estimated over a 10-year period based on continued use of PCV13 compared to a switch to PCV10.The PCV7 and subsequent PCV13 NIP were estimated to prevent over 1.5 million cases of pneumococcal disease and 1,854 deaths, corresponding to a net savings of $34.50 Billion MXN. Continued use of PCV13 was estimated to save over 300 thousand cases of pneumococcal disease and 373 deaths compared to switching to PCV10 over a 10-year period. Despite a higher vaccine cost, maintaining PCV13 was cost-saving compared to PCV10, saving $6.71 billion MXN over 10 years.The PCV program in Mexico has provided a significant return on investment. Sustained PCV13 use was estimated to provide the greatest healthcare and economic impact in Mexico. Changes to the pneumococcal vaccination program could result in serotype replacement and reduction in herd effects.

Background Antimicrobial resistance (AMR) is a global threat to effective prevention and treatment of an ever-increasing range of infections. Pneumococcal conjugate vaccines (PCV) used in infant national immunization programs have been shown to decrease AMR pneumococci. Cost-effectiveness models evaluating the value for money of PCV programs have not considered the economic impact of reducing antimicrobial prescribing or prolonged infections due to treatment failures. Standardized frameworks are needed for models to address outcomes and impact on health resource utilization related to AMR. Methods We developed a conceptual modeling methodology suitable for a health economic evaluation of an infant PCV program. We considered impact of PCVs on pneumococcal disease (PD) specifically related to clinical management of AMR-PD, including AMR epidemiology, antibiotic prescribing patterns, and healthcare resource utilization. Model inputs were evaluated regarding optimal and available data sources considering the complex nature of AMR at the national, regional, and global level. Results The proposed framework considers impact of PCVs on antimicrobial prescribing due to invasive pneumococcal disease (IPD), community acquired pneumonia (CAP), and acute otitis media (AOM) across 3 pathways (Figure 1). The population and pathogen-level pathway describe epidemiology and vaccine impact. The care level pathway describes clinical disease management. The health outcomes pathway characterizes resistant or successfully treated PD costs and quality of life. Conceptual Economic Model Methodology Conclusion We present a generalizable methodology to quantify impact of PCVs on cases and outcomes of PD related to AMR. Modelling vaccine-preventable burden of AMR-PD requires data extrapolations and assumptions due to the myriad of interconnected pathways (i.e. microbiology, epidemiology, environment, health systems). Further work is needed to validate assumptions and linkages across incomplete data sources. Disclosures Raymond Farkouh, PhD, Pfizer (Employee) Arianna Nevo, MPH, Pfizer, Inc. (Other Financial or Material Support, I am an employee of IQVIA. IQVIA received funding from Pfizer to carry out the project.) Jennifer Uyei, PhD, MPH, Pfizer, Inc. (Other Financial or Material Support, I am an employee of IQVIA. IQVIA received funding from Pfizer to carry out the project.) Cassandra Hall-Murray, PharmD, Pfizer, Inc. (Employee) Joseph Lewnard, PhD, Pfizer, Inc. (Consultant, Grant/Research Support, Advisor or Review Panel member) Matthew Wasserman, MSc., Pfizer Inc. (Employee)

Background Clinical trials of PCV7 demonstrate significant reductions in vaccine-type (VT) invasive pneumococcal disease (IPD), clinically diagnosed pneumonia in children less than 5 years of age and VT acute otitis media in children < 2 years of age. Observational, population-based studies demonstrate a reduction in overall IPD in US children following the introduction of PCV7 and PCV13. The cumulative impact of PCV on IPD syndromes over the 20 years following introduction into the US national immunization program has not been detailed. Methods Published and unpublished data from the Active Bacterial Core (ABC) surveillance network were used to calculate annual incidence rates of IPD and the proportional distribution by syndrome in children < 5 years of age. Cases averted were calculated from published incidence for each IPD syndrome and population data, for the pre-PCV, PCV7, and PCV13 eras. Cases averted over 2000-2009 were assumed due to PCV7 only, and those averted from 2010-2019 were assumed due to PCV13 only. It was assumed that in the absence of PCVs, disease incidence would have remained constant. Results Annual cases of overall IPD, pneumococcal meningitis, and bacteremic pneumonia each declined more than 85% between the pre PCV7 incidence and the estimated incidence for 2019 (table 1). Overall, we estimated 282,600 cases of IPD, including 30,500 cases of meningitis and 78,400 cases of bacteremic pneumonia were averted. We calculated a reduction of ~ 287,600 VT cases of IPD minimally offset by an increase of ~5,000 non-VT cases. Deaths per 100,000 children < 5 years of age attributable to IPD declined by 67% in 2009 and by 64% in 2019 compared to 1997-1999. In total, 1,628 deaths in children < 5 years were averted between 2000 and 2019. Table 1. Annual Cases of IPD by syndrome in US Children Less than 5 years of age Conclusion The substantial public health impact of PCVs over the last two decades, as measured in cases and deaths averted in children less than 5 years, re-enforces the important role vaccines play in reducing the burden of serious disease in children. Disclosures Rotem Lapidot, MD, MSCI, Pfizer (Consultant) Ruth Chapman, MSc, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Kelly Sutton, PhD, Evidera (Employee) Desmond Dillon-Murphy, MSc, PhD, Evidera, Inc. (Evidera, Inc. received the funding to conduct this study.) (Consultant) Shreeya Patel, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Erica Chilson, PharmD, Pfizer (Employee, Shareholder) Vincenza Snow, MD, Pfizer (Employee) Raymond Farkouh, PhD, Pfizer (Employee) Matthew Wasserman, MSc., Pfizer Inc. (Employee) Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant)

Background Community-acquired pneumonia (CAP) in infancy (i.e., among children aged < 2 years) may have long-term consequences for the rapidly developing lung. We examined the impact of pneumonia in infancy on subsequent respiratory health. Methods A retrospective matched-cohort design and data from Optum’s de-identified Integrated Claims-Clinical dataset (2009-2018) were employed. Study population comprised children who were hospitalized for CAP before age 2 years (“CAP patients”) as well as matched comparators without evidence of pneumonia before age 2 years (“comparison patients”). CAP patients and comparison patients were matched (fixed 1:5 ratio, without replacement) using estimated propensity scores and a nearest-neighbor approach; those with evidence of selected medical conditions (e.g., extreme prematurity, congenital diseases, respiratory diseases) before age 2 years were excluded. Study outcomes included recurrent pneumonia and a composite of asthma, recurrent wheezing, and hyperactive airway disease. Rates of study outcomes from age 2 to 5 years were estimated for all CAP and comparison patients as well as subgroups of CAP patients (and corresponding comparison patients) stratified by etiology (bacterial, viral, unspecified). Results Study population totaled 1,343 CAP patients and 6,715 comparison patients. CAP patients and comparison patients were well-balanced on their baseline characteristics and mean duration of follow-up was 757 and 729 days, respectively. Rates of chronic respiratory disorders from age 2 to 5 years were significantly higher among CAP patients versus comparison patients. Analyses of subgroups stratified by etiology demonstrated higher rates of study outcomes among CAP patients across all strata. Rates of recurrent pneumonia and a composite of asthma, recurrent wheezing, and hyperactive airway disease from age 2 to 5 years among CAP patients and matched comparison patients Conclusion Infant CAP foreshadows an increase in subsequent risk of chronic respiratory disorders. Further studies are needed to determine whether this elevated risk is due to infant pneumonia or whether infant pneumonia is a marker of at-risk children. Disclosures Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant) Rotem Lapidot, MD, MSCI, Pfizer (Consultant) Matthew Wasserman, MSc., Pfizer Inc. (Employee) Melody Shaff, BA, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Ahuva Hanau, BS, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Alexander Lonshteyn, PhD, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Derek Weycker, PhD, Pfizer Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)

Although a proven and effective preventive health measure, childhood immunization programs remain vulnerable to budgetary pressures. Sustainable financing of immunization programs is an important issue that presents a challenge for middle-income countries (MIC) in particular, in part due to technological advances meaning more vaccines are available. This study aimed to analyse trends in immunization program investment across 15 MIC selected based on availability of data, income level classification, and regional representativeness. We assessed investment trends in relation to vaccine coverage, vaccine access, and broader health indicators. Immunization and expenditure data were obtained from the World Health Organisation (WHO) database and the WHO UNICEF Joint Reporting Form and WHO Vaccine Product, Price and Procurement from 2006–2016. We calculated a weighted average index of vaccine commitment (WAIVC) based on vaccine coverage, vaccine scope, and weighted by vaccine innovation measured by approximating vaccine expenditure. Correlation analyses were conducted between immunization expenditure per-capita and each WAIVC, infant mortality and life expectancy. Correlation analyses at a global and individual country level indicate an improvement in immunization access, vaccination commitment measured by WAIVC, and scope of available vaccines in countries with sustained increases in vaccination funding. Increases in national immunization expenditure were correlated with reduced infant mortality and increased life expectancy. Vaccine expenditure comprises a small proportion (less than 2%) of total healthcare spending and has not uniformly increased in accordance with the scope of available vaccines. The present analysis supports the premise that countries with consistent increases in vaccine expenditure have increased vaccine coverage and commitment measured by WAIVC and improved broader health outcomes, indicating the value of sustained investment in vaccination for improved population health. The benefits of vaccine expenditure in this holistic fashion are critical to inform policy decisions on national budget allocation for vaccine funding.

Background The availability of 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines (PCVs) in the United States (US) since 2000 and 2010, respectively, has substantially reduced the occurrence, morbidity and mortality of pneumococcal disease. This systematic literature review aimed to assess the impact of the PCVs in reducing the pneumococcal disease burden since their introduction. Methods We searched Embase and Medline and disease-surveillance websites for observational studies of US participants < 19 years, published 1999–2019 and reporting incidence or prevalence of acute otitis media, invasive pneumococcal disease, meningitis, or pneumococcal disease-related morbidity, mortality, healthcare resource utilization (HCRU) or costs. Results Of 499 citations identified from the databases and other sources, 125 met inclusion criteria (Figure), all indicating clear reductions in multiple manifestations of pneumococcal disease with PCV7 and PCV13 use. However, variations across studies in outcomes reported, study years, and age strata, confounded assessment of vaccine impact on specific pneumococcal disease outcomes and key burden indicators, such as tympanostomy tube placement and antibiotic prescriptions. Conclusion PCVs have greatly decreased multiple manifestations of pneumococcal disease in the US. However, granular data on the frequency and morbidity associated with specific pneumococcal diseases and on associated HCRU are needed to quantify the public-health impact of these vaccines. Disclosures Kristin Kistler, PhD, Evidera, Inc. (Employee, Evidera, Inc. received the funding to conduct this study.) Evelyn F. Gomez-Espinosa, BSc, PhD, Evidera Inc (Employee, Scientific Research Study Investigator)Pfizer Inc (Consultant, Scientific Research Study Investigator) Kelly Sutton, PhD, Evidera (Other Financial or Material Support, Evidera, Inc. received the funding to conduct this study.) Ruth Chapman, MSc, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Desmond Dillon-Murphy, MSc, PhD, Evidera, Inc. (Evidera, Inc. received the funding to conduct this study.) (Consultant) Matthew Wasserman, MSc., Pfizer Inc. (Employee)

Introduction To evaluate the expected impact of the Algeria national immunization program (NIP) and potential impact for a Tunisia NIP, this study assessed the public health and economic value of vaccination, through a cost-effectiveness analysis, for a PCV13 or PCV10 NIP, compared with no vaccination. Methods A decision-analytic model was programmed in Microsoft Excel™ and adapted to evaluate the clinical and economic outcomes of PCV vaccination. Assuming a steady state, the model estimated invasive pneumococcal disease (IPD; bacteremia and meningitis), all-cause pneumonia (inpatient and outpatient), and all-cause otitis media cases as well as the associated costs from a payer perspective. The base case scenario assumed direct effects for both PCVs and indirect effects (against IPD) for PCV13 only. Results In Algeria, compared with no vaccination program, PCV13 would save 2177 lives and avoid nearly 349,000 cases of IPD, pneumonia, and AOM at a highly cost-effective value of $308 per QALY. In Tunisia, PCV13 would save 308 lives and avoid 1305 cases of IPD, 4833 cases of pneumonia, and 54,957 cases of AOM at a highly cost-effective value of $848 per QALY. PCV10 prevented 1224 deaths and 270,483 cases of disease in Algeria and prevented 172 deaths and 56,610 cases in Tunisia. PCV10 was cost-effective in both Algeria at $731/QALY and in Tunisia at $1366/QALY. Conclusion The ongoing NIP in Algeria is projected to reduce the impact and economic toll of pneumococcal disease in Algeria. If an NIP were also introduced in Tunisia, a commensurate impact would be expected. PCV NIPs are highly cost-effective, highly impactful public health interventions. Funding Pfizer. Electronic supplementary material The online version of this article (10.1007/s40121-018-0226-x) contains supplementary material, which is available to authorized users.

The 13-valent pneumococcal conjugate vaccine (PCV) has been part of routine immunisation in a 2 + 1 schedule (two primary infant doses and one booster during the second year of life) in the UK since 2010. Recently, the UK's Joint Committee on Vaccination and Immunisation recommended changing to a 1 + 1 schedule while conceding that this will increase disease burden; however, uncertainty remains on how much pneumococcal burden – including invasive pneumococcal disease (IPD) and non-invasive disease – will increase. We built a dynamic transmission model to investigate this question. The model predicted that a 1 + 1 schedule would incur 8777–27 807 additional cases of disease and 241–743 more deaths over 5 years. Serotype 19A caused 55–71% of incremental IPD cases. Scenario analyses showed that booster dose adherence, effectiveness against carriage and waning in a 1 + 1 schedule had the most influence on resurgence of disease. Based on the model assumptions, switching to a 1 + 1 schedule will substantially increase disease burden. The results likely are conservative since they are based on relatively low vaccine-type pneumococcal transmission, a paradigm that has been called into question by data demonstrating an increase of IPD due to several vaccine serotypes during the last surveillance year available.

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.

To examine the cost-effectiveness of intravascular ultrasound (IVUS) use during percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in treating coronary artery disease (CAD). A Markov model was constructed with a lifetime horizon to compare costs and health outcomes between IVUS-guided PCI and PCI guided solely by angiography from an Italian healthcare payer perspective. The population examined included CAD patients undergoing PCI with DES. From a healthcare payer perspective, the resulting incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year was negative in the base-case scenario (i.e., IVUS benefit assumed to persist beyond the first year). When IVUS benefit was assumed to be limited to the first year, the ICER increased to €9,624. This conclusion remained consistent even when scenarios varied regarding the duration of the device’s effect. Furthermore, benefits of using IVUS were greater for patients with acute coronary syndrome, renal insufficiency, and diabetes. Using IVUS with angiography is a dominant strategy in Italy, and results demonstrate that it is desirable to target those at a greater risk of restenosis (i.e., patients with diabetes, chronic kidney disease, and acute coronary syndrome), who tend to benefit more from accurate stent implantation. Further information is necessary regarding the long-term benefits of IVUS, however sensitivity analysis presented in this research demonstrates a strong argument supporting the cost-effectiveness of IVUS.

Pneumococcal conjugate vaccines (PCVs) have provided a significant clinical and economic impact globally. The majority of countries which have implemented an infant PCV program have observed a substantial reduction in the burden of invasive pneumococcal disease (IPD), pneumococcal pneumonia, and acute otitis media (AOM) due to vaccine serotypes. After 17 years of use, many countries have evaluated and re-evaluated the value of their vaccine program using cost-effectiveness analyses; however, many of these analyses do not reflect the current body of evidence.This literature review summarizes key assumptions used in cost-effectiveness analyses for PCVs and discusses whether these should be refined.Many existing models continue to project cost-effectiveness of implementing a PCV program into a naïve population, despite sustained PCV use. Furthermore, many assumptions related to program effectiveness are based on evidence from controlled studies or extrapolated from vaccines that are no longer or were never used. Real world effectiveness data published from nearly 10 years of higher-valet vaccine use should be reflected in key assumptions that drive decision makers to choose one vaccine over another. As data continuously emerges, cost-effectiveness of programs should be evaluated in the context of the most current data.

Background: The 13-valent pneumococcal conjugate vaccine (PCV13) is the only PCV licensed to protect against serotype 3 in children. However, conflicting estimates exist of PCV13’s direct and indirect protection vaccine effectiveness (VE) for serotype 3. Objective: Our study examined the of PCV13 for serotype 3 using different assumptions for PCV13 direct and indirect VE to model trends in serotype 3 invasive pneumococcal disease (IPD) and comparing these to observed data from the United Kingdom (UK). Methods: A dynamic transmission model of the spread of pneumococcal carriage and development of IPD was used to fit pre-PCV13–modeled IPD incidence with observed data. To allow for comparison across scenarios, post-PCV13–modeled IPD incidence was fit to observed data using assumptions for three different scenarios: (scenario 1) serotype 3 as a nonvaccine serotype, (scenario 2) VE against serotype 3 IPD of 63.5% based on a recent meta-analysis, and (scenario 3) a model-estimated VE against serotype 3. Results: Post-PCV13 introduction, modeled 2017 and average annual serotype 3 IPD incidence were within 20% and 59% of observed values for scenarios 2 and 3, respectively, but deviated by >100% for scenario 1. For adults aged ≥65 years, modeled 2017 IPD incidence in scenario 1 differed from observed data by 16% versus roughly 8% in scenarios 2 and 3. Conclusions: Observed data do not support a scenario of no serotype 3 VE, but rather a combination of direct protection among vaccinated children and a lower level of indirect protection among older adults. Policymakers should consider transmission dynamics when examining VE against covered serotypes.

Background Vaccines are an important factor in combating the growing global health issue of antimicrobial resistance. Pneumococcal conjugate vaccines (PCVs) have substantially reduced the burden of otitis media (OM) caused by S. pneumoniae, one of the largest causes of antibiotic prescriptions (Abx) in children under 5. The purpose of this study was to quantify the number of Abx avoided since the introduction of a national PCV program in Canada. Methods We adapted a previously published forecasting model to estimate the reduction in OM cases in Canada since the introduction of PCVs in all routine provincial programs in 2005 through 2015 (the last year complete data were available). The impact of PCV on OM was modeled and compared with pre-PCV incidence to estimate net impact of the vaccine. We assumed that 90% of OM episodes were treated with an initial Abx given routine practice. All data were sourced from the published literature. Results Over 10 years, PCVs were estimated to avert 3.7 million cases of OM in Canada. This corresponded to an estimated reduction of 3.3 million Abx, or 0.96 Abx avoided per infant vaccinated with PCV. Conclusion PCVs have had a significant public health impact on reducing the burden of disease and Abx. While most of the PCV impact on reduction of Abx is due to reduction in OM cases, additional Abx reduction from prevention of other invasive and noninvasive pneumococcal diseases is of importance. Further research is necessary to understand the additional net benefit of reducing antibiotics across the disease spectrum given that reductions in net prescribing could avert further downstream resistance by other pathogens. Disclosures M. C. Breton, Pfizer inc.: Employee, Salary. R. Farkouh, Pfizer: Employee, Salary. J. Vojicic, Pfizer: Employee and Shareholder, Benefits and stock and Salary. M. Wilson, Pfizer Inc: Consultant, Consulting fee. C. McDade, Pfizer Inc.: Consultant, Consulting fee. M. Wasserman, Pfizer: Employee, Salary.