The Health and Economic Effects of PCV15 and PCV20 During the First Year of Life in the US
by
,
Aleksandar Ilic
1,
Maria J. Tort
2
Alejandro Cane
2,
Raymond A. Farkouh
2 and
Mark H. Rozenbaum
3,* 1
Pfizer Inc., Tadworth KT20 7NY, UK
2
Pfizer Inc., Collegeville, PA 19426, USA
3
Pfizer Inc., 2909 LD Capelle aan den Ijssel, The Netherlands
*
Author to whom correspondence should be addressed.
Vaccines 2024, 12(11), 1279; https://doi.org/10.3390/vaccines12111279
Submission received: 3 October 2024
/
Revised: 6 November 2024
/
Accepted: 12 November 2024
/
Published: 14 November 2024
(This article belongs to the Special Issue The Effectiveness of Pneumococcal Conjugate Vaccines)
Abstract
:(1) Background/Objectives: Two pneumococcal conjugate vaccines, 15-(PCV15) and 20-(PCV20) valent formulations, are routinely recommended for US children in a 3+1 schedule. The first three doses are administered during the first year of life at 2, 4, and 6 months, while a booster dose is given at 12 to 15 months. This study evaluated the health and economic effects of the PCV20 infant series within the first year of life compared to PCV15. (2) Methods: Using a decision-analytic model, we calculated the health and economic effects of introducing PCV15 or PCV20 for five subsequent birth cohorts. Epidemiological data were drawn from peer-reviewed studies and estimates for vaccine effectiveness were extrapolated from established PCV13 effectiveness and PCV7 efficacy studies. Direct medical costs related to the disease treatment were extracted from the literature and inflated to 2024 dollars. (3) Results: Over the course of five years, the implementation of PCV20 vaccination for newborns in the United States, compared to PCV15, is projected to prevent an additional 220 cases of invasive pneumococcal disease, 6542 cases of community-acquired pneumonia, and 112,095 cases of otitis media within the first year of life across five subsequent birth cohorts. This strategy could prevent 66 infant deaths linked to these illnesses and confer extra health gains, amounting to 5058 years of life and 5037 quality-adjusted life years. These prevented cases are estimated to save approximately USD 147 million over 5 years. (4) Conclusions: This study demonstrated that vaccinating with PCV20 during the first 12 months of life compared to PCV15 in the US would yield a substantially greater health and economic return due to the five additional serotypes covered by PCV20.
1. Introduction
Streptococcus pneumoniae is a major cause of illness and death among children and adults, with vaccination being the key method for preventing pneumococcal infections [1]. The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) (comprising the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) in 2000 resulted in significant decreases in invasive pneumococcal disease (IPD), community-acquired pneumonia (CAP), and otitis media (OM) while also benefiting unvaccinated populations through indirect protection [1,2,3]. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) (which includes serotypes 1, 3, 5, 6A, 7F, and 19A, in addition to PCV7) led to further declines in pneumococcal disease [4,5,6,7,8,9].
Currently, two PCVs, PCV15 and PCV20, are recommended for US infants [10,11]. PCV15 comprises two additional serotypes (22F and 33F) compared to PCV13, while PCV20 comprises five additional serotypes (8, 10A, 12F, 15B, 18B and 19A) compared to PCV15 [10]. These vaccines are given in a 3+1 schedule in the US, with the first three doses being administered at 2, 4, and 6 months, followed by a booster dose given between 12 and 15 months [12].
Previously published cost-effectiveness studies have shown that pediatric use of PCV20 could yield substantive reductions in the clinical burden of pneumococcal disease when compared to PCV13 and PCV15 at the population level [13,14,15,16,17,18,19,20,21,22]. For example, a recent US study showed that PCV20, compared to PCV15, could prevent more than 29,633 cases of IPD, 252,746 cases of all-cause hospitalized non-bacteremic pneumonia (NBP), 1.1 million cases of all-cause ambulatory NBP, 2.7 million cases of all-cause OM, and 9737 deaths associated with these diseases among the US population over a 10-year period [13]. Notably, a substantial portion of these health benefits would accrue in adults and the elderly due to indirect effects.
Currently, no modeling studies have specifically looked at the health and economic effects of PCV15 or PCV20 during the first year of life, when children are at the highest risk of pneumococcal infections. During 2019 (the last pre-COVID19 year) in the US, IPD incidence was approximately 32% higher in the first year of life compared to the second year of life, while IPD and hospitalized pneumonia mortalities among children in the first year of life were approximately 32% and 260% higher, respectively, compared to children in the second year of life [13,23,24].
Protecting infants was the main reason for introducing routine infant pneumococcal vaccination, considering their vulnerability to pneumococcal infections and the potential for severe outcomes. Therefore, our study specifically examines the health and economic effects of a 3-dose infant series of PCV15 and PCV20 within the first year of life. By doing so, we intend to isolate the direct benefits of pre-booster vaccination, providing a clearer understanding of the effects of the infant vaccination series without the confounding influence of herd effects, which typically develops over a longer period as vaccination coverage in the population increases. This approach allows us to focus on the immediate and direct health outcomes for infants who are the primary recipients of these vaccines and underscores the significance of timely vaccination in the first year of life.
2. Materials and Methods
2.1. Model Description
Using a decision-analytic multi-cohort model, we calculated the health and economic effects of PCV15 and PCV20 for infants within the first year of life for 5 subsequent birth cohorts (Figure 1). Infants born into the model were subject to vaccine uptake assumptions and, if vaccinated, were assumed to receive the 3 doses administered at 2, 4, and 6 months [12,25]. Each annual birth cohort was followed for a single year, after which they were removed from the model.
Vaccine uptake was based on estimates from the National Immunization Survey, which is a telephone survey used to monitor vaccination coverage among children and teens [25]. These data suggest that the coverage of PCV13 when all three doses of the vaccine are completed by 13 months of age was 87.5% in the 2021 cohort, which informed our model for 2022–2027.
Clinical outcomes and economic costs were projected for 5 US birth cohorts, beginning in 2022 (n1 = 3.61 M; n2 = 3.55 M; n3 = 3.49 M; n4 = 3.43 M; and n5 = 3.37 M) [13]. Clinical outcomes included (1) cases of IPD, stratified by clinical manifestation into meningitis and bacteremia; (2) cases of CAP, stratified by care setting into hospitalized and non-hospitalized patients; (3) cases of all-cause OM; (4) disease related deaths; (5) life years (LYs); and (6) quality-adjusted life years (QALYs). Economic costs included costs averted (per disease and total), which were generated based on projected clinical outcomes and corresponding direct unit costs. All costs were inflated to 2024 US dollars [26].
Our analysis was performed from a healthcare perspective, focusing on direct medical costs and health outcomes related to the vaccines, excluding indirect costs such as caregiver productivity losses or broader societal impacts. The analyses were carried out in Microsoft Excel, version 365.
2.2. Model Estimation
Input parameters were estimated based on the data from peer-reviewed studies and published sources. These parameter values are summarized in Table 1.
Disease incidence rates. IPD incidence was based on a 2019 (last year prior to onset of COVID-19, used to avoid disruptions) report from the Active Bacterial Core Surveillance System (ABCs) [23]. Incidence rates in 2019 (13.7 per 100,000 for children less than 1 year) were similar to the observed rates of the prior 3 years (11.6–13.3 per 100,000) [36]. The percentage of IPD cases which manifested as meningitis was assumed to be 16% based on the study by Prasad et al. (2023), while the remaining IPD cases were assumed to manifest as bacteremia [24].
Hospitalized CAP incidence rates were based on the all-cause inpatient pneumonia rates, estimated from the 2018 to 2019 averages in the National Inpatient Sample (NIS), as reported in the study by Prasad et al. (2023) [24]. All-cause non-hospitalized pneumonia incidence rates were based on Tong et al. (2018), who retrospectively assessed data from the MarketScan® Commercial Claims and Encounters database to determine the frequency of pneumonia in the US from 2008 to 2014 [29].
All-cause OM was based on the study from Tong et al. (2018) [7]. Rates were adapted to account for underestimation by a factor of 150%, consistent with the approach used by Stoecker et al. (2021) [7,37].
Case fatality rates. Age-specific case fatality rates (CFRs) for IPD were based on the weighted CFR values from ABC reports from 2017 to 2019 [23,38,39]. Hospitalized CAP CFRs were extracted from a recent cost-effectiveness study, which reported 2018 to 2019 CFR averages based on the NIS data [24].
Vaccine effectiveness. Estimates for vaccine effectiveness (VE) on IPD [30], CAP [31,32], and OM [33] were extrapolated from established PCV13 effectiveness and PCV7 efficacy studies and adjusted for 2019 serotype coverage of PCV15 and PCV20. Consistent with other recent cost-effectiveness studies, the direct effect was assumed to be 75.6% to account for the fact that the full VE may not be achieved until the final dose of the vaccine schedule [13,24].
Medical costs. Direct medical costs related to the treatment of IPD [34], CAP [34], and OM [7] were extracted from the literature and inflated to 2024 US dollars [26].
Utilities. Baseline utilities from the general population were sourced from the Melegaro et al. (2004) study [35].
2.3. Analyses
We compared PCV20 to PCV15, as both vaccines are currently recommended for US infants [10,11], and calculated their expected reduction in disease cases (IPD, inpatient CAP, outpatient CAP, and OM), as well s in disease specific costs, deaths, LYs, and QALYs. Outcomes in our analyses, including Lys and QALYs, were not discounted.
One-way deterministic sensitivity analyses (DSAs) were conducted to determine the impact of varying individual data inputs on the results. When available, parameters were adjusted within their reported 95% confidence intervals. If 95% were not provided, standard error (SE) was used to calculate the upper and lower bounds of the 95% confidence interval (CI). If the SE was not reported, we estimated it using the mean and sample size. For data for which no 95% CI or SE was available, we assumed the upper and lower bound to be 20% of the mean. This approach allowed us to systematically assess the robustness of our findings by quantifying the effects of parameter uncertainty. The results of these analyses are presented in tornado diagrams (Figure 2 and Figure 3), which illustrate the influence of each parameter on the overall direct costs averted and QALYs gained.
Additionally, we have included the best- and worst-case scenarios to enhance the robustness of the cost-effectiveness evaluation of PCV20 in our analysis. For the two scenarios, we utilized the DSA-low and DSA-high values.
3. Results
Over the course of five years, the implementation of PCV20 for newborns in the US, in comparison to PCV15, is projected to result in a significant reduction in pneumococcal disease. Specifically, an additional 220 cases of IPD will be prevented, including 47 meningitis and 172 bacteremia cases. Furthermore, the adoption of PCV20 is expected to avert 6542 cases of CAP, with 3870 requiring hospitalization and 2672 being managed on an outpatient basis. Finally, an additional decrease of 112,095 cases of OM is projected.
The implementation of PCV20 is also associated with a decrease in mortality, with 66 fewer deaths expected in comparison to the use of PCV15. The health benefits of PCV20 are considerable, yielding an additional 5058 LYs and 5037 QALYs. From an economic standpoint, PCV20 was estimated to save approximately USD 147 million more than when compared to PCV15 over 5 years for five birth cohorts. Detailed clinical and economic outcomes are provided in Table 2, including the overall results for PCV15 and PCV20, as well as the incremental results comparing PCV20 versus PCv15.
Deterministic one-way sensitivity analyses showed that the most influential model parameters impacting total incremental direct costs were CAP inpatient VE, OM VE, PCV20 and PCV15 serotype coverage and CAP inpatient incidence (Figure 2). Similarly, for QALYs gained, the main impacting drivers included CAP inpatient VE, CAP inpatient CFR, PCV20 and PCV15 serotype coverage, and IPD incidence (Figure 3).
The result of the two scenario analyses, a worst-case and best-case analysis, are shown in Table 3 and Table 4. The worst-case scenario showed that PCV20 was estimated to avert 70,325 disease cases, 15 deaths, corresponding to a gain of 1135.0 LYs and 1274.9 QALYs compared to PCV15 (Table 3). Additionally, it was estimated that PCV20 would save USD 48 million more than PCV15. The best-case scenario showed that PCV20 would avert 176,526 disease cases, 118 deaths corresponding to a gain of 9119.4 Lys, and 9320.2 QALYs compared to PCV15 (Table 4). Additionally, it was estimated that PCV20 would save approximately USD 228 million more than PCV15.
4. Discussion
This study estimates the health and economic effects of PCV15 and PCV20 among US children during their first year of life. The analyses showed that, compared to PCV15, PCV20 could prevent an estimated 118,856 pneumococcal cases and 66 deaths, corresponding to net gains of 5058 LYs and 5037 QALYs. Monetary savings from averted cases were estimated at USD 147 million over 5 years from five birth cohorts. Findings from deterministic sensitivity analyses and worst- and best-case scenario analyses were consistent with those from the base-case analyses. These additional health gains of PCV20 over PCV15 were driven by the broader serotype coverage of PCV20 (55.4%) versus PCV15 (39.8%).
This study represents the first assessment of the health and economic effects of a 3-dose infant series of PCV15 and PCV20 within the first year of life in the US. However, it aligns with the findings of several other studies that have consistently demonstrated the superior health benefits and cost-effectiveness of PCV20 over PCV15, including studies performed in different countries such as Argentina, Canada, Germany, Greece, Japan, South Africa, and the Republic of Korea [15,16,17,18,19,20,21,22]. Indeed, a recent systematic literature review concluded that switching from PCV13 to PCV20 would be more beneficial in terms of direct cost reduction and yield a bigger gain in QALYs compared to switching from PCV13 to PCV15; the review also concluded that the utilization of PCV20 is associated with noteworthy savings in indirect costs attributed to productivity loss in contrast to the employment of PCV15 [22].
The main difference between previously conducted cost-effectiveness studies and our current study is that the previous studies looked at population-wide effects, including indirect effects, while our study specifically focused on the direct effects on those aged less than 1 year, when children are at the highest risk of IPD, CAP, and OM. The current study isolated the direct benefits of pre-booster vaccination, providing a clearer understanding of the effects of the infant vaccination series without the confounding influence of herd effects.
Our comprehensive approach to sensitivity analysis encompasses both one-way and multivariate methods. The one-way sensitivity analysis evaluates the impact of uncertainty associated with individual parameters, while the multivariate scenarios—encompassing best-case and worst-case conditions—explore the range of potential outcomes that could result from various combinations of input variables. Notably, our conclusions remain consistent across all analyses—showing that PCV20 consistently yielded a substantially greater health and economic return compared to PCV15—demonstrating the robustness of our findings even when considering the extremes of the worst-case scenario. This consistency underlines the strength of our conclusions, which are upheld under a spectrum of different assumptions.
As PCV15 and PCV20 are newly introduced vaccines, there are no real-world data on their health impacts. Additionally, due to ethical considerations, no clinical efficacy studies were performed for these vaccines. Therefore, since there are no direct VE data for PCV15 and PCV20 available, these data were derived from studies on lower-valent pneumococcal conjugated vaccines, which is a common approach used in vaccine cost-effectiveness studies [13,15,19]. Although the data used to inform the model parameters were the most robust and up-to-date available, these assumptions introduce uncertainty into the analysis and could affect the accuracy of the health and economic projections, emphasizing the need for further clinical studies that will be necessary to validate these findings. Additionally, we made an assumption about protection during the first year of life, positing that the VE would be 75.6% of the assumed full VE. This aligns with assumptions made by others [13,24] for the VE during the first year of life and was informed by a study by Whitney et al. (2006) [40]. Another limitation is that vaccine uptake was based on estimates from the National Immunization Survey [25], which, despite potential response and recall biases, represent the best data currently available.
Finally, the cycle length of the model was one year. While this approach provided valuable insights, a more granular per-month cycle length could yield a more precise understanding of PCVs. Unfortunately, to our knowledge, data on monthly epidemiological data (such as disease incidence, serotype distribution, vaccine effectiveness, etc.) are not currently available, which restricted our ability to perform such analyses.
Given that this analysis is conducted from the healthcare perspective, which primarily addresses direct medical costs while overlooking broader societal impacts, such as productivity losses, the analysis may underestimate the overall value of PCV15 and PCV20. Consequently, while the findings indicate substantial additional health and economic outcomes of PCV20 over PCV15 from the healthcare perspective, this may represent a conservative estimate, as the true incremental benefits of PCV20 over PCV15 could be even more favorable if wider societal implications were included.
5. Conclusions
This study suggests that using PCV20 in the infant series would yield a significantly greater health and economic return compared to the PCV15 due to the five additional serotypes covered by PCV20.
Author Contributions
Conceptualization, A.I., M.J.T. and M.H.R.; methodology, A.I. and M.H.R.; software, A.I. and M.H.R.; validation, A.I., M.J.T., A.C., R.A.F. and M.H.R.; formal analysis, A.I. and M.H.R.; investigation, A.I. and M.H.R.; investigation, A.I. and M.H.R.; resources, M.H.R.; data curation, A.I. and M.H.R.; writing—original draft preparation, A.I., M.J.T. and M.H.R.; writing—review and editing, A.I., M.J.T., A.C., R.A.F. and M.H.R.; visualization, A.I. and M.H.R.; supervision, R.A.F. and M.H.R.; project administration, M.H.R.; funding acquisition, R.A.F. and M.H.R. All authors have read and agreed to the published version of the manuscript.
Funding
This study was sponsored by Pfizer.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
All data used for estimation of model parameter values may be found in the manuscript.
Conflicts of Interest
The research described herein was supported by Pfizer Inc. Aleksandar Ilic, Mark Rozenbaum, Alejandro Cane, Maria Tort, and Ray Farkouh are employed by Pfizer Inc.
References
- Advisory Committee on Immunization Practices. Preventing pneumococcal disease among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep. 2000, 49, 1–35. Available online: https://www.cdc.gov/mmwr/preview/mmwrhtml/rr4909a1.htm (accessed on 20 September 2024).
- Feikin, D.R.; Kagucia, E.W.; Loo, J.D.; Link-Gelles, R.; Puhan, M.A.; Cherian, T.; Levine, O.S.; Whitney, C.G.; O’Brien, K.L.; Moore, M.R.; et al. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: A pooled analysis of multiple surveillance sites. PLoS Med. 2013, 10, e1001517. [Google Scholar] [CrossRef] [PubMed]
- Pilishvili, T.; Lexau, C.; Farley, M.M.; Hadler, J.; Harrison, L.H.; Bennett, N.M.; Reingold, A.; Thomas, A.; Schaffner, W.; Craig, A.S.; et al. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J. Infect. Dis. 2010, 201, 32–41. [Google Scholar] [CrossRef] [PubMed]
- Centers for Disease Control and Prevention. Invasive Pneumococcal Disease and 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Coverage Among Children Aged ≤59 Months. MMWR Morb. Mortal. Wkly. Rep. 2011, 60, 1477–1481. Available online: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6043a2.htm (accessed on 1 October 2024).
- Marom, T.; Tan, A.; Wilkinson, G.S.; Pierson, K.S.; Freeman, J.L.; Chonmaitree, T. Trends in otitis media-related health care use in the United States, 2001–2011. JAMA Pediatr. 2014, 168, 68–75. [Google Scholar] [CrossRef]
- Simonsen, L.; Taylor, R.J.; Young-Xu, Y.; Haber, M.; May, L.; Klugman, K.P. Impact of pneumococcal conjugate vaccination of infants on pneumonia and influenza hospitalization and mortality in all age groups in the United States. mBio 2011, 2, e00309-10. [Google Scholar] [CrossRef]
- Tong, S.; Amand, C.; Kieffer, A.; Kyaw, M.H. Trends in healthcare utilization and costs associated with acute otitis media in the United States during 2008–2014. BMC Health Serv. Res. 2018, 18, 318. [Google Scholar] [CrossRef]
- Wasserman, M.; Chapman, R.; Lapidot, R.; Sutton, K.; Dillon-Murphy, D.; Patel, S.; Chilson, E.; Snow, V.; Farkouh, R.; Pelton, S. Twenty-Year Public Health Impact of 7- and 13-Valent Pneumococcal Conjugate Vaccines in US Children. Emerg. Infect. Dis. 2021, 27, 1627–1636. [Google Scholar] [CrossRef]
- Zhou, X.; de Luise, C.; Gaffney, M.; Burt, C.W.; Scott, D.A.; Gatto, N.; Center, K.J. National impact of 13-valent pneumococcal conjugate vaccine on ambulatory care visits for otitis media in children under 5 years in the United States. Int. J. Pediatr. Otorhinolaryngol. 2019, 119, 96–102. [Google Scholar] [CrossRef]
- Kobayashi, M. Use of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization Practices—United States, 2022. MMWR Morb. Mortal. Wkly. Rep. 2022, 71, 1174–1181. [Google Scholar] [CrossRef]
- CDC. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): 20-valent pneumococcal conjugate vaccine (PCV20) for children aged <2 years. MMWR Recomm. Rep. 2024, 72, 1–3. Available online: https://www.cdc.gov/acip/grade/PCV20-child.html#:~:text=On%20June%2022%2C%202023%2C%20the%20ACIP%20recommended%20use%20of%20PCV20,certain%20underlying%20medical%20conditions%20at (accessed on 1 October 2024).
- CDC. Pneumococcal Vaccine Recommendations. 2024. Available online: https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/index.html (accessed on 25 September 2024).
- Rozenbaum, M.H.; Huang, L.; Perdrizet, J.; Cane, A.; Arguedas, A.; Hayford, K.; Tort, M.J.; Chapman, R.; Dillon-Murphy, D.; Snow, V.; et al. Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in US infants. Vaccine 2024, 42, 573–582. [Google Scholar] [CrossRef] [PubMed]
- Rozenbaum, M.H.; Huang, L.; Cane, A.; Arguedas, A.; Chapman, R.; Dillon-Murphy, D.; Tort, M.J.; Snow, V.; Chilson, E.; Farkouh, R. Cost-effectiveness and impact on infections and associated antimicrobial resistance of 20-valent pneumococcal conjugate vaccine in US children previously immunized with PCV13. J. Med. Econ. 2024, 27, 644–652. [Google Scholar] [CrossRef] [PubMed]
- Ta, A.; Kühne, F.; Laurenz, M.; von Eiff, C.; Warren, S.; Perdrizet, J. Cost-effectiveness of PCV20 to Prevent Pneumococcal Disease in the Pediatric Population: A German Societal Perspective Analysis. Infect. Dis. Ther. 2024, 13, 1333–1358. [Google Scholar] [CrossRef]
- Rey-Ares, L.; Ta, A.; Freigofaite, D.; Warren, S.; Mac Mullen, M.; Carballo, C.; Huang, L. Cost-effectiveness analysis of the pediatric 20-valent pneumococcal conjugate vaccine compared with lower-valent alternatives in Argentina. Vaccine 2024, 42, 126043. [Google Scholar] [CrossRef]
- Shinjoh, M.; Togo, K.; Hayamizu, T.; Yonemoto, N.; Morii, J.; Perdrizet, J.; Kamei, K. Cost-effectiveness analysis of 20-valent pneumococcal conjugate vaccine for routine pediatric vaccination programs in Japan. Expert Rev. Vaccines 2024, 23, 485–497. [Google Scholar] [CrossRef]
- Kang, D.-W.; Choe, Y.J.; Lee, J.-Y.; Suk, I.-A.; Kim, Y.-S.; Kim, H.-Y.; Byun, B.-K.; Park, S.-K. Cost-effectiveness analysis of the 20-valent pneumococcal conjugate vaccine for the pediatric population in South Korea. Vaccine 2024, 42, 126000. [Google Scholar] [CrossRef]
- Lytle, D.; Beltrán, A.G.G.; Perdrizet, J.; Yahia, N.A.; Cane, A.; Yarnoff, B.; Chapman, R. Cost-effectiveness analysis of PCV20 to prevent pneumococcal disease in the Canadian pediatric population. Hum. Vaccines Immunother. 2023, 19, 2257426. [Google Scholar] [CrossRef]
- Warren, S.; Barmpouni, M.; Kossyvaki, V.; Gourzoulidis, G.; Perdrizet, J. Estimating the Clinical and Economic Impact of Switching from the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) to Higher-Valent Options in Greek Infants. Vaccines 2023, 11, 1369. [Google Scholar] [CrossRef]
- Huang, L.; McDade, C.L.; Perdrizet, J.E.; Wilson, M.R.; Warren, S.A.; Nzenze, S.; Sewdas, R. Cost-Effectiveness Analysis of the South African Infant National Immunization Program for the Prevention of Pneumococcal Disease. Infect. Dis. Ther. 2023, 12, 933–950. [Google Scholar] [CrossRef]
- Vo, N.X.; Pham, H.L.; Bui, U.M.; Ho, H.T.; Bui, T.T. Cost-Effectiveness Analysis of Pneumococcal Vaccines in the Pediatric Population: A Systematic Review. Healthcare 2024, 12, 1950. [Google Scholar] [CrossRef] [PubMed]
- Centers for Disease Control and Prevention. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Streptococcus pneumoniae, 2019. 2019. Available online: www.cdc.gov/abcs/downloads/SPN_Surveillance_Report_2019.pdf (accessed on 17 November 2022).
- Prasad, N.; Stoecker, C.; Xing, W.; Cho, B.H.; Leidner, A.J.; Kobayashi, M. Public health impact and cost-effectiveness of 15-valent pneumococcal conjugate vaccine use among the pediatric population of the United States. Vaccine 2023, 41, 2914–2921. [Google Scholar] [CrossRef] [PubMed]
- Centers for Disease Control and Prevention. Vaccination Coverage Among Young Children (0–35 Months). 2020. Available online: https://www.cdc.gov/vaccines/imz-managers/coverage/childvaxview/interactive-reports/index.html (accessed on 16 December 2022).
- Health Care Inflation in the United States (1948–2024). 2024. Available online: https://www.usinflationcalculator.com/inflation/health-care-inflation-in-the-united-states/ (accessed on 1 October 2024).
- United States Census Bureau. National Demographic Analysis Tables: 2020. 2020. Available online: https://www.census.gov/data/tables/2020/demo/popest/2020-demographic-analysis-tables.html (accessed on 25 September 2024).
- CDC. Mortality in the United States, 2022. 2024. Available online: https://www.cdc.gov/nchs/data/databriefs/db492.pdf (accessed on 1 October 2024).
- Tong, S.; Amand, C.; Kieffer, A.; Kyaw, M.H. Trends in healthcare utilization and costs associated with pneumonia in the United States during 2008–2014. BMC Health Serv. Res. 2018, 18, 715. [Google Scholar] [CrossRef] [PubMed]
- Moore, M.R.; Link-Gelles, R.; Schaffner, W.; Lynfield, R.; Holtzman, C.; Harrison, L.H.; Zansky, S.M.; Rosen, J.B.; Reingold, A.; Scherzinger, K.; et al. Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease in children in the USA: A matched case-control study. Lancet Respir. Med. 2016, 4, 399–406. [Google Scholar] [CrossRef]
- Hansen, J.; Black, S.; Shinefield, H.; Cherian, T.; Benson, J.; Fireman, B.; Lewis, E.; Ray, P.; Lee, J. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than 5 years of age for prevention of pneumonia: Updated analysis using World Health Organization standardized interpretation of chest radiographs. Pediatr. Infect. Dis. J. 2006, 25, 779–781. [Google Scholar] [CrossRef]
- Black, S.B.; Shinefield, H.R.; Ling, S.; Hansen, J.; Fireman, B.; Spring, D.; Noyes, J.; Lewis, E.; Ray, P.; Lee, J.; et al. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia. Pediatr. Infect. Dis. J. 2002, 21, 810–815. [Google Scholar] [CrossRef]
- Black, S.; Shinefield, H.; Fireman, B.; Lewis, E.; Ray, P.; Hansen, J.R.; Elvin, L.; Ensor, K.M.; Hackell, J.; Siber, G.; et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr. Infect. Dis. J. 2000, 19, 187–195. [Google Scholar] [CrossRef]
- Weycker, D.; Farkouh, R.A.; Strutton, D.R.; Edelsberg, J.; Shea, K.M.; Pelton, S.I. Rates and costs of invasive pneumococcal disease and pneumonia in persons with underlying medical conditions. BMC Health Serv. Res. 2016, 16, 182. [Google Scholar] [CrossRef]
- Melegaro, A.; Edmunds, W.J. Cost-effectiveness analysis of pneumococcal conjugate vaccination in England and Wales. Vaccine 2004, 22, 4203–4214. [Google Scholar] [CrossRef]
- CDC. ABCs Bact Facts Interactive Data Dashboard. 2024. Available online: https://www.cdc.gov/abcs/bact-facts/data-dashboard.html (accessed on 1 October 2024).
- Stoecker, C. Economic assessment of PCV15 & PCV20. In Proceedings of the Advisory Committee on Immunization Practices Meeting, Atlanta, GA, USA, 2–3 November 2021. [Google Scholar]
- Centers for Disease Control and Prevention. Active Bacterial Core Surveillance (ABCs) Report, Emerging Infections Program Network, Streptococcus pneumoniae, 2018. 2018. Available online: https://stacks.cdc.gov/view/cdc/109750 (accessed on 15 March 2023).
- Centers for Disease Control and Prevention. Active Bacterial Core Surveillance (ABCs) Report, Emerging Infections Program Network, Streptococcus pneumoniae, 2017. 2017. Available online: https://stacks.cdc.gov/view/cdc/78826 (accessed on 15 March 2023).
- Whitney, C.G.; Pilishvili, T.; Farley, M.M.; Schaffner, W.; Craig, A.S.; Lynfield, R.; Nyquist, A.-C.; A Gershman, K.; Vazquez, M.; Bennett, N.M.; et al. Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: A matched case-control study. Lancet 2006, 368, 1495–1502. [Google Scholar] [CrossRef]
Figure 1.
Model schematic.
Figure 2.
Results of the Deterministic Sensitivity Analysis (DSA)–PCV20 vs. PCV15 costs averted.
Figure 3.
Results of the Deterministic Sensitivity Analysis (DSA)–PCV20 vs. PCV15 QALYs gained.
Table 1.
Input parameters.
| Input | Value [Upper and Lower Bound] | Reference |
|---|---|---|
| Population (# of births in 2023) | ||
| Birth cohort 1 population | 3,613,647 | [13,27] |
| Birth cohort 2 population | 3,552,215 | [2,13] |
| Birth cohort 3 population | 3,491,827 | [13,27] |
| Birth cohort 4 population | 3,432,466 | [13,27] |
| Birth cohort 5 population | 3,374,114 | [13,27] |
| Life expectancy (years) | 77.5 | [28] |
| Vaccine uptake | 87.5 (86.1–88.7) | [25] |
| Incidence (per 100 k) | ||
| IPD | 13.7 (10.1–17.4) | [13,23] |
| Hospitalized pneumonia | 684 (635–733) | [13,24] |
| Non-hospitalized pneumonia | 2007 (1939.5–2016.0) | [13,29] |
| AOM | 64,770 (58.71–293) | [7,13] |
| Case fatality rate | ||
| IPD | 7% (6.9–7.1) | [13,23] |
| Inpatient CAP | 1.3% (1.0–1.6) | [13,24] |
| PCV15 VE | ||
| IPD | 67.3% (61.5–70.5) | [13,30] |
| Hospitalized pneumonia | 9.4% (1.6–12.6) | [13,31] |
| Non-hospitalized pneumonia | 2.2% (−0.6–4.1) | [13,32] |
| AOM | 2.9% (1.9–3.9) | [13,33] |
| PCV20 VE | ||
| IPD | 67.3% (61.5–70.5) | [13,30] |
| Hospitalized pneumonia | 13.1% (2.3–17.5) | [13,31] |
| Non-hospitalized pneumonia | 3.1% (−0.8–5.7) | [13,32] |
| AOM | 4.0% (2.7–5.4) | [13,33] |
| Serotype coverage for <1 year | ||
| PCV15 | 39.8% (31.8–47.7) | [13] |
| PCV20 | 55.4% (44.3–66.5) | [13] |
| Direct medical costs | ||
| IPD | USD 57,925.74 (38,947.34–80,611.27) | [13,34] |
| Hospitalized pneumonia | USD 21,318.34 (19,929.57–22,753.23) | [13,34] |
| Non-hospitalized pneumonia | USD 717.30 (707.19–727.48) | [13,34] |
| AOM | USD 443.74 (439.63–447.88) | [7,13] |
| QALY decrements | ||
| Meningitis | 0.0232 (0.0–0.111) | [35] |
| Bacteremia | 0.0079 (0.0–0.0291449) | [35] |
| Hospitalized pneumonia | 0.006 (0.0–0.05) | [35] |
| Non-hospitalized pneumonia | 0.004 (0.003–0.005) | [35] |
| AOM | 0.005 (0.004–0.006) | [35] |
Table 2.
Overall results of five birth cohorts.
| Prevented Disease Cases | PCV15 | PCV20 | PCV20 vs. PCV15 |
|---|---|---|---|
| IPD | 561 | 780 | 220 |
| Meningitis | 121 | 169 | 47 |
| Non-meningitis | 439 | 612 | 172 |
| CAP | 16,690 | 23,232 | 6542 |
| CAP (inpatient) | 9874 | 13,744 | 3870 |
| CAP (outpatient) | 6817 | 9489 | 2672 |
| OM | 285,985 | 398,080 | 112,095 |
| Total | 303,236 | 422,092 | 118,856 |
| Prevented deaths | |||
| IPD | 39 | 55 | 15 |
| Meningitis | 8 | 12 | 3 |
| Non-meningitis | 31 | 43 | 12 |
| CAP | 128 | 179 | 50 |
| Total | 168 | 233 | 66 |
| Direct costs saved | |||
| IPD | USD 32,470,382 | USD 45,197,466 | USD 12,727,084 |
| CAP (inpatient) | USD 210,486,814 | USD 292,989,183 | USD 82,502,369 |
| CAP (outpatient) | USD 4,889,648 | USD 6,806,193 | USD 1,916,545 |
| OM | USD 126,904,740 | USD 176,646,296 | USD 49,741,556 |
| Total | USD 374,751,584 | USD 521,639,139 | USD 146,887,555 |
| LYG | |||
| IPD deaths | 3021.4 | 4205.6 | 1184.3 |
| Meningitis | 652.6 | 908.4 | 255.8 |
| Non-meningitis | 2368.8 | 3297.2 | 928.5 |
| CAP deaths | 9883.4 | 13,757.3 | 3873.9 |
| Total | 12,904.8 | 17,962.9 | 5058.1 |
| QALYs gained | |||
| IPD cases | 6.3 | 8.7 | 2.5 |
| Meningitis | 2.8 | 3.9 | 1.1 |
| Non-meningitis | 3.5 | 4.8 | 1.4 |
| OM cases | 1429.9 | 1990.4 | 560.5 |
| CAP cases (inpatient) | 59.2 | 82.5 | 23.2 |
| CAP cases (outpatient) | 27.3 | 38.0 | 10.7 |
| IPD deaths | 2651.9 | 3691.4 | 1039.5 |
| CAP deaths | 8674.9 | 12,075.1 | 3400.2 |
| Total | 12,849.6 | 17,886.1 | 5036.5 |
Table 3.
Worst-case scenario results of five birth cohorts.
| Prevented Disease Cases | PCV15 | PCV20 | PCV20 vs. PCV15 |
|---|---|---|---|
| IPD | 297 | 414 | 117 |
| Meningitis | 64 | 89 | 25 |
| Non-meningitis | 233 | 324 | 92 |
| CAP | −222 | −137 | 85 |
| CAP (inpatient) | 1528 | 2196 | 668 |
| CAP (outpatient) | −1750 | −2333 | −583 |
| OM | 166,542 | 236,665 | 70,123 |
| Total | 166,617 | 236,942 | 70,325 |
| Prevented deaths | |||
| IPD | 20 | 29 | 8 |
| Meningitis | 4 | 6 | 2 |
| Non-meningitis | 16 | 22 | 6 |
| CAP | 15 | 22 | 7 |
| Total | 36 | 51 | 15 |
| Direct costs saved | |||
| IPD | USD 11,567,811 | USD 16,114,906 | USD 4,547,096 |
| CAP (inpatient) | USD 30,447,049 | USD 43,767,632 | USD 13,828,137 |
| CAP (outpatient) | USD −1,237,459 | USD −1,649,945 | USD −412,486 |
| OM | USD 73,216,825 | USD 104,044,962 | USD 30,828,137 |
| Total | USD 113,994,226 | USD 162,277,556 | USD 48,283,330 |
| LYG | |||
| IPD deaths | 1578.0 | 2198.3 | 620.3 |
| Meningitis | 340.9 | 474.8 | 134.0 |
| Non-meningitis | 1237.2 | 1723.5 | 486.3 |
| CAP deaths | 1176.4 | 1691.0 | 514.7 |
| Total | 2754.4 | 3889.3 | 1135.0 |
| QALYs gained | |||
| IPD cases | 0.0 | 0.0 | 0.0 |
| Meningitis | 0.0 | 0.0 | 0.0 |
| Non-meningitis | 0.0 | 0.0 | 0.0 |
| CAP cases (inpatient) | 0.0 | 0.0 | 0.0 |
| CAP cases (outpatient) | −5.2 | −7.0 | −1.7 |
| OM cases | 666.2 | 946.7 | 280.5 |
| IPD deaths | 1385.1 | 1929.5 | 544.5 |
| CAP deaths | 1032.5 | 1484.2 | 451.7 |
| Total | 3078.5 | 4353.4 | 1274.9 |
Table 4.
Best-case scenario results of 5 birth cohorts.
| Prevented Disease Cases | PCV15 | PCV20 | PCV20 vs. PCV15 |
|---|---|---|---|
| IPD | 849 | 1264 | 414 |
| Meningitis | 183 | 273 | 89 |
| Non-meningitis | 666 | 991 | 325 |
| CAP | 27,111 | 37,672 | 10,561 |
| CAP (inpatient) | 14,307 | 19,871 | 5564 |
| CAP (outpatient) | 12,804 | 17,801 | 4997 |
| OM | 430,433 | 595,984 | 165,551 |
| Total | 458,393 | 634,919 | 176,526 |
| Prevented deaths | |||
| IPD | 60 | 90 | 29 |
| Meningitis | 13 | 19 | 6 |
| Non-meningitis | 47 | 70 | 23 |
| CAP | 229 | 318 | 89 |
| Total | 289 | 408 | 118 |
| Direct costs saved | |||
| IPD | USD 68,472,421 | USD 101,866,130 | USD 33,393,709 |
| CAP (inpatient) | USD 325,530,443 | USD 452,125,615 | USD 126,595,172 |
| CAP (outpatient) | USD 9,314,713 | USD 12,949,723 | USD 3,635,010 |
| OM | USD 192,782,182 | USD 266,929,175 | USD 74,146,993 |
| Total | USD 596,099,758 | USD 833,870,642 | USD 237,770,884 |
| LYG | |||
| IPD deaths | 4643.8 | 6908.5 | 2264.7 |
| Meningitis | 1003.1 | 1492.2 | 489.2 |
| Non-meningitis | 3640.7 | 5416.3 | 1775.6 |
| CAP deaths | 17,626.2 | 24,480.9 | 6854.6 |
| Total | 22,270.0 | 31,389.4 | 9119.4 |
| QALYs gained | |||
| IPD cases | 39.8 | 59.2 | 19.4 |
| Meningitis | 20.4 | 30.3 | 9.9 |
| Non-meningitis | 19.4 | 28.9 | 9.5 |
| CAP cases (inpatient) | 715.3 | 993.5 | 278.2 |
| CAP cases (outpatient) | 64.0 | 89.0 | 25.0 |
| OM cases | 2582.6 | 3575.9 | 993.3 |
| IPD deaths | 4075.9 | 6063.8 | 1987.8 |
| CAP deaths | 15,471.0 | 21,487.5 | 6016.5 |
| Total | 22,948.7 | 32,268.9 | 9320.2 |
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Ilic, A.; Tort, M.J.; Cane, A.; Farkouh, R.A.; Rozenbaum, M.H. The Health and Economic Effects of PCV15 and PCV20 During the First Year of Life in the US. Vaccines 2024, 12, 1279. https://doi.org/10.3390/vaccines12111279
AMA Style
Ilic A, Tort MJ, Cane A, Farkouh RA, Rozenbaum MH. The Health and Economic Effects of PCV15 and PCV20 During the First Year of Life in the US. Vaccines. 2024; 12(11):1279. https://doi.org/10.3390/vaccines12111279
Chicago/Turabian StyleIlic, Aleksandar, Maria J. Tort, Alejandro Cane, Raymond A. Farkouh, and Mark H. Rozenbaum. 2024. "The Health and Economic Effects of PCV15 and PCV20 During the First Year of Life in the US" Vaccines 12, no. 11: 1279. https://doi.org/10.3390/vaccines12111279
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