Value of the Immunization Program for Children in the 2017 US Birth Cohort

We developed a decision-tree model in Microsoft Excel (Microsoft Corporation; Redmond, Washington) to analyze the impact of vaccination on the 2017 US birth cohort (3 855 500 children)¹⁸  during its lifetime (Fig 1), focusing on 9 childhood vaccines routinely administered from birth to age 10 years: diphtheria, tetanus, and acellular pertussis (DTaP); hepatitis A (HepA); hepatitis B (HepB); Haemophilus influenzae type b (Hib); inactivated polio vaccine (IPV); measles, mumps, rubella (MMR); PCV13; rotavirus; and varicella.²  Since influenza vaccination is recommended for children and adults, vaccination impact cannot be attributed solely to the pediatric schedule. Additionally, both vaccination coverage and effectiveness vary year to year^19,20 ; thus, annual influenza vaccine was included only in the scenario analyses. Vaccination of the 2017 cohort was assumed to follow the ACIP child immunization schedule, with coverage based on national estimates.²¹ 

For each disease, outcomes were calculated without and with vaccination for every month until 12 months, and then for every year thereafter. From birth to 100 years, we subtracted the number of individuals who died because of all-cause or disease-specific mortality from that period’s cohort and progressed the remaining individuals to the next period (month or, after 12 months, year). Age-specific all-cause mortality, disease incidence, treatment costs, and probability of different outcomes were used to parameterize the decision tree for each disease (see Supplemental Tables 5–25).

The model compared vaccination according to the recommended schedule against no vaccination. For each disease and for the vaccination and no-vaccination scenarios, we calculated the total number of cases of a given severity by multiplying the likelihood of different clinical outcomes by the total number of expected cases. Total disease-related costs were calculated by multiplying costs for a given clinical outcome by the number of clinical outcomes among the total number of disease cases and summing over the different clinical outcomes per disease (see Disease Costs and Quality of Life Impacts section). Surviving individuals who developed long-term complications for some diseases accumulated disability-related costs, which were discounted over their remaining lifetimes. Costs were inflated to 2019 USD using the healthcare component of the personal consumption expenditures index for treatment costs, the general component of the consumer price index for nonmedical costs such as transport costs,²²  and the employment cost index for productivity costs.²³  Costs and outcomes were calculated from the healthcare payer and societal perspectives and discounted using the standard annual discount rate of 3%.²⁴ 

After calculating clinical outcomes for the vaccination and no-vaccination scenarios, we estimated the reductions in overall and age-specific cases of disease caused by vaccination. For the scenarios without and with immunization, treatment costs associated with disease cases were assumed to be based on current standard of care. Similarly, deaths caused by each disease were estimated in both scenarios, using the most recent mortality rates when available.

For each vaccination scenario, we reported the total disease-related cases, deaths, costs, life-years (LYs) and quality-adjusted life-years (QALYs). Then, we calculated averted cases by subtracting the number of cases with vaccination from the number of cases without vaccination. Similarly, we calculated LYs and QALYs gained by subtracting LYs and QALYs with vaccination from those obtained in the without vaccination scenario. We calculated the incremental cost-effectiveness ratio by dividing the net costs of the immunization program by incremental QALYs gained. The BCR was calculated by dividing the incremental disease-related cost-savings by the net costs of the immunization program.

We calculated cases before and after each vaccine was routinely recommended; these incidence estimates are described in a companion article.²⁵  Prevaccine incidence estimates were calculated from disease surveillance data (National Notifiable Diseases Surveillance System and Active Bacterial Core surveillance reports) or obtained from the literature. Vaccine-era disease incidence estimates were calculated as average values over the most recent 5 years of available data or obtained from estimates of cases averted or event rate reductions. Incidence estimates in each era were adjusted for underreporting when applicable.

We calculated the costs of the vaccination program, which included vaccine acquisition, administration, and adverse event costs. Vaccination coverage, which was obtained from the 2017 National Immunization Survey-Child^21,26  and 2019 to 2020 state and local immunization program²⁷  data, was used to estimate the number of individuals vaccinated and number of doses administered.

Public and private vaccine acquisition costs were taken from the 2019 Centers for Disease Control and Prevention’s Vaccine Price List for Children²⁸  (Table 1). The model assumed that 53% of childhood vaccines were purchased at the public price, such as through the Vaccines for Children program, and that 47% were purchased at the private price.⁷  When multiple vaccines were available for the same disease (eg, HepA vaccines), vaccine acquisition costs per dose were estimated by averaging the price across brands, without accounting for market share of specific products. To account for combination vaccines, which typically have a small price premium, higher average vaccine acquisition costs were tested in sensitivity analyses. The vaccine wastage rate was assumed to be 5%.⁷  Federal excise taxes for the Vaccine Injury Compensation Program were not included in vaccine acquisition costs, as they are collected from vaccine manufacturers.²⁹ 

For vaccine administration costs, we assumed that 80% of vaccines were administered by private providers and that the remaining 20% of vaccines were administered in public clinics.⁷  Unit costs of administration were obtained from the Centers for Medicare and Medicaid Services’ Physician Fee Schedule³⁰  for privately administered vaccines, with the administration cost per dose dependent on the number of disease components included in each vaccine. For example, for the DTaP vaccine, which protects against 3 diseases, administration costs were equal to the costs associated with reimbursement for the initial disease component plus each of the 2 other disease components. Vaccines administered in a public setting incurred an administration cost of $8.40 per dose (2019 USD).⁷ 

We estimated the productivity loss costs associated with vaccination by multiplying 2 hours of lost caregiver time for each vaccination visit⁷  by the hourly cost of caregiver time of $21.24.³¹  Additionally, caregiver travel costs for each visit ($25.74) were applied.⁷  For vaccines typically administered during routine well-child visits, and in the presence of a wide variation in indirect costs associated with pediatric vaccination, we assumed that 50% of caregiver time and travel costs were attributed to vaccination.^7,32–40 

Vaccinated individuals were assumed to experience adverse events and associated direct medical costs and disutilities (Supplemental Tables 5 and 6). Incidence, cost, and disutility estimates for vaccine-related adverse events were obtained from previous economic analyses^{6,7,32,33,35,36,41–43}  and validated with clinical expert opinion; events that were not considered causally attributable to vaccination by the Institute of Medicine were excluded.^44–53 

To capture the costs and impact of infectious diseases on quality of life, we used disease-specific severity distributions to calculate the number of clinical outcomes for each disease. The direct medical cost, disutility value, and duration of disease per clinical outcome were based on the published literature (Supplemental Table 21).

Productivity loss costs were calculated using the human capital approach.^6,7,54,55  Specifically, disease-related productivity costs were calculated as the number of cases at each age multiplied by mean workdays lost divided by 365, which was then multiplied by the age-specific market and nonmarket annual productivity³¹  (Supplemental Tables 22 and 24). For disease cases resulting in long-term sequelae, the model assumed the percentage reduction in annual productivity was equal to the percentage reduction in health-related utility weights associated with the complication (Supplemental Table 23). Average age-specific estimates of annual productivity and life expectancy were used to calculate the discounted present value of lifetime productivity loss costs associated with disease-related mortality and long-term sequelae (Supplemental Tables 24 and 25).^31,56,57 

In addition to base-case analyses, we conducted additional univariate scenario analyses to assess the robustness of health and economic outcomes to changes in key analysis assumptions. Scenarios considered variations to assumptions for the following: (1) 100% increase in vaccine administration costs, (2–3) 10% increase and reduction in the percentage of vaccines publicly purchased, (4) 5% increase in vaccine acquisition costs, (5) 100% of indirect costs for caregiver time and travel for vaccination at well-child visits attributable to vaccination, (6) 0% annual discount rates, (7) 10% reduction in prevaccine disease incidence, (8) 50% increase in vaccine-era disease incidence, (9–10) 20% increase and decrease in healthcare payer disease-related costs, and (11) 20% reduction in case-fatality rates for modeled diseases. Another scenario (12) was conducted to include annual influenza vaccination and disease for children aged 0 to 10 years in the economic analysis. Annual influenza vaccination coverage was based on coverage from the 2017 to 2018 season (67.8% and 59.5% for ages <5 years and 5–10 years, respectively).⁵⁸  All children vaccinated received 2 doses at the time of their first influenza vaccination, per the ACIP-recommended schedule. Vaccine acquisition costs for influenza vaccines were obtained from the 2019 vaccines price list,²⁸  and an average cost across products was calculated ($14.24 and $18.73 for public and private purchasing sources, respectively). Details for disease-related inputs are presented in Supplemental Table 11.

An additional scenario (13) included the value of QALYs saved in the societal BCR calculation.⁵⁹  The value of QALYs saved was included in the benefits of vaccination by multiplying the number of QALYs saved by a willingness-to-pay threshold of $100 000 per QALY gained.⁶⁰  Finally, a worst-case scenario (14) was presented by combining all input variations that negatively impacted the BCR, which included scenarios 1, 3, 4, 5, 7, 8, 10, and 11.

Over the lifetime of the 2017 US birth cohort, 21.2 million preventable disease cases were estimated without routine childhood immunization, resulting in 33 000 disease-related deaths, 876 500 LYs lost, and 931 400 QALYs lost. When vaccine-preventable diseases were modeled with routine childhood immunization, 3.4 million cases and 1600 disease-related deaths occurred, with 23 400 LYs and 39 800 QALYs lost. As a result, routine childhood immunization was associated with 17.8 million disease cases averted, 31 400 disease-related deaths averted, and an incremental gain of 853 000 LYs and 891 600 QALYs (Table 2). Incremental results varied by disease, with the most cases averted for pneumococcal disease, measles, and varicella and the most deaths averted for pneumococcal disease, diphtheria, and measles. Gains in LYs and QALYs were largest for diphtheria, pneumococcal disease, and measles (Table 2).

Undiscounted outcomes are shown in Table 2. For each disease evaluated, inclusion of the associated vaccine in the routine childhood immunization program reduced the number of cases; reductions ranged from approximately 47% for rotavirus cases to 100% for polio cases. More than 90% reduction in cases was achieved for 10 of the 13 diseases evaluated.

Lifetime societal disease-related costs for the 2017 birth cohort were $66.8 billion without childhood immunization, which included $22.4 billion in healthcare payer costs to treat cases of disease, $8.4 billion in productivity losses caused by cases of disease and long-term sequelae, and $36.0 billion in productivity losses caused by disease-related mortality (Fig 2). With routine childhood immunization, lifetime societal disease-related costs were $3.2 billion, including $1.3 billion in healthcare payer costs to treat cases of disease, $0.9 billion in productivity losses caused by cases of disease and long-term sequelae, and $1.0 billion in productivity losses caused by disease-related mortality.

Thus, societal disease-related cost-savings totaled $63.6 billion, with the highest savings being caused by averted cases of diphtheria, measles, and pneumococcal disease (Fig 3). For disease-related costs averted, direct medical costs to treat acute cases and long-term sequelae accounted for 33% of the savings, whereas the remaining costs averted were from productivity losses caused by cases and long-term sequelae (12%) and productivity loss caused by mortality (55%) (Table 3).

The societal costs of the US routine vaccination program were $8.5 billion for the 2017 birth cohort. Most societal vaccination costs were from vaccine acquisition (62%), administration (23%), and caregiver time and travel (13%); adverse events constituted a small proportion of costs (2%). As a result of the disease-related costs averted, the US childhood immunization program was associated with a net savings of $55.1 billion and a BCR of 7.5 from the societal perspective. This BCR indicates that every dollar invested in the childhood immunization program is expected to result in $7.50 in savings to society. A BCR of 2.8 was observed from the healthcare payer perspective. Incremental costs per LY and per QALY saved were not applicable because the immunization program was cost-saving. However, using a willingness-to-pay threshold of $100 000 per QALY saved,⁶⁰  the value of total QALYs saved by the childhood immunization program was approximately $89.2 billion.

BCRs were most impacted by variations of annual discount rates, vaccine administration costs, and direct medical costs of disease cases (Table 4). Healthcare payer and societal BCRs were minimally impacted when assumptions impacting vaccine acquisition costs were varied. The economic value of routine childhood immunization was lower when annual influenza vaccination for children aged 0 to 10 years was included in the economic analysis, with healthcare payer and societal BCRs of 2.6 and 5.8 (compared with 2.8 and 7.5 in the base case), respectively. The societal BCR substantially increased when the value of QALYs saved was included in the BCR calculation (BCR = 18.0). When the scenarios negatively impacting the BCR of childhood immunization were simultaneously observed (ie, worst-case scenario), the healthcare payer and societal BCRs were 1.5 and 3.8, respectively.

We estimated that routine childhood immunization averted 17.8 million cases and 31 400 disease-related deaths for the 2017 US birth cohort over its lifetime, resulting in a net savings of $55.1 billion (BCR of 7.5) and $13.7 billion (BCR of 2.8) from a societal and healthcare payer perspective, respectively. Results were robust to variations in key input values. These estimates could be used to aid US national vaccination goals for increasing public awareness of the individual and societal benefits of the childhood immunization program,^61,62  which are particularly important given recent decreases in childhood vaccination rates observed in the United States during the COVID-19 pandemic.⁶³ 

Previous analyses have evaluated the economic impact of prior US pediatric vaccination schedules.^6,7  From the healthcare perspective, the current BCR was similar to results previously obtained (2.8 versus 3.0 from Zhou and colleagues⁷ ); from a societal perspective, however, the estimated BCR was lower (7.5 versus 10.1 from Zhou and colleagues⁷ ). The difference in the societal BCR could be explained by the current model’s higher lost productivity caused by vaccination-related caregiver time and transport costs; we also calculated lower reductions in lifetime productivity losses from long-term complications and death.

Our analysis is useful for health economists, policy makers, and other stakeholders interested in ascertaining the benefits and observed impacts of childhood vaccination. Additional analyses should evaluate the impact of childhood vaccination among racial and ethnic groups that may be at increased risk for vaccine-preventable disease or that may have lower vaccination rates. Our analyses could not explore the impact of childhood vaccination within specific population strata because data on differences among racial and ethnic groups in vaccine coverage and disease incidence estimates are scarce and/or based on small population size. Further, continued changes to the ACIP vaccination schedule over time and the epidemiologic impacts of changes to vaccination patterns justify periodic economic evaluations of the childhood vaccination program. Future updates to these evaluations are of particular importance after a shock or disruption to a vaccination program, such as the COVID-19 pandemic, which may impact both disease incidence and population-level vaccination rates.

Some limitations of this analysis must be considered. Our model followed a birth cohort over its lifetime but modeled only pediatric vaccines and did not include the impact or cost of adolescent, adult, maternal, or booster vaccines relevant to our analysis (eg, influenza, TDaP booster, pneumococcal vaccines); this may overestimate the value of childhood immunization. However, our model did not capture the reduced incidence and associated cost-savings of diseases avoided for age groups outside the birth cohort through herd immunity. This was a conservative approach, thus underestimating the value of childhood immunization. Similarly, for the scenario including annual influenza vaccination, influenza incidence and vaccination were modeled only in children aged 0 to 10 years and therefore only captured direct protection of the influenza vaccine.

Prevaccine incidence estimates, for some diseases, corresponded to different historic periods, with possible differences in contact patterns affecting transmission. Vaccine-era incidence estimates use an average across multiple years, thus capturing but not accurately reflecting seasonal fluctuations or periodic outbreaks in a given year. This analytic framework also limits the analysis results to the time periods compared, and as such, our analysis does not account for potential changes in disease incidence over time. In addition, estimates of case-fatality ratios and disease management costs in the vaccine era could not be obtained for diseases that are nearly or fully eradicated. Of note, our sensitivity analyses showed that cost-savings from the childhood vaccination program were robust to variations in assumptions across these parameters.

In addition, each disease was modeled separately and did not allow for interaction across the diseases. For example, disease-related deaths for diphtheria did not reduce the size of the cohort modeled for tetanus. However, during prevaccine periods, children were exposed to multiple infectious disease risks and could die of multiple causes. Thus, the model expresses the value of reducing infectious disease morbidity and mortality across a variety of diseases. Additionally, this analysis did not capture all extended benefits of vaccination, such as increased educational attainment and productivity, reduced household financial risk, and reduced use of antimicrobial agents because of the averted cases of diseases that would have warranted such treatment.^64–66  Furthermore, some aspects of vaccination impact are difficult to capture in models and may lead to underestimation of vaccination benefits. For example, natural measles infections may negatively affect immunologic memory for other pathogens^67–69 ; this phenomenon is not observed in individuals with vaccine-induced immunity.⁶⁸  Thus, our results serve as a conservative estimate of the value of the childhood immunization program.

From the healthcare payer and societal perspectives, the US childhood immunization program results in cost-savings caused by reductions in cases of disease and disease-related costs. This highlights the continued value of routine childhood immunization in reducing the clinical and economic burden of vaccine-preventable disease. Sustaining high levels of vaccination coverage and adherence to the recommended vaccination schedule are necessary to continue observing the benefits of the vaccination program.

Thank you to Kate Lothman of RTI Health Solutions, who provided medical writing support for the development of this manuscript and whose services were funded by Merck Sharp and Dohme LLC, a subsidiary of Merck and Co., Inc., Rahway, NJ.

ACIP

Advisory Committee on Immunization Practices

BCR

benefit-cost ratio

DTaP

diphtheria, tetanus, and acellular pertussis vaccine

HepA

hepatitis A vaccine

HepB

hepatitis B vaccine

Hib

Haemophilus influenzae type b vaccine

IPV

inactivated polio vaccine

LY

life-year

MMR

measles, mumps, rubella vaccine

PCV13

13-valent pneumococcal conjugate vaccine

QALY

quality-adjusted life-year

USD

United States dollars