Return On Investment From Childhood Immunization In Low- And Middle-Income Countries, 2011–20

At the start of the decade 2011–20, declared the Decade of Vaccines, the global health community committed itself to accelerating the introduction of new vaccines and increasing coverage of existing vaccines to save lives and avert illness in the world’s poorest countries. Endorsed by all 194 member states of the World Health Organization (WHO) in May 2012, the Global Vaccine Action Plan identified vaccination as an essential public health tool for improving global health and advancing economic development. Despite increased global attention to immunization, comprehensive evidence on its value remains limited. For key stakeholders, including funders and multilateral organizations, estimating the global return on investment (ROI) associated with immunization can play an integral role in advocating for expanded investment during the decade.

The return on investment quantifies the net benefits gained from every dollar invested on an aggregate level. It can serve as a useful policy-making tool with advantages beyond estimates of costs or benefits alone because it provides an assessment of the returns in relation to their costs. Unlike cost-effectiveness analysis, which employs various health metrics such as disability-adjusted life-years or quality-adjusted life-years to measure benefits, return on investment measures benefits in monetary units, thus providing more comparability and easier comprehension. In addition, ROI analyses typically incorporate productivity losses and societal costs that go beyond the economic benefits captured in cost-effectiveness analyses. This versatility is particularly important for policy makers who require evidence to make financial decisions across sectors. Unfortunately, ROI estimates for health care interventions are rare, which limits their use in policy making.

This work built on our collaboration with a consortium of researchers organized by the Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance, an international organization committed to creating equitable access to vaccines by delivering support to eligible countries’ immunization programs. The analysis estimated the return on investment for achieving projected coverage for vaccinations related to ten antigens throughout the decade across ninety-four low- and middle-income countries, including seventy-three countries currently supported by Gavi. The return on investment presented is the culmination of models developed throughout the Decade of Vaccine Economics project, which focuses on quantifying the economic impact of immunization in low- and middle-income countries across the Decade of Vaccines. ^1–6

Study Data And Methods

We estimated the return on investment for immunization programs to prevent diseases caused by ten antigens: Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae , and yellow fever ( Exhibit 1 ). The effects of routine and supplementary immunization activities were examined together to assess the impact of entire national immunization programs.

Based on Gavi’s eligibility policy and World Bank country classifications in 2015, the ninety-four low- and middle-income countries included thirty-six low-income countries, seventeen countries above the World Bank’s low-income threshold that received Gavi support, twenty countries that will graduate from receiving Gavi support during the period 2016–20, and twenty-one countries not eligible for Gavi support. We adopted a societal perspective commonly used in ROI analyses, which considers all costs and benefits of national immunization programs regardless of funding sources across beneficiaries.

Economic Benefits Estimation

We used outputs from health impact models that estimated the avoided mortality and morbidity by comparing disease burden with vaccination to a counterfactual of no vaccination. More information on these models can be found in an article by Lisa Lee and coauthors ⁷ and our companion publication on economic benefits. ¹ Specifically, the models estimated the deaths and cases averted because of immunization based on the latest epidemiological data on disease burden. We used Gavi’s 2014 strategic demand forecast for vaccine introductions in national immunization programs and coverage projections, ⁸ which is based on data provided by the WHO and the United Nations Children’s Fund (UNICEF).

Taking a well-accepted but conservative approach, we first used the cost-of-illness method to evaluate the economic burden prevented by averting deaths, cases, and disabilities through vaccination. ⁶ This burden included treatment costs, transportation costs for seeking care, caretakers’ reduced economic output as a result of taking care of sick children, and lost productivity due to premature death and morbidity in survivors. We constructed decision tree models to capture the costs of illnesses avoided for each antigen considered in the study. ¹

For treatment costs, we applied costs of care ^9,10 and country-specific estimates of the proportion of sick individuals seeking care, ¹¹ as well as duration and rates of hospital admission by severity of disease, ^12–17 from the literature. Transportation costs were estimated by applying the country-specific cost per trip to a health care facility to each outpatient visit and hospital stay. ¹⁰ We calculated productivity loss among caretakers by multiplying an estimate of a caretaker’s daily productivity by the number of days lost because of care seeking. ¹⁸ We used the human capital approach to determine the economic impact of lost productivity due to disability and death. This approach uses the discounted lifetime earnings of an individual in full health as an approximation of the economic value of the productive years lost during someone’s lifetime. ^19,20 Our models used per capita gross domestic product (GDP) as a proxy for the economic contribution of affected individuals in each year. ²¹

To incorporate the broader economic benefits of vaccination not accounted for in the cost-of-illness method, we also estimated the economic impact based on a full-income approach, which can quantify the value that people place on living longer and healthier lives. To do this, we used the value-of-statistical-life method to evaluate population-level reductions in mortality risk. Specifically, we assumed that the global value of a one-year increase in life expectancy was 1.6 times the GDP per capita, ²² which is consistent with the values adopted by similar studies. ^23,24 We applied this value to the numbers of life-years saved though immunization. We extended this methodology to estimate the impact of disability by applying disability weights for permanent long-term disability associated with diseases caused by six of the ten antigens ( H. influenzae type b, Japanese encephalitis, measles, N. meningitidis serogroup A, rubella, and S. pneumoniae ). ¹

Cost Estimation

We also built a companion cost model, aligned with our benefits models, to estimate the costs associated with national immunization programs for the ninety-four low- and middle-income countries. ⁵ Immunization program costs were modeled to include costs of vaccines, supply chains, and service delivery. Vaccine introductions and uptake levels (referred to as “coverage”) were projected primarily using Gavi’s 2014 adjusted demand forecast, ²⁵ which incorporates country-reported vaccination coverage data and is used by the Gavi Secretariat to make financial commitments.

We used separate forecasts for the costing analysis (the adjusted demand forecast) and the economic benefits analysis (the strategic demand forecast), given the different purposes for which these forecasts were developed by and used at Gavi (for example, the former is used for financing and the latter for impact projections). Because the adjusted demand forecast tends to project higher coverage than the strategic demand forecast, using the two together results in a conservative estimation of return on investment. Differences between the two forecasting methods and the additional steps we took to align the cost and economic benefits models are presented in the online Appendix. ²⁶

We estimated vaccine costs using Gavi price forecasts for eligible countries, prices from the Pan American Health Organization’s (PAHO’s) Revolving Fund for PAHO countries, and prices from UNICEF for the remaining middle-income countries included in the analysis. ^27–29 We calculated supply-chain costs—including costs of transportation, storage, and labor—using data generated by discrete event simulation models. ^30–32 Service delivery costs were abstracted from comprehensive multiyear plans for the majority of Gavi-supported countries and supplemented by regression analysis. ³³ Costs for projected doses are presented irrespective of financing source (country governments, Gavi, or other development partners), and we assumed that these costs would be met—although in reality a funding gap may exist between required financing and dedicated funding. ²

Return-On-Investment Calculation

The return on investment was calculated by first subtracting costs from economic benefits and then dividing the result by costs. We performed the return on investment analysis for total costs and total benefits for the period 2011–20 as compared to a counterfactual of no vaccination. Our analysis predicted that meeting the total projected costs for all ninety-four countries across the decade would yield the net total benefits presented. The results are presented in per unit costs. However, they should be interpreted in absolute terms over the decade (that is, returns during 2011–20) instead of as incremental returns (that is, $x$ dollars in benefits for every additional dollar spent).

We calculated separate ROI estimates by antigen and WHO region to examine variation in returns across these subgroups. All costs and economic benefits are presented in 2010 US dollars, and future costs are discounted at 3 percent to the year of vaccination.

We conducted a probabilistic sensitivity analysis using Monte Carlo simulations to determine a 90 percent uncertainty range for the base-case scenario. Key inputs in each model were assigned a probability distribution—a beta distribution for non-cost-related variables and a gamma distribution for cost-related variables—to represent the positive skew of observed costing data. Variables were simultaneously sampled 10,000 times in a simulation to obtain the uncertainty ranges for return on investment results. Additional details on the methods are presented in the Appendix. ²⁶

Limitations

Given the ambitious scope and complex nature of this analysis, we note several important limitations. First, the economic benefits were based on data from multiple health impact models, many of which are static (meaning that the analyses are run assuming that the models maintain a state of equilibrium and that model parameters are not differentially affected by the passage of time). The health impact models may have limited country-level empirical data and may not include long-term effects, environmental effects, or “herd immunity” (the indirect protection of unimmunized individuals after a certain proportion of the population has been immunized), because of a lack of input data across countries and years.

Second, there were limited accurate, reliable, and complete primary data for low- and middle-income countries on the trade-off between income and mortality risk in the full-income approach, so we used some data on the value of a life-year from high-income countries.

Third, the economic impact did not capture macroeconomic benefits such as growth in GDP or the economic implications of demographic changes resulting from vaccination. This led to a conservative estimate.

Fourth, the cost estimates were limited by the lack of available data on vaccine prices for middle-income countries and weaknesses in data in comprehensive multiyear plans for estimating the costs for service delivery.

Fifth, because of differences in projection methodologies used for Gavi’s demand forecasts, some misalignments in coverage may have remained between costs and benefits.

Finally, given the many models involved in the analysis, the sensitivity analysis was carried out sequentially instead of concurrently. This made it difficult to determine the relative influence of varying individual parameters across the health impact, economic impact, and cost models.

Despite these limitations, this analysis provides for the first time an estimate of the return on investment for immunization during the Decade of Vaccines across ten antigens in ninety-four low- and middle-income countries. It illustrates the value of commitments to national immunization programs by governments and funding partners and highlights the net benefits gained from investments in vaccination.

Study Results

From a societal perspective using the cost-of-illness approach, meeting the projected costs of national immunization programs for vaccines related to ten antigens in ninety-four low- and middle-income countries throughout the Decade of Vaccines was estimated to result in a return that is 16 times (uncertainty range: 10–25) greater than the initial costs ( Exhibit 2 ). In other words, the net benefits of averted treatment costs and lost productivity across the lifespan of immunized cohorts, compared to unimmunized cohorts, were worth 16 times the required investment. Immunization programs within the seventy-three Gavi-supported countries had a similar return, at 18 times (uncertainty range: 11–26) the associated cost.

Using the full-income approach to estimate the broader economic benefits of vaccination resulted in a return on investment more than double that generated using the cost-of-illness approach. Taking into account the broader economic and social value of preventing death and disability, every dollar invested in vaccination during the decade was estimated to result in a return of 44 times the costs (uncertainty range: 27–67) ( Exhibit 2 ). The high return on investment using the full-income approach provides a more complete picture of the contribution of health to a nation’s economic well-being.

We found a wide variation in the estimated return on investment by antigen based on the costs of illnesses ( Exhibit 3 ). However, across all antigens the return on investment was greater than 1, which implies a net gain greater than costs and thus supports immunization as a worthwhile investment from an economic perspective. The highest returns were associated with averting measles, at 58 times the cost (uncertainty range: 28–105) through two routine immunization doses and outreach campaigns. The return on investment for the other antigens ranged from 13 (uncertainty range: 6–22) for yellow fever to 1.3 (uncertainty range: 0.2–3) for rotavirus. The differential ROI values for antigens should not be interpreted as their absolute value relative to one another or as a method for ranking. Instead, these values represent the return on investment for each antigen for those countries in which the associated vaccines are delivered in the period 2011–20.

SOURCE Authors’ analysis based on health impact estimates derived from Gavi’s 2014 strategic demand forecast and dose estimates from Gavi’s 2014 adjusted demand forecast (Notes  8 and 25 , respectively, in text). NOTES Costs and economic benefits are reported in 2010 US dollars. Men A is Neisseria meningitidis serogroup A. Hib is Haemophilus influenzae type b. Hep B is hepatitis B. Sp is Streptococcus pneumoniae . JE is Japanese encephalitis. HPV is human papillomavirus.

An examination of the return on investment based on costs of illnesses by WHO region demonstrates the potential for large relative returns, particularly in South and Southeast Asia (return on investment: 27) and in sub-Saharan Africa (16) (see the Appendix). ²⁶ We observed moderately lower but strong returns in the Western Pacific region (12) and the Middle East (9). Investments in Europe (5) and the Americas (2) resulted in the lowest returns.

The variation across regions is the result of a number of causes, particularly the combination of vaccines included in immunization programs in countries within each region. For example, there was a distinctly larger contribution of nonmeasles vaccines in Europe and the Americas, compared to other regions ( Exhibit 4 ). The low return on investment in the Americas can be explained largely by low ratios of measles cases to fatalities in health impact estimates and by the combination of vaccines introduced within countries in the region.

SOURCE Authors’ analysis based on health impact estimates derived from Gavi’s 2014 strategic demand forecast and dose estimates from Gavi’s 2014 adjusted demand forecast (Notes  8 and 25 , respectively, in text). NOTES Economic benefits are reported in billions of 2010 US dollars. AFRO is the African region. AMRO is the region of the Americas. EMRO is the Eastern Mediterranean region. EURO is the European region. SEARO is the South-East Asian region. WPRO is the Western Pacific region. JE is Japanese encephalitis. HPV is human papillomavirus. Men A is Neisseria meningitidis serogroup A. Hep B is hepatitis B. Sp is Streptococcus pneumoniae . Hib is Haemophilus influenzae type b.

It is important to note that this analysis does not suggest that investments in certain regions should be prioritized. Instead, it demonstrates that spending in national immunization programs across ten antigens is projected to result in these returns over this period of time.

Results of separate uncertainty analyses for the costing and economic benefits models revealed that ROI results were largely driven by measures of health impact, countries’ GDP per capita, vaccine prices, and estimated doses administered.

Discussion

Our analysis found that vaccines are an excellent investment, achieving an estimated return on investment of more than 16 times the costs (uncertainty range: 10–25) across ninety-four low- and middle-income countries during the Decade of Vaccines based on the costs of illnesses. The return on investment increased to 44 times the cost (uncertainty range: 27–67) when we accounted for some of the broader economic benefits of vaccination. The ninety-four countries in our analysis include the world’s poorest nations, where immunization can have the largest impact in terms of lives saved and illnesses prevented. Return on investment was particularly high in South and Southeast Asia and sub-Saharan Africa, where vaccines are estimated to prevent significant disease burden over this decade. Across all ten antigens, immunization was found to result in net benefits that exceeded the required investment across all funding sources for the decade. The results highlight the absolute impact of vaccination programs for the Decade of Vaccines, with combined investments by countries, Gavi, and other development partners leading to significant returns.

Among the ten antigens, the notably high return on investment for measles can be primarily attributed to low vaccine cost, relatively high efficacy and coverage levels, and an epidemiological profile with a high burden of vaccine-preventable disease occurring in young children. While investing in measles vaccination certainly brings significant returns, it is important to remember that our estimates are based on the impact of vaccines delivered through national immunization programs and on projected coverage levels. As vaccine formulations change (for example, the transition from measles alone to a combination measles and rubella vaccine and then to a combination measles, mumps, and rubella vaccine), the return on investment associated with these vaccines will also likely change, as a result of changes in price, dosage requirements, vial sizes, efficacy, and coverage.

Our analysis did not compare the return on investment for vaccines at similar coverage levels or examine incremental returns associated with new vaccine introductions. Nor are the results intended to be used in absolute comparisons between vaccines. The return on investment for antigens associated with more recently licensed vaccines (human papillomavirus, rotavirus, and S. pneumoniae ) tend to be lower than those for antigens associated with traditional vaccines (measles and yellow fever). However, it is likely that the return on investment for newer vaccines will increase over time, as the prices of these vaccines fall because of economies of scale and market competition.

It is also important to note that our estimated return on investment depends upon realizing the financial investment required for national immunization programs over the next five years. ² Our analysis projected costs independent of financing, and thus there is an inherent assumption in our results that the costs to achieve projected coverage levels will be met. This investment includes costs of the vaccines, supply chains, and service delivery based on projected vaccination coverage levels over the decade. The costs used include those incurred by countries as well as by Gavi and other development partners. The combination of these investments can result in significant benefits to individuals, families, communities, and governments as illnesses are prevented, hospitalizations are averted, disabilities are avoided, and lives are saved.

Our estimated return on investment based on costs of illnesses is conservative, as it captures only the benefits of averting treatment costs and productivity losses. ^1,6 In contrast, the estimated return on investment based on the full-income approach provides a more complete picture of economic benefits by placing a value on people living longer and healthier lives. ^4,24,34 The full-income approach has been adopted in other cases of global investment, ^22,23 and the need to consider the full social and economic benefits of vaccination has been documented. ³⁵ Our analysis included results generated using both methods to demonstrate the range and impact of approaches. Comparisons should be made between ROI estimates that capture similar scopes of benefits.

Because our results consider only the total impact of achieving projected coverage levels relative to a 0 percent coverage scenario over the decade, there are a number of additional analyses that could be explored. For example, a scenario looking at the incremental returns using previous coverage levels as a baseline could prove informative. Such a scenario could be used to examine the returns attributable to scaling coverage up and new vaccine introductions. Additional analyses could also look at the impact of demand forecasts on costs and benefits.

Another area of future work involves the incorporation of newer versions of inputs used in the costing and economic benefits models as they become available. Estimated return on investment could be updated with new data expected to be released from comprehensive multiyear plans, the WHO, and the United Nations Population Division. Our analyses could also be extended to examine the return on investment over a time period beyond the current decade. More research is needed to understand the underlying drivers of variation, including the degree to which incomplete or imprecise data may affect the results.

Our findings that the economic benefits of immunization greatly outweigh the costs correspond to the results of cost-effectiveness studies, which have consistently demonstrated that vaccines are one of the most cost-effective public health interventions. ³ Our results also add to a distinct but related analysis that found that Gavi’s support for immunization would yield an estimated 18 percent internal rate of return by 2020. ³⁴

Other research on return on investment for health interventions includes a study of investment in community health workers in sub-Saharan Africa, which estimated an economic net return of $9 for every $1 invested based on increased productivity from a healthier population, potentially reducing the risk of epidemics, and generating economic impact because of increased employment. ³⁶ Improving road safety in Malaysia, Chile, Costa Rica, and South Africa was found to have a net return of $19 in crash costs avoided for every dollar invested over twenty years. ³⁷ Our results are consistent with the findings of the Copenhagen Consensus, in which an expert panel of economists found expanded childhood immunization to be one of the best investments for humanity in terms of value for money. ³⁸

Conclusion

Our findings present the societal return on investment associated with vaccination efforts, both current and projected, during the Decade of Vaccines. Return on investment is easily interpreted by professionals in all fields, not just those related to health, which makes this a unique and useful estimate to assess the gains from immunization programs. To realize the projected returns during this decade will take adequate resource mobilization and sustained vaccine delivery, which in turn require commitments from governments and donors to provide universal access to immunization programs.

ACKNOWLEDGMENTS

This study was performed with financial support from the Bill & Melinda Gates Foundation (Contract No. 23120). The views expressed herein are those of the authors and do not necessarily reflect the official policy or position of the Bill & Melinda Gates Foundation. The authors thank other members of the Global Vaccine Action Plan Costing and Financing Steering Committee (Thomas Cherian, Santiago Cornejo, Gian Gandhi, Hope Johnson, Thomas O’Connell, and Claudio Politi) for guidance of this research. The authors thank the health impact modelers (Andrew Clark, Matthew Ferrari, Ingrid K. Friberg, Tini Garske, Sue J. Goldie, Gavin Grant, Susan Reef, Chutima Suraratdecha, Steven Sweet, Yvonne Tam, Emilia Vynnycky, and Neff Walker) for the disease model estimates. The authors thank the Highly Extensible Resource for Modeling Event-Driven Supply Chains (HERMES) modeling team (Shawn T. Brown, Katrin M. Gorham, Leila A. Haidari, Bruce Y. Lee, Bryan A. Norman, and Jayant Rajgopal) for the supply-chain costing analysis. The authors also thank Diane Coraggio, Grace Morgan, and Julie Buss Younkin for their valuable comments.

NOTES

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