The Full Value of Vaccine Assessments (FVVA): a framework for assessing and communicating the value of vaccines for investment and introduction decision-making.

BACKGROUND: Several economic obstacles can deter the development and use of vaccines. This can lead to limited product options for some diseases, delays in new product development, and inequitable access to vaccines. Although seemingly distinct, these obstacles are actually interrelated and therefore need to be addressed through a single over-arching strategy encompassing all stakeholders. METHODS: To help overcome these obstacles, we propose a new approach, the Full Value of Vaccines Assessments (FVVA) framework, to guide the assessment and communication of the value of a vaccine. The FVVA framework is designed to facilitate alignment across key stakeholders and to enhance decision-making around investment in vaccine development, policy-making, procurement, and introduction, particularly for vaccines intended for use in low- and middle-income countries. RESULTS: The FVVA framework has three key elements. First, to enhance assessment, existing value-assessment methods and tools are adapted to include broader benefits of vaccines as well as opportunity costs borne by stakeholders. Second, to improve decision-making, a deliberative process is required to recognize the agency of stakeholders and to ensure country ownership of decision-making and priority setting. Third, the FVVA framework provides a consistent and evidence-based approach that facilitates communication about the full value of vaccines, helping to enhance alignment and coordination across diverse stakeholders. CONCLUSIONS: The FVVA framework provides guidance for stakeholders organizing global-level efforts to promote investment in vaccines that are priorities for LMICs. By providing a more holistic view of the benefits of vaccines, its application also has the potential to encourage greater take-up by countries, thereby leading to more sustainable and equitable impacts of vaccines and immunization programmes.

Financing And Funding Gap For 16 Vaccines Across 94 Low- And Middle-Income Countries, 2011-30.

We estimated immunization program costs, financing, and funding gaps for sixteen vaccines among ninety-four low- and middle-income countries during the period 2011-30. Inputs were obtained from the Institute for Health Metrics and Evaluation, the 2020 Decade of Vaccine Economics costing analysis, the World Health Organization, Gavi, and the United Nations Children's Fund. We found a total funding gap of $38.4 billion between 2011 and 2030, with the cost of immunization delivery being the main driver (86 percent) of the funding gap. On average, government financing of vaccination programs steadily rises throughout the period. However, the decline in both Gavi and development assistance for health (DAH) financing anticipated between 2011 and 2030 outpaces the forecasted increases in domestic government immunization spending. Probabilistic sensitivity analysis was applied to both the costing and the scenario analyses to address uncertainty in the financing of vaccines and vaccine delivery. The results highlight a narrowing gap for vaccine acquisition but a growing gap for vaccine delivery, which emphasizes the critical need for resource mobilization and sustainable financial strategies for immunization programs at national and global levels, as well as a need to address the COVID-19 pandemic's potential effects on government financing for vaccines between 2021 and 2030.

The cost and cost-effectiveness of novel tuberculosis vaccines in low- and middle-income countries: A modeling study.

BACKGROUND: Tuberculosis (TB) is preventable and curable but eliminating it has proven challenging. Safe and effective TB vaccines that can rapidly reduce disease burden are essential for achieving TB elimination. We assessed future costs, cost-savings, and cost-effectiveness of introducing novel TB vaccines in low- and middle-income countries (LMICs) for a range of product characteristics and delivery strategies. METHODS AND FINDINGS: We developed a system of epidemiological and economic models, calibrated to demographic, epidemiological, and health service data in 105 LMICs. For each country, we assessed the likely future course of TB-related outcomes under several vaccine introduction scenarios, compared to a "no-new-vaccine" counterfactual. Vaccine scenarios considered 2 vaccine product profiles (1 targeted at infants, 1 at adolescents/adults), both assumed to prevent progression to active TB. Key economic inputs were derived from the Global Health Cost Consortium, World Health Organization (WHO) patient cost surveys, and the published literature. We estimated the incremental impact of vaccine introduction for a range of health and economic outcomes. In the base-case, we assumed a vaccine price of $4.60 and used a 1× per-capita gross domestic product (GDP) cost-effectiveness threshold (both varied in sensitivity analyses). Vaccine introduction was estimated to require substantial near-term resources, offset by future cost-savings from averted TB burden. From a health system perspective, adolescent/adult vaccination was cost-effective in 64 of 105 LMICs. From a societal perspective (including productivity gains and averted patient costs), adolescent/adult vaccination was projected to be cost-effective in 73 of 105 LMICs and cost-saving in 58 of 105 LMICs, including 96% of countries with higher TB burden. When considering the monetized value of health gains, we estimated that introduction of an adolescent/adult vaccine could produce $283 to 474 billion in economic benefits by 2050. Limited data availability required assumptions and extrapolations that may omit important country-level heterogeneity in epidemiology and costs. CONCLUSIONS: TB vaccination would be highly impactful and cost-effective in most LMICs. Further efforts are needed for future development, adoption, and implementation of novel TB vaccines.

Costs of Immunization Programs for 10 Vaccines in 94 Low- and Middle-Income Countries From 2011 to 2030.

OBJECTIVES: Understanding the level of investment needed for the 2021-2030 decade is important as the global community faces the next strategic period for vaccines and immunization programs. To assist with this goal, we estimated the aggregate costs of immunization programs for ten vaccines in 94 low- and middle-income countries from 2011 to 2030. METHOD: We calculated vaccine, immunization delivery and stockpile costs for 94 low- and middle-income countries leveraging the latest available data sources. We conducted scenario analyses to vary assumptions about the relationship between delivery cost and coverage as well as vaccine prices for fully self-financing countries. RESULTS: The total aggregate cost of immunization programs in 94 countries for 10 vaccines from 2011 to 2030 is $70.8 billion (confidence interval: $56.6-$93.3) under the base case scenario and $84.1 billion ($72.8-$102.7) under an incremental delivery cost scenario, with an increasing trend over two decades. The relative proportion of vaccine and delivery costs for pneumococcal conjugate, human papillomavirus, and rotavirus vaccines increase as more countries introduce these vaccines. Nine countries in accelerated transition phase bear the highest burden of the costs in the next decade, and uncertainty with vaccine prices for the 17 fully self-financing countries could lead to total costs that are 1.3-13.1 times higher than the base case scenario. CONCLUSION: Resource mobilization efforts at the global and country levels will be needed to reach the level of investment needed for the coming decade. Global-level initiatives and targeted strategies for transitioning countries will help ensure the sustainability of immunization programs.

Economic Benefits of Immunization for 10 Pathogens in 94 Low- and Middle-Income Countries From 2011 to 2030 Using Cost-of-Illness and Value-of-Statistical-Life Approaches.

OBJECTIVES: Vaccination has prevented millions of deaths and cases of disease in low- and middle-income countries (LMICs). During the Decade of Vaccines (2011-2020), international organizations, including the World Health Organization and Gavi, the Vaccine Alliance, focused on new vaccine introduction and expanded coverage of existing vaccines. As Gavi, other organizations, and country governments look to the future, we aimed to estimate the economic benefits of immunization programs made from 2011 to 2020 and potential gains in the future decade. METHODS: We used estimates of cases and deaths averted by vaccines against 10 pathogens in 94 LMICs to estimate the economic value of immunization. We applied 3 approaches-cost of illness averted (COI), value of statistical life (VSL), and value of statistical life-year (VSLY)-to estimate observable and unobservable economic benefits between 2011 and 2030. RESULTS: From 2011 to 2030, immunization would avert $1510.4 billion ($674.3-$2643.2 billion) (2018 USD) in costs of illness in the 94 modeled countries, compared with the counterfactual of no vaccination. Using the VSL approach, immunization would generate $3436.7 billion ($1615.8-$5657.2 billion) in benefits. Applying the VSLY approach, $5662.7 billion ($2547.2-$9719.4) in benefits would be generated. CONCLUSION: Vaccination has generated significant economic benefits in LMICs in the past decade. To reach predicted levels of economic benefits, countries and international donor organizations need to meet coverage projections outlined in the Gavi Operational Forecast. Estimates generated using the COI, VSL, or VSLY approach may be strategically used by donor agencies, decision makers, and advocates to inform investment cases and advocacy campaigns.

Cost of Nine Pediatric Infectious Illnesses in Low- and Middle-Income Countries: A Systematic Review of Cost-of-Illness Studies.

BACKGROUND: Cost-of-illness data from empirical studies provide insights into the use of healthcare resources including both expenditures and the opportunity cost related to receiving treatment. OBJECTIVE: The objective of this systematic review was to gather cost data and relevant parameters for hepatitis B, pneumonia, meningitis, encephalitis caused by Japanese encephalitis, rubella, yellow fever, measles, influenza, and acute gastroenteritis in children in low- and middle-income countries. DATA SOURCES: Peer-reviewed studies published in public health, medical, and economic journals indexed in PubMed (MEDLINE), Embase, and EconLit. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Studies must (1) be peer reviewed, (2) be published in 2000-2016, (3) provide cost data for one of the nine diseases in children aged under 5 years in low- and middle-income countries, and (4) generated from primary data collection. LIMITATIONS: We cannot exclude missing a few articles in our review. Measures were taken to reduce this risk. Several articles published since 2016 are omitted from the systematic review results, these articles are included in the discussion. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The review yielded 37 articles and 267 sets of cost estimates. We found no cost-of-illness studies with cost estimates for hepatitis B, measles, rubella, or yellow fever from primary data. Most estimates were from countries in Gavi preparatory (28%) and accelerated (28%) transition, followed by those who are initiating self-financing (22%) and those not eligible for Gavi support (19%). Thirteen articles compared household expenses to manage illnesses with income and two articles with other household expenses, such as food, clothing, and rent. An episode of illness represented 1-75% of the household's monthly income or 10-83% of its monthly expenses. Articles that presented both household and government perspectives showed that most often governments incurred greater costs than households, including non-medical and indirect costs, across countries of all income statuses, with a few notable exceptions. Although limited for low- and middle-income country settings, cost estimates generated from primary data collection provided a 'real-world' estimate of the economic burden of vaccine-preventable diseases. Additional information on whether common situations preventing the application of official clinical guidelines (such as medication stock-outs) occurred would help reveal deficiencies in the health system. Improving the availability of cost-of-illness evidence can inform the public policy agenda about healthcare priorities and can help to operationalize the healthcare budget in local health systems to respond adequately to the burden of illness in the community.

Return On Investment From Immunization Against 10 Pathogens In 94 Low- And Middle-Income Countries, 2011-30.

Estimating the value of global investment in immunization programs is critical to helping decision makers plan and mobilize immunization programs and allocate resources required to realize their full benefits. We estimated economic benefits using cost-of-illness and value-of-a-statistical-life approaches and combined this estimation with immunization program costs to derive the return on investment from immunization programs against ten pathogens for ninety-four low- and middle-income countries for the period 2011-30. Using the cost-of-illness approach, return on investment for one dollar invested in immunization against our ten pathogens was 26.1 for the ninety-four countries from 2011 to 2020 and 19.8 from 2021 to 2030. Using the value-of-a-statistical-life approach, return on investment was 51.0 from 2011 to 2020 and 52.2 from 2021 to 2030. The results demonstrate continued high return on investment from immunization programs. The return-on-investment estimates from this study will inform country policy makers and decision makers in funding agencies and will contribute to efforts to mobilize resources for immunization. Realization of the full benefits of immunization will depend on sustained investment in and commitment to immunization programs.

The Potential Economic Value of a Zika Vaccine for a Woman of Childbearing Age.

INTRODUCTION: With Zika vaccine candidates under development and women of childbearing age being the primary target population, now is the time to map the vaccine (e.g., efficacy and duration of protection) and vaccination (e.g., cost) characteristic thresholds at which vaccination becomes cost effective, highly cost effective, and cost saving. METHODS: A Markov model was developed (to represent 2019 circumstances, US$ and INT$, Region of the Americas) to simulate a woman of childbearing age and the potential risk and clinical course of a Zika infection. RESULTS: Compared with no vaccination, vaccination was cost effective (incremental cost-effectiveness ratio: US$1,254-$82,900/disability-adjusted life years averted) when the risk of infection was ≥0.05%-0.08% (varying with country income), vaccine efficacy was ≥25%, and vaccination cost was US$1-$7,500 (INT$5-$10,000 depending on country income level). Vaccination was dominant (i.e., saved costs and provided beneficial health effects) when the infection risk was ≥0.1% for a vaccine efficacy ≥75% and when the infection risk was ≥0.5% for a vaccine efficacy ≥25%, for scenarios where vaccination conferred a 1-year duration of protection and cost ≤$200. In some cases, the vaccine was cost effective when the risk was as low as 0.015%, the cost was as high as $7,500 (INT$10,000), the efficacy was as low as 25%, and the duration of protection was 1 year. CONCLUSIONS: The thresholds at which vaccination becomes cost effective and cost saving can provide targets for Zika vaccine development and implementation.

A Scoping Review of Investment Cases for Vaccines and Immunization Programs.

BACKGROUND: Many investment cases have recently been published intending to show the value of new health investments, but without consistent methodological approaches. OBJECTIVES: To conduct a scoping review of existing investment cases (using vaccines and immunization programs as an example), identify common characteristics that define these investment cases, and examine their role within the broader context of the vaccine development and introduction. METHODS: A systematic search was conducted from January 1980 to November 2017 to identify investment cases in the area of vaccines and immunization programs from gray literature and electronic bibliographic databases. Investment case outcomes, objectives, key variables, target audiences, and funding sources were extracted and analyzed according to their reporting frequency. RESULTS: We found 24 investment cases, and most of them aim to provide information for decisions (12 cases) or advocate for a specific agenda (9 cases). Outcomes presented fell into 4 broad categories-burden of disease, cost of investment, impact of investment, and other considerations for implementation. Number of deaths averted (70%), incremental cost-effectiveness ratios (67%), and reduction in health and socioeconomic inequalities (54%) were the most frequently reported outcome measures for impact of investment. Health system capacity (79%) and vaccine financing landscape (75%) were the most common considerations for implementation. A sizable proportion (41.4%) of investment cases did not reveal their funding sources. CONCLUSIONS: This review describes information that is critical to decision making about resource mobilization and allocation concerning vaccines. Global efforts to harmonize investment cases more broadly will increase transparency and comparability.