Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization.

BACKGROUND: WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally. To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception. METHODS: In this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI. For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination. We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period. FINDINGS: Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year. For every death averted, 66 years of full health were gained on average, translating to 10·2 billion years of full health gained. We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region. In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination. Increased survival probability is observed even well into late adulthood. INTERPRETATION: Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years. In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality. FUNDING: WHO.

The impact of alternative delivery strategies for novel tuberculosis vaccines in low-income and middle-income countries: a modelling study.

BACKGROUND: Tuberculosis is a leading infectious cause of death worldwide. Novel vaccines will be required to reach global targets and reverse setbacks resulting from the COVID-19 pandemic. We estimated the impact of novel tuberculosis vaccines in low-income and middle-income countries (LMICs) in several delivery scenarios. METHODS: We calibrated a tuberculosis model to 105 LMICs (accounting for 93% of global incidence). Vaccine scenarios were implemented as the base-case (routine vaccination of those aged 9 years and one-off vaccination for those aged 10 years and older, with country-specific introduction between 2028 and 2047, and 5-year scale-up to target coverage); accelerated scale-up similar to the base-case, but with all countries introducing vaccines in 2025, with instant scale-up; and routine-only (similar to the base-case, but including routine vaccination only). Vaccines were assumed to protect against disease for 10 years, with 50% efficacy. FINDINGS: The base-case scenario would prevent 44·0 million (95% uncertainty range 37·2-51·6) tuberculosis cases and 5·0 million (4·6-5·4) tuberculosis deaths before 2050, compared with equivalent estimates of cases and deaths that would be predicted to occur before 2050 with no new vaccine introduction (the baseline scenario). The accelerated scale-up scenario would prevent 65·5 million (55·6-76·0) cases and 7·9 million (7·3-8·5) deaths before 2050, relative to baseline. The routine-only scenario would prevent 8·8 million (95% uncertainty range 7·6-10·1) cases and 1·1 million (0·9-1·2) deaths before 2050, relative to baseline. INTERPRETATION: Our results suggest novel tuberculosis vaccines could have substantial impact, which will vary depending on delivery strategy. Including a one-off vaccination campaign will be crucial for rapid impact. Accelerated introduction-at a pace similar to that seen for COVID-19 vaccines-would increase the number of lives saved before 2050 by around 60%. Investment is required to support vaccine development, manufacturing, prompt introduction, and scale-up. FUNDING: WHO (2020/985800-0). TRANSLATIONS: For the French, Spanish, Italian and Dutch translations of the abstract see Supplementary Materials section.

The Cost Analysis of Human Papillomavirus Vaccination Program in Indonesia.

OBJECTIVES: This study aimed to analyze and describe the cost of HPV vaccination program in Indonesia. METHODS: This study identified the cost-related HPV vaccination program implemented in Makassar, Manado, and Surabaya cities, Indonesia, according to the previous activities performed. Cost information was collected and analyzed in each specific activity for each cost components, using the HPV vaccination module of the World Health Organization Cervical Cancer Prevention and Control Costing tool. RESULTS: According to the Cervical Cancer Prevention and Control Costing tool, the recurrent costs, both financial and economic costs, dominated the HPV vaccination program costs in Surabaya (US dollars [USD] 264 618; USD 268 724), Makassar (USD 166 852; USD 293 300), and Manado (USD 270 815; USD 270 946), with a total cost of USD 702 285 for financial cost and USD 832 970 for economic cost. Vaccine procurement drives the recurrent cost. CONCLUSIONS: The implementation of demonstration program in Surabaya, Makassar, and Manado cities was considerably succeed. Any prediction related to the cost of implementation of HPV vaccination in Indonesia can be calculated and used to advocate regional or national government.

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.

The CAPACITI Decision-Support Tool for National Immunization Programs.

OBJECTIVES: Immunization programs in low-income and middle-income countries (LMICs) are faced with an ever-growing number of vaccines of public health importance recommended by the World Health Organization, while also financing a greater proportion of the program through domestic resources. More than ever, national immunization programs must be equipped to contextualize global guidance and make choices that are best suited to their setting. The CAPACITI decision-support tool has been developed in collaboration with national immunization program decision makers in LMICs to structure and document an evidence-based, context-specific process for prioritizing or selecting among multiple vaccination products, services, or strategies. METHODS: The CAPACITI decision-support tool is based on multi-criteria decision analysis, as a structured way to incorporate multiple sources of evidence and stakeholder perspectives. The tool has been developed iteratively in consultation with 12 countries across Africa, Asia, and the Americas. RESULTS: The tool is flexible to existing country processes and can follow any type of multi-criteria decision analysis or a hybrid approach. It is structured into 5 sections: decision question, criteria for decision making, evidence assessment, appraisal, and recommendation. The Excel-based tool guides the user through the steps and document discussions in a transparent manner, with an emphasis on stakeholder engagement and country ownership. CONCLUSIONS: Pilot countries valued the CAPACITI decision-support tool as a means to consider multiple criteria and stakeholder perspectives and to evaluate trade-offs and the impact of data quality. With use, it is expected that LMICs will tailor steps to their context and streamline the tool for decision making.

GRADE Guidelines 30: the GRADE approach to assessing the certainty of modeled evidence-An overview in the context of health decision-making.

OBJECTIVES: The objective of the study is to present the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) conceptual approach to the assessment of certainty of evidence from modeling studies (i.e., certainty associated with model outputs). STUDY DESIGN AND SETTING: Expert consultations and an international multidisciplinary workshop informed development of a conceptual approach to assessing the certainty of evidence from models within the context of systematic reviews, health technology assessments, and health care decisions. The discussions also clarified selected concepts and terminology used in the GRADE approach and by the modeling community. Feedback from experts in a broad range of modeling and health care disciplines addressed the content validity of the approach. RESULTS: Workshop participants agreed that the domains determining the certainty of evidence previously identified in the GRADE approach (risk of bias, indirectness, inconsistency, imprecision, reporting bias, magnitude of an effect, dose-response relation, and the direction of residual confounding) also apply when assessing the certainty of evidence from models. The assessment depends on the nature of model inputs and the model itself and on whether one is evaluating evidence from a single model or multiple models. We propose a framework for selecting the best available evidence from models: 1) developing de novo, a model specific to the situation of interest, 2) identifying an existing model, the outputs of which provide the highest certainty evidence for the situation of interest, either "off-the-shelf" or after adaptation, and 3) using outputs from multiple models. We also present a summary of preferred terminology to facilitate communication among modeling and health care disciplines. CONCLUSION: This conceptual GRADE approach provides a framework for using evidence from models in health decision-making and the assessment of certainty of evidence from a model or models. The GRADE Working Group and the modeling community are currently developing the detailed methods and related guidance for assessing specific domains determining the certainty of evidence from models across health care-related disciplines (e.g., therapeutic decision-making, toxicology, environmental health, and health economics).

Comparing 3 Approaches for Making Vaccine Adoption Decisions in Thailand.

BACKGROUND: The World Health Organization (WHO) has developed the Total System Effectiveness (TSE) framework to assist national policy-makers in prioritizing vaccines. The pilot was launched in Thailand to explore the potential use of TSE in a country with established governance structures and accountable decision-making processes for immunization policy. While the existing literature informs vaccine adoption decisions in GAVI-eligible countries, this study attempts to address a gap in the literature by examining the policy process of a non-GAVI eligible country. METHODS: A rotavirus vaccine (RVV) test case was used to compare the decision criteria made by the existing processes (Expanded Program on Immunization [EPI], and National List of Essential Medicines [NLEM]) for vaccine prioritization and the TSE-pilot model, using Thailand specific data. RESULTS: The existing decision-making processes in Thailand and TSE were found to offer similar recommendations on the selection of a RVV product. CONCLUSION: The authors believe that TSE can provide a well-reasoned and step by step approach for countries, especially low- and middle-income countries (LMICs), to develop a systematic and transparent decision-making process for immunization policy.

'It takes two to tango': Bridging the gap between country need and vaccine product innovation.

BACKGROUND: Despite a growing global commitment to universal health coverage, considerable vaccine coverage and uptake gaps persist in resource-constrained settings. One way of addressing the gaps is by ensuring product innovation is relevant and responsive to the needs of these contexts. Total Systems Effectiveness (TSE) framework has been developed to characterize preferred vaccine attributes from the perspective of country decision-makers to inform research and development (R&D) of products. A proof of concept pilot study took place in Thailand in 2018 to examine the feasibility and usefulness of the TSE approach using a rotavirus hypothetical test-case. METHODS: The excel-based model used multiple-criteria decision analysis (MCDA) to compare and evaluate five hypothetical rotavirus vaccine products. The model was populated with local data and products were ranked against decision criteria identified by Thai stakeholders. A one-way sensitivity analysis was performed to identify criteria that influenced vaccine ranking. Self-assessment forms were distributed to R&D stakeholders on the usability of the approach and were subsequently analysed. RESULTS: The model identified significant parameters that impacted on MCDA rankings. Self-assessment forms revealed that TSE was perceived as being able to encourage closer collaboration between country decision makers and vaccine developers. CONCLUSIONS: The pilot study demonstrates that it is feasible to use an MCDA approach to elicit stakeholder preferences and determine influential parameters to help identify the preferred product characteristics for R&D from the perspective of country decision-makers. It found that TSE can help steer manufacturers to develop products that are better aligned with country need. Findings will guide further development of the TSE concept.

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.

Evidence-informed vaccine decision making: The introduction of Human Papilloma Virus (HPV) vaccination in the Netherlands.

Little is known about the role of (economic) information or evidence in the different stages of the decision-making process on vaccine introduction. By conducting a document analysis on the public decision-making process of introducing human Papilloma virus (HPV) vaccine into the national vaccination program (NVP) in the Netherlands, we aim to gain insight into which information plays a role during the introduction of a vaccination programme. A document analysis was performed on the public decision-making process regarding the introduction of HPV vaccine into the NVP in the Netherlands. Information used or asked for by various stakeholders during different stages of the policymaking process was identified. In total, 42 documents were found, analyzed and synthesized, for the period between August 2006 and September 2009. Documents were analyzed using directed content analysis based on eight broad categories of criteria used in decision-making frameworks for introducing a vaccine. Our analysis demonstrates that a wide variety of stakeholders is involved in the process. Financial or economic issues were stipulated in 64.3% of the documents and information on vaccine characteristics were discussed in 59.5%. Economic information from economic evaluations was discussed most (47.6%). Based on our analysis, it can be concluded that economic information, in particular information from economic evaluations, played an important role in the decision-making process regarding the introduction of HPV-vaccination.

Quadrivalent influenza vaccines in low and middle income countries: Cost-effectiveness, affordability and availability.

In high-income countries, there is an increased tendency to replace inactivated seasonal trivalent influenza (TIV) vaccines with quadrivalent (QIV) vaccines as these are considered to give a greater public health benefit. In addition, several recent studies from the USA and Europe indicate that replacement with QIV might also be cost-effective; however, the situation in low- and middle-income countries (LMIC) is less clear as few studies have investigated this aspect. The paper by de Boer et al. (2008) describes a dynamic modelling study commissioned by WHO that suggests that in LMICs, under certain conditions, QIV might also be more cost-effective than TIV. In this commentary, we discuss some important aspects that policymakers in LMICs might wish to take into account when considering replacing TIV by QIV. Indeed, from the data presented in the paper by de Boer et al. it can be inferred that replacing QIV for TIV would mean a 25-29% budget increase for seasonal influenza vaccination in South Africa and Vietnam, resulting in an incremental influenza-related health impact reduction of only 7-8% when a 10% symptomatic attack rate is assumed. We argue that national health budget considerations in LMIC might lead decision-makers to choose other investments with higher health impact for a budget equivalent to roughly a quarter of the yearly TIV immunization costs. In addition to an increased annual cost that would be associated with a decision to replace TIV with QIV, there would be an increased pressure on manufacturers to produce QIV in time for the influenza season requiring manufacturers to produce some components of the seasonal vaccine at risk prior to the WHO recommendations for influenza vaccines. Unless the current uncertainties, impracticalities and increased costs associated with QIVs are resolved, TIVs are likely to remain the more attractive option for many LMICs. Each country should establish its context-specific process for decision-making based on national data on disease burden and costs in order to determine whether the health gains out-weigh the additional cost of moving to QIV. For example, immunizing more people in the population, especially those in higher risk groups, with TIV might not only provide better value for money but also deliver better health outcomes in LMICs. Countries with local influenza vaccine manufacturing capacity should include in their seasonal influenza vaccine procurement process an analysis of the pros- and cons- of TIV versus QIV, to ensure both feasibility and sustainability of local manufacturing.

Thresholds for decision-making: informing the cost-effectiveness and affordability of rotavirus vaccines in Malaysia.

Cost-effectiveness thresholds (CETs) based on the Commission on Macroeconomics and Health (CMH) are extensively used in low- and middle-income countries (LMICs) lacking locally defined CETs. These thresholds were originally intended for global and regional prioritization, and do not reflect local context or affordability at the national level, so their value for informing resource allocation decisions has been questioned. Using these thresholds, rotavirus vaccines are widely regarded as cost-effective interventions in LMICs. However, high vaccine prices remain a barrier towards vaccine introduction. This study aims to evaluate the cost-effectiveness, affordability and threshold price of universal rotavirus vaccination at various CETs in Malaysia. Cost-effectiveness of Rotarix and RotaTeq were evaluated using a multi-cohort model. Pan American Health Organization Revolving Fund's vaccine prices were used as tender price, while the recommended retail price for Malaysia was used as market price. We estimate threshold prices defined as prices at which vaccination becomes cost-effective, at various CETs reflecting economic theories of human capital, societal willingness-to-pay and marginal productivity. A budget impact analysis compared programmatic costs with the healthcare budget. At tender prices, both vaccines were cost-saving. At market prices, cost-effectiveness differed with thresholds used. At market price, using 'CMH thresholds', Rotarix programmes were cost-effective and RotaTeq were not cost-effective from the healthcare provider's perspective, while both vaccines were cost-effective from the societal perspective. Using other CETs, both vaccines were not cost-effective at market price, from the healthcare provider's and societal perspectives. At tender and cost-effective prices, rotavirus vaccination cost ∼1 and 3% of the public health budget, respectively. Using locally defined thresholds, rotavirus vaccination is cost-effective at vaccine prices in line with international tenders, but not at market prices. Thresholds representing marginal productivity are likely to be lower than those reflecting human capital and individual preference measures, and may be useful in determining affordable vaccine prices.

Global economic evaluation of oral cholera vaccine: A systematic review.

World Health Organization recommends oral cholera vaccine (OCV) to prevent and control cholera, but requires cost-effectiveness evidence. This review aimed to provide a critical appraisal and summary of global economic evaluation (EE) studies involving OCV to guide future EE study. Full EE studies, published from inception to December 2015, evaluating OCV against cholera disease were included. The included studies were appraised using WHO guide for standardization of EE of immunization programs. Out of 14 included studies, almost all (13/14) were in low- and middle-income countries. Most studies (11/14) evaluated mass vaccination program. Most of the studies (9/14) incorporated herd protective effect. The most common influential parameters were cholera incidence, OCV coverage, herd protection and OCV price. OCV vaccination is likely to be cost-effective when targeted at the population with high-risk of cholera and poor access to health care facilities when herd protection effect is incorporated and OCV price is low.

WHO guide on the economic evaluation of influenza vaccination.

Influenza is responsible for substantial morbidity and mortality across the globe, with a large share of the total disease burden occurring in low- and middle-income countries (LMICs). There have been relatively few economic evaluations assessing the value of seasonal influenza vaccination in LMICs. The purpose of this guide is to outline the key theoretical concepts and best practice in methodologies and to provide guidance on the economic evaluation of influenza vaccination in LMICs. It outlines many of the influenza vaccine-specific challenges and should help to provide a framework for future evaluations in the area to build upon.

Rationale and opportunities in estimating the economic burden of seasonal influenza across countries using a standardized WHO tool and manual.

Influenza disease burden is recognized as one of the major public health problems globally. Much less is known about the economic burden of influenza especially in low- and middle-income countries (LMICs). A recent systematic review on the economic burden of influenza in LMICs suggests that information is scarce and/or incomplete and that there is a lack of standardized approaches for cost evaluations in LMICs. WHO commissioned and publicized a Manual for estimating the economic burden of seasonal influenza to support the standardization of estimates of the economic burden of seasonal influenza across countries. This article aims to describe the rationale of this manual development and opportunities that lie in collecting data to help policymakers estimate the economic burden of seasonal influenza. It describes a manual developed by WHO to help such estimation and also links to relevant literature and tools to ensure robustness of applied methods to assess the economic burden associated with seasonal influenza, including direct medical costs, direct non-medical costs and indirect costs.

Capturing Budget Impact Considerations Within Economic Evaluations: A Systematic Review of Economic Evaluations of Rotavirus Vaccine in Low- and Middle-Income Countries and a Proposed Assessment Framework.

BACKGROUND: In low- and middle-income countries, budget impact is an important criterion for funding new interventions, particularly for large public health investments such as new vaccines. However, budget impact analyses remain less frequently conducted and less well researched than cost-effectiveness analyses. OBJECTIVE: The objective of this study was to fill the gap in research on budget impact analyses by assessing (1) the quality of stand-alone budget impact analyses, and (2) the feasibility of extending cost-effectiveness analyses to capture budget impact. METHODS: We developed a budget impact analysis checklist and scoring system for budget impact analyses, which we then adapted for cost-effectiveness analyses, based on current International Society for Pharmacoeconomics and Outcomes Research Task Force recommendations. We applied both budget impact analysis and cost-effectiveness analysis checklists and scoring systems to examine the extent to which existing economic evaluations provide sufficient evidence about budget impact to enable decision making. We used rotavirus vaccination as an illustrative case in which low- and middle-income countries uptake has been limited despite demonstrated cost effectiveness. A systematic literature review was conducted to identify economic evaluations of rotavirus vaccine in low- and middle-income countries published between January 2000 and February 2017. We critically appraised the quality of budget impact analyses, and assessed the extension of cost-effectiveness analyses to provide useful budget impact information. RESULTS: Six budget impact analyses and 60 cost-effectiveness analyses were identified. Budget impact analyses adhered to most International Society for Pharmacoeconomics and Outcomes Research recommendations, with key exceptions being provision of undiscounted financial streams for each budget period and model validation. Most cost-effectiveness analyses could not be extended to provide useful budget impact information; cost-effectiveness analyses also rarely presented undiscounted annual costs, or estimated financial streams during the first years of programme scale-up. CONCLUSIONS: Cost-effectiveness analyses vastly outnumber budget impact analyses of rotavirus vaccination, despite both being critical for policy decision making. Straightforward changes to the presentation of cost-effectiveness analyses results could facilitate their adaptation into budget impact analyses.

Experiences of operational costs of HPV vaccine delivery strategies in Gavi-supported demonstration projects.

From 2012 to 2016, Gavi, the Vaccine Alliance, provided support for countries to conduct small-scale demonstration projects for the introduction of the human papillomavirus vaccine, with the aim of determining which human papillomavirus vaccine delivery strategies might be effective and sustainable upon national scale-up. This study reports on the operational costs and cost determinants of different vaccination delivery strategies within these projects across twelve countries using a standardized micro-costing tool. The World Health Organization Cervical Cancer Prevention and Control Costing Tool was used to collect costing data, which were then aggregated and analyzed to assess the costs and cost determinants of vaccination. Across the one-year demonstration projects, the average economic and financial costs per dose amounted to US$19.98 (standard deviation ±12.5) and US$8.74 (standard deviation ±5.8), respectively. The greatest activities representing the greatest share of financial costs were social mobilization at approximately 30% (range, 6-67%) and service delivery at about 25% (range, 3-46%). Districts implemented varying combinations of school-based, facility-based, or outreach delivery strategies and experienced wide variation in vaccine coverage, drop-out rates, and service delivery costs, including transportation costs and per diems. Size of target population, number of students per school, and average length of time to reach an outreach post influenced cost per dose. Although the operational costs from demonstration projects are much higher than those of other routine vaccine immunization programs, findings from our analysis suggest that HPV vaccination operational costs will decrease substantially for national introduction. Vaccination costs may be decreased further by annual vaccination, high initial investment in social mobilization, or introducing/strengthening school health programs. Our analysis shows that drivers of cost are dependent on country and district characteristics. We therefore recommend that countries carry out detailed planning at the national and district levels to define a sustainable strategy for national HPV vaccine roll-out, in order to achieve the optimal balance between coverage and cost.

Identification and Prioritization of the Economic Impacts of Vaccines.

Understanding the most important economic impacts of vaccines can provide relevant information to stakeholders when selecting vaccine immunization strategies from a broader perspective. This study was therefore designed to first identify economic impacts to vaccinated individuals and, second, assess the relative importance of these economic impacts. A four-step approach was used, including a review of the literature, a pilot study, and expert consultation. As a fourth step, a survey utilizing a best-worst scaling was conducted among 26 different stakeholders to assess the relative importance of the identified economic impacts. In each of the 15 choice tasks, participants were asked to choose the most important and the least important economic impact from a set of four from the master list. We identified 23 economic impacts relevant for vaccine introduction. Four domains were identified, namely, health related benefits to vaccinated individuals, short- and long-term productivity gains, community or health systems externalities, and broader economic indicators. The first domain was seen as especially important with mortality, health care expenditure, and morbidity ranking in the top three overall. In conclusion, our study suggests that domain A "health related benefits to vaccinated individuals" are valued as more important than the other economic impacts.

Stakeholders' perception on including broader economic impact of vaccines in economic evaluations in low and middle income countries: a mixed methods study.

BACKGROUND: Current health economic evaluation guidelines mainly concentrate on immediate health gains and cost savings for the individual involved in the intervention. However, it has been argued that these guidelines are too narrow to capture the full impact of vaccination in low and middle income countries. The inclusion of broader economic impact of vaccines (BEIV) has therefore been proposed. Some examples of these are productivity-related gains, macro-economic impact, and different externalities. Despite their potency, the extent to which such benefits can and should be incorporated into economic evaluations of vaccination is still unclear. This mixed methods study aims to assess the relevance of BEIV to different stakeholders involved in the vaccine introduction decision making process. METHODS: In this mixed method study an internet based survey was sent to attendees of the New and Underutilized Vaccines Initiative meeting in Montreux, Switzerland in 2011. Additionally, semi-structured interviews of 15 minutes each were conducted during the meeting. Study participants included decision makers, experts and funders of vaccines and immunization programs in low and middle income countries. Descriptive analysis of the survey, along with identification of common themes and factors extracted from the interviews and open survey questions was undertaken. RESULTS: Evidence on macro-economic impact, burden of disease and ecological effects were perceived as being most valuable towards aiding decision making for vaccine introduction by the 26 survey respondents. The 14 interviewees highlighted the importance of burden of disease and different types of indirect effects. Furthermore, some new interpretations of BEIVs were discussed, such as the potential negative impact of wastage during immunization programs and the idea of using vaccines as a platform for delivering other types of health interventions. Interviewees also highlighted the importance of using a broader perspective in connection to measuring economic impacts, particularly when attempting to derive the value of newer, more expensive vaccines. CONCLUSION: According to participants, BEIVs were seen as being equally important as traditional outcome measures used in cost-effectiveness analyses. Such insight can be used to shape research agendas within this field and to eventually create broader, more inclusive practical guidelines for economic evaluations of vaccines.

Fiscal consequences of changes in morbidity and mortality attributed to rotavirus immunisation.

Changes in population health status are known to influence government fiscal transfers both in terms of lost tax revenue and increased expenditure for health and social services. To estimate the fiscal impact of changes in morbidity and mortality attributed to rotavirus immunisation, we developed a government perspective model to estimate discounted net tax revenue for Ghana and Vietnam. The model derived the impact of rotavirus morbidity and mortality on lifetime productive capacity and related tax transfers, and demand for government transfers in relation to education and healthcare in immunised and non-immunised cohorts. The discounted age-specific net tax revenue was derived by deducting transfers from gross taxes and discounting for time preference. In Ghana, taking into account immunisation costs, tax and transfers, the estimated net discounted tax for the immunised cohort was estimated to generate $2.6 billion in net taxes up to age 65. In Vietnam, the net revenue attributed to the immunised cohort reached $55.17 billion suggesting an incremental benefit of approximately $29 million. We posit that the government perspective fiscal framework described here is a valid approach for estimating how governments benefit from investments in immunisation that can be considered supplementary to conventional cost-effectiveness approaches for defining value.