Economic Analysis of Vaccination Programs: An ISPOR Good Practices for Outcomes Research Task Force Report.

This report provides recommendations for budget holders and decision makers in high-, middle, and low-income countries requiring economic analyses of new vaccination programs to allocate scarce resources given budget constraints. ISPOR's Economic Evaluation of Vaccines Designed to Prevent Infectious Disease: Good Practices Task Force wrote guidelines for three analytic methods and solicited comments on them from external reviewers. Cost-effectiveness analyses use decision-analytic models to estimate cumulative changes in resource use, costs, and changes in quality- or disability-adjusted life-years attributable to changes in disease outcomes. Constrained optimization modeling uses a mathematical objective function to be optimized (e.g. disease cases avoided) for a target population for a set of interventions including vaccination programs within established constraints. Fiscal health modeling estimates changes in net present value of government revenues and expenditures attributable to changes in disease outcomes. The task force recommends that those designing economic analyses for new vaccination programs take into account the decision maker's policy objectives and country-specific decision context when estimating: uptake rate in the target population; vaccination program's impact on disease cases in the population over time using a dynamic transmission epidemiologic model; vaccination program implementation and operating costs; and the changes in costs and health outcomes of the target disease(s). The three approaches to economic analysis are complementary and can be used alone or together to estimate a vaccination program's economic value for national, regional, or subregional decision makers in high-, middle-, and low-income countries.

The temporal impact of aging on the burden of herpes zoster.

BACKGROUND: The risk of Herpes Zoster (HZ) increases with age and various studies have also demonstrated an increasing HZ incidence globally. Simultaneously, the global trend of an aging population has placed a greater burden on the healthcare system. This study aims to estimate the potential burden of HZ over time accounting for the increasing trends of both HZ incidence and global aging. METHODS: A recent systematic review on HZ incidence identified studies that evaluated the temporal effects of HZ incidence. Data from the identified studies were extracted to estimate the trend of HZ incidence in the ≥65-year-old age cohort. The incidence rates were estimated up to the year 2030 using two scenarios: a linear extrapolation and a last observation carried forward. Three countries were chosen to perform the analysis on: Australia, Japan and the United States. RESULTS: The incidence data from the three countries showed an average annual increase between 2.35 and 3.74% over the time period of the studies selected. The elderly population for the US, Japan and Australia are expected to increase by 55, 10 and 53% respectively by the year 2030 compared to the levels in 2015. Under the first scenario between 2001 and 2030, the number of annual incident cases of HZ in those aged ≥65 years is expected to increase by +343% (293,785 to 1,303,328), +176% (158,616 to 437,867) and +376% (18,105 to 86,268) in the US, Japan and Australia respectively while those for the second scenario are +150%, +83% and +223% respectively. In the US alone, the estimated annual cost of HZ-related cases in the ≥65 age cohort is approximately 4.74 Billion US$ in 2030. CONCLUSIONS: The increasing incidence of HZ coupled with the demographic trends (i.e., aging population and greater life expectancy) in many countries are likely to imply a rising economic burden of HZ on already constrained healthcare budgets.

Budget constraint and vaccine dosing: a mathematical modelling exercise.

BACKGROUND: Increasing the number of vaccine doses may potentially improve overall efficacy. Decision-makers need information about choosing the most efficient dose schedule to maximise the total health gain of a population when operating under a constrained budget. The objective of this study is to identify the most efficient vaccine dosing schedule within a fixed vaccination budget from a healthcare payer perspective. METHODS: An optimisation model is developed in which maximizing the disease reduction is the functional objective and the constraint is the vaccination budget. The model allows variation in vaccination dosing numbers, in cost difference per dose, in vaccine coverage rate, and in vaccine efficacy. We apply the model using the monovalent rotavirus vaccine as an example. RESULTS: With a fixed budget, a 2-dose schedule for vaccination against rotavirus infection with the monovalent vaccine results in a larger reduction in disease episodes than a 3-dose scheme with the same vaccine under most circumstances. A 3-dose schedule would only be better under certain conditions: a cost reduction of >26% per dose, combined with vaccine efficacy improvement of ≥5% and a target coverage rate of 75%. Substantial interaction is observed between cost reduction per dose, vaccine coverage rate, and increased vaccine efficacy. Sensitivity analysis shows that the conditions required for a 3-dose strategy to be better than a 2-dose strategy may seldom occur when the budget is fixed. The model does not consider vaccine herd effect, precise timing for additional doses, or the effect of natural immunity development. CONCLUSIONS: Under budget constraint, optimisation modelling is a helpful tool for a decision-maker selecting the most efficient vaccination dosing schedule. The low dosing scheme could be the optimal option to consider under the many scenarios tested. The model can be applied under many different circumstances of changing dosing schemes with single or multiple vaccines.

The Economic Value of Rotavirus Vaccination When Optimally Implemented in a High-Income Country.

Rotavirus vaccination was introduced in high-income countries starting in 2006, with no recommendation for optimal implementation. Economic evaluations were presented before launch projecting potential impacts. Few economic reassessments have been reported following reimbursement. This study compares the short- to long-term economic value of rotavirus vaccination between pre-launch predictions and real-world evidence collected over 15 years, proposing recommendations for optimal vaccine launch. A cost-impact analysis compared rotavirus hospitalisation data after the introduction of vaccination between pre-launch modelled projections and observed data collected in the RotaBIS study in Belgium. A best model fit of the observed data was used to simulate launch scenarios to identify the optimal strategy. Data from other countries in Europe were used to confirm the potential optimal launch assessment. The Belgian analysis in the short term (first 8 years) indicated a more favourable impact for the observed data than predicted pre-launch model results. The long-term assessment (15 years) showed bigger economic disparities in favour of the model-predicted scenario. A simulated optimal vaccine launch, initiating the vaccination at least 6 months prior the next seasonal disease peak with an immediate very high vaccine coverage, indicated important additional potential gains, which would make vaccination very cost impactful. Finland and the UK are on such a route leading to long-term vaccination success, whereas Spain and Belgium have difficulties in achieving optimum vaccine benefits. An optimal launch of rotavirus vaccination may generate substantial economic gains over time. For high-income countries that are considering implementing rotavirus vaccination, achieving an optimal launch is a critical factor for long-term economic success.

Comment on Postma et al. Predicted Public Health and Economic Impact of Respiratory Syncytial Virus Vaccination with Variable Duration of Protection for Adults ≥60 Years in Belgium. Vaccines 2023, 11, 990.

Presently, there are at least five important vaccine producers that have already launched or intend to launch a new vaccine designed to prevent infections caused by the Respiratory Syncytial Virus (RSV), which is highly prevalent in the youngest as well as the oldest age groups [...].

Discounting health gain: a different view.

At least since the Age of Enlightenment, good health has been a tenet for society. Healthy societies could learn better, work harder, improve their wealth, and live longer. Today societies focus on life expectancy, as we value long and healthy lives. As illustrated by the provision of COVID-19 vaccines first for the elderly, societies value life-saving actions. Paradoxically, health economic assessments conventionally devalue long-lasting health through the practice of discounting health benefits along with costs. However, health, with its intrinsic and instrumental characteristics, is not synonymous with money cash, a tradeable asset that devalues with time. If improving healthy life expectancy is a societal ambition, it seems counter-intuitive to value future health less as a result of an artificial mathematical construct when evaluating economically new medical interventions. In this paper, we investigate the application of discounting health in healthcare and consider paradoxical findings, especially in relation to disease prevention with vaccination. We argue that there is no economically sustainable argument to discount health gains, except for the benefit of the payer with a goal of spending less on life-saving products. If that is the objective for discounting health, there are other means to achieve the same goal in a more transparent and simpler way. From the long-term perspective of healthcare development, not discounting health gains would encourage research that values long-term effects. This in turn has the potential to benefit the investor, the payer, and the patient/consumer, improving the situation from multiple perspectives.

Identification of an Optimal COVID-19 Booster Allocation Strategy to Minimize Hospital Bed-Days with a Fixed Healthcare Budget.

Healthcare decision-makers face difficult decisions regarding COVID-19 booster selection given limited budgets and the need to maximize healthcare gain. A constrained optimization (CO) model was developed to identify booster allocation strategies that minimize bed-days by varying the proportion of the eligible population receiving different boosters, stratified by age, and given limited healthcare expenditure. Three booster options were included: B1, costing US $1 per dose, B2, costing US $2, and no booster (NB), costing US $0. B1 and B2 were assumed to be 55%/75% effective against mild/moderate COVID-19, respectively, and 90% effective against severe/critical COVID-19. Healthcare expenditure was limited to US$2.10 per person; the minimum expected expense using B1, B2, or NB for all. Brazil was the base-case country. The model demonstrated that B1 for those aged <70 years and B2 for those ≥70 years were optimal for minimizing bed-days. Compared with NB, bed-days were reduced by 75%, hospital admissions by 68%, and intensive care unit admissions by 90%. Total costs were reduced by 60% with medical resource use reduced by 81%. This illustrates that the CO model can be used by healthcare decision-makers to implement vaccine booster allocation strategies that provide the best healthcare outcomes in a broad range of contexts.

Defining the Recipe for an Optimal Rotavirus Vaccine Introduction in a High-Income Country in Europe.

Observational data over 15 years of rotavirus vaccine introduction in Belgium have indicated that rotavirus hospitalisations in children aged <5 years plateaued at a higher level than expected, and was followed by biennial disease peaks. The research objective was to identify factors influencing these real-world vaccine impact data. We constructed mathematical models simulating rotavirus-related hospitalisations by age group and year for those children. Two periods were defined using different model constructs. First, the vaccine uptake period encompassed the years required to cover the whole at-risk population. Second, the post-uptake period covered the years in which a new infection/disease equilibrium was reached. The models were fitted to the observational data using optimisation programmes with regression and differential equations. Modifying parameter values identified factors affecting the pattern of hospitalisations. Results indicated that starting vaccination well before the peak disease season in the first year and rapidly achieving high coverage was critical in maximising early herd effect and minimising secondary sources of infection. This, in turn, would maximise the reduction in hospitalisations and minimise the size and frequency of subsequent disease peaks. The analysis and results identified key elements to consider for countries initiating an optimal rotavirus vaccine launch programme.

Explaining the formation of a plateau in rotavirus vaccine impact on rotavirus hospitalisations in Belgium.

BACKGROUND: Observational data on the reduction in hospitalisations after rotavirus vaccine introduction in Belgium suggest that vaccine impact plateaued at an unexpectedly high residual hospitalisation rate. The objective of this analysis was to identify factors that influence real-world vaccine impact. METHODS: Data were collected on hospitalisations in children aged ≤ 5 years with rotavirus disease from 11 hospitals since 2005 (the RotaBIS study). The universal rotavirus vaccination campaign started late in 2006. A mathematical model simulated rotavirus hospitalisations in different age groups using vaccine efficacy and herd effect, influenced by vaccine coverage, vaccine waning, and secondary infection sources. The model used optimisation analysis to fit the simulated curve to the observed data, applying Solver add-in software. It also simulated an 'ideal' vaccine introduction maximising hospitalisation reduction (maximum coverage, maximum herd effect, no waning), and compared this with the best-fit simulated curve. Modifying model input values identified factors with the largest impact on hospitalisations. RESULTS: Compared with the 'ideal' simulation, observed data showed a slower decline in hospitalisations and levelled off after three years at a higher residual hospitalisation rate. The slower initial decline was explained by the herd effect in unvaccinated children. The higher residual hospitalisation rate was explained by starting the vaccine programme in November, near the rotavirus seasonal peak. This resulted in low accumulated vaccine coverage during the first rotavirus disease peak season, with the consequential appearance of secondary infection sources. This in turn reduced the herd effect, resulting in a diminished net impact. CONCLUSIONS: Our results indicate that countries wishing to maximise the impact of rotavirus vaccination should start vaccinating well ahead of the rotavirus seasonal disease peak. This maximises herd effect during the first year leading to rapid and high reduction in hospitalisations. Secondary infection sources explain the observed data in Belgium better than vaccine waning.

Infections and hospital bed-days among aging adults: A five-year retrospective study in a Belgian general hospital.

Background: Infectious disease in aging adults (≥61 years) often occurs in combination with other health conditions leading to long hospital stays. Detailed studies on infection in aging adults investigating this problem are sparse. Aim: To quantify the effect of primary and secondary diagnosed infections on hospitalization bed-days among aging adult patients. Design: Retrospective patient-file study. Setting: Ziekenhuis Netwerk Antwerpen (ZNA) Hospital, a 1,858-bed general hospital in Belgium, with 364 beds allocated to geriatric patients. Data source: Database of hospitalized adult patients aged ≥61 years. Methods: All adult patients aged ≥61 years hospitalized on two wards, Geriatrics and Pulmonology, from 2010 to 2014 were included. Primary diagnosed infections were defined as infections known at entry to be treated first. Secondary diagnosed infections included infections known at entry but treated in parallel to primary non-infectious causes of entry, infections unknown at entry, and hospital-acquired (nosocomial) infections. Data were analyzed by patient age, gender, year, ward type, bed-days of hospitalization, infection rates, and seasonality. Results: There were 3,306 primary diagnosed infections (18%) and 14,758 secondary infections (82%) identified in the two wards combined (54.7% of all hospital stays at those 2 wards). Secondary diagnosed infections accounted for a significantly higher proportion of hospitalizations in both wards (+40% for Geriatric ward; +20% for Pulmonology ward; p < 0.001) and were associated with a significantly longer average hospital stay (+4 days for Geriatric ward; +5 days for Pulmonology ward; p < 0.001). Nosocomial infections (12% for Geriatric ward; 7% for Pulmonology ward) were associated with particularly high bed-days of hospitalization, at approximately +15 days and +12 days on Geriatric and Pulmonology wards, respectively. Both wards showed marked seasonality for respiratory infections with winter peaks. Conclusion: Real-world data showed that secondary diagnosed infections in aging adults imposed a high burden on hospital care along with longer hospital stays. This hampered bed availability during peak seasons.

Estimated public health impact of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) on child morbidity and mortality in Gavi-supported countries.

Vaccine impact models against rotavirus disease (RD) and pneumococcal disease (PD) in low- and middle-income countries assume vaccine coverage based on other vaccines. We propose to assess the impact on severe disease cases and deaths avoided based on vaccine doses delivered by one manufacturer to Gavi-supported countries. From the number of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) doses delivered, we estimated the averted burden of disease 1) in a specific year and 2) for all children vaccinated during the study period followed-up until 5 years (y) of age. Uncertainty of the estimated impact was assessed in a probabilistic sensitivity analysis using Monte-Carlo simulations to provide 95% confidence intervals. From 2009 to 2019, approximately 143 million children received HRV in 57 Gavi-supported countries, avoiding an estimated 18.7 million severe RD cases and 153,000, deaths. From 2011 to 2019, approximately 146 million children received PHiD-CV in 36 countries, avoiding an estimated 5.0 million severe PD cases and 587,000 deaths. The number of severe cases and deaths averted for all children vaccinated during the study period until 5 years of age were about 23.2 million and 190,000, respectively, for HRV, and 6.6 million and 749,000, respectively, for PHiD-CV. Models based on doses delivered help to assess the impact of vaccination, plan vaccination programs and understand public health benefits. In 2019, HRV and PHiD-CV doses delivered over a 5-y period may have, on average, averted nine severe disease cases every minute and one child death every 4 min.

What is the context?The WHO added the pneumococcal conjugate vaccine and the rotavirus vaccine in the recommended vaccination schedule of all countries in 2007 and 2009, respectively.Previous studies estimated the public health benefit of these vaccines by approximating the number of children who received them.What is new?We used an alternative approach to estimate the benefit based on actual number of doses of the vaccines, human rotavirus vaccine (HRV; Rotarix) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV; Synflorix) delivered to each country considered.The study analyzed data from children under 5 years of age in 60 Gavi-supported countries by identifying the number of vaccine doses delivered, estimating the number of children fully covered, applying the country-specific disease epidemiology, estimating the number of severe disease cases and deaths avoided.From 2009 to 2019, approximately 143 million children were vaccinated with HRV avoiding an estimated 18.7 million severe rotavirus disease cases and 153,000 deaths.From 2011 to 2019, about 146 million children were vaccinated with pneumococcal vaccine avoiding an estimated 5.0 million severe pneumococcal disease cases and 587,000 deaths.What is the impact? The benefit of HRV and PHiD-CV in Gavi-supported countries is often estimated based on assumptions of vaccine coverage rates.A modeling approach based on doses delivered by the vaccine manufacturer can provide an additional view on the potential vaccine benefits and improve planning, contribution, and sustainability of the immunization programs at a country level.In 2019, HRV and PHiD-CV together averted nine cases of severe disease each minute and one child death every 4 minutes.

Comparative review of three cost-effectiveness models for rotavirus vaccines in national immunization programs; a generic approach applied to various regions in the world.

BACKGROUND: This study aims to critically review available cost-effectiveness models for rotavirus vaccination, compare their designs using a standardized approach and compare similarities and differences in cost-effectiveness outcomes using a uniform set of input parameters. METHODS: We identified various models used to estimate the cost-effectiveness of rotavirus vaccination. From these, results using a standardized dataset for four regions in the world could be obtained for three specific applications. RESULTS: Despite differences in the approaches and individual constituting elements including costs, QALYs Quality Adjusted Life Years and deaths, cost-effectiveness results of the models were quite similar. Differences between the models on the individual components of cost-effectiveness could be related to some specific features of the respective models. Sensitivity analysis revealed that cost-effectiveness of rotavirus vaccination is highly sensitive to vaccine prices, rotavirus-associated mortality and discount rates, in particular that for QALYs. CONCLUSIONS: The comparative approach followed here is helpful in understanding the various models selected and will thus benefit (low-income) countries in designing their own cost-effectiveness analyses using new or adapted existing models. Potential users of the models in low and middle income countries need to consider results from existing studies and reviews. There will be a need for contextualization including the use of country specific data inputs. However, given that the underlying biological and epidemiological mechanisms do not change between countries, users are likely to be able to adapt existing model designs rather than developing completely new approaches. Also, the communication established between the individual researchers involved in the three models is helpful in the further development of these individual models. Therefore, we recommend that this kind of comparative study be extended to other areas of vaccination and even other infectious disease interventions.

Comparing the Analysis and Results of a Modified Social Accounting Matrix Framework with Conventional Methods of Reporting Indirect Non-Medical Costs.

BACKGROUND: Assessing the societal perspective in economic evaluations of new interventions requires estimates of indirect non-medical costs caused by the disease. Different methods exist for measuring the labor input function as a surrogate for these costs. They rarely specify the effect of health on labor and who gains and who loses money. Social accounting matrix (SAM) is an established framework that evaluates public policies with multiple perspectives that could help. OBJECTIVES: We evaluated the use of a modified SAM to assess money flows between different economic agents resulting in economic transactions following policy changes of medical interventions. METHODS: We compared conventional methods of measuring indirect non-medical costs related to rotavirus vaccination in the Netherlands with a modified SAM framework. To compare the outcome of each method, we calculated returns on investment (ROI) as the net amount of money per euro invested in the vaccine. One-way and probabilistic sensitivity analyses were carried out for each method, focusing on critical variables with the largest impact on indirect cost estimates. RESULTS: The ROI was higher for the modified SAM (1.33) than for the conventional methods assessing income calculations (range - 0.178 to 1.22). Probabilistic sensitivity analyses showed wide distributions in the ROI estimates, with variation in the variable impact on the indirect cost results per method selected. CONCLUSIONS: In contrast to conventional methods, the SAM approach provides detailed and comprehensive assessments of the impact of new interventions on the indirect non-medical costs and the financial interactions between agents, disclosing useful information for different stakeholders.

Informing decision makers seeking to improve vaccination programs: case-study Serbia.

Background:The optimisation of vaccine policies before their implementation is beholden upon public health decision makers, seeking to maximise population health. In this case study in Serbia, the childhood vaccines under consideration included pneumococcal conjugate vaccination (PCV), rotavirus (RV) vaccination and varicella zoster virus (VZV) vaccination. Objective: The objective of this study is to define the optimal order of introduction of vaccines to minimise deaths, quality adjusted life years (QALYs) lost, or hospitalisation days, under budget and vaccine coverage constraints. Methods: A constrained optimisation model was developed including a static multi-cohort decision-tree model for the three infectious diseases. Budget and vaccine coverage were constrained, and to rank the vaccines, the optimal solution to the linear programming problem was based upon the ratio of the outcome (deaths, QALYs or hospitalisation days) per unit of budget. A probabilistic decision analysis Monte Carlo simulation technique was used to test the robustness of the rankings. Results: PCV was the vaccine ranked first to minimise deaths, VZV vaccination for QALY loss minimisation and RV vaccination for hospitalisation day reduction. Sensitivity analysis demonstrated the most robust ranking was that for PCV minimizing deaths. Conclusion: Constrained optimisation modelling, whilst considering all potential interventions currently, provided a comprehensive and rational approach to decision making.

Constrained Optimization for Pneumococcal Vaccination in Brazil.

OBJECTIVES: To identify the most cost-efficient combination of pneumococcal vaccines in infants and aging adults for a 10-year period in Brazil. METHODS: Constrained optimization (CO) prioritized 9 pneumococcal vaccine regimens according to their gain in quality-adjusted life-years (QALYs) and their related costs over a prespecified time horizon with defined constraints for 2 age groups, infants and aging adults. The analysis starts from the current universal infant vaccination of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV), 2 primary and 1 booster dose at 2, 4, and 12 months, respectively. Key constraints are the fixed annual vaccine budget increase and the relative return on investment (ROIR) per regimen, which must be > 1, the reference intervention being the current vaccination strategy in infants and the most cost-efficient one in aging adults. RESULTS: The CO analysis including all the constraints indicates that over 10 years the maximum extra health gain is 126 194 QALYs for an extra budget of $974 million Brazilian reals (ROIR = 1.15). Results could be improved with a higher proportion of the at-risk population in aging adults, less herd effect, and better QALY scores. CONCLUSION: The study shows that with 4 constraints on budget, time horizon, vaccine coverage, and cost efficiency, a CO analysis could identify the most cost-efficient overall pneumococcal vaccination strategy for Brazil, allowing for limited vaccine budget increase while obtaining appropriate health gain.

Fifteen years of experience with the oral live-attenuated human rotavirus vaccine: reflections on lessons learned.

INTRODUCTION: Rotavirus (RV) disease remains a prominent cause of disease burden in children <5 years of age worldwide. However, implementation of RV vaccination has led to significant reductions in RV mortality, compared to the pre-vaccination era. This review presents 15 years of real-world experience with the oral live-attenuated human RV vaccine (HRV; Rotarix). HRV is currently introduced in ≥80 national immunization programs (NIPs), as 2 doses starting from 6 weeks of age. AREAS COVERED: The clinical development of HRV and post-marketing experience indicating the impact of HRV vaccination on RV disease was reviewed. EXPERT OPINION: In clinical trials, HRV displayed an acceptable safety profile and efficacy against RV-gastroenteritis, providing broad protection against heterotypic RV strains by reducing the consequences of severe RV disease in infants. Real-world evidence shows substantial, rapid reduction in the number of RV infections and associated hospitalizations following introduction of HRV in NIPs, regardless of economic setting. Indirect effects against RV disease are also observed, such as herd protection, decrease in nosocomial infections incidence, and a reduction of disease-related societal/healthcare costs. However, not all countries have implemented RV vaccination. Coverage remains suboptimal and should be improved to maximize the benefits of RV vaccination.

Lessons Learned from Long-Term Assessment of Rotavirus Vaccination in a High-Income Country: The Case of the Rotavirus Vaccine Belgium Impact Study (RotaBIS).

INTRODUCTION: The rotavirus (RV) vaccine Belgium Impact Study (RotaBIS) evaluated the vaccine effect on RV-related hospital care in children up to 5 years old over a period of 13 years. Different forces were identified that influence the reduction in hospital care. Our analysis aims to report on the current RotaBIS dataset and explore through model simulation whether, how, and when the results could have been improved. METHODS: As performed in previous assessments, this analysis evaluated RV-related events per year, per age group, RV nosocomial infections, hospitalization duration, and herd effect. It subsequently identified results that were surprising or unexpected. To know whether those data could have been improved through specific interventions, we developed a model with the forces acting on the disease transmission and the vaccine effect on RV-related hospital care. Scenario analysis of the forces should explain the current findings and identify ways to optimize the results. RESULTS: The RotaBIS data show that annual RV-related hospital cases (n = 1345 pre-vaccination) dropped by 70% (95% confidence interval [CI] 66-74%) by year 5 (n = 395) after vaccine introduction, and by 84% (95% CI 79-89%) by year 10 (n = 217). The herd effect during the first year was limited to 14% extra gain. During the last 5 years, small disease increases were seen biennially. The simulation model indicates that higher vaccine coverage of the major transmitters during the peak season of the first year of vaccination could have reduced RV-related hospital care by nearly 90% at 5 and 10 years after vaccine introduction owing to a higher herd effect. The smaller peaks observed in recent years would have been dramatically reduced. CONCLUSION: The current RotaBIS data show a maintained reduction, around 76%, in RV hospitalization cases. Simulations show that these results could have been improved to an important extent with a more optimal initiation of the vaccination program. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01563146 and NCT01563159.

Estimating the money flow in the economy attributed to rotavirus disease and vaccination in the Netherlands using a Social Accounting Matrix (SAM) framework.

Background: The economics of rotavirus gastroenteritis in infants <5 years old is well-known within healthcare. The financial consequences for families, employers and authorities are not so well explored. The present study evaluates how vaccine prevention changes money flows among those involved in the management of disease, and its consequences. Methods: A Social Accounting Matrix (SAM) framework has been developed reflecting the distribution of income and spending at equilibrium affected by rotavirus disease among all those concerned for 1 year. The data came from official sources and published literature. A comparison of the financial equilibrium between with and without a national rotavirus immunization program has been conducted, along with sensitivity analysis for the results. Results: The total financial cost difference at equilibrium between presence and absence of rotavirus vaccination was +€26.758 million over one year as a net economic surplus. The payment of vaccination (€19.194 million) by the government was offset by the increase in tax revenue (€14.561 million) and by the lower spending in treatment care (€7.998 million). Conclusion: Studying the financial flows between different transacting agents can demonstrate the financial burden of a disease and the benefits of its prevention on agents' income and spending.

How to assess for the full economic value of vaccines? From past to present, drawing lessons for the future.

Background:Cost-effectiveness analysis (CEA) is the economic analysis method most commonly applied today in the context of replacing one treatment with a new one in a developed healthcare system to improve efficiency. CEA is often requested by local healthcare decision-makers to grant reimbursement. New preventative interventions, such as new vaccines, may however have much wider benefits inside and outside healthcare, when compared with treatment. These additional benefits include externalities on indirect clinical impact, reallocation of specific healthcare resources, improved quality of care, better productivity, better disease control, better fiscal revenues, and others. But these effects are sometimes difficult to integrate into a meaningful CEA result. They may appear as specific benefits for specific stakeholders, other than the stakeholders in healthcare. Objective: Based on a historical view about the application of economic assessments for vaccines our objective has been to make the inventory of who was/is interested in knowing the economic value of vaccines, in what those different stakeholders are likely to see the benefit from their perspective and how  were/are we able to measure those benefits and to report them well. Results: The historical view disclosed a limited interest in the economic assessment of vaccines at start, more than 50 years ago, that was comparable to the assessment of looking for more efficiency in new industries through optimization exercises. Today, we are exposed to a very rich panoply of different stakeholders (n= 16). They have their specific interest in many different facets of the vaccine benefit of which some are well known in the conventional economic analysis (n=9), but most outcomes are hidden and not enough evaluated and reported (n=26). Meanwhile we discovered that many different methods of evaluation have been explored to facilitate the measurement and reporting of the benefits (n=18). Conclusion: Our recommendation for future economic evaluations of new vaccines is therefore to find the right combination among the three entities of stakeholder type selection, outcome measure of interest for each stakeholder, and the right method to apply. We present at the end examples that illustrate how successful this approach can be.

Preventing infectious diseases for healthy ageing: The VITAL public-private partnership project.

Prevention of infectious diseases through immunisation of the growing ageing adult population is essential to improve healthy ageing. However, many licenced and recommended vaccines for this age group show signs of waning of the protective effect due to declining immune responses (immuno-senescence) and decreasing vaccine uptake. Today's major challenge is to improve vaccine effectiveness and uptake and to deploy efficient vaccination strategies for this age group. The Vaccines and InfecTious diseases in the Ageing popuLation (VITAL) project, with partners from 17 academic & research groups and public institutes as well as seven industry collaborators, aims to address this challenge. The ambition is to provide evidence-based knowledge to local decision makers. Using a holistic and multidisciplinary approach and novel analytical methods, VITAL will provide tools that allow the development of targeted immunisation programs for ageing adults in European countries. The project is based on four pillars focussing on the assessment of the burden of vaccine-preventable diseases in ageing adults, the dissection of the mechanisms underlying immuno-senescence, the analysis of the clinical and economic public health impact of vaccination strategies and the development of educational resources for healthcare professionals. By the end of the project, a clear, detailed, and integrated program should be available for implementing a consistent, affordable, and sustainable vaccination strategy for ageing adults with regular evaluations of its impact over time.