Search

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. Electronic supplementary material The online version of this article (10.1007/s40121-020-00345-y) contains supplementary material, which is available to authorized users.

Rotavirus (RV) disease remains a prominent cause of disease burden in children5 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;The clinical development of HRV and post-marketing experience indicating the impact of HRV vaccination on RV disease was reviewed.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.

Background: The economics of rotavirus gastroenteritis in infants

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. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). BS was an employee of GSK until retirement in September 2020. The current research was conducted after he left GSK. He recently joined the Faculty of Medicine and Life Sciences, Research Group Care and Ethics, at the University of Hasselt, Hasselt, Belgium, as guest professor. DS is a consultant and has not been paid for her contribution to this work. MR is a paediatric professor and clinician. He has not been paid for his contribution to this work. BB is an employee of GSK and holds shares of the GSK group of companies. The authors would like to thank Carole Nadin (Fleetwith Ltd, on behalf of HEBO) for editorial assistance.

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.

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.

Background More than 10 years after the authorisation of two rotavirus vaccines of demonstrated efficacy and with a strongly positive benefit-risk profile, uptake in Europe remains low. Only 13 countries in Europe provide a fully-funded rotavirus universal mass vaccination (UMV) programme, three provide a partially-funded programme, and one provides full funding for a reduced programme targeting at-risk infants. Around 40% of countries in Europe currently have no existing recommendations for rotavirus vaccine use in children from the national government. Methods We provide an overview of the status of rotavirus vaccine recommendations across Europe and the factors impeding uptake. We consider the evidence for the benefits and risks of vaccination, and argue that cost-effectiveness and cost-saving benefits justify greater access to rotavirus vaccines for infants living in Europe. Results Lack of awareness of the direct and indirect burden caused by rotavirus disease, potential cost-saving from rotavirus vaccination including considerable benefits to children, families and society, and government/insurer cost constraints all contribute to complacency at different levels of health policy in individual countries. Conclusions More than 10 years after their introduction, available data confirm the benefits and acceptable safety profile of infant rotavirus UMV programmes. Europe serves to gain considerably from rotavirus UMV in terms of reductions in healthcare resource utilization and related costs in both vaccinated subjects and their unvaccinated siblings through herd protection.

Background During each winter the hospital quality of care (QoC) in pediatric wards decreases due to a surge in pediatric infectious diseases leading to overcrowded units. Bed occupancy rates often surpass the good hospital bed management threshold of 85%, which can result in poor conditions in the workplace. This study explores how QoC-scores could be improved by investing in additional beds and/or better vaccination programs against vaccine-preventable infectious diseases. Methods The Cobb–Douglas model was selected to define the improvement in QoC (%) as a function of two strategies (rotavirus vaccination coverage [%] and addition of extra hospital beds [% of existing beds]), allowing improvement-isocurves to be produced. Subsequently, budget minimization was applied to determine the combination of the two strategies needed to reach a given QoC improvement at the lowest cost. Data from Jessa Hospital (Hasselt, Belgium) were chosen as an example. The annual population in the catchment area to be vaccinated was 7000 children; the winter period was 90 days with 34 pediatric beds available. Rotavirus vaccination cost per course was €118.26 and the daily cost of a pediatric bed was €436.53. The target QoC increase was fixed at 50%. The model was first built with baseline parameter values. Results The model predicted that a combination of 64% vaccine coverage and 39% extra hospital beds (≈ 13 extra beds) in winter would improve QoC-scores by 50% for the minimum budget allocation. Conclusion The model allows determination of the most efficient allocation of the healthcare budget between rotavirus vaccination and bed expansion for improving QoC-scores during the annual epidemic winter seasons.

Influenza is an infectious disease causing a high annual economic and public health burden. The most efficient management of the disease is through prevention with vaccination. Many influenza vaccines are available, with varying efficacy and cost, targeting different age groups. Therefore, strategic decision-making about which vaccine to deliver to whom is warranted to improve efficiency. We present the use of a constrained optimization (CO) model to evaluate targeted strategies for providing influenza vaccines in three adult age groups in the USA. CO was considered for identifying an influenza vaccine provision strategy that maximizes the benefits at constrained annual budgets, by prioritizing vaccines based on return on investment. The approach optimizes a set of predefined outcome measures over several years resulting from an increasing investment using the best combination of influenza vaccines. Results indicate the importance of understanding the relative differences in benefits for each vaccine type within and across age groups. Scenario and threshold analyses demonstrate the impact of changing budget distribution over time, price setting per vaccine type, and selection of outcome measure to optimize. Significant gains in cost efficiency can be realized for a decision maker using a CO model, especially for a disease like influenza with many vaccine options. Testing the model under different scenarios offers powerful insights into maximum achievable benefit overall and per age group within the predefined constraints of a vaccine budget.

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.

Objectives Countries have constrained healthcare budgets and must prioritize new interventions depending on health goals and time frame. This situation is relevant in the sphere of national immunization programs, for which many different vaccines are proposed, budgets are limited, and efficient choices must be made in the order of vaccine introduction. Methods A constrained optimization (CO) model for infectious diseases was developed in which different intervention types (prophylaxis and treatment) were combined for consideration in Malaysia. Local experts defined their priority public health issues: pneumococcal disease, dengue, hepatitis B and C, rotavirus, neonatal pertussis, and cholera. Epidemiological, cost, and effectiveness data were informed from local or regionally published literature. The model aimed to maximize quality-adjusted life-year (QALY) gain through the reduction of events in each of the different diseases, under budget and intervention coverage constraints. The QALY impact of the interventions was assessed over 2 periods: lifetime and 20 years. The period of investment was limited to 15 years. Results The assessment time horizon influenced the prioritization of interventions maximizing QALY gain. The incremental health gains compared with a uninformed prioritization were large for the first 8 years and declined thereafter. Rotaviral and pneumococcal vaccines were identified as key priorities irrespective of time horizon, hepatitis B immune prophylaxis and hepatitis C treatment were priorities with the lifetime horizon, and dengue vaccination replaced these with the 20-year horizon. Conclusions CO modeling is a useful tool for making economically efficient decisions within public health programs for the control of infectious diseases by helping prioritize the selection of interventions to maximize health gain under annual budget constraints.

Background. Preventative malaria interventions include long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS), and seasonal malaria chemoprevention (SMC). The RTS,S vaccine candidate is now also approved for pilot introduction. This analysis estimates the optimal approach when combining current interventions with the vaccine to reduce under-five malaria mortality in Ghana at the lowest cost. Methods. A vector model was combined with a static human cohort model, using country-specific unit costs. Current coverage of each intervention was used as baseline. The base-case vaccine price was US$5/dose, with US$2 or US$10 tested in sensitivity analysis. Model simulations used a goal for extra mortality reduction in children aged

Introduction Rotavirus (RV) vaccination was introduced in Belgium in 2006. With the high uptake it had (>85%), a sharp decline in hospitalizations was observed during the first years after vaccine introduction. The objective of this study was to investigate whether this decline was maintained and to simulate projections. Methods The Rotavirus Belgium Impact Study allowed an analysis of the RV vaccine impact amongst children in 11 hospitals in Belgium over a 9-year period (2005–2013) with 2 years pre- and 7 years post-vaccine introduction. Results were compared by year and by subsequent birth cohort aging up to 5 years. The two different analysis methods helped dismantling the different (direct and indirect) effects of vaccine protection to simulate future hospitalization trends. Results During the whole observation period, 40,552 RV detection tests were performed of which 5832 were positive (14.4%). After RV vaccine introduction, a significant reduction in number of tests performed (−38%) was combined with a dramatic drop in numbers of positive tests (−76.6%). The decreases were spectacular during the first two years of vaccine introduction; after that period, the decrease flattened. Cross-sectional comparison with cohort data showed that the initial drop was heavily influenced by the herd effect of the vaccine. Cohort analysis demonstrated a low rate of residual disease over time, suggesting another infection source other than the child population. Conclusion The residual disease will be maintained in the community when a same vaccination strategy is continued over time, starting vaccination of children only at 6 weeks’ time. Funding GlaxoSmithKline Biologicals SA. Trial registration ClinicalTrials.gov identifier, NCT01563146. Electronic supplementary material The online version of this article (doi:10.1007/s40121-015-0099-1) contains supplementary material, which is available to authorized users.

Vaccination directly protects vaccinated individuals, but it also has the potential for indirectly protecting the unvaccinated in a population (herd protection). Unintended negative consequences such as the re-manifestation of infection, mainly expressed as age shifts, result from vaccination programs as well. We discuss the necessary conditions for achieving optimal herd protection (i.e., high quality vaccine-induced immunity, substantial effect on the force of infection, and appropriate vaccine coverage and distribution), as well as the conditions under which age shifts are likely to occur. We show examples to illustrate these effects. Substantial ambiguity in observing and quantifying these indirect vaccine effects makes accurate evaluation troublesome even though the nature of these outcomes may be critical for accurate assessment of the economic value when decision makers are evaluating a novel vaccine for introduction into a particular region or population group. More investigation is needed to identify and develop successful assessment methodologies for precisely analyzing these outcomes.

PURPOSE Although the World Health Organization recommends universal rotavirus immunization, uptake of the vaccine is low in Poland and Hungary, where it is not covered by the National Immunization Program. This study aimed to quantify mothers' preferences for vaccines preventing children's diarrheal illness and to examine whether willingness to vaccinate varies with working status. METHODS Mothers of children aged

The administration of a vaccine dose involves a series of activities prior to and on the day of vaccine delivery. Total vaccination cost should include the cost of each activity, which is often not done or poorly reported. To calculate those costs a field study was performed in 6 United Kingdom (UK) sites (General Practitioner (GP) practices) during a 4-month period (April-June 2015). First, a workflow map of all the relevant vaccine-related activities per site was obtained through interviews. Second, time estimates for activities happening prior to the vaccination day were obtained through interviews and associated costs were calculated. A prospective, non-interventional study using Time & Motion (T&M) methodology was used to measure time for activities happening on the day of vaccination. Consumables, wastage, and guardian time were also collected. Third, the time for each task and for all tasks combined during the T&M study was analyzed using a random intercept model to account for site effect. Hundred and twenty-three T&M observations with approximately 20 per site were collected and were equally stratified by vaccination visit during the first year of a baby's life. Total cost per visit was £11.9 (site range: £8.6-£17.0) when supply cost and time for activities prior to the vaccination day were included. Time per dose administrated was 7.1 min (site range: 5.7-9.2) and the associated cost was £4.3 (site range: £3.1-£6.2). The study demonstrates an accurate reflection of the time and cost involved in a vaccine dose administration in a pediatric setting in the UK. The amount measured is consistent with the current National Health Services fee schedule.

This paper describes how the economic assessment of vaccines is performed today. It discusses why it may be incomplete and explores potential approaches to adjust the analysis to be more comprehensive. Besides helping protect against serious disease, vaccines also help avoid mild disease episodes that may not receive medical attention but which have important societal consequences. They also benefit unvaccinated individuals by reducing disease transmission. Wider societal benefits may extend beyond a decrease in disease incidence, as lower transmission rates reduce the risk of epidemics, which in turn reduces the pressure on healthcare providers, and may improve the quality of care for patients with unrelated diseases. Vaccines also lower the use of antibiotics leading to less pressure on anti-microbial resistance. Conventional ICUA focuses on individual health benefits, like increased survival. Therefore, this approach may not adequately capture the wider vaccination benefits. We discuss differences between treatment and vaccine prevention in the economic assessment, and how ICUA has been adapted to cope with the inconsistencies. Although such adaptations may fulfil the demand of one specific stakeholder, they may not meet the needs of other stakeholders who operate at the societal level, such as ministries other than healthcare, employers, caregivers, and insurers.

We developed a cohort model to evaluate the expected public health impact of accelerated regimens for immunization against rotavirus gastroenteritis (RVGE). Alternative strategies for vaccination with the pentavalent human-bovine reassortant vaccine, Rotateq(®) (RV5, Merck) and the oral live attenuated human rotavirus vaccine, Rotarix(®) (RV1, GlaxoSmithKline Vaccines) were considered, including acceleration of the 1st dose only (by 2 weeks) as well as acceleration of the 1st (by 2 weeks) and subsequent doses (by up to 10 weeks). Assuming vaccine coverage levels consistent with current US clinical practice, accelerated regimens would be expected to reduce annual numbers of RVGE-related hospitalizations by 300-400, emergency department visits by 3000-4000, and outpatient visits by 3000-4000 (i.e., by 9-14%) among US children aged6 months. Accordingly, accelerating the immunization of children against RVGE may yield substantive reductions in the number of RV-related encounters in US clinical practice.

ObjectiveHospitals in the UK are under increasing clinical and financial pressures. Following introduction of childhood rotavirus vaccination in the UK in 2013, rotavirus gastroenteritis (RVGE) hospitalisations reduced significantly. We evaluated changes in ‘hospital pressures’ (demand on healthcare resources and staff) following rotavirus vaccine introduction in a paediatric setting in the UK.DesignRetrospective hospital database analysis between July 2007 and June 2015.SettingA large paediatric hospital providing primary, secondary and tertiary care in Merseyside, UK.ParticipantsHospital admissions aged MethodsHospital pressures were compared before and after rotavirus vaccine introduction: these included bed occupancy, hospital-acquired infection rate, unplanned readmission rate and outlier rate (medical patients admitted to surgical wards due to lack of medical beds). Interrupted time-series analysis was used to evaluate changes in bed occupancy.ResultsThere were 116 871 admissions during the study period. Lower bed occupancy in the rotavirus season in the postvaccination period was observed for RVGE (−89%, 95% CI 73% to 95%), acute gastroenteritis (−63%, 95% CI 39% to 78%) and any infection (−23%, 95% CI 15% to 31%). No significant overall reduction in bed occupancy was observed (−4%, 95% CI −1% to 9%). No changes were observed for the other outcomes.ConclusionsRotavirus vaccine introduction was not associated with reduced hospital pressures. A reduction in RVGE hospitalisation without change in overall bed occupancy suggests that beds available were used for a different patient population, possibly reflecting a previously unmet need.Trials registration numberNCT03271593

Many countries struggle with the prioritisation of introducing new vaccines because of budget limitations and lack of focus on public health goals. A model has been developed that defines how specific health goals can be optimised through immunisation within vaccination budget constraints.Japan, as a country example, could introduce 4 new pediatric vaccines targeting influenza, rotavirus, pneumococcal disease and mumps with known burden of disease, vaccine efficacies and maximum achievable coverages. Operating under budget constraints, the Portfolio-model for the Management of Vaccines (PMV) identifies the optimal vaccine ranking and combination for achieving the maximum QALY gain over a period of 10 calendar years in children5 years old. This vaccine strategy, of interest and helpful for a healthcare decision maker, is compared with an unranked vaccine selection process.Results indicate that the maximum QALY gain with a fixed annual vaccination budget of 500 billion Japanese Yen over a 10-year period is 72,288 QALYs using the optimal sequence of vaccine introduction (mumps [1st], followed by influenza [2nd], rotavirus [3rd], and pneumococcal [4th]). With exactly the same budget but without vaccine ranking, the total QALY gain can be 20% lower.The PMV model could be a helpful tool for decision makers in those environments with limited budget where vaccines have to be selected for trying to optimise specific health goals.

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.

Unlike most drugs, whose benefit is restricted to the individual who takes the drug, prophylactic vaccines have the potential for far-reaching effects that encompass health service utilisation, general health and wellbeing, cognitive development and, ultimately, economic productivity. The impact of immunisation is measured by evaluating effects directly on the vaccinated individual, indirectly on the unvaccinated community (herd protection), the epidemiology of the pathogen (such as changing circulating serotypes or prevention of epidemic cycles), and the additional benefits arising from improved health. Aside from protection of the individual, the broader success of immunisation is dependent on achieving a level of coverage sufficient to interrupt transmission of the pathogen. When evaluating the cost-effectiveness of vaccines, all of these potential benefits need to be accounted for. In many countries where immunisation programmes have been highly successful, the control of disease has meant that the benefits of immunisation have become less obvious. Once a well-known and much-feared disease appears to have disappeared, individuals, including healthcare professionals, no longer view ongoing prevention with the same sense of urgency. Reduced coverage is inevitably associated with resurgence in disease, with outbreaks potentially leading to significant morbidity and loss of life. Ensuring the continued success of immunisation programmes is the responsibility of all: individuals, healthcare professionals, government and industry.

Two rotavirus vaccines are currently approved in the United States: 3-dose RotaTeq (RV5; MerckCo., Inc., Whitehouse Station, NJ, USA) is administered at ages 2, 4, and 6 months; and 2-dose Rotarix (RV1; GlaxoSmithKline, Research Triangle Park, NC, USA) is administered at ages 2 and 4 months. Our objective was to compare rotavirus vaccine series completion and dosing schedule compliance between cohorts of infants who received these vaccines.Infants aged less than 1 year who initiated a rotavirus vaccine series between 01 January 2009 and 30 June 2009 were identified in US health insurance claims data. Cohorts were formed based on vaccine brand use. Series completion and compliance with the FDA-approved and ACIP-recommended harmonized schedules were analyzed descriptively and a log binomial model was used to estimate the difference in series completion by vaccine brand while adjusting for demographic variables.Among infants in the RV1 and RV5 cohorts (N=55,584), 84.3% completed a full series. A greater proportion of the RV1 cohort than the RV5 cohort completed their series (91.0% vs. 83.4%; P0.001; multivariate-adjusted relative risk 1.07; 95% CI 1.06-1.08). In the RV1 and RV5 cohorts, respectively, 75.0% and 59.5% of infants were fully compliant with the FDA-approved administration schedule for their vaccine (P0.001); 83.3% and 76.4% of infants were fully compliant with the harmonized schedule (P0.001).The proportion of infants that completed the series was greater and compliance with respective FDA-approved and harmonized dosing schedules was higher among infants vaccinated with RV1 than among infants who received RV5.

While no single type of model can provide adequate answers under all circumstances, any modelling endeavour should incorporate three fundamental considerations in any decision-making question: the target population, the disease and the intervention characteristics. A target population is likely to be characterized by various types of heterogeneity and a dynamic evolution over time. It is therefore important to adequately capture these population effects on the results of a model. There are essentially two different approaches in modelling a population over time: a cohort-based approach and a population-based approach. In a cohort-based model, a closed group of individuals who have at least one specific characteristic or experience in common over a defined period of time is run through a state transition process. The cohort is generally composed of a hypothetical number of representative or 'average' individuals (i.e. the target population is considered to be a homogeneous group). The population-based approach projects the evolution of the estimated prevalent target population and intends to reflect as much as possible the demographic, epidemiological and clinical characteristics of the prevalent target population relevant for the decision problem. A cohort-based approach is generally used in most published healthcare decision models. However, this choice is rarely discussed by modellers. In this article, we challenge this assumption. To address the underlying decision problem, we affirm it is crucial that modellers consider the characteristics of the target population. Then, they could opt for using the most appropriate approach. Decision makers should also understand the impact on the results of both types of models in order to make informed healthcare decisions.

Background:Background: We evaluated national rotavirus (RV) immunization programme costs to estimate how resulting changes in morbidity and mortality will influence government fiscal accounts over time. The assumption was that increased childhood survival in vaccinated cohorts leads to increased numbers of children consuming government resource, and an increased number of future tax payers. Abstract: Objective:Objective: Our objective was to evaluate the difference in lifetime discounted net tax revenue generated by RV vaccinated and unvaccinated cohorts from the Egyptian government perspective. Abstract: Methods:Methods: The model framework adopts the Egyptian government perspective for RV immunization costs (year 2009 values) and all government transfers (e.g. education costs, health costs, pensions). To reflect the government tax revenue, we applied a fixed income tax burden to earnings over the lifetime of vaccinated and unvaccinated cohorts. At each year of the model, we derive net taxes (gross taxes less transfers) discounted to the immunization year to reflect the present value of RV vaccination investment costs. Abstract: Results:Results: Projected incremental net present values of the vaccinated cohort versus the unvaccinated cohort are &dollar;US6.1 million, &dollar;US58.1 million and &dollar;US55.7 million at 25-, 50- and 72-year time horizons, respectively. The internal rate of return for the government based on RV vaccination at years 25, 50 and 72 was 10.8%, 15.1% and 14.9, respectively. Within the first 5 years of vaccination, 76% of vaccine acquisition costs were offset due to direct and indirect cost savings attributed to a reduction in RV-related disease burden. Investments in RV vaccination in a single year are entirely offset when the vaccinated cohort of newborns reach 22 years of age. Abstract: Conclusion:Conclusion: The government perspective is useful for evaluating investments in RV vaccination because of ongoing government transfers and tax receipts attributed to changes in RV-attributed morbidity and mortality. The analysis described here illustrates that investing in RV offers tangible long-term fiscal benefits for government over many generations that would not ordinarily be captured in economic evaluations typically applied to healthcare interventions.

Background:Background: Screening and vaccination against human papillomavirus (HPV) can protect against cervical cancer. Neither alone can provide 100% protection. Consequently it raises the important question about the most efficient combination of screening at specified time intervals and vaccination to prevent cervical cancer. Abstract: Objective:Objective: Our objective was to identify the mix of cervical cancer prevention strategies (screening and/or vaccination against HPV) that achieves maximum reduction in cancer cases within a fixed budget. Abstract: Methods:Methods: We assessed the optimal mix of strategies for the prevention of cervical cancer using an optimization program. The evaluation used two models. One was a Markov cohort model used as the evaluation model to estimate the costs and outcomes of 52 different prevention strategies. The other was an optimization model in which the results of each prevention strategy of the previous model were entered as input data. The latter model determined the combination of the different prevention options to minimize cervical cancer under budget, screening coverage and vaccination coverage constraints. We applied the model in two countries with different healthcare organizations, epidemiology, screening practices, resource settings and treatment costs: the UK and Brazil. 100 000 women aged 12 years and above across the whole population over a 1-year period at steady state were included. The intervention was papanicolaou (Pap) smear screening programmes and/or vaccination against HPV with the bivalent HPV 16/18 vaccine (Cervarix &lsqb;Cervarix is a registered trademark of the GlaxoSmithKline group of companies&rsqb;). The main outcome measures were optimal distribution of the population between different interventions (screening, vaccination, screening plus vaccination and no screening or vaccination) with the resulting number of cervical cancer and associated costs. Abstract: Results:Results: In the base-case analysis (- same budget as today), the optimal prevention strategy would be, after introducing vaccination with a coverage rate of 80% in girls aged 12 years and retaining screening coverage at pre-vaccination levels (65% in the UK, 50% in Brazil), to increase the screening interval to 6 years (from 3) in the UK and to 5 years (from 3) in Brazil. This would result in a reduction of cervical cancer by 41% in the UK and by 54% in Brazil from pre-vaccination levels with no budget increase. Sensitivity analysis shows that vaccination alone at 80% coverage with no screening would achieve a cervical cancer reduction rate of 20% in the UK and 43% in Brazil compared with the pre-vaccination situation with a budget reduction of 30% and 14%, respectively. In both countries, the sharp reduction in cervical cancer is seen when the vaccine coverage rate exceeds the maximum screening coverage rate, or when screening coverage rate exceeds the maximum vaccine coverage rate, while maintaining the budget. As with any model, there are limitations to the value of predictions depending upon the assumptions made in each model. Abstract: Conclusions:Conclusions: Spending the same budget that was used for screening and treatment of cervical cancer in the pre-vaccination era, results of the optimization program show that it would be possible to substantially reduce the number of cases by implementing an optimal combination of HPV vaccination (80% coverage) and screening at pre-vaccination coverage (65% UK, 50% Brazil) while extending the screening interval to every 6 years in the UK and 5 years in Brazil.

Cohort and population models estimate vaccine impact on disease events, and yield different estimates in countries with different demographic compositions. We compared administration of the new 10-valent pneumococcal Haemophilus influenzae-protein D conjugate vaccine (PHiD-CV) with no vaccination in two countries, the United Kingdom (UK) and Mexico, using two modelling strategies: a cohort model and a population model. The cohort model followed a birth cohort over a lifetime, beginning 10 years after initiation of the vaccine program, when vaccine efficacy steady state had been reached. The population model examined the country-specific population over 1 year, also beginning 10 years after initiation of the vaccine program. Both models included the same age-specific disease rates of meningitis, bacteraemia, pneumonia, and otitis media. The output variables were the numbers of specific events, with and without indirect vaccine effects. Without indirect effects, the cohort and population models produced similar results for both countries (deviation of

Two human papillomavirus (HPV) vaccines are on the market. Based on expected differences in sustained- and cross-protection between the two vaccines, their long-term economic value is modelled and compared for France, Ireland and Italy.A Markov cohort model reproducing the natural history of HPV infections, screening and vaccination, is adapted to country-specific data. Two hypothetical HPV vaccines (VA and VB) are compared. At baseline VA provides lifetime protection against HPV-16 and 10-year protection against HPV-18 before waning. VB is the same as VA with a 10-year protection against HPV-6 and 11. Sustained- and cross-protection is varied over wide ranges in VA to define the levels that could make VA cost-effective or dominant compared with VB.Under baseline conditions VB dominates VA. VA becomes cost-effective when the difference in cross-protection alone reaches 13-15% (undiscounted), and 22-44% (discounted). A combination of sustained- and cross-protection is required for VA to dominate VB (discounted). The results are dependent upon country, the base-case value and the discount applied.Realistic additional sustained- and cross-protection in one HPV vaccine may confer benefits that offset the economic value of protection against low-risk HPV in the other. The results are country specific.

This study estimated the cost-effectiveness of infant rotavirus vaccination with Rotarix in the UK, taking into account community rotavirus infections that do not present to the healthcare system. A Markov model compared the costs and outcomes of vaccination versus no vaccination in a hypothetical birth cohort of children followed over a lifetime, from a societal perspective and the perspective of the National Health Service (NHS). The model estimated costs and quality-adjusted life-years (QALYs) lost due to death, hospitalisation, general practitioner (GP) consultation, emergency attendance and calls to NHS Direct for rotavirus infection in children aged