Cost-effectiveness analysis measuring the total costs against the health benefits of three different rotavirus vaccines for Mexico.

Rotavirus (RV) infection causes acute rotavirus gastroenteritis (RVGE) in infants. Safe and effective RV vaccines are available, of which Mexico has included one in its national immunization program (NIP) since 2007. Health outcome gains, expressed in quality-adjusted life years (QALYs), and cost improvements are important additional factors for the selection of a NIP vaccine. These two factors were analyzed here for Mexico over one year implementing three RV vaccines: 2-dose Rotarix (HRV), versus 3-dose RotaTeq (HBRV), and 3-dose Rotasiil (BRV-PV), presented in a 1-dose or 2-dose vial). HRV would annually result in discounted QALY gains of 263 extra years compared with the other vaccines by averting an extra 24,022 homecare cases, 10,779 medical visits, 392 hospitalizations, and 12 deaths. From a payer's perspective and compared with HRV, BRV-PV 2-dose vial and BRV-PV 1-dose vial would annually result in $13,548,179 and $4,633,957 net savings, respectively, while HBRV would result in $3,403,309 extra costs. The societal perspective may also show savings compared with HRV for BRV-PV 2-dose vial of $4,875,860, while BRV-PV 1-dose vial and HBRV may show extra costs of $4,038,363 and $12,075,629 respectively. HRV and HBRV were both approved in Mexico, with HRV requiring less investment than HBRV with higher QALY gains and cost savings. The HRV vaccine produced those higher health gains due to its earlier protection and greater coverage achieved after its schedule completion with two doses only, providing full protection at four months of age instead of longer periods for the other vaccines.

Rotavirus (RV) infection causes acute diarrhea in infants and can be life-threatening. Several safe and effective vaccines against RV and its complications exist. For many governments choosing vaccines for national immunization programs, total costs or savings and health gains are important factors in the selection process. We compared the costs and health benefits of three RV vaccines for Mexico: HRV, HBRV, and BRV-PV, that have different dosing schedules: two doses for HRV and three doses for HBRV and BRV-PV. HRV is currently part of the national immunization program in Mexico. HRV would result in more health benefits as it incurs fewer RV-related cases, medical visits, hospitalizations, and infant deaths than the other vaccines due to its early protection achieved after only two doses to complete its schedule. However, from a payer's perspective, the least expensive vaccine was BRV-PV, while HRV was less expensive than HBRV. From a societal perspective, also accounting for families' costs and loss in income due to an infant's RV disease, and the families' costs and loss in income when accompanying the infant to the vaccination center, the HRV vaccine was less expensive than HBRV and BRV-PV presented in a 1-dose vial, while more expensive than BRV-PV presented in a 2-dose vial. HRV and HBRV are both approved in Mexico, although HBRV requires a greater investment at lower health benefits than HRV, from both a payer's and a societal perspective. A 2-dose vaccination scheme is an important asset for the economic value of this vaccination program.

A Chimeric Vaccine against Porcine Circovirus Type 2: Meta-Analysis of Comparative Clinical Trials.

This meta-analysis compared the efficacy of a chimeric vaccine against porcine circovirus type 2 (PCV2) containing the genotypes PCV2a+b (Fostera® Gold PCV MH [FOS-G]), with commonly used vaccines being derived from genotype PCV2a, considering the following parameters: average daily gain (ADG), mortality and market classification as full value and cull. Data from seven hitherto unpublished comparative US field trials with FOS-G (two experimental challenges and five natural environmental studies) were provided by the manufacturer. A complementary literature review revealed a Korean study, which was considered separately in meta-analysis. Competitors were Circumvent® PCV-M (CV) and Ingelvac Circoflex® + Ingelvac Mycoflex® (IC + IM) in the US, and Porcilis® (POR) in Republic of Korea. Heterogeneity between experimental and environmental challenge studies in the US was not significant, justifying a combined analysis. Over the entire feeding period, ADG (11 comparisons), mortality (12 comparisons) and market classification were not significantly different between FOS-G and its competitor in the US setting. In the Korean study, however, ADG was higher in pigs vaccinated with FOS-G compared to POR, whereas mortality was not significantly different.

Cost-utility analysis of increasing uptake of universal seasonal quadrivalent influenza vaccine (QIV) in children aged 6 months and older in Germany.

Seasonal influenza causes many cases and related deaths in Europe annually, despite ongoing vaccination programs for older adults and people at high-risk of complications. Children have the highest risk of infection and play a key role in disease transmission. Our cost-utility analysis, based on a dynamic transmission model, estimated the impact of increasing the current vaccination coverage with inactivated quadrivalent influenza vaccine in Germany to all (healthy and high-risk) children under 5 years of age (40% uptake), or under 18 years (40% uptake), or only high-risk children under 18 years (90% uptake). Eight influenza complications were modeled, hospitalization and death rates were based on age and risk status. All three vaccination strategies provided more health benefits than the existing vaccination situation, reducing influenza cases, complications, hospitalizations and deaths across the entire population. The strategy targeting all children under 5 years was highly cost-effective (€6/quality-adjusted life-year gained, payer perspective). The other strategies were cost saving from the payer and societal perspectives. The vaccination strategy targeting all children under 18 years was estimated to provide the most health benefits (preventing on average 1.66 million cases, 179,000 complications, 14,000 hospitalizations and 3,600 deaths due to influenza annually) and the most cost savings (annually €20.5 million and €731.3 million from payer and societal perspectives, respectively). Our analysis provides policy decision-makers with evidence supporting strategies to expand childhood influenza vaccination, to directly protect children, and indirectly all other unvaccinated age groups, in order to reduce the humanistic and economic burden on healthcare systems and society.

What is the context? Every winter, millions of people in Europe become ill due to influenza (flu), and some need to be hospitalized for complications that can sometimes lead to death.While mainly older adults and people with chronic illness are at higher risk of complications from influenza, children have the highest risk of infection and of transmitting the disease.Current vaccination policies in Europe, including Germany, target older adults and high-risk populations (pregnant women, children and other age groups with chronic diseases).What is new? This analysis simulates the effects of expanding current German vaccination programs in high-risk children to include healthy children, and of increasing vaccination coverage rates, for direct protection against infection, and to reduce the disease transmission in the rest of the population.We modeled three vaccination strategies: vaccinating 40% of all (healthy and high- risk) children under 5 years old;vaccinating 40% of all (healthy and high-risk) children under 18 years old;vaccinating 90% of high-risk children under 18 years old.What is the impact? All three strategies resulted in health gains, as more influenza cases, complications and deaths were prevented in all age groups of the population compared to the current situation.The strategies targeting both healthy and high-risk children provided the greatest health benefits. In particular, a vaccination policy targeting all children under 18 years old was predicted to provide the most health benefits as well as the highest cost savings: the increased costs of vaccination were more than offset by the savings in disease management costs as a result of having fewer influenza patients.Vaccinating healthy children against influenza is expected to significantly reduce the disease burden in the total population while saving costs, due to reduced transmission of the disease.

Do High Levels of Maternally Derived Antibodies Interfere with the Vaccination of Piglets against Porcine Circovirus Type 2? A Literature Review and Data Analysis.

Vaccination against porcine circovirus type 2 (PCV2) is commonly performed in piglets worldwide, and increasingly also in sows. We conducted a literature search and review to assess the potential interference of maternally derived antibodies (MDA) in piglets with vaccination against PCV2. The effectiveness of vaccination was compared to no vaccination in the presence of high levels of MDA (≥8 log2 IPMA titer), as reported in field studies. In total, 13 papers fulfilled the predefined inclusion criteria, allowing up to 24 comparisons per parameter. In the presence of high levels of MDA, vaccinated pigs had, on average, a 20 g/d higher mean daily weight gain and a 34% lower mortality compared to non-vaccinates. The maximum percentage of viremic pigs was reduced by 63% and the maximum viral load in serum was 0.72 log10 PCV2 DNA copies lower. Vaccination at 3 weeks of age was associated with the highest improvements in production parameters and reductions in viremia. Our findings suggest that the vaccination of piglets is effective with respect to production parameters and viremia even in the presence of high MDA, with an age of 3 weeks at vaccination being most beneficial.

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.

Applying a Constrained Optimization Portfolio Model to Aid Prioritization of Public Health Interventions in Malaysia.

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.

Constrained Optimization for the Selection of Influenza Vaccines to Maximize the Population Benefit: A Demonstration Project.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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: 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. CONCLUSION: 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.

Economic Impact of Introducing the RTS,S Malaria Vaccine: Cost-Effectiveness and Budget Impact Analysis in 41 Countries.

Background. Malaria is a major public health burden in sub-Saharan Africa. This study estimated the cost-effectiveness and budget impact of adding four-dose malaria vaccination in infants or children to existing interventions in 41 endemic countries in sub-Saharan Africa. Methods. A static Markov cohort model followed a simulated 2017 birth cohort (36.5 million children) for 15 years in 5-day cycles, comparing three strategies: child vaccination (doses at ages 6, 7.5, 9, and 27 months); infant vaccination (doses at ages 6, 10, and 14 weeks and 21 months); no malaria vaccination. The base-case analysis was conducted from the health system perspective with vaccine price assumed at USD5/dose and annual discounting of 3% for costs and disability-adjusted life-years (DALYs). Efficacy was based on the Phase III RTS,S clinical trial. Results. The model projected that 24.6 million children, or 26.2 million infants, would be vaccinated. Compared with no vaccination, child (infant) vaccination was projected to avert 16.8 million (16 million) cases of malaria and 113,000 (107,000) malaria deaths in the birth cohort over the 15-year period. The incremental cost-effectiveness ratio was USD200/DALY averted (USD225/DALY averted) for child (infant) vaccination, which represents 14% (17%) of the gross domestic product (GDP) per capita threshold. The estimated budget impact was overall larger for infant vaccination but mixed situations occurred across countries. Vaccine price, discount rate, and parasite prevalence had the largest effect on cost-effectiveness. Conclusions. Child vaccination with RTS,S would be more cost-effective than infant vaccination across countries. Adding RTS,S malaria vaccination to existing interventions would be cost-effective assuming one GDP per capita threshold for both child and infant vaccination in all examined countries except for 6 countries with lower transmission.

Reducing Malaria Mortality at the Lowest Budget: An Optimization Tool for Selecting Malaria Preventative Interventions Applied to Ghana.

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 <5 years, and identified the optimal combination of interventions to reach that goal at the lowest cost. The time horizon was 5 years. Results. The optimal sequence of investments would be the following: (1) introduce RTS,S; (2) introduce SMC; (3) increase LLINs and IRS concurrently. RTS,S introduction was associated with mortality reduction of 16% for a budget increase of US$15.6 million. Adding SMC with a partial coverage of 4% further reduced mortality by 1% at an additional budget of US$1.4 million. Subsequently scaling-up IRS, LLINs, and SMC at their maximum achievable coverage further reduced mortality by 82% (total reduction 98%) at an additional budget of US$474 million. At an RTS,S price of US$10/dose, SMC was first in the optimal sequence. A lower RTS,S price maintained the sequence but reduced the budget need. Conclusions. In Ghana, RTS,S introduction in addition to the existing measures would be the optimal first step for reducing under-five malaria mortality at the lowest cost, followed by SMC in relevant areas, and then further scaling-up of IRS and LLINs.

Cost-utility of quadrivalent versus trivalent influenza vaccine in Brazil - comparison of outcomes from different static model types.

BACKGROUND: Influenza burden in Brazil is considerable with 4.2-6.4 million cases in 2008 and influenza-like-illness responsible for 16.9% of hospitalizations. Cost-effectiveness of influenza vaccination may be assessed by different types of models, with limitations due to data availability, assumptions, and modelling approach. OBJECTIVE: To understand the impact of model complexity, the cost-utility of quadrivalent versus trivalent influenza vaccines in Brazil was estimated using three distinct models: a 1-year decision tree population model with three age groups (FLOU); a more detailed 1-year population model with five age groups (FLORA); and a more complex lifetime multi-cohort Markov model with nine age groups (FLORENCE). METHODS: Analysis 1 (impact of model structure) compared each model using the same data inputs (i.e., best available data for FLOU). Analysis 2 (impact of increasing granularity) compared each model populated with the best available data for that model. RESULTS: Using the best data for each model, the discounted cost-utility ratio of quadrivalent versus trivalent influenza vaccine was R$20,428 with FLOU, R$22,768 with FLORA (versus R$20,428 in Analysis 1), and, R$19,257 with FLORENCE (versus R$22,490 in Analysis 1) using a lifetime horizon. Conceptual differences between FLORA and FLORENCE meant the same assumption regarding increased all-cause mortality in at-risk individuals had an opposite effect on the incremental cost-effectiveness ratio in Analysis 2 versus 1, and a proportionally higher number of vaccinated elderly in FLORENCE reduced this ratio in Analysis 2. DISCUSSION: FLOU provided adequate cost-effectiveness estimates with data in broad age groups. FLORA increased insights (e.g., in healthy versus at-risk, paediatric, respiratory/non-respiratory complications). FLORENCE provided greater insights and precision (e.g., in elderly, costs and complications, lifetime cost-effectiveness). CONCLUSION: All three models predicted a cost per quality-adjusted life year gained for quadrivalent versus trivalent influenza vaccine in the range of R$19,257 (FLORENCE) to R$22,768 (FLORA) with the best available data in Brazil (Appendix A).

Cost-utility of quadrivalent versus trivalent influenza vaccine in Brazil - comparison of outcomes from different static model types

ABSTRACT Background: Influenza burden in Brazil is considerable with 4.2-6.4 million cases in 2008 and influenza-like-illness responsible for 16.9% of hospitalizations. Cost-effectiveness of influenza vaccination may be assessed by different types of models, with limitations due to data availability, assumptions, and modelling approach. Objective: To understand the impact of model complexity, the cost-utility of quadrivalent versus trivalent influenza vaccines in Brazil was estimated using three distinct models: a 1-year decision tree population model with three age groups (FLOU); a more detailed 1-year population model with five age groups (FLORA); and a more complex lifetime multi-cohort Markov model with nine age groups (FLORENCE). Methods: Analysis 1 (impact of model structure) compared each model using the same data inputs (i.e., best available data for FLOU). Analysis 2 (impact of increasing granularity) compared each model populated with the best available data for that model. Results: Using the best data for each model, the discounted cost-utility ratio of quadrivalent versus trivalent influenza vaccine was R$20,428 with FLOU, R$22,768 with FLORA (versus R$20,428 in Analysis 1), and, R$19,257 with FLORENCE (versus R$22,490 in Analysis 1) using a lifetime horizon. Conceptual differences between FLORA and FLORENCE meant the same assumption regarding increased all-cause mortality in at-risk individuals had an opposite effect on the incremental cost-effectiveness ratio in Analysis 2 versus 1, and a proportionally higher number of vaccinated elderly in FLORENCE reduced this ratio in Analysis 2. Discussion: FLOU provided adequate cost-effectiveness estimates with data in broad age groups. FLORA increased insights (e.g., in healthy versus at-risk, paediatric, respiratory/non-respiratory complications). FLORENCE provided greater insights and precision (e.g., in elderly, costs and complications, lifetime cost-effectiveness). Conclusion: All three models predicted a cost per quality-adjusted life year gained for quadrivalent versus trivalent influenza vaccine in the range of R$19,257 (FLORENCE) to R$22,768 (FLORA) with the best available data in Brazil (Appendix A).

Optimising the introduction of multiple childhood vaccines in Japan: A model proposing the introduction sequence achieving the highest health gains.

BACKGROUND: 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. METHODS: 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 children <5 years old. This vaccine strategy, of interest and helpful for a healthcare decision maker, is compared with an unranked vaccine selection process. RESULTS: 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. CONCLUSION: 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.

Cost-Utility of Quadrivalent Versus Trivalent Influenza Vaccine in Germany, Using an Individual-Based Dynamic Transmission Model.

BACKGROUND: Seasonal influenza infection is primarily caused by circulation of two influenza A strain subtypes and strains from two B lineages that vary each year. Trivalent influenza vaccine (TIV) contains only one of the two B-lineage strains, resulting in mismatches between vaccine strains and the predominant circulating B lineage. Quadrivalent influenza vaccine (QIV) includes both B-lineage strains. The objective was to estimate the cost-utility of introducing QIV to replace TIV in Germany. METHODS: An individual-based dynamic transmission model (4Flu) using German data was used to provide realistic estimates of the impact of TIV and QIV on age-specific influenza infections. Cases were linked to health and economic outcomes to calculate the cost-utility of QIV versus TIV, from both a societal and payer perspective. Costs and effects were discounted at 3.0 and 1.5 % respectively, with 2014 as the base year. Univariate and probabilistic sensitivity analyses were conducted. RESULTS: Using QIV instead of TIV resulted in additional quality-adjusted life-years (QALYs) and cost savings from the societal perspective (i.e. it represents the dominant strategy) and an incremental cost-utility ratio (ICUR) of €14,461 per QALY from a healthcare payer perspective. In all univariate analyses, QIV remained cost-effective (ICUR <€50,000). In probabilistic sensitivity analyses, QIV was cost-effective in >98 and >99 % of the simulations from the societal and payer perspective, respectively. CONCLUSION: This analysis suggests that QIV in Germany would provide additional health gains while being cost-saving to society or costing €14,461 per QALY gained from the healthcare payer perspective, compared with TIV.

Potential public health impact of RTS,S malaria candidate vaccine in sub-Saharan Africa: a modelling study.

BACKGROUND: Adding malaria vaccination to existing interventions could help to reduce the health burden due to malaria. This study modelled the potential public health impact of the RTS,S candidate malaria vaccine in 42 malaria-endemic countries in sub-Saharan Africa. METHODS: An individual-based Markov cohort model was constructed with three categories of malaria transmission intensity and six successive malaria immunity levels. The cycle time was 5 days. Vaccination was assumed to reduce the risk of infection, with no other effects. Vaccine efficacy was assumed to wane exponentially over time. Malaria incidence and vaccine efficacy data were taken from a Phase III trial of the RTS,S vaccine with 18 months of follow-up (NCT00866619). The model was calibrated to reproduce the malaria incidence in the control arm of the trial in each transmission category and published age distribution data. Individual-level heterogeneity in malaria exposure and vaccine protection was accounted for. Parameter uncertainty and variability were captured by using stochastic model transitions. The model followed a cohort from birth to 10 years of age without malaria vaccination, or with RTS,S malaria vaccination administered at age 6, 10 and 14 weeks or at age 6, 7-and-a-half and 9 months. Median and 95% confidence intervals were calculated for the number of clinical malaria cases, severe cases, malaria hospitalizations and malaria deaths expected to be averted by each vaccination strategy. Univariate sensitivity analysis was conducted by varying the values of key input parameters. RESULTS: Vaccination assuming the coverage of diphtheria-tetanus-pertussis (DTP3) at age 6, 10 and 14 weeks is estimated to avert over five million clinical malaria cases, 119,000 severe malaria cases, 98,600 malaria hospitalizations and 31,000 malaria deaths in the 42 countries over the 10-year period. Vaccination at age 6, 7-and-a-half and 9 months with 75% of DTP3 coverage is estimated to avert almost 12.5 million clinical malaria cases, 250,000 severe malaria cases, 208,000 malaria hospitalizations and 65,400 malaria deaths in the 42 countries. Univariate sensitivity analysis indicated that for both vaccination strategies, the parameters with the largest impact on the malaria mortality estimates were waning of vaccine efficacy and malaria case-fatality rate. CONCLUSIONS: Addition of RTS,S malaria vaccination to existing malaria interventions is estimated to reduce substantially the incidence of clinical malaria, severe malaria, malaria hospitalizations and malaria deaths across 42 countries in sub-Saharan Africa.

The potential cost-effectiveness of quadrivalent versus trivalent influenza vaccine in elderly people and clinical risk groups in the UK: a lifetime multi-cohort model.

OBJECTIVE: To estimate the potential cost-effectiveness of quadrivalent influenza vaccine compared with trivalent influenza vaccine in the UK. METHODS: A lifetime, multi-cohort, static Markov model was constructed, with nine age groups each divided into healthy and at-risk categories. Influenza A and B were accounted for separately. The model was run in one-year cycles for a lifetime (maximum age: 100 years). The analysis was from the perspective of the UK National Health Service. Costs and benefits were discounted at 3.5%. 2010 UK vaccination policy (vaccination of people at risk and those aged ≥65 years) was applied. Herd effect was not included. Inputs were derived from national databases and published sources where possible. The quadrivalent influenza vaccine price was not available when the study was conducted. It was estimated at £6.72,15% above the trivalent vaccine price of £5.85. Sensitivity analyses used an incremental price of up to 50%. RESULTS: Compared with trivalent influenza vaccine, the quadrivalent influenza vaccine would be expected to reduce the numbers of influenza cases by 1,393,720, medical visits by 439,852 complications by 167,357, hospitalisations for complications by 26,424 and influenza deaths by 16,471. The estimated base case incremental cost-effectiveness ratio (ICER) was £5,299/quality-adjusted life-year (QALY). Sensitivity analyses indicated that the ICER was sensitive to changes in circulation of influenza virus subtypes and vaccine mismatch; all other parameters had little effect. In 96% of simulations the ICER was <£20,000/QALY. Since this analysis was completed, quadrivalent influenza vaccine has become available in the UK at a list price of £9.94. Using this price in the model, the estimated ICER for quadrivalent compared with trivalent vaccination was £27,378/QALY, still within the NICE cost-effectiveness threshold (£20,000-£30,000). CONCLUSIONS: Quadrivalent influenza vaccine could reduce influenza disease burden and would be cost-effective compared with trivalent influenza vaccine in elderly people and clinical risk groups in the UK.

An approximation of herd effect due to vaccinating children against seasonal influenza - a potential solution to the incorporation of indirect effects into static models.

BACKGROUND: Indirect herd effect from vaccination of children offers potential for improving the effectiveness of influenza prevention in the remaining unvaccinated population. Static models used in cost-effectiveness analyses cannot dynamically capture herd effects. The objective of this study was to develop a methodology to allow herd effect associated with vaccinating children against seasonal influenza to be incorporated into static models evaluating the cost-effectiveness of influenza vaccination. METHODS: Two previously published linear equations for approximation of herd effects in general were compared with the results of a structured literature review undertaken using PubMed searches to identify data on herd effects specific to influenza vaccination. A linear function was fitted to point estimates from the literature using the sum of squared residuals. RESULTS: The literature review identified 21 publications on 20 studies for inclusion. Six studies provided data on a mathematical relationship between effective vaccine coverage in subgroups and reduction of influenza infection in a larger unvaccinated population. These supported a linear relationship when effective vaccine coverage in a subgroup population was between 20% and 80%. Three studies evaluating herd effect at a community level, specifically induced by vaccinating children, provided point estimates for fitting linear equations. The fitted linear equation for herd protection in the target population for vaccination (children) was slightly less conservative than a previously published equation for herd effects in general. The fitted linear equation for herd protection in the non-target population was considerably less conservative than the previously published equation. CONCLUSIONS: This method of approximating herd effect requires simple adjustments to the annual baseline risk of influenza in static models: (1) for the age group targeted by the childhood vaccination strategy (i.e. children); and (2) for other age groups not targeted (e.g. adults and/or elderly). Two approximations provide a linear relationship between effective coverage and reduction in the risk of infection. The first is a conservative approximation, recommended as a base-case for cost-effectiveness evaluations. The second, fitted to data extracted from a structured literature review, provides a less conservative estimate of herd effect, recommended for sensitivity analyses.

Participating or not in a cardiac rehabilitation programme: factors influencing a patient's decision.

BACKGROUND: International research indicates that attendance of patients to a proposed cardiac rehabilitation (CR) programme varies between 21% and 75%. Addressing the reasons why cardiac patients are not participating will improve accessibility to CR. The objective of this study was to investigate patient compliance with cardiac rehabilitation and the reasons of refusing or abandoning the programme. METHODS: Twenty hospital centres were recruited to participate. Each centre was asked to recruit patients from three patient groups, namely: percutaneous coronary intervention patients, patients that underwent major cardiac surgery, and patients being admitted because of an acute myocardial infarction and not belonging to the other two groups. Patients were asked to fill out a questionnaire during a follow-up outpatient consultation after the cardiac intervention. RESULTS: In total, 226 patients participated in the survey. Most patients were proposed (86%) and accepted (81% out of proposed) to attend a CR programme. Of those who accepted, 77% completed the programme. The main reasons that led to patients' refusal to participate in a CR programme were distance to the CR centre, patients' belief they could handle their own problems, and lack of time. The main three reasons for not completing an initiated CR programme were other physical problems, patients' belief they could handle their own problems, and the cost of rehabilitation. CONCLUSION: Our findings demonstrate the importance of raising patients' awareness of the benefits of CR. Addressing potential barriers to attend a CR programme should be investigated with patients individually in order to ensure compliance.

Multidisciplinary outpatient rehabilitation following cardiac revascularization or valve surgery: patient-related factors for uptake.

BACKGROUND: There are concerns in Europe regarding the service provision and accessibility of multidisciplinary cardiac rehabilitation (MDCR) in general, and particularly in ambulatory settings. This paper analyses the utilization of outpatient MDCR and its determinants after cardiac revascularization or valve surgery in Belgium. METHODS: Claims rehabilitation data for all patients discharged in 2007 after a percutaneous cardiac intervention or cardiac surgery were available from the Belgian Common Sickness Funds Agency. Logistic regressions were performed to identify patients demographic and socioeconomic characteristics associated with the uptake of outpatient MDCR during the year following the hospital discharge. RESULTS: A total of 29,021 patients were included. During the hospitalization for the cardiac procedure, 44% were offered inpatient MDCR. After discharge, only 15.6% followed at least one session of outpatient MDCR. The chance of attending outpatient MDCR was lower for female, disabled, and older patients, as well as unemployed patients. The absence of an authorized MDCR centre in the neighbourhood of the patient's residence decreased the chance of attending outpatient MDCR, while living in a neighbourhood with a high education and income level increased this probability. CONCLUSION: These results confirm the low rates of MDCR attendance found in a previous study performed by the European Association of Cardiovascular Prevention and Rehabilitation. The study shows specific patient groups that should be targeted in priority, i.e. women, elderly, unemployed patients, disabled persons, and patients with a low socioeconomic status.

Estimation of the clinical and economic consequences of non-compliance with antimicrobial treatment of canine skin infections.

The goal of this study was to estimate the health and economic consequences of non-compliance with oral antimicrobial treatment in dogs with superficial pyoderma, wounds or abscesses in the US. A mathematical model (Markov model) which simulated treatment with long-term injectable cefovecin versus oral amoxicillin/clavulanic acid was developed and accounted for the effect of non-compliance on clinical outcomes and mean total treatment costs per patient. Efficacy parameters considered in the model were derived from clinical studies. Treatment failure due to oral antimicrobial treatment non-compliance was approximated from published data at 13.6%. US cost data for 2009 were derived from public sources. When non-compliance was considered as a cause of treatment failure with oral medication, the long-term injectable antibiotic was more effective than oral comparator (162 versus 158 days without clinical signs). Mean total treatment costs were lower with cefovecin (USD 376.74) versus amoxicillin/clavulanic acid (USD 382.34) in dogs of 25 kg; and cefovecin remained cost-saving up to a body weight of 31 kg. In large dogs, cefovecin was more costly; however, total therapy costs were less than 6% greater than with amoxicillin/clavulanic acid. Accordingly the higher drug and administration costs of the long-term injectable antibiotic were totally or substantially offset when non-compliance was considered as reason for treatment failure with oral medication. The model also allowed for the estimation of the impact of various non-compliance scenarios.