Reducing dengue fever cases at the lowest budget: a constrained optimization approach applied to Thailand.

BACKGROUND: With the challenges that dengue fever (DF) presents to healthcare systems and societies, public health officials must determine where best to allocate scarce resources and restricted budgets. Constrained optimization (CO) helps to address some of the acknowledged limitations of conventional health economic analyses and has typically been used to identify the optimal allocation of resources across interventions subject to a variety of constraints. METHODS: A dynamic transmission model was developed to predict the number of dengue cases in Thailand at steady state. A CO was then applied to identify the optimal combination of interventions (release of Wolbachia-infected mosquitoes and paediatric vaccination) within the constraints of a fixed budget, set no higher than cost estimates of the current vector control programme, to minimize the number of dengue cases and disability-adjusted life years (DALYs) lost. Epidemiological, cost, and effectiveness data were informed by national data and the research literature. The time horizon was 10 years. Scenario analyses examined different disease management and intervention costs, budget constraints, vaccine efficacy, and optimization time horizon. RESULTS: Under base-case budget constraints, the optimal coverage of the two interventions to minimize dengue incidence was predicted to be nearly equal (Wolbachia 50%; paediatric vaccination 49%) with corresponding coverages under lower bound (Wolbachia 54%; paediatric vaccination 10%) and upper bound (Wolbachia 67%; paediatric vaccination 100%) budget ceilings. Scenario analyses indicated that the most impactful situations related to the costs of Wolbachia and paediatric vaccination with decreases/ increases in costs of interventions demonstrating a direct correlation with coverage (increases/ decreases) of the respective control strategies under examination. CONCLUSIONS: Determining the best investment strategy for dengue control requires the identification of the optimal mix of interventions to implement in order to maximize public health outcomes, often under fixed budget constraints. A CO model was developed with the objective of minimizing dengue cases (and DALYs lost) over a 10-year time horizon, within the constraints of the estimated budgets for vector control in the absence of vaccination and Wolbachia. The model provides a tool for developing estimates of optimal coverage of combined dengue control strategies that minimize dengue burden at the lowest budget.

The economic impact and cost-effectiveness of combined vector-control and dengue vaccination strategies in Thailand: results from a dynamic transmission model.

BACKGROUND AND AIMS: Dengue fever is a major public health problem in tropical/subtropical regions. Prior economic analyses have predominantly evaluated either vaccination or vector-control programmes in isolation and do not really consider the incremental benefits and cost-effectiveness of mixed strategies and combination control. We estimated the cost-effectiveness of single and combined approaches in Thailand. METHODS: The impacts of different control interventions were analysed using a previously published mathematical model of dengue epidemiology and control incorporating seasonality, age structure, consecutive infection, cross protection, immune enhancement and combined vector-host transmission. An economic model was applied to simulation results to estimate the cost-effectiveness of 4 interventions and their various combinations (6 strategies): i) routine vaccination of 1-year olds; ii) chemical vector control strategies targeting adult and larval stages separately; iii) environmental management/ public health education and awareness [EM/ PHEA]). Payer and societal perspectives were considered. The health burden of dengue fever was assessed using disability-adjusted life-years (DALYs) lost. Costs and effects were assessed for 10 years. Costs were discounted at 3% annually and updated to 2013 United States Dollars. Incremental cost-effectiveness analysis was carried out after strategies were rank-ordered by cost, with results presented in a table of incremental analysis. Sensitivity and scenario analyses were undertaken; and the impact and cost-effectiveness of Wolbachia was evaluated in exploratory scenario analyses. RESULTS: From the payer and societal perspectives, 2 combination strategies were considered optimal, as all other control strategies were dominated. Vaccination plus adulticide plus EM/ PHEA was deemed cost-effective according to multiple cost-effectiveness criteria. From the societal perspective, incremental differences vs. adulticide and EM/ PHEA resulted in costs of $157.6 million and DALYs lost of 12,599, giving an expected ICER of $12,508 per DALY averted. Exploratory scenario analyses showed Wolbachia to be highly cost-effective ($343 per DALY averted) vs. other single control measures. CONCLUSIONS: Our model shows that individual interventions can be cost-effective, but that important epidemiological reductions and economic impacts are demonstrated when interventions are combined as part of an integrated approach to combating dengue fever. Exploratory scenario analyses demonstrated the potential epidemiological and cost-effective impact of Wolbachia when deployed at scale on a nationwide basis. Our findings were robust in the face of sensitivity analyses.

Health-Related Quality of Life and Health Utilities in Metastatic Castrate-Resistant Prostate Cancer: A Survey Capturing Experiences from a Diverse Sample of UK Patients.

BACKGROUND: The collection of preference-based health outcomes data (or utility values) is required to support cost-effectiveness analyses. OBJECTIVE: This study aimed to collect health-related quality of life (HRQOL) data in men with metastatic castration-resistant prostate cancer (CRPC) stratified by disease states. METHODS: Men with metastatic CRPC were recruited via UK patient associations, patient panels, and specialist recruiters and classified into four subgroups reflecting disease state: asymptomatic/mildly symptomatic before chemotherapy, symptomatic before chemotherapy, receiving chemotherapy, and postchemotherapy. HRQOL data (including five-level EuroQol five-dimensional questionnaire [EQ-5D-5L], European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire [EORTC QLQ-C30], and 25-item prostate cancer-specific questionnaire module designed to supplement the EORTC QLQ-C30) along with background and medical history data were collected via an online survey. The EQ-5D-5L and the EORTC-8D (EORTC-8D is an 8 dimensional utility index scored from QLQ-C30 data) were both used to estimate utilities. RESULTS: Data were collected from a total sample of 163 men with metastatic CRPC. Utility values elicited by the EQ-5D-5L ranged from 0.830 for the asymptomatic/mildly symptomatic before chemotherapy disease state (95% confidence interval [CI] 0.795-0.865) to 0.625 for the symptomatic before chemotherapy disease state (95% CI 0.577-0.673). EORTC-8D utilities ranged from 0.856 (95% CI 0.831-0.882) to 0.697 (95% CI 0.664-0.731) for the same disease/treatment states. CONCLUSIONS: This online survey was designed to capture real-world HRQOL data describing men with CRPC. The study estimated utilities using two alternative methods, and the results show good agreement, suggesting that they are robust. This methodology offers a potentially higher quality alternative to vignette-based methods that are commonly used in oncology submissions.

Cost-effectiveness of adding bedaquiline to drug regimens for the treatment of multidrug-resistant tuberculosis in the UK.

OBJECTIVE: To evaluate the cost-effectiveness of adding bedaquiline to a background regimen (BR) of drugs for multidrug-resistant tuberculosis (MDR-TB) in the United Kingdom (UK). METHODS: A cohort-based Markov model was developed to estimate the incremental cost-effectiveness ratio of bedaquiline plus BR (BBR) versus BR alone (BR) in the treatment of MDR-TB, over a 10-year time horizon. A National Health Service (NHS) and personal social services perspective was considered. Cost-effectiveness was evaluated in terms of Quality-Adjusted Life Years (QALYs) and Disability-Adjusted Life Years (DALYs). Data were sourced from a phase II, placebo-controlled trial, NHS reference costs, and the literature; the US list price of bedaquiline was used and converted to pounds (£18,800). Costs and effectiveness were discounted at a rate of 3.5% per annum. Probabilistic and deterministic sensitivity analysis was conducted. RESULTS: The total discounted cost per patient (pp) on BBR was £106,487, compared with £117,922 for BR. The total discounted QALYs pp were 5.16 for BBR and 4.01 for BR. The addition of bedaquiline to a BR resulted in a cost-saving of £11,434 and an additional 1.14 QALYs pp over a 10-year period, and is therefore considered to be the dominant (less costly and more effective) strategy over BR. BBR remained dominant in the majority of sensitivity analyses, with a 81% probability of being dominant versus BR in the probabilistic analysis. CONCLUSIONS: In the UK, bedaquiline is likely to be cost-effective and cost-saving, compared with the current MDR-TB standard of care under a range of scenarios. Cost-savings over a 10-year period were realized from reductions in length of hospitalization, which offset the bedaquiline drug costs. The cost-benefit conclusions held after several sensitivity analyses, thus validating assumptions made, and suggesting that the results would hold even if the actual price of bedaquiline in the UK were higher than in the US.

Impact of combined vector-control and vaccination strategies on transmission dynamics of dengue fever: a model-based analysis.

Dengue fever is a vector-borne disease prevalent in tropical and subtropical regions. It is an important public health problem with a considerable and often under-valued disease burden in terms of frequency, cost and quality-of-life. Recent literature reviews have documented the development of mathematical models of dengue fever both to identify important characteristics for future model development as well as to assess the impact of dengue control interventions. Such reviews highlight the importance of short-term cross-protection; antibody-dependent enhancement; and seasonality (in terms of both favourable and unfavourable conditions for mosquitoes). The compartmental model extends work by Bartley (2002) and combines the following factors: seasonality, age-structure, consecutive infection by all four serotypes, cross-protection and immune enhancement, as well as combined vector-host transmission. The model is used to represent dengue transmission dynamics using parameters appropriate for Thailand and to assess the potential impact of combined vector-control and vaccination strategies including routine and catch-up vaccination strategies on disease dynamics. When seasonality and temporary cross-protection between serotypes are included, the model is able to approximate the observed incidence of dengue fever in Thailand. We find vaccination to be the most effective single intervention, albeit with imperfect efficacy (30.2 %) and limited duration of protection. However, in combination, control interventions and vaccination exhibit a marked impact on dengue fever transmission. This study shows that an imperfect vaccine can be a useful weapon in reducing disease spread within the community, although it will be most effective when promoted as one of several strategies for combating dengue fever transmission.

A cost-effectiveness analysis of a 10-valent pneumococcal conjugate vaccine in children in six Latin American countries.

BACKGROUND: A recently developed 10-valent pneumococcal non-typeable H influenzae protein D-conjugate vaccine (PHiD-CV) is expected to afford protection against more than two thirds of isolates causing IPD in children in Latin America, and also against acute otitis media caused by both Spn and NTHi. The objective of this study is to assess the cost-effectiveness of PHiD-CV in comparison to non-vaccination in children under 10 years of age in Argentina, Brazil, Chile, Colombia, Mexico and Peru. METHODS: We used a static, deterministic, compartmental simulation model. The dosing regimen considered included three vaccine doses (at 2 months, 4 months and 6 months) and a booster dose (at 13 months) (3 + 1 schedule). Model outcomes included number of cases prevented, deaths averted, quality-adjusted life-years (QALYs) gained and costs. Discount for costs and benefits of long term sequelae was done at 3.5%, and currency reported in 2008-2009 U$S varying between countries. RESULTS: The largest effect in case prevention was observed in pneumococcal meningitis (from 27% in Peru to 47% in Colombia), neurologic sequelae after meningitis (from 38% in Peru to 65% in Brazil) and bacteremia (from 42% in Argentina to 49% in Colombia). The proportion of predicted deaths averted annually ranged from 18% in Peru to 33% in Brazil. Overall, the health benefits achieved with PHiD-CV vaccination resulted in a lower QALY loss (from 15% lower in Peru to 26% in Brazil). At a cost of USD 20 per vaccine dose, vaccination was cost-effective in all countries, from being cost saving in Chile to a maximum Incremental Cost-effectiveness Ratio of 7,088 US$ Dollars per QALY gained. Results were robust in the sensitivity analysis, and scenarios with indirect costs affected results more than those with herd immunity. CONCLUSIONS: The incorporation of the 10-valent pneumococcal conjugate vaccine into routine infant immunization programs in Latin American countries could be a cost-effective strategy to improve infant population health in the region.

A cost-effectiveness analysis of a 10-valent pneumococcal conjugate vaccine in children in six Latin American countries

BACKGROUND: A recently developed 10-valent pneumococcal non-typeable H influenzae protein D-conjugate vaccine (PHiD-CV) is expected to afford protection against more than two thirds of isolates causing IPD in children in Latin America, and also against acute otitis media caused by both Spn and NTHi. The objective of this study is to assess the cost-effectiveness of PHiD-CV in comparison to non-vaccination in children under 10 years of age in Argentina, Brazil, Chile, Colombia, Mexico and Peru. METHODS: We used a static, deterministic, compartmental simulation model. The dosing regimen considered included three vaccine doses (at 2 months, 4 months and 6 months) and a booster dose (at 13 months) (3 + 1 schedule). Model outcomes included number of cases prevented, deaths averted, quality-adjusted life-years (QALYs) gained and costs. Discount for costs and benefits of long term sequelae was done at 3.5%, and currency reported in 2008-2009 U$S varying between countries. RESULTS: The largest effect in case prevention was observed in pneumococcal meningitis (from 27% in Peru to 47% in Colombia), neurologic sequelae after meningitis (from 38% in Peru to 65% in Brazil) and bacteremia (from 42% in Argentina to 49% in Colombia). The proportion of predicted deaths averted annually ranged from 18% in Peru to 33% in Brazil. Overall, the health benefits achieved with PHiD-CV vaccination resulted in a lower QALY loss (from 15% lower in Peru to 26% in Brazil). At a cost of USD 20 per vaccine dose, vaccination was cost-effective in all countries, from being cost saving in Chile to a maximum Incremental Cost-effectiveness Ratio of 7,088 US$ Dollars per QALY gained. Results were robust in the sensitivity analysis, and scenarios with indirect costs affected results more than those with herd immunity. CONCLUSIONS: The incorporation of the 10-valent pneumococcal conjugate vaccine into routine infant immunization programs in Latin American countries could be a cost-effective strategy to improve infant population health in the region.(AU)

Health and economic impact of PHiD-CV in Canada and the UK: a Markov modelling exercise.

OBJECTIVE: The spectrum of diseases caused by Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) represents a large burden on healthcare systems around the world. Meningitis, bacteraemia, community-acquired pneumonia (CAP), and acute otitis media (AOM) are vaccine-preventable infectious diseases that can have severe consequences. The health economic model presented here is intended to estimate the clinical and economic impact of vaccinating birth cohorts in Canada and the UK with the 10-valent, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared with the newly licensed 13-valent pneumococcal conjugate vaccine (PCV-13). METHODS: The model described herein is a Markov cohort model built to simulate the epidemiological burden of pneumococcal- and NTHi-related diseases within birth cohorts in the UK and Canada. Base-case assumptions include estimates of vaccine efficacy and NTHi infection rates that are based on published literature. RESULTS: The model predicts that the two vaccines will provide a broadly similar impact on all-cause invasive disease and CAP under base-case assumptions. However, PHiD-CV is expected to provide a substantially greater reduction in AOM compared with PCV-13, offering additional savings of Canadian $9.0 million and £4.9 million in discounted direct medical costs in Canada and the UK, respectively. LIMITATIONS: The main limitations of the study are the difficulties in modelling indirect vaccine effects (herd effect and serotype replacement), the absence of PHiD-CV- and PCV-13-specific efficacy data and a lack of comprehensive NTHi surveillance data. Additional limitations relate to the fact that the transmission dynamics of pneumococcal serotypes have not been modelled, nor has antibiotic resistance been accounted for in this paper. CONCLUSION: This cost-effectiveness analysis suggests that, in Canada and the UK, PHiD-CV's potential to protect against NTHi infections could provide a greater impact on overall disease burden than the additional serotypes contained in PCV-13.