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1.  Revisiting the cost-effectiveness of universal HPV-vaccination in Denmark accounting for all potentially vaccine preventable HPV-related diseases in males and females 
Objective
The purpose of this study was to assess the consequences of a national immunization program with HPV vaccine for both boys and girls in Denmark, including the prophylactic effects on all potentially vaccine preventable HPV-associated diseases in male and female.
Methods
The study focussed on the quadrivalent vaccine which protects against HPV type 6, 11, 16 and 18, and the vaccine’s protection against genital warts, cervical intraepithelial neoplasia, cervical cancer, anogenital cancer (anal, penile, vaginal and vulvar cancer) and head and neck cancer (oral cavity, oropharyngeal, hypopharyngeal and laryngeal cancer) were included in the analyses. In general, the analysis was performed in two phases. First, an agent-based transmission model that described the HPV transmission without and with HPV vaccination was applied. Second, an analysis of the incremental costs and effects was performed. The model did not include naturally-acquired immunity to HPV in the simulations.
Results
In the base case result (i.e. vaccination of girls only, 85% vaccination rate, private market price at € 123 per dose ex. VAT) an ICER of 3583 €/QALY (3-dose regime) is estimated when all HPV-related diseases are taken into account. Vaccination of girls & boys vs. vaccination of girls only an ICER of 28,031 €/QALY (2-dose regime) and 41,636 €/QALY (3-dose regime) is estimated.
Conclusions
Extension of the current HPV programme in Denmark to include boys and girls is a cost effective preventive intervention that would lead to a faster prevention of cancers, cancer precursors and genital warts in men and women.
doi:10.1186/s12962-015-0029-9
PMCID: PMC4331443
HPV-vaccination; Cost-effectiveness; HPV-related diseases; Cancer; Genital warts; Gender neutral vaccination
2.  Cost-effectiveness of using a social franchise network to increase uptake of oral rehydration salts and zinc for childhood diarrhea in rural Myanmar 
Introduction
This paper examines the cost-effectiveness of achieving increases in the use of oral rehydration solution and zinc supplementation in the management of acute diarrhea in children under 5 years through social franchising. The study uses cost and outcome data from an initiative by Population Services International (PSI) in 3 townships of Myanmar in 2010 to promote an ORS-Zinc product called ORASEL.
Background
The objective of this study was to determine the incremental cost-effectiveness of a strategy to promote ORS-Z use through private sector franchising compared to standard government and private sector practices.
Methods
Costing from a societal perspective included program, provider, and household costs for the 2010 calendar year. Program costs including ORASEL program launch, distribution, and administration costs were obtained through a retrospective review of financial records and key informant interviews with staff in the central Yangon office. Household out of pocket payments for diarrheal episodes were obtained from a household survey conducted in the study area and additional estimates of household income lost due to parental care-giving time for a sick child were estimated. Incremental cost-effectiveness relative to status quo conditions was calculated per child death and DALY averted in 2010. Health effects included deaths and DALYs averted; the former modeled based on coverage estimates from a household survey that were entered into the Lives Saved Tool (LiST). Uncertainty was modeled with Monte Carlo methods.
Findings
Based on the model, the promotional strategy would translate to 2.85 (SD 0.29) deaths averted in a community population of 1 million where there would be 81,000 children under 5 expecting 48,373 cases of diarrhea. The incremental cost effectiveness of the franchised approach to improving ORASEL coverage is estimated at a median $5,955 (IQR: $3437-$7589) per death averted and $214 (IQR: $127-$287) per discounted DALY averted.
Interpretation
Investing in developing a network of private sector providers and keeping them stocked with ORS-Z as is done in a social franchise can be a highly cost-effective in terms of dollars per DALY averted.
Electronic supplementary material
The online version of this article (doi:10.1186/s12962-015-0030-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12962-015-0030-3
PMCID: PMC4332918
Costing; Zinc; Oral rehydration; Private providers; Social franchise; Myanmar; Burma; Cluster randomized trial
3.  Cost-effectiveness and affordability of community mobilisation through women’s groups and quality improvement in health facilities (MaiKhanda trial) in Malawi 
Background
Understanding the cost-effectiveness and affordability of interventions to reduce maternal and newborn deaths is critical to persuading policymakers and donors to implement at scale. The effectiveness of community mobilisation through women’s groups and health facility quality improvement, both aiming to reduce maternal and neonatal mortality, was assessed by a cluster randomised controlled trial conducted in rural Malawi in 2008–2010. In this paper, we calculate intervention cost-effectiveness and model the affordability of the interventions at scale.
Methods
Bayesian methods are used to estimate the incremental cost-effectiveness of the community and facility interventions on their own (CI, FI), and together (FICI), compared to current practice in rural Malawi. Effects are estimated with Monte Carlo simulation using the combined full probability distributions of intervention effects on stillbirths, neonatal deaths and maternal deaths. Cost data was collected prospectively from a provider perspective using an ingredients approach and disaggregated at the intervention (not cluster or individual) level. Expected Incremental Benefit, Cost-effectiveness Acceptability Curves and Expected Value of Information (EVI) were calculated using a threshold of $780 per disability-adjusted life-year (DALY) averted, the per capita gross domestic product of Malawi in 2013 international $.
Results
The incremental cost-effectiveness of CI, FI, and combined FICI was $79, $281, and $146 per DALY averted respectively, compared to current practice. FI is dominated by CI and FICI. Taking into account uncertainty, both CI and combined FICI are highly likely to be cost effective (probability 98% and 93%, EVI $210,423 and $598,177 respectively). Combined FICI is incrementally cost effective compared to either intervention individually (probability 60%, ICER $292, EIB $9,334,580 compared to CI). Future scenarios also found FICI to be the optimal decision. Scaling-up to the whole of Malawi, CI is of greatest value for money, potentially averting 13.0% of remaining annual DALYs from stillbirths, neonatal and maternal deaths for the equivalent of 6.8% of current annual expenditure on maternal and neonatal health in Malawi.
Conclusions
Community mobilisation through women’s groups is a highly cost-effective and affordable strategy to reduce maternal and neonatal mortality in Malawi. Combining community mobilisation with health facility quality improvement is more effective, more costly, but also highly cost-effective and potentially affordable in this context.
Electronic supplementary material
The online version of this article (doi:10.1186/s12962-014-0028-2) contains supplementary material, which is available to authorized users.
doi:10.1186/s12962-014-0028-2
PMCID: PMC4299571  PMID: 25649323
Cost-effectiveness; Affordability; Community mobilisation; Women’s groups; Quality improvement; MaiKhanda; Scale-up; Future scenarios; Malawi
4.  An approach to prioritization of medical devices in low-income countries: an example based on the Republic of South Sudan 
Background
Efficient and evidence-based medical device and equipment prioritization is of particular importance in low-income countries due to constraints in financing capacity, physical infrastructure and human resource capabilities.
Methods
This paper outlines a medical device prioritization method developed in first instance for the Republic of South Sudan. The simple algorithm offered here is a starting point for procurement and selection of medical devices and can be regarded as a screening test for those that require more labour intensive health economic modelling.
Conclusions
A heuristic method, such as the one presented here, is appropriate for reaching many medical device prioritization decisions in low-income settings. Further investment and purchasing decisions that cannot be reached so simply require more complex health economic modelling approaches.
Electronic supplementary material
The online version of this article (doi:10.1186/s12962-014-0027-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12962-014-0027-3
PMCID: PMC4298960  PMID: 25606027
Medical devices; Equipment; Prioritization; Purchasing; Selection; Low-income country
5.  Modelling the cost-effectiveness of a new infant vaccine to prevent tuberculosis disease in children in South Africa 
Background
Tuberculosis remains the leading cause of death in South Africa. A number of potential new TB vaccine candidates have been identified and are currently in clinical trials. One such candidate is MVA85A. This study aimed to estimate the cost-effectiveness of adding the MVA85A vaccine as a booster to the BCG vaccine in children from the perspective of the South African government.
Methods
The cost-effectiveness was assessed by employing Decision Analytic Modelling, through the use of a Markov model. The model compared the existing strategy of BCG vaccination to a new strategy in which infants receive BCG and a booster vaccine, MVA85A, at 4 months of age. The costs and outcomes of the two strategies are estimated through modelling the vaccination of a hypothetical cohort of newborns and following them from birth through to 10 years of age, employing 6-monthly cycles.
Results
The results of the cost-effectiveness analysis indicate that the MVA85A strategy is both more costly and more effective – there are fewer TB cases and deaths from TB than BCG alone. The South African government would need to spend an additional USD 1,105 for every additional TB case averted and USD 284,017 for every additional TB death averted. The threshold analysis shows that, if the efficacy of the MVA85A vaccine was 41.3% (instead of the current efficacy of 17.3%), the two strategies would have the same cost but more cases of TB and more deaths from TB would be prevented by adding the MVA85A vaccine to the BCG vaccine. In this case, the government chould consider the MVA85A strategy.
Conclusions
At the current level of efficacy, the MVA85A vaccine is neither effective nor cost-effective and, therefore, not a good use of limited resources. Nevertheless, this study contributes to developing a standardized Markov model, which could be used, in the future, to estimate the potential cost-effectiveness of new TB vaccines compared to the BCG vaccine, in children between the ages of 0–10 years. It also provides an indicative threshold of vaccine efficacy, which could guide future development.
doi:10.1186/1478-7547-12-20
PMCID: PMC4169661  PMID: 25242892
Cost-effectiveness analysis; New TB vaccine; Markov modelling; Childhood TB; South Africa; Tuberculosis; BCG vaccine
6.  Cost-utility of ferric carboxymaltose (Ferinject®) for iron-deficiency anemia patients with chronic heart failure in South Korea 
Background
Iron-deficiency anemia (IDA) is prevalent in patients with advanced chronic heart failure (CHF). It affects the patients’ overall physical condition and is suggested as a strong outcome predictor in CHF. Recent clinical trials suggested that intravenous iron supplementation improves CHF functional status and quality of life. The aim of this study was to assess the cost-effectiveness of ferric carboxymaltose(FCM) in CHF patients with IDA.
Methods
Ferric carboxymaltose, an intravenous iron preparation, was compared with placebo. The target population comprised CHF patients with IDA in hospital and outpatient care settings. We conducted this study from the Korean healthcare payers’ perspective with a time horizon of 24 weeks. One clinical trial provided the clinical outcomes of ferric carboxymaltose therapy. The improvement rates of the New York Heart Association (NYHA) functional class in the placebo and ferric carboxymaltose groups were used to estimate effectiveness in the base-case model. We also conducted a scenario 2 analysis using quality of life investigated in the clinical trial. A panel survey was conducted to obtain the ratio of healthcare resource use based on NYHA class in Korea. Cost-effectiveness was expressed as incremental cost (US dollars) per quality-adjusted life-year (QALY) gained.
Results
In the base-case analysis, the incremental cost-effectiveness ratio (ICER) of ferric carboxymaltose compared with placebo was $22,192 (₩25,010,451) per QALY gained. The sensitivity analysis showed robust results, with the ICERs of ferric carboxymaltose ranging from $5,156 to $29,796 per QALY gained. In the scenario 2 analysis, ICER decreased to $12,598 (₩14,198,501) per QALY gained.
Conclusions
Iron repletion with ferric carboxymaltose for IDA in CHF patients was cost-effective compared with placebo.
doi:10.1186/1478-7547-12-19
PMCID: PMC4166574  PMID: 25278814
Cost-effectiveness; Cost utility; Chronic heart failure; Iron-deficiency anemia; New York heart association (NYHA) functional class
7.  Guidance on priority setting in health care (GPS-Health): the inclusion of equity criteria not captured by cost-effectiveness analysis 
This Guidance for Priority Setting in Health Care (GPS-Health), initiated by the World Health Organization, offers a comprehensive map of equity criteria that are relevant to health care priority setting and should be considered in addition to cost-effectiveness analysis. The guidance, in the form of a checklist, is especially targeted at decision makers who set priorities at national and sub-national levels, and those who interpret findings from cost-effectiveness analysis. It is also targeted at researchers conducting cost-effectiveness analysis to improve reporting of their results in the light of these other criteria.
The guidance was develop through a series of expert consultation meetings and involved three steps: i) methods and normative concepts were identified through a systematic review; ii) the review findings were critically assessed in the expert consultation meetings which resulted in a draft checklist of normative criteria; iii) the checklist was validated though an extensive hearing process with input from a range of relevant stakeholders.
The GPS-Health incorporates criteria related to the disease an intervention targets (severity of disease, capacity to benefit, and past health loss); characteristics of social groups an intervention targets (socioeconomic status, area of living, gender; race, ethnicity, religion and sexual orientation); and non-health consequences of an intervention (financial protection, economic productivity, and care for others).
doi:10.1186/1478-7547-12-18
PMCID: PMC4171087  PMID: 25246855
Priority setting; Resource allocation; Cost-effectiveness; Equity; Population health
8.  Changes in costs and effects after the implementation of disease management programs in the Netherlands: variability and determinants 
Objectives
The aim of the study was to investigate the changes in costs and outcomes after the implementation of various disease management programs (DMPs), to identify their potential determinants, and to compare the costs and outcomes of different DMPs.
Methods
We investigated the 1-year changes in costs and effects of 1,322 patients in 16 DMPs for cardiovascular risk (CVR), chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DMII) in the Netherlands. We also explored the within-DMP predictors of these changes. Finally, a cost-utility analysis was performed from the healthcare and societal perspective comparing the most and the least effective DMP within each disease category.
Results
This study showed wide variation in development and implementation costs between DMPs (range:€16;€1,709) and highlighted the importance of economies of scale. Changes in health care utilization costs were not statistically significant. DMPs were associated with improvements in integration of CVR care (0.10 PACIC units), physical activity (+0.34 week-days) and smoking cessation (8% less smokers) in all diseases. Since an increase in physical activity and in self-efficacy were predictive of an improvement in quality-of-life, DMPs that aim to improve these are more likely to be effective. When comparing the most with the least effective DMP in a disease category, the vast majority of bootstrap replications (range:73%;97) pointed to cost savings, except for COPD (21%). QALY gains were small (range:0.003;+0.013) and surrounded by great uncertainty.
Conclusions
After one year we have found indications of improvements in level of integrated care for CVR patients and lifestyle indicators for all diseases, but in none of the diseases we have found indications of cost savings due to DMPs. However, it is likely that it takes more time before the improvements in care lead to reductions in complications and hospitalizations.
doi:10.1186/1478-7547-12-17
PMCID: PMC4118650  PMID: 25089122
Costs; Effectiveness; Coordinated care; Cardiovascular disease; Diabetes; COPD
9.  Making use of equity sensitive QALYs: a case study on identifying the worse off across diseases 
Background
Resource allocation decisions currently lack standard quantitative methods for incorporating concerns about the worse off when analysing the cost-effectiveness of medical interventions.
Objective
To explore and demonstrate how to identify who are the worse off without a new intervention by measuring lifetime Quality-Adjusted Life Years (QALYs) for patients across different conditions, and compare the results to using proportional shortfall of QALYs.
Methods
Case study of eight condition-intervention pairs that are relevant to priority setting in Norway; childhood deafness (unilateral cochlear implant), unruptured cerebral aneurysm (coiling), morbid obesity (RY gastric bypass), adult deafness (unilateral cochlear implant), atrial fibrillation (catheter ablation), hip osteoarthritis (hip replacement), rheumatoid arthritis (TNF inhibitor) and acute stroke (stroke unit). We extracted prospective QALYs without and with new interventions from published health technology assessments and economic evaluations.
Results
Among the eight cases, the lifetime QALY method and the proportional shortfall method yielded conflicting worse-off rank orders. Particularly two conditions had a substantial shift in ranking across the applications of the two methods: childhood deafness and acute stroke. Deaf children had the lowest expected lifetime QALYs (38.5 without a cochlear implant) and were worst off according to the lifetime approach, while patients with acute stroke had the second-highest lifetime QALYs (76.4 without stroke units). According to proportional shortfall of QALYs, patients with acute stroke were ranked as worse off than deaf children, which seems counterintuitive.
Conclusion
This study shows that it is feasible to identify who are the worse off empirically by the application of lifetime QALYs and proportional shortfalls. These methods ease further examination of whether there is a true conflict between maximization and equity or whether these two concerns actually coincide in real world cases. It is yet to be solved whether proportional prospective health losses are more important than absolute shortfalls in expected lifetime health in judgements about who are worse off.
doi:10.1186/1478-7547-12-16
PMCID: PMC4118218  PMID: 25089121
Priority setting in health; Quality-adjusted life years; Severity; Healthcare rationing; Equity
10.  Do economic evaluation studies inform effective healthcare resource allocation in Iran? A critical review of the literature 
To aid informed health sector decision-making, data from sufficient high quality economic evaluations must be available to policy makers. To date, no known study has analysed the quantity and quality of available Iranian economic evaluation studies. This study aimed to assess the quantity, quality and targeting of economic evaluation studies conducted in the Iranian context.
The study systematically reviewed full economic evaluation studies (n = 30) published between 1999 and 2012 in international and local journals. The findings of the review indicate that although the literature on economic evaluation in Iran is growing, these evaluations were of poor quality and suffer from several major methodological flaws. Furthermore, the review reveals that economic evaluation studies have not addressed the major health problems in Iran.
While the availability of evidence is no guarantee that it will be used to aid decision-making, the absence of evidence will certainly preclude its use. Considering the deficiencies in the data identified by this review, current economic evaluations cannot be a useful source of information for decision makers in Iran. To improve the quality and overall usefulness of economic evaluations we would recommend; 1) developing clear national guidelines for the conduct of economic evaluations, 2) highlighting priority areas where information from such studies would be most useful and 3) training researchers and policy makers in the calculation and use of economic evaluation data.
doi:10.1186/1478-7547-12-15
PMCID: PMC4105166  PMID: 25050084
Economic evaluation; Pharmacoeconomics; Review; Iran
11.  Incremental cost of increasing access to maternal health care services: perspectives from a demand and supply side intervention in Eastern Uganda 
Introduction
High maternal and infant mortality continue to be major challenges to the attainment of the Millennium Development Goals for many low and middle-income countries. There is now evidence that voucher initiatives can increase access to maternal health services. However, a dearth of knowledge exists on the cost implications of voucher schemes. This paper estimates the incremental costs of a demand and supply side intervention aimed at increasing access to maternal health care services.
Methods
This costing study was part of a quasi-experimental voucher study conducted in two districts in Eastern Uganda to explore the impact of demand and supply - side incentives on increasing access to maternal health services. The provider’s perspective was used and the ingredients approach to costing was employed. Costs were based on market prices as recorded in program records. Total, unit, and incremental costs were calculated.
Results
The estimated total financial cost of the intervention for the one year of implementation was US$525,472 (US$1 = 2200UgShs). The major cost drivers included costs for transport vouchers (35.3%), health system strengthening (29.2%) and vouchers for maternal health services (18.2%). The average cost of transport per woman to and from the health facility was US$4.6. The total incremental costs incurred on deliveries (excluding caesarean section) was US$317,157 and US$107,890 for post natal care (PNC). The incremental costs per additional delivery and PNC attendance were US$23.9 and US$7.6 respectively.
Conclusion
Subsidizing maternal health care costs through demand and supply – side initiatives may not require significant amounts of resources contrary to what would be expected. With Uganda’s Gross Domestic Product (GDP) per capita of US$55` (2012), the incremental cost per additional delivery (US$23.9) represents about 5% of GDP per capita to save a mother and probably her new born. For many low income countries, this may not be affordable, yet reliance on donor funding is often not sustainable. Alternative ways of raising additional resources for health must be explored. These include; encouraging private investments in critical sectors such as rural transport, health service provision; mobilizing households to save financial resources for preparedness, and financial targeting for the most vulnerable.
doi:10.1186/1478-7547-12-14
PMCID: PMC4074383  PMID: 24976793
Vouchers; Maternal health; Costs; Sustainability; Demand-side; Supply-side
12.  Multi-criteria decision analysis of breast cancer control in low- and middle- income countries: development of a rating tool for policy makers 
Background
The objective of this study was to develop a rating tool for policy makers to prioritize breast cancer interventions in low- and middle- income countries (LMICs), based on a simple multi-criteria decision analysis (MCDA) approach. The definition and identification of criteria play a key role in MCDA, and our rating tool could be used as part of a broader priority setting exercise in a local setting. This tool may contribute to a more transparent priority-setting process and fairer decision-making in future breast cancer policy development.
Methods
First, an expert panel (n = 5) discussed key considerations for tool development. A literature review followed to inventory all relevant criteria and construct an initial set of criteria. A Delphi study was then performed and questionnaires used to discuss a final list of criteria with clear definitions and potential scoring scales. For this Delphi study, multiple breast cancer policy and priority-setting experts from different LMICs were selected and invited by the World Health Organization. Fifteen international experts participated in all three Delphi rounds to assess and evaluate each criterion.
Results
This study resulted in a preliminary rating tool for assessing breast cancer interventions in LMICs. The tool consists of 10 carefully crafted criteria (effectiveness, quality of the evidence, magnitude of individual health impact, acceptability, cost-effectiveness, technical complexity, affordability, safety, geographical coverage, and accessibility), with clear definitions and potential scoring scales.
Conclusions
This study describes the development of a rating tool to assess breast cancer interventions in LMICs. Our tool can offer supporting knowledge for the use or development of rating tools as part of a broader (MCDA based) priority setting exercise in local settings. Further steps for improving the tool are proposed and should lead to its useful adoption in LMICs.
doi:10.1186/1478-7547-12-13
PMCID: PMC4031156  PMID: 24855456
Multi-criteria decision analysis; Priority setting; Breast cancer
13.  A pilot study to assess feasibility of value based pricing in Cyprus through pharmacoeconomic modelling and assessment of its operational framework: sorafenib for second line renal cell cancer 
Background
The continuing increase of pharmaceutical expenditure calls for new approaches to pricing and reimbursement of pharmaceuticals. Value based pricing of pharmaceuticals is emerging as a useful tool and possess theoretical attributes to help health system cope with rising pharmaceutical expenditure.
Aim
To assess the feasibility of introducing a value-based pricing scheme of pharmaceuticals in Cyprus and explore the integrative framework.
Methods
A probabilistic Markov chain Monte Carlo model was created to simulate progression of advanced renal cell cancer for comparison of sorafenib to standard best supportive care. Literature review was performed and efficacy data were transferred from a published landmark trial, while official pricelists and clinical guidelines from Cyprus Ministry of Health were utilised for cost calculation. Based on proposed willingness to pay threshold the maximum price of sorafenib for the indication of second line renal cell cancer was assessed.
Results
Sorafenib value based price was found to be significantly lower compared to its current reference price.
Conclusion
Feasibility of Value Based Pricing is documented and pharmacoeconomic modelling can lead to robust results. Integration of value and affordability in the price are its main advantages which have to be weighed against lack of documentation for several theoretical parameters that influence outcome. Smaller countries such as Cyprus may experience adversities in establishing and sustaining essential structures for this scheme.
doi:10.1186/1478-7547-12-12
PMCID: PMC4029980  PMID: 24910539
JEL 110; JEL 130; JEL 300; Value based pricing; Pharmacoeconomic modelling; Sorafenib; Markov Model
14.  Cost-effectiveness of community vegetable gardens for people living with HIV in Zimbabwe 
Background
There is little evidence to date of the potential impact of vegetable gardens on people living with HIV (PLHIV), who often suffer from social and economic losses due to the disease. From 2008 through 2011, Action Contre la Faim France (ACF) implemented a project in Chipinge District, eastern Zimbabwe, providing low-input vegetable gardens (LIGs) to households of PLHIV. Program partners included Médecins du Monde, which provided medical support, and Zimbabwe's Agricultural Extension Service, which supported vegetable cultivation. A survey conducted at the end of the program found LIG participants to have higher Food Consumption Scores (FCS) and Household Dietary Diversity Scores (HDDS) relative to comparator households of PLHIV receiving other support programs. This study assessed the incremental cost-effectiveness of LIGs to improve FCS and HDDS of PLHIV compared to other support programs.
Methods
This analysis used an activity-based cost model, and combined ACF accounting data with estimates of partner and beneficiary costs derived using an ingredients approach to build an estimate of total program resource use. A societal perspective was adopted to encompass costs to beneficiary households, including their opportunity costs and an estimate of their income earned from vegetable sales. Qualitative methods were used to assess program benefits to beneficiary households. Effectiveness data was taken from a previously-conducted survey.
Results
Providing LIGs to PLHIV cost an additional 8,299 EUR per household with adequate FCS and 12,456 EUR per household with HDDS in the upper tertile, relative to comparator households of PLHIV receiving other support programs. Beneficiaries cited multiple tangible and intangible benefits from LIGs, and over 80% of gardens observed were still functioning more than one year after the program had finished.
Conclusions
Cost outcomes were 20–30 times Zimbabwe's per capita GDP, and unlikely to be affordable within government services. This analysis concludes that LIGs are not cost-effective or affordable relative to other interventions for improving health and nutrition status of PLHIV. Nonetheless, given the myriad benefits acquired by participant households, such programs hold important potential to improve quality of life and reduce stigma against PLHIV.
doi:10.1186/1478-7547-12-11
PMCID: PMC4022439  PMID: 24834014
Vegetable gardens; Livelihoods; People living with HIV; Food consumption score; Household dietary diversity score; Cost-effectiveness; Societal costs; Mixed methods; Activity-based cost analysis; Zimbabwe
15.  Estimating the cost-effectiveness of nutrition supplementation for malnourished, HIV-infected adults starting antiretroviral therapy in a resource-constrained setting 
Background
Low body mass index (BMI) individuals starting antiretroviral therapy (ART) for HIV infection in sub-Saharan Africa have high rates of death and loss to follow-up in the first 6 months of treatment. Nutritional supplementation may improve health outcomes in this population, but the anticipated benefit of any intervention should be commensurate with the cost given resource limitations and the need to expand access to ART in the region.
Methods
We used Markov models incorporating historical data and program-wide estimates of treatment costs and health benefits from the Zambian national ART program to estimate the improvements in 6-month survival and program retention among malnourished adults necessary for a combined nutrition support and ART treatment program to maintain cost-effectiveness parity with ART treatment alone. Patients were stratified according to World Health Organization criteria for severe (BMI <16.0 kg/m2), moderate (16.00-16.99 kg/m2), and mild (17.00-18.49 kg/m2) malnutrition categories.
Results
19,247 patients contributed data between May 2004 and October 2010. Quarterly survival and retention were lowest in the BMI <16.0 kg/m2 category compared to higher BMI levels, and there was less variation in both measures across BMI strata after 180 days. ART treatment was estimated to cost $556 per year and averted 7.3 disability-adjusted life years. To maintain cost-effectiveness parity with ART alone, a supplement needed to cost $10.99 per quarter and confer a 20% reduction in both 6-month mortality and loss to follow-up among BMI <16.0 kg/m2 patients. Among BMI 17.00-18.49 kg/m2 patients, supplement costs accompanying a 20% reduction in mortality and loss to follow-up could not exceed $5.18 per quarter. In sensitivity analyses, the maximum permitted supplement cost increased if the ART program cost rose, and fell if patients classified as lost to follow-up at 6 months subsequently returned to care.
Conclusions
Low BMI adults starting ART in sub-Saharan Africa are at high risk of early mortality and loss to follow-up. The expense of providing nutrition supplementation would require only modest improvements in survival and program retention to be cost-effective for the most severely malnourished individuals starting ART, but interventions are unlikely to be cost-effective among those in higher BMI strata.
doi:10.1186/1478-7547-12-10
PMCID: PMC4024113  PMID: 24839400
HIV; Antiretroviral therapy; Nutrition; Malnutrition; Zambia; Africa
16.  Ownership and technical efficiency of hospitals: evidence from Ghana using data envelopment analysis 
Background
In order to measure and analyse the technical efficiency of district hospitals in Ghana, the specific objectives of this study were to (a) estimate the relative technical and scale efficiency of government, mission, private and quasi-government district hospitals in Ghana in 2005; (b) estimate the magnitudes of output increases and/or input reductions that would have been required to make relatively inefficient hospitals more efficient; and (c) use Tobit regression analysis to estimate the impact of ownership on hospital efficiency.
Methods
In the first stage, we used data envelopment analysis (DEA) to estimate the efficiency of 128 hospitals comprising of 73 government hospitals, 42 mission hospitals, 7 quasi-government hospitals and 6 private hospitals. In the second stage, the estimated DEA efficiency scores are regressed against hospital ownership variable using a Tobit model. This was a retrospective study.
Results
In our DEA analysis, using the variable returns to scale model, out of 128 district hospitals, 31 (24.0%) were 100% efficient, 25 (19.5%) were very close to being efficient with efficiency scores ranging from 70% to 99.9% and 71 (56.2%) had efficiency scores below 50%. The lowest-performing hospitals had efficiency scores ranging from 21% to 30%.
Quasi-government hospitals had the highest mean efficiency score (83.9%) followed by public hospitals (70.4%), mission hospitals (68.6%) and private hospitals (55.8%). However, public hospitals also got the lowest mean technical efficiency scores (27.4%), implying they have some of the most inefficient hospitals.
Regarding regional performance, Northern region hospitals had the highest mean efficiency score (83.0%) and Volta Region hospitals had the lowest mean score (43.0%).
From our Tobit regression, we found out that while quasi-government ownership is positively associated with hospital technical efficiency, private ownership negatively affects hospital efficiency.
Conclusions
It would be prudent for policy-makers to examine the least efficient hospitals to correct widespread inefficiency. This would include reconsidering the number of hospitals and their distribution, improving efficiency and reducing duplication by closing or scaling down hospitals with efficiency scores below a certain threshold. For private hospitals with inefficiency related to large size, there is a need to break down such hospitals into manageable sizes.
doi:10.1186/1478-7547-12-9
PMCID: PMC4108084  PMID: 24708886
Data envelopment analysis; Technical efficiency; Scale efficiency; Hospitals; Ownership
17.  The impact of incorporating Bayesian network meta-analysis in cost-effectiveness analysis - a case study of pharmacotherapies for moderate to severe COPD 
Objective
To evaluate the impact of using network meta-analysis (NMA) versus pair wise meta-analyses (PMA) for evidence synthesis on key outputs of cost-effectiveness analysis (CEA).
Methods
We conducted Bayesian NMA of randomized clinical trials providing head-to-head and placebo comparisons of the effect of pharmacotherapies on the exacerbation rate in chronic obstructive pulmonary disease (COPD). Separately, the subset of placebo–comparison trials was used in a Bayesian PMA. The pooled rate ratios (RR) were used to populate a decision-analytic model of COPD treatment to predict 10-year outcomes.
Results
Efficacy estimates from the NMA and PMA were similar, but the NMA provided estimates with higher precision. This resulted in similar incremental cost-effectiveness ratios (ICER). Probabilities of being cost-effective at willingness-to-pay thresholds (WTPs) between $25,000 and $100,000 per quality adjusted life year (QALY) varied considerably between the PMA- and NMA-based approaches. The largest difference in the probabilities of being cost-effective was observed at a WTP of approximately $40,000/QALY. At this threshold, with the PMA-based analysis, ICS, LAMA and placebo had a 43%, 30, and 18% probability of being the most cost-effective. By contrast, with the NMA based approach, ICS, LAMA, and placebo had a 56%, 19%, and 21% probability of being cost-effective. For larger WTP thresholds the probability of LAMA being the most cost-effective became higher than that of ICS. Under the PMA-based analyses the cross-over occurred at a WTP threshold between $60,000/QALY-$65,000/QALY, whereas under the NMA-based approach, the cross-over occurred between $85,000/QALY-$90,000/QALY.
Conclusion
Use of NMAs in CEAs is feasible and, as our case study showed, can decrease uncertainty around key cost-effectiveness measures compared with the use of PMAs. The approval process of health technologies in many jurisdictions requires estimates of comparative efficacy and cost-effectiveness. NMAs play an increasingly important role in providing estimates of comparative efficacy. Their use in the CEAs therefore results in methodological consistency and reduced uncertainty.
doi:10.1186/1478-7547-12-8
PMCID: PMC4007707  PMID: 24625208
Meta-analysis; Multiple treatment comparison; Bayesian analysis; Cost-effectiveness
18.  Economic evaluation of policy initiatives in the organisation and delivery of healthcare: a case study of gastroenterology endoscopy services 
Background
Complex clinical interventions are increasingly subject to evaluation by randomised trial linked to economic evaluation. However evaluations of policy initiatives tend to eschew experimental designs in favour of interpretative perspectives which rarely allow the economic evaluation methods used in clinical trials. As evidence of the cost effectiveness of such initiatives is critical in informing policy, it is important to explore whether conventional economic evaluation methods apply to experimental evaluations of policy initiatives.
Methods
We used mixed methods based on a quasi-experimental design to evaluate a policy initiative whose aim was to expedite the modernisation of gastroenterology endoscopy services in England. We compared 10 sites which had received funding and support to modernise their endoscopy services with 10 controls. We collected data from five waves of patients undergoing endoscopy. The economic component of the study compared sites by levels of investment in modernisation and patients’ use of health service resources, time off work and health related quality of life.
Results
We found no statistically significant difference between intervention and control sites in investment in modernisation or any patient outcome including health.
Conclusions
This study highlights difficulties in applying the rigour of a randomised trial and associated technique of economic evaluation to a policy initiative. It nevertheless demonstrates the feasibility of using this approach although further work is needed to demonstrate its generalisability in other applications. The present application shows that the small incentives offered to intervention sites did not enhance modernisation of gastroenterology endoscopy services or improve patient outcomes.
doi:10.1186/1478-7547-12-7
PMCID: PMC3945072  PMID: 24597703
Cost effectiveness; Evaluation; Health policy; Modernisation; Endoscopy; Cost
19.  Cost-effectiveness of eye care services in Zambia 
Objective
To estimate the cost-effectiveness of cataract surgery and refractive error/presbyopia correction in Zambia.
Methods
Primary data on costs and health related quality of life were collected in a prospective cohort study of 170 cataract and 113 refractive error/presbyopia patients recruited from three health facilities. Six months later, follow-up data were available from 77 and 41 patients who had received cataract surgery and spectacles, respectively. Costs were determined from patient interviews and micro-costing at the three health facilities. Utility values were gathered by administering the EQ-5D quality of life instrument immediately before and six months after cataract surgery or acquiring spectacles. A probabilistic state-transition model was used to generate cost-effectiveness estimates with uncertainty ranges.
Results
Utility values significantly improved across the patient sample after cataract surgery and acquiring spectacles. Incremental costs per Quality Adjusted Life Years gained were US$ 259 for cataract surgery and US$ 375 for refractive error correction. The probabilities of the incremental cost-effectiveness ratios being below the Zambian gross national income per capita were 95% for both cataract surgery and refractive error correction.
Conclusion
In spite of proven cost-effectiveness, severe health system constraints are likely to hamper scaling up of the interventions.
doi:10.1186/1478-7547-12-6
PMCID: PMC3944959  PMID: 24568593
Costs; Cataract; Refractive error; Presbyopia; Quality of life
20.  Economic evaluation of rivaroxaban in stroke prevention for patients with atrial fibrillation in Greece 
Background
To undertake an economic evaluation of rivaroxaban relative to the standard of care for stroke prevention in patients with non-valvular atrial fibrillation (AF) in Greece.
Methods
An existing Markov model designed to reflect the natural progression of AF patients through different health states, in the course of three month cycles, was adapted to the Greek setting. The analysis was undertaken from a payer perspective. Baseline event rates and efficacy data were obtained from the ROCKET-AF trial for rivaroxaban and vitamin-K-antagonists (VKAs). Utility values for events were based on literature. A treatment-related disutility of 0.05 was applied to the VKA arm. Costs assigned to each health state reflect the year 2013. An incremental cost effectiveness ratio (ICER) was calculated where the outcome was quality-adjusted-life year (QALY) and life-years gained. Probabilistic analysis was undertaken to deal with uncertainty. The horizon of analysis was over patient life time and both cost and outcomes were discounted at 3.5%.
Results
Based on safety-on-treatment data, rivaroxaban was associated with a 0.22 increment in QALYs compared to VKA. The average total lifetime cost of rivaroxaban-treated patients was €239 lower compared to VKA. Rivaroxaban was associated with additional drug acquisition cost (€4,033) and reduced monitoring cost (-€3,929). Therefore, rivaroxaban was a dominant alternative over VKA. Probabilistic analysis revealed that there is a 100% probability of rivaroxaban being cost-effective versus VKA at a willingness to pay threshold of €30,000/QALY gained.
Conclusion
Rivaroxaban may represent for payers a dominant option for the prevention of thromboembolic events in moderate to high risk AF patients in Greece.
doi:10.1186/1478-7547-12-5
PMCID: PMC3942277  PMID: 24512351
Cost-effectiveness; Vitamin-K-antagonists; Cost-utility
21.  Cost-effectiveness of a universal strategy of brief dietary intervention for primary prevention in primary care: population-based cohort study and Markov model 
Background
A healthy diet is associated with reduced risk of diabetes, cardiovascular disease and cancer. The study aimed to evaluate the cost-effectiveness of a universal strategy to promote healthy diet through brief intervention in primary care.
Methods
The research was informed by a systematic review of randomised trials which found that brief interventions in primary care may be associated with a 0.5 portion per day increase in fruit and vegetable consumption. A Markov model that included five long-term conditions (diabetes, coronary heart disease, stroke, colorectal cancer and depression) was developed. Empirical data from a large cohort of United Kingdom-based participants sampled from the Clinical Practice Research Datalink populated the model. Simulations compared an intervention promoting healthy diet over 5 years in healthy adults, and standard care in which there was no intervention. The annual cost of intervention, in the base case, was one family practice consultation per participant year. Health service costs were included and the model adopted a lifetime perspective. The primary outcome was net health benefit in quality adjusted life years (QALYs).
Results
A cohort of 262,704 healthy participants entered the model. Intervention was associated with an increase in life years lived free from physical disease of 41.9 (95% confidence interval -17.4 to 101.0) per 1,000 participants entering the model (probability of increase 88.0%). New incidences of disease states were reduced by 28.4 (18.7 to 75.8) per 1,000, probability reduced 84.6%. Discounted incremental QALYs were 4.3 (-8.8 to 18.0) per 1,000, while incremental costs were £139,755 (£60,466 to 220,059) per 1,000. Net health benefits at £30,000 per QALY were -0.32 (-13.8 to 13.5) QALYs per 1,000 participants (probability cost-effective 47.9%). When the intervention was restricted to adults aged 50 to 74 years, net health benefits were 2.94 (-21.3 to 26.4) QALYs per 1000, probability increased 59.0%.
Conclusions
A universal strategy to promote healthy diet through brief intervention in primary care is unlikely to be cost-effective, even when delivered at low unit cost. A targeted strategy aimed at older individuals at higher risk of disease might be more cost-effective. More effective dietary change interventions are needed.
doi:10.1186/1478-7547-12-4
PMCID: PMC4015683  PMID: 24485221
Dietary intervention; Primary care; Markov model; Cost effectiveness; Outcomes; Diabetes; Coronary heart disease; Stroke; Colorectal cancer; Depression
22.  Budget constraint and vaccine dosing: a mathematical modelling exercise 
Background
Increasing the number of vaccine doses may potentially improve overall efficacy. Decision-makers need information about choosing the most efficient dose schedule to maximise the total health gain of a population when operating under a constrained budget. The objective of this study is to identify the most efficient vaccine dosing schedule within a fixed vaccination budget from a healthcare payer perspective.
Methods
An optimisation model is developed in which maximizing the disease reduction is the functional objective and the constraint is the vaccination budget. The model allows variation in vaccination dosing numbers, in cost difference per dose, in vaccine coverage rate, and in vaccine efficacy. We apply the model using the monovalent rotavirus vaccine as an example.
Results
With a fixed budget, a 2-dose schedule for vaccination against rotavirus infection with the monovalent vaccine results in a larger reduction in disease episodes than a 3-dose scheme with the same vaccine under most circumstances. A 3-dose schedule would only be better under certain conditions: a cost reduction of >26% per dose, combined with vaccine efficacy improvement of ≥5% and a target coverage rate of 75%. Substantial interaction is observed between cost reduction per dose, vaccine coverage rate, and increased vaccine efficacy. Sensitivity analysis shows that the conditions required for a 3-dose strategy to be better than a 2-dose strategy may seldom occur when the budget is fixed. The model does not consider vaccine herd effect, precise timing for additional doses, or the effect of natural immunity development.
Conclusions
Under budget constraint, optimisation modelling is a helpful tool for a decision-maker selecting the most efficient vaccination dosing schedule. The low dosing scheme could be the optimal option to consider under the many scenarios tested. The model can be applied under many different circumstances of changing dosing schemes with single or multiple vaccines.
doi:10.1186/1478-7547-12-3
PMCID: PMC3904011  PMID: 24450591
Rotavirus; Vaccination; Economic evaluation; Budget optimisation modelling
23.  Lifetime QALY prioritarianism in priority setting: quantification of the inherent trade-off 
Background
Multiple principles are relevant in priority setting, two of which are often considered particularly important. According to the greater benefit principle, resources should be directed toward the intervention with the greater health benefit. This principle is intimately linked to the goal of health maximization and standard cost-effectiveness analysis (CEA). According to the worse off principle, resources should be directed toward the intervention benefiting those initially worse off. This principle is often linked to an idea of equity. Together, the two principles accord with prioritarianism; a view which can motivate non-standard CEA. Crucial for the actual application of prioritarianism is the trade-off between the two principles, and this trade-off has received scant attention when the worse off are specified in terms of lifetime health. This paper sheds light on that specific trade-off and on the public support for prioritarianism by providing fresh empirical evidence and by clarifying the close links between the findings and normative theory.
Methods
A new, self-administered, computer-based questionnaire was used, to which 96 students in Norway responded. How respondents wanted to balance quality-adjusted life years (QALYs) gained against benefiting those with few lifetime QALYs was quantified for a range of different cases.
Results
Respondents supported both principles and were willing to make trade-offs in a particular way. In the baseline case, the median response valued a QALY 3.3 and 2.5 times more when benefiting someone with lifetime QALYs of 10 and 25 rather than 70. Average responses harbored fundamental disagreements and varied modestly across distributional settings.
Conclusion
In the specific context of lifetime health, the findings underscore the insufficiency of pure QALY maximization and explicate how people make trade-offs in a way that can help operationalize lifetime prioritarianism and non-standard CEA. Seen through the lens of normative theory, the findings highlight key challenges for prioritarianism applied to priority setting.
doi:10.1186/1478-7547-12-2
PMCID: PMC3896665  PMID: 24418267
Priority setting; Prioritarianism; Cost-effectiveness; Equity weights; Quality-adjusted life years; Political philosophy; Empirical ethics
24.  Cost-effectiveness of changes in alcohol taxation in Denmark: a modelling study 
Introduction
Excessive alcohol consumption is a public health problem in many countries including Denmark, where 6% of the burden of disease is due to alcohol consumption, according to the new estimates from the Global Burden of Disease 2010 study. Pricing policies, including tax increases, have been shown to effectively decrease the level of alcohol consumption.
Methods
We analysed the cost-effectiveness of three different scenarios of changed taxation of alcoholic beverages in Denmark (20% and 100% increase and 10% decrease). The lifetime health effects are estimated as the difference in disability-adjusted life years between a Danish population that continues to drink alcohol at current rates and an identical population that changes their alcohol consumption due to changes in taxation. Calculation of cost offsets related to treatment of alcohol-related diseases and injuries, was based on health care system costs from Danish national registers. Cost-effectiveness was evaluated by calculating cost-effectiveness ratios (CERs) compared to current practice.
Results
The two scenarios of 20% and 100% increased taxation could avert 20,000 DALY and 95,500 DALY respectively, and yield cost savings of -€119 million and -€575 million, over the life time of the Danish population. Both scenarios are thus cost saving. The tax decrease scenario would lead to 10,100 added DALY and an added cost of €60 million. For all three interventions the health effects build up and reach their maximum around 15–20 years after implementation of the tax change.
Conclusion
Our results show that decreased taxation will lead to an increased burden of disease and related increases in health care costs, whereas both a doubling of the current level of alcohol taxation and a scenario where taxation is only increased by 20% can be cost-saving ways to reduce alcohol related morbidity and mortality. Our results support the growing evidence that population strategies are cost-effective and should be considered for policy making and prevention of alcohol abuse.
doi:10.1186/1478-7547-12-1
PMCID: PMC3914680  PMID: 24405884
Cost-effectiveness; Taxation; Alcohol; Public health; Health effects; Health care costs; Simulation modelling
25.  Surrogate outcomes: experiences at the Common Drug Review 
Background
Surrogate outcomes are a significant challenge in drug evaluation for health technology assessment (HTA) agencies. The research objectives were to: identify factors associated with surrogate use and acceptability in Canada’s Common Drug Review (CDR) recommendations, and compare the CDR with other HTA or regulatory agencies regarding surrogate concerns.
Methods
Final recommendations were identified from CDR inception (September 2003) to December 31, 2010. Recommendations were classified by type of outcome (surrogate, final, other) and acceptability of surrogates (determined by the presence/absence of statements of concern regarding surrogates). Descriptive and statistical analyses examined factors related to surrogate use and acceptability. For thirteen surrogate-based submissions, recommendations from international HTA and regulatory agencies were reviewed for statements about surrogate acceptability.
Results
Of 156 final recommendations, 68 (44%) involved surrogates. The overall ‘do not list’ (DNL) rate was 48%; the DNL rate for surrogates was 41% (p = 0.175). The DNL rate was 64% for non-accepted surrogates (n = 28) versus 25% for accepted surrogates (odds ratio 5.4, p = 0.002). Clinical uncertainty, use of economic evidence over price alone, and a premium price were significantly associated with non-accepted surrogates. Surrogates were used most commonly for HIV, diabetes, rare diseases, cardiovascular disease and cancer. For the subset of drugs studied, other HTA agencies did not express concerns for most recommendations, while regulatory agencies frequently stated surrogate acceptance.
Conclusions
The majority of surrogates were accepted at the CDR. Non-accepted surrogates were significantly associated with clinical uncertainty and a DNL recommendation. There was inconsistency of surrogate acceptability across several international agencies. Stakeholders should consider collaboratively establishing guidelines on the use, validation, and acceptability of surrogates.
doi:10.1186/1478-7547-11-31
PMCID: PMC3866929  PMID: 24341379
Reimbursement; Decision-making; Surrogate outcomes; Health technology assessment

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