Methodological Challenges to Economic Evaluations of Vaccines: Is a Common Approach Still Possible?

Economic evaluation of vaccination is a key tool to inform effective spending on vaccines. However, many evaluations have been criticised for failing to capture features of vaccines which are relevant to decision makers. These include broader societal benefits (such as improved educational achievement, economic growth and political stability), reduced health disparities, medical innovation, reduced hospital beds pressures, greater peace of mind and synergies in economic benefits with non-vaccine interventions. Also, the fiscal implications of vaccination programmes are not always made explicit. Alternative methodological frameworks have been proposed to better capture these benefits. However, any broadening of the methodology for economic evaluation must also involve evaluations of non-vaccine interventions, and hence may not always benefit vaccines given a fixed health-care budget. The scope of an economic evaluation must consider the budget from which vaccines are funded, and the decision-maker's stated aims for that spending to achieve

Programme costs in the economic evaluation of health interventions

Estimating the costs of health interventions is important to policy-makers for a number of reasons including the fact that the results can be used as a component in the assessment and improvement of their health system performance. Costs can, for example, be used to assess if scarce resources are being used efficiently or whether there is scope to reallocate them in a way that would lead to improvements in population health. As part of its WHO-CHOICE project, WHO has been developing a database on the overall costs of health interventions in different parts of the world as an input to discussions about priority setting. Programme costs, defined as costs incurred at the administrative levels outside the point of delivery of health care to beneficiaries, may comprise an important component of total costs. Cost-effectiveness analysis has sometimes omitted them if the main focus has been on personal curative interventions or on the costs of making small changes within the existing administrative set-up. However, this is not appropriate for non-personal interventions where programme costs are likely to comprise a substantial proportion of total costs, or for sectoral analysis where questions of how best to reallocate all existing health resources, including administrative resources, are being considered. This paper presents a first effort to systematically estimate programme costs for many health interventions in different regions of the world. The approach includes the quantification of resource inputs, choice of resource prices, and accounts for different levels of population coverage. By using an ingredients approach, and making tools available on the World Wide Web, analysts can adapt the programme costs reported here to their local settings. We report results for a selected number of health interventions and show that programme costs vary considerably across interventions and across regions, and that they can contribute substantially to the overall costs of interventions

Cost-effectiveness analysis for sector-wide priority setting in health

Cost-effectiveness analysis (CEA) provides one means by which decision-makers may assess and potentially improve the performance of health systems. The process can help to ensure that resources devoted to health systems are achieving the maximum possible benefit in terms of outcomes that people value. Over the past three decades there has been an exponential growth in the number of economic appraisals performed in health. Following standard textbooks on economic evaluations, most of these CEA studies pursue an incremental approach which requires comparison of the additional costs of an intervention over current practice with additional health benefits. Such an incremental approach, however, is unable to provide policy makers with all necessary information relating to decisions like: "Do the resources currently devoted to health achieve as much as they could?", or "How best to use additional resources if they become available?". This thesis proposes a broader sectoral approach via the application of a generalized CEA framework which also al!ows examination of existing inefficiencies in the health system- that is, the wide variations in CE ratios observed among interventions that are currently in use suggest there is considerable room to improve efficiency by moving from inefficient interventions currently in use to efficient interventions that are under-utilised. In developing countries in particular reallocation of scarce financial resources is most important

Cost-eff ectiveness of female human papillomavirus vaccination in 179 countries: a PRIME modelling study

Background Introduction of human papillomavirus (HPV) vaccination in settings with the highest burden of HPV is not universal, partly because of the absence of quantitative estimates of country-specifi c eff ects on health and economic costs. We aimed to develop and validate a simple generic model of such eff ects that could be used and understood in a range of settings with little external support. Methods We developed the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to assess cost-eff ectiveness and health eff ects of vaccination of girls against HPV before sexual debut in terms of burden of cervical cancer and mortality. PRIME models incidence according to proposed vaccine effi cacy against HPV 16/18, vaccine coverage, cervical cancer incidence and mortality, and HPV type distribution. It assumes lifelong vaccine protection and no changes to other screening programmes or vaccine uptake. We validated PRIME against existing reports of HPV vaccination cost-eff ectiveness, projected outcomes for 179 countries (assuming full vaccination of 12-year-old girls), and outcomes for 71 phase 2 GAVI-eligible countries (using vaccine uptake data from the GAVI Alliance). We assessed diff erences between countries in terms of cost-eff ectiveness and health eff ects. Findings In validation, PRIME reproduced cost-eff ectiveness conclusions for 24 of 26 countries from 17 published studies, and for all 72 countries in a published study of GAVI-eligible countries. Vaccination of a cohort of 58 million 12-year-old girls in 179 countries prevented 690 000 cases of cervical cancer and 420 000 deaths during their lifetime (mostly in low-income or middle-income countries), at a net cost of US$4 billion. HPV vaccination was very cost eff ective (with every disability-adjusted life-year averted costing less than the gross domestic product per head) in 156 (87%) of 179 countries. Introduction of the vaccine in countries without national HPV vaccination at present would prevent substantially more cases of cervical cancer than in countries with such programmes, although the disparity has narrowed since 2012. If 71 phase 2 GAVI-eligible countries adopt vaccination according to forecasts, then in 2070 GAVI Alliance-funded vaccination could prevent 200 000 cases of cervical cancer and 100 000 deaths in some of the highest-burden countries. Interpretation Large between-country disparities exist for HPV vaccination, with countries with the most to gain yet to introduce national HPV vaccination. Support from the GAVI Alliance could help to reduce such disparities, but a substantial burden will remain even after presently projected vaccine introductions

Model Comparisons of the Effectiveness and Cost-Effectiveness of Vaccination: A Systematic Review of the Literature.

OBJECTIVES: To describe all published articles that have conducted comparisons of model-based effectiveness and cost-effectiveness results in the field of vaccination. Specific objectives were to 1) describe the methodologies used and 2) identify the strengths and limitations of the studies. METHODS: We systematically searched MEDLINE and Embase databases for studies that compared predictions of effectiveness and cost-effectiveness of vaccination of two or more mathematical models. We categorized studies into two groups on the basis of their data source for comparison (previously published results or new simulation results) and performed a qualitative synthesis of study conclusions. RESULTS: We identified 115 eligible articles (only 5% generated new simulations from the reviewed models) examining the effectiveness and cost-effectiveness of vaccination against 14 pathogens (69% of studies examined human papillomavirus, influenza, and/or pneumococcal vaccines). The goal of most of studies was to summarize evidence for vaccination policy decisions, and cost-effectiveness was the most frequent outcome examined. Only 33%, 25%, and 3% of studies followed a systematic approach to identify eligible studies, assessed the quality of studies, and performed a quantitative synthesis of results, respectively. A greater proportion of model comparisons using published studies followed a systematic approach to identify eligible studies and to assess their quality, whereas more studies using new simulations performed quantitative synthesis of results and identified drivers of model conclusions. Most comparative modeling studies concluded that vaccination was cost-effective. CONCLUSIONS: Given the variability in methods used to conduct/report comparative modeling studies, guidelines are required to enhance their quality and transparency and to provide better tools for decision making

Capturing Budget Impact Considerations Within Economic Evaluations: A Systematic Review of Economic Evaluations of Rotavirus Vaccine in Low- and Middle-Income Countries and a Proposed Assessment Framework.

BACKGROUND: In low- and middle-income countries, budget impact is an important criterion for funding new interventions, particularly for large public health investments such as new vaccines. However, budget impact analyses remain less frequently conducted and less well researched than cost-effectiveness analyses. OBJECTIVE: The objective of this study was to fill the gap in research on budget impact analyses by assessing (1) the quality of stand-alone budget impact analyses, and (2) the feasibility of extending cost-effectiveness analyses to capture budget impact. METHODS: We developed a budget impact analysis checklist and scoring system for budget impact analyses, which we then adapted for cost-effectiveness analyses, based on current International Society for Pharmacoeconomics and Outcomes Research Task Force recommendations. We applied both budget impact analysis and cost-effectiveness analysis checklists and scoring systems to examine the extent to which existing economic evaluations provide sufficient evidence about budget impact to enable decision making. We used rotavirus vaccination as an illustrative case in which low- and middle-income countries uptake has been limited despite demonstrated cost effectiveness. A systematic literature review was conducted to identify economic evaluations of rotavirus vaccine in low- and middle-income countries published between January 2000 and February 2017. We critically appraised the quality of budget impact analyses, and assessed the extension of cost-effectiveness analyses to provide useful budget impact information. RESULTS: Six budget impact analyses and 60 cost-effectiveness analyses were identified. Budget impact analyses adhered to most International Society for Pharmacoeconomics and Outcomes Research recommendations, with key exceptions being provision of undiscounted financial streams for each budget period and model validation. Most cost-effectiveness analyses could not be extended to provide useful budget impact information; cost-effectiveness analyses also rarely presented undiscounted annual costs, or estimated financial streams during the first years of programme scale-up. CONCLUSIONS: Cost-effectiveness analyses vastly outnumber budget impact analyses of rotavirus vaccination, despite both being critical for policy decision making. Straightforward changes to the presentation of cost-effectiveness analyses results could facilitate their adaptation into budget impact analyses

Costs of delivering human papillomavirus vaccination to schoolgirls in Mwanza Region, Tanzania.

BACKGROUND: Cervical cancer is the leading cause of female cancer-related deaths in Tanzania. Vaccination against human papillomavirus (HPV) offers a new opportunity to control this disease. This study aimed to estimate the costs of a school-based HPV vaccination project in three districts in Mwanza Region (NCT ID: NCT01173900), Tanzania and to model incremental scaled-up costs of a regional vaccination program. METHODS: We first conducted a top-down cost analysis of the vaccination project, comparing observed costs of age-based (girls born in 1998) and class-based (class 6) vaccine delivery in a total of 134 primary schools. Based on the observed project costs, we then modeled incremental costs of a scaled-up vaccination program for Mwanza Region from the perspective of the Tanzanian government, assuming that HPV vaccines would be delivered through the Expanded Programme on Immunization (EPI). RESULTS: Total economic project costs for delivering 3 doses of HPV vaccine to 4,211 girls were estimated at about US$349,400 (including a vaccine price of US$5 per dose). Costs per fully-immunized girl were lower for class-based delivery than for age-based delivery. Incremental economic scaled-up costs for class-based vaccination of 50,290 girls in Mwanza Region were estimated at US$1.3 million. Economic scaled-up costs per fully-immunized girl were US$26.41, including HPV vaccine at US$5 per dose. Excluding vaccine costs, vaccine could be delivered at an incremental economic cost of US$3.09 per dose and US$9.76 per fully-immunized girl. Financial scaled-up costs, excluding costs of the vaccine and salaries of existing staff were estimated at US$1.73 per dose. CONCLUSIONS: Project costs of class-based vaccination were found to be below those of age-based vaccination because of more eligible girls being identified and higher vaccine uptake. We estimate that vaccine can be delivered at costs that would make HPV vaccination a very cost-effective intervention. Potentially, integrating HPV vaccine delivery with cost-effective school-based health interventions and a reduction of vaccine price below US$5 per dose would further reduce the costs per fully HPV-immunized girl

Rotavirus vaccines contribute towards universal health coverage in a mixed public-private healthcare system.

OBJECTIVES: To evaluate rotavirus vaccination in Malaysia from the household's perspective. The extended cost-effectiveness analysis (ECEA) framework quantifies the broader value of universal vaccination starting with non-health benefits such as financial risk protection and equity. These dimensions better enable decision-makers to evaluate policy on the public finance of health programmes. METHODS: The incidence, health service utilisation and household expenditure related to rotavirus gastroenteritis according to national income quintiles were obtained from local data sources. Multiple birth cohorts were distributed into income quintiles and followed from birth over the first five years of life in a multicohort, static model. RESULTS: We found that the rich pay more out of pocket (OOP) than the poor, as the rich use more expensive private care. OOP payments among the poorest although small are high as a proportion of household income. Rotavirus vaccination results in substantial reduction in rotavirus episodes and expenditure and provides financial risk protection to all income groups. Poverty reduction benefits are concentrated amongst the poorest two income quintiles. CONCLUSION: We propose that universal vaccination complements health financing reforms in strengthening Universal Health Coverage (UHC). ECEA provides an important tool to understand the implications of vaccination for UHC, beyond traditional considerations of economic efficiency

Lifetime health effects and costs of diabetes treatment

BACKGROUND: This article presents cost-effectiveness analyses of the major diabetes interventions as formulated in the revised Dutch guidelines for diabetes type 2 patients in primary and secondary care. The analyses consider two types of care: diabetes control and the treatment of complications, each at current care level and according to the guidelines. METHODS: A validated probabilistic diabetes model describes diabetes and its complications over a lifetime in the Dutch population, computing quality-adjusted life years and medical costs. Effectiveness data and costs of diabetes interventions are from observational current care studies and intensive care experiments. Lifetime consequences of in total sixteen intervention mixes are compared with a baseline glycaemic control of 10% HBA1C. RESULTS: The interventions may reduce the cumulative incidence of blindness, lower-extremity amputation, and end-stage renal disease by >70% in primary care and >60% in secondary care. All primary care guidelines together add 0.8 quality-adjusted life years per lifetime. CONCLUSION: In case of few resources, treating complications according to guidelines yields the most health benefits. Current care of diabetes complications is inefficient. If there are sufficient resources, countries may implement all guidelines, also on diabetes control, and improve efficiency in diabetes care

Stakeholders' perception on including broader economic impact of vaccines in economic evaluations in low and middle income countries: a mixed methods study.

BACKGROUND: Current health economic evaluation guidelines mainly concentrate on immediate health gains and cost savings for the individual involved in the intervention. However, it has been argued that these guidelines are too narrow to capture the full impact of vaccination in low and middle income countries. The inclusion of broader economic impact of vaccines (BEIV) has therefore been proposed. Some examples of these are productivity-related gains, macro-economic impact, and different externalities. Despite their potency, the extent to which such benefits can and should be incorporated into economic evaluations of vaccination is still unclear. This mixed methods study aims to assess the relevance of BEIV to different stakeholders involved in the vaccine introduction decision making process. METHODS: In this mixed method study an internet based survey was sent to attendees of the New and Underutilized Vaccines Initiative meeting in Montreux, Switzerland in 2011. Additionally, semi-structured interviews of 15 minutes each were conducted during the meeting. Study participants included decision makers, experts and funders of vaccines and immunization programs in low and middle income countries. Descriptive analysis of the survey, along with identification of common themes and factors extracted from the interviews and open survey questions was undertaken. RESULTS: Evidence on macro-economic impact, burden of disease and ecological effects were perceived as being most valuable towards aiding decision making for vaccine introduction by the 26 survey respondents. The 14 interviewees highlighted the importance of burden of disease and different types of indirect effects. Furthermore, some new interpretations of BEIVs were discussed, such as the potential negative impact of wastage during immunization programs and the idea of using vaccines as a platform for delivering other types of health interventions. Interviewees also highlighted the importance of using a broader perspective in connection to measuring economic impacts, particularly when attempting to derive the value of newer, more expensive vaccines. CONCLUSION: According to participants, BEIVs were seen as being equally important as traditional outcome measures used in cost-effectiveness analyses. Such insight can be used to shape research agendas within this field and to eventually create broader, more inclusive practical guidelines for economic evaluations of vaccines