Meeting Report: WHO Workshop on modelling global mortality and aetiology estimates of enteric pathogens in children under five. Cape Town, 28-29th November 2018.

Investment in vaccine product development should be guided by up-to-date and transparent global burden of disease estimates, which are also fundamental to policy recommendation and vaccine introduction decisions. For low- and middle-income countries (LMICs), vaccine prioritization is primarily driven by the number of deaths caused by different pathogens. Enteric diseases are known to be a major cause of death in LMICs. The two main modelling groups providing mortality estimates for enteric diseases are the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle and the Maternal Child Epidemiology Estimation (MCEE) group, led by Johns Hopkins Bloomberg School of Public Health. Whilst previous global diarrhoea mortality estimates for under five-year-olds from these two groups were closely aligned, more recent estimates for 2016 have diverged, particularly with respect to numbers of deaths attributable to different enteric pathogens. This has impacted prioritization and investment decisions for vaccines in the development pipeline. The mission of the Product Development for Vaccines Advisory Committee (PDVAC) at the World Health Organisation (WHO) is to accelerate product development of vaccines and technologies that are urgently needed and ensure they are appropriately targeted for use in LMICs. At their 2018 meeting, PDVAC recommended the formation of an independent working group of subject matter experts to explore the reasons for the difference between the IHME and MCEE estimates, and to assess the respective strengths and limitations of the estimation approaches adopted, including a review of the data on which the estimates are based. Here, we report on the proceedings and recommendations from a consultation with the working group of experts, the IHME and MCEE modelling groups, and other key stakeholders. We briefly review the methodological approaches of both groups and provide a series of proposals for investigating the drivers for the differences in enteric disease burden estimates.

Are current cost-effectiveness thresholds for low- and middle-income countries useful? Examples from the world of vaccines.

The World Health Organization's CHOosing Interventions that are Cost Effective (WHO-CHOICE) thresholds for averting a disability-adjusted life-year of one to three times per capita income have been widely cited and used as a measure of cost effectiveness in evaluations of vaccination for low- and middle-income countries (LMICs). These thresholds were based upon criteria set out by the WHO Commission on Macroeconomics and Health, which reflected the potential economic returns of interventions. The CHOICE project sought to evaluate a variety of health interventions at a subregional level and classify them into broad categories to help assist decision makers, but the utility of the thresholds for within-country decision making for individual interventions (given budgetary constraints) has not been adequately explored. To examine whether the 'WHO-CHOICE thresholds' reflect funding decisions, we examined the results of two recent reviews of cost-effectiveness analyses of human papillomavirus and rotavirus vaccination in LMICs, and we assessed whether the results of these studies were reflected in funding decisions for these vaccination programmes. We found that in many cases, programmes that were deemed cost effective were not subsequently implemented in the country. We consider the implications of this finding, the advantages and disadvantages of alternative methods to estimate thresholds, and how cost perspectives and the funders of healthcare may impact on these choices.

Socio-cultural determinants of anticipated acceptance of an oral cholera vaccine in Western Kenya.

Determinants of anticipated acceptance of an oral cholera vaccine (OCV) were studied in urban and rural communities of Western Kenya. An explanatory model interview administered to 379 community residents assessed anticipated vaccine acceptance at various prices from no cost to full-cost recovery, socio-cultural features of cholera and social characteristics. Nearly all (99%) residents indicated willingness to accept a no-cost OCV, 95% at a price of US$ 0·8, 73% at US$ 4·2 and 59% at US$ 8·4. Logistic regression models analysed socio-cultural determinants of anticipated OCV acceptance. Prominence of non-specific symptoms for cholera was negatively associated with acceptance. A cholera-specific symptom (thirst), self-help referring to prayer, income and education were positively associated. In the high-cost model, education was no longer significant and reliance on herbal treatment was a significant determinant of vaccine non-acceptance. Findings suggest high motivation for OCVs, if affordable. Socio-cultural determinants are better predictors of anticipated acceptance than socio-demographic factors alone.

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.

[Initiating insulin therapy in patients with diabetes mellitus type 2: in a transmural setting is at least as effective as in an outpatient setting; a retrospective study with a 4-year follow-up]. / Het instellen op insuline van patiënten met diabetes mellitus type 2: in een transmurale organisatievorm minstens even effectief als poliklinisch; een retrospectief onderzoek met 4 jaar follow-up.

OBJECTIVE: Assessing whether the initiation of insulin therapy in patients with diabetes mellitus type 2 can be delivered as effectively in a structured transmural care model as in the more usual outpatients structure. DESIGN: Retrospective comparative cohort study. METHOD: In 1997 data were collected from 52 patients with diabetes mellitus type 2 all of whom were above 40 years of age and transferred to insulin therapy in 1993: 25 in a transmural care setting and 27 in an outpatients setting, both in Amsterdam, the Netherlands. Both groups were treated according to one protocol concerning the initiation and monitoring of insulin therapy, treatment goals and follow-up. Outcome measures were: percentage of glycated haemoglobin (HbA1c), health status, self-care behaviour and patient satisfaction. In 1993 the mean age was (transmural/outpatients setting): 67.5/65.3 years; percentage of men: 32%/48%; mean duration of diabetes: 7.3/10.6 years; HbA1c: 9.1%/9.3%; mean body mass index: 27.4/29.1 kg/m2. RESULTS: In the period 1993-1997 the mean HbA1c decreased from 9.1% to 7.2% in the transmural care group and from 9.3% to 7.6% in the outpatients care group (both: p = 0.000). The percentage of patients with poor glycaemic control (HbA1c > 8%) decreased from 60 to 8 in the transmural care group and from 59 to 15 in the outpatients care group. The percentage of patients with good glycaemic control (HbA1c < 7%) increased from 4 to 52 in the transmural care group and from 11 to 30 in the outpatients care group. No statistically significant differences were found between the patient groups with respect to health status, self-care behaviour and patient satisfaction. CONCLUSION: The transfer of patients with diabetes mellitus type 2 insulin therapy in a shared care setting was at least as effective as in an outpatients setting.

Stochastic league tables: communicating cost-effectiveness results to decision-makers.

The presentation of the results of uncertainty analysis in cost-effectiveness analysis (CEA) in the literature has been relatively academic with little attention paid to the question of how decision-makers should interpret the information particularly when confidence intervals overlap. This question is especially relevant to sectorial CEA providing information on the costs and effects of a wide range of interventions. This paper introduces stochastic league tables to inform decision-makers about the probability that a specific intervention would be included in the optimal mix of interventions for various levels of resource availability, taking into account the uncertainty surrounding costs and effectiveness. This information helps decision-makers decide on the relative attractiveness of different intervention mixes, and also on the implications for trading gains in efficiency for gains in other goals such as reducing health inequalities and increasing health system responsiveness.

Critical issues in the economic evaluation of interventions against communicable diseases.

Economic appraisal seeks to provide policy-makers with guidance about how scarce resources can be used to derive the greatest possible social benefit. Its use in the health sector has increased dramatically over the last decade although much of it has been focused on the problems of the more developed countries. The relatively sparse literature on communicable diseases has been dominated by interventions related to HIV/AIDS, hepatitis, malaria and tropical diseases. Reviews of this literature from the perspective of specific conditions such as Hepatitis B are already available, and recently the entire literature has been evaluated against the technical criteria for economic evaluations published in standard textbooks. Accordingly, this paper focuses on issues which would make economic appraisal more useful to policy-makers than it currently is. Given that few countries have the resources to undertake all the necessary analysis in their own settings, it is important that studies in one setting are undertaken in a way that allow generalisability to similar settings. Some of the most important challenges this poses for cost-effectiveness analysis (CEA) are identified. Firstly, incremental analysis is appropriate to local decision making when policy-makers are constrained to keep the current interventions and can consider only marginal improvements. However, it does not allow re-evaluation of existing interventions and is not transferable across settings. A version of Generalised CEA is proposed as an alternative. Secondly, data on costs and effectiveness are often not presented appropriately. The challenge for effectiveness is to adjust the evidence from efficacy studies to allow for different patient or population groups, and local variations in adherence, coverage, and infrastructure. For costs, it is important for studies to report the physical resources used in an intervention as well as unit prices. Thirdly, some long-term effects are still not well incorporated into CEA, especially those affecting child development and drug resistance. These questions are technically challenging and require more concerted efforts over the next few years. Finally, it is important for analysts to provide decision-makers with estimates of the resources that would be required to implement interventions claimed to be cost-effective. These improvements would better enable the evidence from economic analyses to enter the policy debate and be weighed against the other goals and objectives of the health system when allocating scarce resources.

Indirect costs of back pain in the Netherlands: a comparison of the human capital method with the friction cost method.

In this study we estimated the indirect costs of back pain in 1991 in The Netherlands on the basis of two approaches: the traditionally used human capital method and the more recently developed friction cost method. The indirect costs of illness were defined as the value of production losses of paid labour and related costs to society due to back pain. The results of this study in 1991 in The Netherlands show that the short-term indirect costs estimated by the human capital method were more than three times as high as the indirect costs estimated by the friction cost method (US$ 4.6 billion vs. USS 1.5 billion, respectively). The lower estimate of indirect costs when using the friction cost method is mainly due to the fact that in this method actual production losses are estimated during a relatively short friction period, which is defined as the period needed to restore the initial production level. In contrast with the human capital method, long-term absenteeism and disability do not induce additional costs when applying the friction cost method. Since the friction cost method takes into account that employees can be replaced, we believe that this method produces a more accurate estimate of indirect costs than the human capital method. Notwithstanding the resulting decrease in indirect costs of back pain, these costs are still impressive, representing 0.28% of the GNP in The Netherlands in 1991. As a consequence, but particularly stimulated by structural changes in the Dutch social security system, policies aimed at reducing indirect costs of back pain, increasingly concentrate on the development and evaluation of interventions early after the onset of disease. This is complemented, on the one hand, by the development of clinical guidelines for the management of back pain in primary care and, on the other hand, by governmental policies aimed at reintegration of chronically ill in the labour force.

Application of geographical information systems to co-analysis of disease and economic resources: dengue and malaria in Thailand.

Two vector-borne communicable diseases, malaria and dengue, are among a number of diseases of particular importance in relation to economic development in Southeast Asia and thus need to be assessed in relation to economic parameters in the region. Geographical Information Systems (GIS) provide one means of comparing disease and resource data versus time and place, to facilitate rapid visualization by planners and administrators. Given that Thailand is a global epicenter of multidrug resistant falciparum malaria and of dengue hemorrhagic fever, both of which are mosquito-borne, application of GIS methods to these two diseases gives opportunity for comparison of resource needs and allocation in relation to disease epidemiologic patterns. This study examined per capita gross provincial product (GPPpc) and health care resources in relation to geographic distribution of malaria and dengue in Thailand. The two diseases vary greatly in overall seasonal patterns and in relation to provincial economic status, and present differing demands on resource utilization: planned integration of control of malaria and dengue could utilize such analyses in relation to resource sharing and consideration of allocative efficiency. The concentration of malaria (and to a lesser extent dengue) along international border areas underscores the desirability of multi-country coordination of disease management and control programs. Because socio-economic and disease data are collected by quite different means and in different time frames, there are some limitations to the dynamic interpolation of these two broad data sets, but useful inferences can be drawn from this approach for application to overall planning, at both national and multi-country levels.