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Institute of Medicine (US) Committee on Preventing the Global Epidemic of Cardiovascular Disease: Meeting the Challenges in Developing Countries; Fuster V, Kelly BB, editors. Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health. Washington (DC): National Academies Press (US); 2010.

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Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health.

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7Making Choices to Reduce the Burden of Cardiovascular Disease

It is clear from preceding chapters that the health and economic burden of cardiovascular disease (CVD) is high. This burden is likely to rise and remain unacceptably high in developing countries unless bold moves are made to implement policies and programs to contain the growth in prevalence of CVD and other chronic diseases, to develop and implement affordable and accessible health services and technology, and to reduce the financial risks to individuals and economies.

Aggressively reducing population and individual CVD risks would not only help low and middle income countries avert a potential crisis by reducing their chronic disease burden, it could also be viewed as an opportunity to improve both their economies and their public health. However, many developing countries face a difficult challenge: to make further headway against infectious diseases and other health concerns where they remain rampant while transforming health systems to accomplish chronic disease prevention and care. Very limited resources are available for health in developing countries, and there are great gaps in meeting needs. Therefore, the strategy in developing countries should be to seek low-cost approaches with a high potential return on investment to achieve structural and behavioral changes to reduce risk, and low-cost technology and health delivery to effectively treat and manage CVD.

There is a particular urgency to the need to identify and implement those interventions that can reap the biggest CVD reduction benefits in low and middle income countries while at the same time offering good “value for money.” Many of these countries are confronting a mounting gap between the dual disease burden they experience and the ability of their health systems to deliver adequate care. Other countries are making headway as they and/or donors increase resource allocations to health. In both instances, informed choices about what the available resources will buy can better align needed and realized health improvements.

ECONOMIC INFORMATION TO HELP ALLOCATE RESOURCES

Economic measurements and analysis are critically important to inform decisions both about allocating resources and choosing among alternative solutions to the problem within and beyond the health sector. The health economics literature relies almost exclusively on cost-effectiveness measures to assess value for money. Cost-effectiveness analysis of interventions can be an important tool for choosing among interventions targeted to the same outcomes, and the first section of this chapter summarizes the available cost-effectiveness evidence for CVD interventions in low and middle income countries. However, cost-effectiveness provides little information about the affordability of given interventions or the actual value to the beneficiaries, and it does not allow for ready comparisons of interventions across different sectors and different health and development priorities. The potential return on investment needs to be assessed within a broad socioeconomic context, and guidance derived from cost-effectiveness analysis may be superseded by broader policy choices for allocating resources across competing priorities within the parameters that society sets for achieving better health and well-being. Economic benefit–cost analysis can be used to balance tradeoffs in choosing among alternatives, such as new technologies or investments in structural and policy changes. However, the analytical and data demands are much higher, and there are almost no cost–benefit studies available from developing countries on CVD interventions. Ultimately, decisions about how to prioritize investments will necessitate carefully defining feasible options for change and determining the willingness of stakeholders to shift resources to implement those changes.

Summary of Cost-Effectiveness Evidence1

The preceding chapters have provided a thorough summary of the relevant CVD interventions under consideration in low and middle income countries. This section discusses the available evidence on their cost-effectiveness, drawing primarily on two rapid reviews commissioned for this report, which built on and updated major recent efforts such as the Disease Control Priorities Project (DCP2) (Musgrove and Fox-Rushby, 2006) and the WHO initiative on Choosing Interventions That are Cost-effective (CHOICE) (WHO, 2010).2 While there is a large body of evidence on the cost-effectiveness of CVD-related interventions in developed countries, this chapter considers only evidence with an explicit focus on low and middle income countries.

Most of the available studies identified in the commissioned reviews were focused on clinical prevention strategies and case management for individuals, with far fewer studies on population-based prevention approaches. Overall, most studies in both of these categories focused on risk-factor reduction.

About half the economic studies relied on modeling analysis using estimated cost assumptions and secondary data for intervention effectiveness and epidemiological conditions rather than on primary empirical data on costs and effectiveness from observational trials or randomized controlled trials in the setting of interest. In these models, developing-country data was the source for most of the epidemiological data, but developed countries were the source of data for intervention effectiveness. The advantages and limitations of these secondary versus primary analyses will be discussed further in the final section of this chapter on future research needs.

It is also important to note that cost-effectiveness studies are difficult to compare because the threshold of what is considered cost-effective varies (the standard is 3× the per capita gross domestic product [GDP] for the country, but 1× GDP is sometimes used). In addition, the outcome measures and comparator are often not the same across studies (the standard comparator is either no intervention or current standard care in the country). Different approaches for economic evaluation are also used, as well as different measures to express cost-effectiveness (the standard is an incremental cost-effectiveness ratio [ICER] reporting the cost per averted disability-adjusted life year [DALY] or quality-adjusted life year [QALY], but an average cost-effectiveness ratio [CER] is also used).

Cost-Effectiveness of Population-Based and Other Lifestyle Interventions

Population-based and other public health interventions typically target nutrition, physical activity, and tobacco risk-factor reduction. There has been remarkably little research on non-clinical, population-based approaches, such as legislative actions, education campaigns, or health promotion through social marketing, as a way to tackle CVD in developing countries. Changes in health policy are beginning to be observed in developed countries such as the United Kingdom, Finland, and the United States. New strategies are being implemented, such as legislation for salt reduction and labeling of food (Karppanen and Mervaala, 2006), and some analysis has been done about the potential revenue and dietary benefits of taxes on sugared drinks and junk food (Brownell and Frieden, 2009) as well as the potential cost-effectiveness of community-based physical activity programs in the United States (Roux et al., 2008).

However, most of these strategies have yet to be implemented with a rigorous economic evaluation component. In addition, since interventions targeted to change health behaviors are highly dependent on political, cultural, infrastructural, and other system-related aspects, it is deemed less feasible to assume effectiveness results from studies in developed regions can be applied to developing regions than is commonly accepted for clinical effectiveness evidence (Jamison et al., 2006). In pharmaceutical research, for example, a common assumption is that a drug affecting biomedical processes would have approximately identical effects, irrespective of the context in which it is applied. This is less likely to be the case for a health communication campaign or for legislative or regulatory approaches.

Nonetheless, evidence from both modeling and some primary economic analysis is building that population-level interventions targeted to reduce CVD are likely to be cost-effective in low and middle income countries. Table 7.5a at the end of this chapter summarizes the cost-effectiveness results for population-based CVD interventions in a developing-country setting.

TABLE 7.5a. Summary of Economic Analyses for Population-Based and Other Lifestyle CVD Intervention Approaches for Low and Middle Income Countries.

TABLE 7.5a

Summary of Economic Analyses for Population-Based and Other Lifestyle CVD Intervention Approaches for Low and Middle Income Countries.

The antitobacco regulatory interventions, such as taxation, smoke-free public places, restrictions on marketing, and youth cessation are strongly supported. In particular, taxation and legislation options have been relatively well evaluated, certainly for developed regions and countries but also for developing-country settings (Chisholm et al., 2006). Those include reviews such as an article by Shibuya et al. (2003) and the Disease Control Priorities in Developing Countries publication (Jha et al., 2006), both of which describe an increase in tobacco tax as the most cost-effective strategy to reduce smoking prevalence, followed by comprehensive advertisement campaigns and bans on smoking in public places. Tobacco taxes combined with smoking and advertising bans is also cost-effective (Gaziano, 2008; Lai et al., 2007). A modeling study also showed cost savings from a community-based pharmacist-driven education and counseling program for prevention of CVD risk from smoking among high-risk groups of men and women in Thailand (Thavorn and Chaiyakunapruk, 2008).

A number of studies have found food regulation (including regulation of salt or substitution of transfats) to be highly cost-effective, even cost-saving. These studies included cooperation among government, industry, and consumer organizations to reduce the salt content in bread in Argentina (Rubinstein et al., 2009) and salt reduction in processed foods through industry agreements or legislation in South-East Asia, Latin America, and Sub-Saharan Africa (Gaziano, 2008; Murray et al., 2003). However, the few studies of this type that exist have not conducted a thorough examination of the true costs of achieving policy or regulatory change, which can be high during the policy advocacy phase and then generally diminish.

Promoting physical activity is a CVD prevention intervention that has been largely overlooked by economic evaluation. The Agita São Paulo program, described in Chapter 5, is known globally as an effective intervention to promote physical activity in Brazil. It was evaluated by the World Bank and also found to be cost-effective (Matsudo et al., 2006). In a more narrow approach, a randomized controlled trial of home-based physical activity education for rehabilitation of post-MI coronary patients in Brazil showed significant improvements in all domains at a low cost (Salvetti et al., 2008).

Educational campaigns for outcomes beyond tobacco use are also shown as highly cost-effective in the few studies of this type (mainly addressing high blood pressure, high cholesterol, and lowering body mass index [BMI]), and some are even cost-saving. Cost-effectiveness modeling of health education programs for multi-risk reduction in multiple regions demonstrated positive results (Murray et al., 2003). Salt reduction through communication and mass media programs were deemed likely to be cost-effective, as well as similar programs for tobacco control, in a range of low and middle income countries at about $0.40 per person per day (Asaria et al., 2007). A population-based social marketing study with experimental and control groups in Thailand shows effective hypertension risk reduction at very low cost when village health workers were mobilized with trained health workers (Getpreechaswas et al., 2007). Bi-weekly home counseling visits by a trained health professional in Mexico were also very cost-effective in reducing hypertension (García-Peña et al., 2002). A community-based primary prevention program in Beijing to alter food intake also showed cost savings (Huang et al., 2001). However, the reported ICERs for health education interventions were quite variable. This suggests a degree of variation and uncertainty in the parameters used for such studies. It is also difficult to judge the effects of mass education programs due to difficulties in assessing numbers of persons reached.

In summary, legislated reductions in salt and transfats in foods, tobacco taxation and restrictions, and health education campaigns all show some promising cost-effectiveness across a range of countries. However, except for antitobacco measures in developed countries, the cost-effectiveness of population-based interventions has been measured almost entirely through modeling techniques. These few studies are generally supportive of one another, but need confirmation from a broad range of empirical examples using primary data.

Cost-Effectiveness of Pharmaceutical and Other Clinical Interventions

Cost-effectiveness results for pharmaceutical and other clinical interventions for CVD in a developing-country setting are summarized in Table 7.5b at the end of this chapter. These strategies have been the predominant focus of economic analysis to date. In summary, the cost-effectiveness of pharmaceutical interventions to reduce CVD depends heavily on the risk group targeted. Prevention with pharmacological treatment for high-risk individuals is likely to be cost-effective across a range of country settings. Prevention with pharmacological treatment is not generally likely to be cost-effective for reducing risk factors in individuals without high absolute risk.

TABLE 7.5b. Summary of Cost Effectiveness Evidence for Pharmaceutical Intervention Approaches Against Cardiovascular Disease for Low and Middle Income Countries.

TABLE 7.5b

Summary of Cost Effectiveness Evidence for Pharmaceutical Intervention Approaches Against Cardiovascular Disease for Low and Middle Income Countries.

In conclusion, just as with the available intervention effectiveness reviewed in Chapter 5, there are limitations on the available economic analyses. These limitations guide future needs, which will be discussed later in this chapter. However, they do not preclude intervening now, and some determinations can be made about priorities for investment in intervention approaches. Indeed, both intervention and economic evidence support selected population-based interventions and pharmacological interventions for high-risk target groups to reduce CVD and hypertension. Although there are interventions that are likely to be cost-effective, it remains difficult to make comparisons to draw definitive conclusions about which interventions are the most cost-effective. This is both due to the challenges of making comparisons across the available studies and due to gaps in the economic evaluation literature in some important areas of intervention that have promise for effective impact on health outcomes.

Economic Information to Compare Prevention and Treatment Strategies

When comparing interventions to reduce the burden of CVD, it is tempting to try to look to the economic analysis to make a determination about whether it would be more advisable to invest in prevention strategies or treatment strategies. To many, prevention seems like the most promising investment because of its potential for avoidance of costly treatment interventions (technology, hospitalization, etc.). On the other hand, many see potential for a high return on investment in terms of health outcomes from advances in technology and health services if made more available in the developing world.

The evidence does not provide a definitive choice between prevention and treatment on economic grounds. There is economic evidence to support the cost-effectiveness of implementation on a wider scale of certain pharmaceutical strategies in developing countries (Gaziano et al., 2007). However, the issue of how best to approach implementation remains unresolved (Gaziano, 2007), which was also a central message of Chapter 5. There is also an unresolved discussion between those who advocate for the targeting of patients with a single but high-risk factor (e.g., high blood pressure) and those arguing for an overall absolute risk approach (e.g., on the basis of 10-year risk of CVD), independent from the particular risk factor. These are debates on medical effectiveness, but they also spill over into the economic evaluation literature, as evidenced by the differences in therapeutic combinations and assessments of patient risks across the cost-effectiveness studies summarized in Table 7.5b at the end of this chapter. In addition, there has been limited economic evaluation of screening strategies, a necessary component of scaling up interventions to target individuals at high risk that is certainly not without cost. Therefore, considering the potential costs of scaling up and screening for risk factors as well as for delivering adequate supplies of drugs for persons identified through screening, there is still room for debate about whether pharmaceutical interventions are the right priority. In addition, factors such as the risk of adverse events in such a large untreated population, inequalities in access to care, and limited patient and system compliance need to be addressed.

Despite a general endorsement of scaling up pharmaceutical support from the economic perspective, it is also important to be mindful of the limitations of a strategy focused narrowly on pharmaceutical support. Clinically managed chronic care can be expensive and is often necessary for the remaining lifetime of an individual. In addition, clincial approaches targeted at segments of the population with higher risk (e.g., based on blood pressure) miss the typically large number of people below the threshold but nevertheless with risk factor-related ailments (Blackburn, 1983; Kottke et al., 1985; Puska et al., 1985; Schooler et al., 1997). A population-based approach, like one aiming for a reduction in salt intake, would at least in principle effect change in the entire population and not only those in the population at the highest risk, and in principle over the long term this could reduce the ultimate need for costly clinical interventions. This may render such population-based approaches attractive because of the rationale for a likelihood of cost-effectiveness over time, although the population risk reduction with these approaches can be limited (Neal et al., 2007).

In reality, the issue of prevention versus treatment is probably not the most useful question. The epidemic of CVD is not going to be addressed through the eradication of the disease in an entire population, the way one might hope to eradicate a disease with an acute infectious etiology. Instead, the goals for reducing the population burden of disease are that a greater proportion of the population can avoid developing the disease, that the average age of onset can be delayed, and that morbidity, mortality, and financial consequences due to CVD can be reduced. Indeed, the totality of the available epidemiological, intervention, and economic evidence support a balanced approach in which health promotion and prevention is emphasized but which also recognizes the need for effective, appropriate, quality delivery of medical interventions for risk reduction and treatment. The distribution of investment in health promotion, prevention, and treatment approaches within that balance is something that will need to be determined based on the specific needs, capacity, and political and societal will of the stakeholder making the investment. The potential for improving the information available to inform this decision making is described in the final section of this chapter.

Costs to Address Gaps in CVD Needs3

One of the key questions asked by policy makers wishing to make investments to address an unmet health need is, “What will it cost?” The total cost to reduce the burden of disease is determined not only by the costs of interventions but also by the number of affected people in need of them. The difference between the proportion of the population that could benefit from intervention and that currently receiving such intervention is commonly called the “treatment gap.” This treatment gap can be defined in terms of any intervention approach, including population-based approaches and individual prevention or treatment. Determining the treatment gap depends on knowing four key parameters: prevalence in the population of a health condition; proportion of people with the condition that are treated and, conversely, the proportion that are not; proportion with the condition under control and, conversely the proportion not controlled; and cost of treatment. It is generally recognized that, particularly in developing countries, there are significant numbers of individuals who are in need but have not benefited from potentially effective and cost-effective interventions to treat or reduce risk for CVD and related chronic diseases. However, this treatment gap would need to be more specifically defined and linked to accurate cost information in order to more precisely determine the investment that would be required. This section of the chapter offers a discussion of illustrative evidence to demonstrate the analytic approaches available to determine what it will cost to reduce the burden of CVD in developing countries.

A short review was commissioned for this report of the treatment gaps in the developing world for CVD and related risk factors (Jan and Hayes, 2009).4 The objective of the review was to assess the feasibility of an approach to investment appraisal that brings together two sources of data: the nature and the scale of treatment gaps in CVD in developing countries and the costs and cost-effectiveness of a range of interventions. The review extracted evidence on treatment gaps from systematic reviews of treatment gaps for hypertension, comparative studies of risk reduction in individuals with CVD, and numerous studies of treatment gaps for specific diseases and risk factors in individual countries. A fair degree of standardization in the approaches taken to measuring treatment gaps enables some comparisons to be made across studies, but the appropriateness of generalizations about average overall rates is limited because the studies are derived from multiple sources across different settings and involve varying methodologies. In addition, although the available evidence establishes the treatment gap for some risk factors related to CVD, there remain methodological problems that make it difficult to reliably link the current evidence on treatment gaps with the current evidence on costs and cost-effectiveness in order to determine the total investment required to fill the treatment gap.

The studies extracted in this review provided sufficient information to assess treatment gaps in some countries for some risk factors for CVD, including hypertension, high cholesterol, and diabetes as well as ongoing risk reduction in individuals with CVD. The results show large treatment gaps. For other risk factors, such as obesity, lack of physical activity, and tobacco use, there is sufficient data to derive population estimates that indicate the potential numbers of individuals who could benefit from added intervention but not sufficient data on the numbers receiving interventions to determine a treatment gap.

For hypertension, a number of recent studies indicate that hypertension prevalence is on average around 30 percent of the adult population in developing countries, with a wide variation across settings, from 5 percent in rural India to 70 percent in Poland (Kearney et al., 2004). The available evidence indicates that around 30 percent of individuals with reported hypertension across developing countries are receiving treatment—thus a 70 percent treatment gap (Pereira et al., 2009). This gap varies not only across countries but also over time. For example, evidence from China indicates treatment levels at 17 percent in urban populations and 5 percent in rural populations in 1991 (Whelton et al., 2004), but levels were more recently observed at 28.2 percent overall in 2000–2001 (Gu et al., 2002). These variations demonstrate the difficulties with generalizing over time and across countries that are at differing stages of epidemiological and economic transition.

An interesting finding from the studies reviewed is that even in countries with relatively high proportions of patients getting treatment, the percent of hypertension under control is sometimes low. Across countries, around 30 percent of those receiving treatment in developing countries have their hypertension under control, which is similar to the rate of around 35 percent that has been observed in developed countries (Pereira et al., 2009).

Although most studies review gaps in treatment using pharmaceutical interventions to reduce hypertension, recent evidence from China through the InterASIA study sheds some light on treatment coverage for nonpharmacotherapies. This study found that 47.2 percent of people with hypertension were using at least one of five nonpharmacological approaches, including salt reduction, weight loss or weight control therapies, exercise, alcohol reduction, and potassium supplementation at the time of the survey (Gu et al., 2002).

For cholesterol and diabetes, data is much less available than for hypertension. Evidence for both derives mainly from recent systematic reviews in China. The prevalence of moderate hypercholesterolemia (defined as ≥ 200 mg/dl total cholesterol) was 32.8 percent and the prevalence of high hypercholesterolemia (defined as ≥ 240 mg/dl total cholesterol or taking cholesterol lowering medications) was 9.0 percent. For those with moderately high cholesterol levels, 3.5 percent of men and 3.4 percent of women were receiving treatment, while 14 percent of men and 11.6 percent of women with very high cholesterol levels were receiving treatment. This suggests significant treatment gaps as high as 96 percent or 86 percent, depending on the criteria used for treatment (He et al., 2004). The prevalence of diabetes in China is around 5 percent, but only 20.3 percent are currently on treatment and 8.3 percent report being able to achieve control (Hu et al., 2008).

A study based on the WHO Study on Prevention of Recurrences of Myocardial Infarction and Stroke (PREMISE) project examined the level at which patients already diagnosed with coronary heart disease or cerebrovascular disease are being treated for ongoing risk-factor reduction. This study was conducted across 10 countries (Brazil, Egypt, India, Indonesia, Iran, Pakistan, Russia, Sri Lanka, Tunisia, and Turkey) and assessed patients’ awareness and uptake of lifestyle and pharmacological interventions (Mendis et al., 2005). Table 7.1a shows the percentage of patients with coronary heart disease and cerbrovascular disease on pharmaceutical interventions for risk reduction. For both conditions, the levels of medication use are highest for aspirin and lowest for statins. Also, although there was a high level of awareness of the benefits of various lifestyle interventions, uptake of these interventions was variable (Table 7.1b). Looking at a country-specific analysis, India was quite similar to the overall findings in terms of pharmaceutical interventions (Table 7.1c). However, another study in rural India showed much lower levels of patients on medication antiplatelet therapy, blood pressure-lowering drugs, and statins (Joshi et al., 2009) (Table 7.1d).

TABLE 7.1a. Patients on Medications in 10 Low and Middle Income Countries.

TABLE 7.1a

Patients on Medications in 10 Low and Middle Income Countries.

TABLE 7.1b. Awareness and Uptake of Lifestyle Interventions in Patients in 10 Low and Middle Income Countries.

TABLE 7.1b

Awareness and Uptake of Lifestyle Interventions in Patients in 10 Low and Middle Income Countries.

TABLE 7.1c. Patients on Medications in India.

TABLE 7.1c

Patients on Medications in India.

TABLE 7.1d. Patients on Medications in Rural India.

TABLE 7.1d

Patients on Medications in Rural India.

Estimated Costs to Fill the Hypertension Treatment Gap in 10 Countries

In addition to the review of the available literature described earlier, a modeling analysis of treatment gaps for hypertension and costs to achieve reductions in blood pressure in select countries representing the different World Bank regions was commissioned for this report (Gaziano and Kim, 2009). This analysis was not focused on aggregated findings to determine global treatment gap and costs, but rather on country-specific analyses of the kind that might be most useful for decisions about funding and implementing country-specific policies and programs.

Based on a meta-analysis of published articles on nationally representative health surveys, Table 7.2 shows the prevalence, awareness, treatment, and control rates for hypertension in adult populations across 9 developing countries, including at least 1 country in each of the World Health Organization Developing World Regions, as well as in the United States as a comparison. Overall, control of hypertension is poor, with most countries having control rates of less than 15 percent. In the 10 countries examined in the commissioned analysis there were nearly 400 million individuals with hypertension, and it was currently controlled in fewer than 50 million (Gaziano and Kim, 2009).

TABLE 7.2. Global Prevalence, Awareness, and Control Rates for Hypertension.

TABLE 7.2

Global Prevalence, Awareness, and Control Rates for Hypertension.

The goal of the analysis was to provide, for each of the countries examined, an estimate of the likely total costs to address this “treatment gap” by achieving reduction of hypertension using one of two strategies. The first is a treatment program, where all individuals with hypertension would be treated and given medications to successfully control their high blood pressure. The second is a lifestyle change strategy aimed at reducing the mean blood pressure across the population. This analysis estimates only the cost of additional control and treatment programs; it does not report or evaluate current expenditures on efforts already implemented for drug treatment and population strategies to decrease blood pressure (Gaziano and Kim, 2009).

Table 7.3 shows the estimated total cost per country for the first approach, to treat and control all those with a blood pressure greater than 140 mmHg to a level below 140 mmHg, where the benefits of reducing risk are most robust. The estimate of costs reflects the overall population; the prevalence of hypertension; the blood pressure distribution in the country; and country-specific costs of care, including lab costs, health worker wages, use of facilities, and the costs of medication regimens administered according to current treatment guidelines and tailored to the starting blood pressure. It is important to note that this estimate only includes costs to achieve control once diagnosed and does not include the costs of screening, which would add necessary expenditures to identify those in need of treatment (Gaziano and Kim, 2009).

TABLE 7.3. Estimated Annual Cost to Control Hypertension with Medication.

TABLE 7.3

Estimated Annual Cost to Control Hypertension with Medication.

The total estimated cost that would be accrued to meet treatment needs is also shown in Table 7.3 as a percentage of the nation’s gross domestic product (GDP) in 2008 and as a percentage of the nation’s total health expenditures in 2006. The estimated costs relative to both GDP and total health expenditures show considerable variability across countries, with India and Chile standing out at the high end of the range.

In summary, the available evidence from a sample of developing countries shows relatively low treatment coverage of the estimated at-risk population, with an even lower proportion of cases of hypertension under control. The costs that would need to be added to current health expenditures in order to address this unmet need are variable across countries. In some countries it may seem like a manageable shift in expenditures, whereas in others it is much higher. India is a particularly alarming case. The current estimate is that 28 percent of the population is hypertensive, but only half of those individuals are aware of their condition and half of that number receive treatment. Most alarmingly, only 7 percent of those treated have their blood pressure under control. Using current costs, it is estimated that India would need to add on additional spending of almost 3 percent of health care expenditures to control hypertension. This suggests that addressing the unmet needs for screening and effective treatment would require a much more effective health system to reduce those costs.

Hypertension can also be successfully averted through lifestyle and dietary changes, and implementing nation-wide strategies to promote lifestyle changes would possibly reduce mean blood pressure in a population. A population-wide strategy, by reducing the incidence of hypertension, could also produce cost reductions in the long term due to fewer patients requiring the treatment costs estimated above. The most reliable cost estimates currently available for population-based lifestyle changes to reduce hypertension are for salt-reduction strategies (Asaria et al., 2007). For the analysis commissioned for this report, a population-wide salt-reduction strategy assumed to result in a 3 mmHg reduction in mean population blood pressure was used to estimate the costs that would be accrued to achieve this in each country, as shown in Table 7.4 (Gaziano and Kim, 2009).

TABLE 7.4. Estimated Total Cost to Achieve Mean Systolic Blood Pressure Reduction via Population Salt-Reduction Strategies (Intl $ millions).

TABLE 7.4

Estimated Total Cost to Achieve Mean Systolic Blood Pressure Reduction via Population Salt-Reduction Strategies (Intl $ millions).

Combining population-based strategies with treatment approaches theoretically should produce some cost efficiencies, as one outcome of the population-based approaches would be to reduce the number in need of treatment. Successfully filling the treatment gap for hypertension could also potentially produce cost savings in the longer term by reducing not only the burden of CVD but also the burden of complications of other chronic diseases, such as diabetes and kidney failure.

This analysis provided an example of country-specific analyses of one risk factor for CVD. Further analyses using country-specific costs and treatment needs, taking into account other risk factors and other disease endpoints, would serve to inform the investment priorities of national governments and other stakeholders.

FUTURE NEEDS IN ECONOMIC ANALYSIS OF INTERVENTIONS5

As the previous sections demonstrate, economic analysis is a critical tool for evaluating different interventions to address CVD in developing countries, but there has been relatively little carried out in those settings, and what exists is not easily comparable (Behrman et al., 2009). Given the growing importance of CVD and other chronic diseases in developing countries, and the potential to seriously thwart or delay economic development—further research will be critical to determine, for specific countries, which investments are needed to address CVD and which investments are likely to produce the highest returns.

Conclusion 7.1: Governments need better health-sector and intersectoral economic analysis to guide decision making about resource allocations among health conditions and interventions.

This section details several high-priority areas for economic research on CVD.

Costs, Cost-Effectiveness, and Potential for Return on Investment in Public Health and Health Systems

The available evidence for low and middle income countries on cost-effectiveness of CVD interventions is informative and valuable, but scarce when compared to developed countries (Schwappach et al., 2007). Although the number of published economic evaluations of interventions for CVD in developing countries has increased substantially in recent years, beyond antitobacco strategies, the gaps in the evidence base limit the ability to conclude with confidence general recommendations that would apply to CVD in developing countries across countries and across all available intervention approaches. This is because there is a lack of primary economic analyses in developing countries, variation in costs and population health across countries, and reason to question whether and how the evidence-based strategies to prevent and manage CVD that have been shown to be cost-effective in developed countries are applicable in a developing-country context where resources are more limited and health care systems are less strong and more variable.

The available research studies are biased toward individual interventions, mostly pharmaceutical, targeted at persons with already established risk factors. Approaches using a population-based, public health intervention strategy, such as communications strategies or legislative actions, have not undergone cost-effectiveness analysis as extensively in developing- country contexts, especially using primary effectiveness data. However, the available studies do show promise for the likely cost-effectiveness of these approaches. There are even fewer cost-effectiveness studies from developing countries on multi-level and multivalent CVD interventions.

Therefore, as described in the following section, there is a pressing need for research efforts to improve methodologies to evaluate the transferability of cost-effectiveness evidence from developed to developing settings and to increase the primary evidence base for cost-effectiveness evaluations in developing-country settings. There is also a need to expand economic analyses to be more inclusive of countries and regions that have a high burden of disease but are not well represented in the available economic literature, such as former Soviet Republics and the Middle East. Increasing the research in these and other neglected regions should be part of an international global health strategy to address CVD.

Improving the Use of Modeling to Transfer Cost-Effectiveness Evidence from Developed to Developing Countries

It is not realistic to expect primary economic evaluations to be conducted for every intervention in every developing country. The use of modeling methodologies to transfer results from developed to developing countries and between developing countries, as well as to estimate long- term effects, remains a necessary alternative that has and will continue to be highly informative, as described earlier in this chapter. However, there are several major challenges to using this approach to guide implementation choices at the national level in low and middle income countries. These include differences in health care costs across countries, differential effectiveness of interventions in different settings, differential disease prevalence, differential valuation of outcomes, and differential efficiency in implementing interventions. As a result, the applicability of economic modeling results is highly dependent on the methods applied and the assumptions that are incorporated in the model.

Broadly speaking, there is a need to improve modeling methods to take into account the potential effects, including regional/country-level variations, of demographics, epidemiological transition, emerging changes in availability of technology, and financial conditions. In particular, there are two key areas that emerge as a priority to improve models used to evaluate interventions to address CVD.

First, the available modeling analyses almost exclusively calculate effectiveness based on studies conducted in developed countries. Therefore, there is a great need to perform effectiveness studies in developing-country settings and for these results to inform economic models. This is especially important for interventions targeted to changing health behaviors and those that use methods such as communications, which are highly dependent on cultural and infrastructural characteristics. In addition, for interventions to target high-risk individuals, the effectiveness of strategies for screening/identification must be taken into account. The predominance of the use of developed-country effectiveness data in these models is due primarily to the lack of effectiveness data for CVD interventions in developing countries, as has been described in Chapters 5 and 6. Efforts to fill this knowledge gap will also serve to improve the quality of economic analyses by making more relevant secondary data available.

Second, and similarly, many models calculate resource utilization based on implemented data from developed countries. Therefore, there is also a great need for modeling that instead calculates resource utilization based on implemented data from developing-country settings. This is true for all types of interventions. Even interventions for which effectiveness data is arguably more readily transferred across populations and stage of development (such as pharmaceutical interventions), developing-country settings will have vastly different implementation resources and infrastructure. Addressing this gap will require greater research efforts to project, or ideally measure, the actual costs of implementing interventions in at least a representative sample of developing countries. This includes realistic assessments of the costs of implementing non-clinical primary prevention and population-based strategies in these settings, the true costs of which can be very difficult to determine. As above for effectiveness, this also means that to conduct realistic assessments of the costs of interventions to target high-risk individuals, costs of screening/identification must be taken into account.

Although the challenges of transferring evidence using modeling methodologies is acknowledged by both the Disease Control Priorities Project (Musgrove and Fox-Rushby, 2006) and the WHO CHOICE project (Evans and Ulasevich, 2005), there are currently no validated methodologies or consensus guidelines within the scientific community on how to handle this uncertainty in modeling interventions for developing countries. Consensus standards for conducting and reviewing evaluations among researchers and journals in the field could elevate the quality of evidence and allow for greater comparability across studies. A potential model for such standards could come from the task force on research practices in modeling studies of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) (Weinstein et al., 2003). At a minimum, the capacity for this kind of data to be useful for policy decisions would be greatly improved if information about the assumptions influencing the model and the sources of secondary data were more clearly stated in the published literature. In both reviews commissioned by this committee, for example, the authors found that there was a lack of full information in many modeling studies.

Increasing the Evidence Base of Primary Economic Analyses of Interventions Conducted in Developing-Country Settings

Modeling methodologies to transfer results from developed to developing countries and between developing countries will continue to be an important approach to assessing the most cost-effective ways to address CVD. However, it is also a crucial goal to increase the evidence base of primary economic analyses from developing countries. Once again, this relates directly to the need for more primary intervention evidence from developing countries. Therefore, it is important that steps taken to increase effectiveness and implementation research in these countries be accompanied by an emphasis on conducting economic analyses as part of the evaluation, especially for population-based and public health approaches such as community-based interventions, communications strategies, or legislative actions. These are areas where economic evidence is lacking and the specificity of the setting potentially has the largest impact on effectiveness. This should be an achievable goal if made a priority by global health funders (see Chapter 8).

Making the Evidence More Useful for Policy Makers

Few of the currently available economic analyses adopted a comprehensive perspective in their analysis. In general, the more comprehensive a study is, the easier it is for decision makers to compare the intervention to other alternatives available for funding. In developing countries, budgets are highly constrained, and not only is CVD competing with other health priorities, but also all investments in health care are in crucial competition with other budgetary sectors, such as education or public infrastructure. A greater focus on comprehensive evaluations would facilitate policy decisions.

One way to address this is through the expression of health benefits in comprehensive units (such as “life-years gained” or the surrogate measure of QALYs or DALYs) rather than CVD-specific measures that may be easier to measure but are difficult to compare to other interventions within or outside the health care sector. In addition, the utility to policy makers can be improved through the use of methods such as benefit–cost analysis, which offers the capability of expressing all benefits of an intervention, occurring in the health care sector or not, in monetary units. With respect to affordability and adherence to treatment, the use of willingness to pay approaches could also be informative, especially in health care systems in which patients are required to contribute some or all of the costs. For example, in a rare willingness-to-pay analysis from a developing country, patients in China were not willing to pay the annual cost of $73 for anti-hypertensive medicine until their 5-year absolute risk for CVD exceeded 35 percent (Tang et al., 2009).

This also applies to the economic perspective applied in the analysis, which relates to the question of who will incur the costs of an intervention and who will receive the benefits. Key perspectives that are relevant to policy makers include, for example, the health care provider, the patient, the government, third-party payers, and the societal perspective, which has not yet been explicitly applied to the evaluation of interventions for CVD in the developing world.

Defining Resource Needs

As described in this chapter, there has not been sufficient analysis to determine what it will cost to reduce the burden of CVD in developing countries. Ideally, this type of analysis—linking evidence of prevention and disease management needs (the “treatment gap”) with evidence of costs and cost-effectiveness—would be carried out at a country level to inform the implementation of interventions to address high-priority health conditions. If provided within a specific macroeconomic and epidemiological context, it would give decision makers an indication of not only what options represent the “best buys” but also how investment in such buys is anticipated to contribute to a reduction in the overall burden of disease. For instance it would indicate that, for a defined population, $X invested in treatment Y would be needed to eliminate a particular treatment gap. Health and finance policy makers would then have clear guidance on where to shift resources to achieve the maximum health benefit. There is very limited available evidence for this type of health investment appraisal. Therefore, there needs to be an ongoing program of research in this area, especially given the rapid changes over time in risk-factor prevalence, treatment levels (and gaps), technology, and costs of treatment.

Recommendation: Define Resource Needs

The Global Alliance for Chronic Disease should commission and coordinate case studies of the CVD financing needs for five to seven countries representing different geographical regions, stages of the CVD epidemic, and stages of development. These studies should require a comprehensive assessment of the future financial needs within the health, public health, and agricultural systems to prevent and reduce the burden of CVD and related chronic diseases. Several scenarios for different prevention and treatment efforts, technology choices, and demographic trends should be evaluated. These assessments should explicitly establish the gap between current investments and future investment needs, focusing on how to maximize population health gains. These initial case studies should establish an analytical framework with the goal of expanding beyond the initial pilot countries.

A number of considerations should be taken into account for these studies and other future research to accurately project costs to address untreated CVD. First, as mentioned earlier, if estimates of treatment gaps are to offer specific guidance to decision makers they must be contextualized based on local circumstances—including demographics, epidemiological transition, and financial conditions—and must be provided in conjunction with cost and cost-effectiveness analysis. The reasons for treatment gaps are likely to be varied and differ according to context and intervention. Factors such as cost, geographical access, availability of treatment technologies, and provider incentives are likely to be significant determinants. At present the treatment gap literature focuses mainly on patient awareness. Further work should be conducted into investigating the broader determinants of treatment gaps because they are crucial in establishing any policy response.

Second, existing evidence of treatment gaps generally focuses on a single risk factor. However, ideally this assessment would take into account multiple risk factors based on an absolute risk approach. This includes reorienting risk-factor prevalence studies so that they are based on absolute risk rather than on the prevalence of a single risk factor. This would also allow such studies to be better linked with most of the available cost-effectiveness evidence. However, it is important to consider that risk-factor measures required by models such as the risk assessment tool based on the Framingham Study may not always be available or may be cost-prohibitive in a low income setting (e.g., if they include lab tests). These measures also may not be readily applicable to different populations in developing countries. A priority for future research is the development of specific risk- prediction screening tools appropriate for low income settings and for such forms of risk stratification to then be reflected in cost-effectiveness and treatment gap analysis.

In addition, the role of system constraints in determining treatment gaps needs to be assessed (e.g., geographical and financial constraints on access to health care; human resource constraints such as lack of staff, misaligned incentives for providers, lack of infrastructure, and inadequate regulatory systems), as well as the effectiveness and cost-effectiveness of addressing these constraints. Better information is also needed on the extrapolation of cost-effectiveness estimates in relation to the scaling up of interventions to meet the treatment gap. Assumptions made in economic modeling of constant returns to scale and of continued and constant treatment effect are currently not well supported by evidence. Finally, studies on costs and cost-effectiveness of interventions to address CVD are generally health sector-specific. Further research is required to investigate intersectoral approaches that work beyond conventional health-sector boundaries as potential innovations in interventions to address the treatment gap.

CONCLUSION

Given limited resources and political energy to allocate to CVD programming, many countries will want to focus their efforts on goals that are economically feasible, have the highest likelihood of intervention success, and have the largest morbidity impact. The limitations on the available evidence do not preclude intervening now as initial priorities can be ascertained. Indeed, the totality of intervention and economic analysis suggests that substantial progress in reducing CVD can be made in the near term through a prioritized subset of intervention approaches—if they can be successfully and efficiently adapted and implemented. These include staretegies for tobacco control, reduction of salt in the food supply and in consumption, and improved delivery of clinical prevention using pharmaceutical interventions in high-risk patients, especially if linked to existing health systems strengthening efforts. The evidence for lowered CVD morbidity associated with achieving these priority goals is credible, there are examples of successful implementation of programs in each of these focus areas with the potential to be adapted for low and middle income countries, and economic analyses have shown that they are likely to be cost-effective.

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This section is based in part on papers written for the committee by Marc Suhrcke et al. and by Stephen Jan and Alison Hayes.

Searches were conducted using the PubMed and EconLit databases. In addition, the references of retrieved articles and the relevant publications of the DCP2 and the WHO CHOICE program were hand-searched for relevant articles. The search strategy consisted of free text and MeSH terms related to economic evaluation and CVD disease or risk factors endpoints, filtered for the occurrence of the term “developing countries” or any country name defined as middle or low income country according to the World Bank definition. Only published full economic evaluations were included.

This section is based in part on papers written for the committee by Stephen Jan and Alison Hayes and by Thomas Gaziano and Grace Kim.

The authors conducted a non-systematic search of the published and grey literature using PubMed and Google Scholar databases as well as hand-searches and snowballing. Search terms included “treatment gap and chronic diseases” and “treatment gap and cardiovascular disease.”

This section is based in part on papers written for the committee by Stephen Jan and Alison Hayes, by Marc Suhrcke et al., and by Thomas Gaziano and Grace Kim.

Footnotes

1

This section is based in part on papers written for the committee by Marc Suhrcke et al. and by Stephen Jan and Alison Hayes.

2

Searches were conducted using the PubMed and EconLit databases. In addition, the references of retrieved articles and the relevant publications of the DCP2 and the WHO CHOICE program were hand-searched for relevant articles. The search strategy consisted of free text and MeSH terms related to economic evaluation and CVD disease or risk factors endpoints, filtered for the occurrence of the term “developing countries” or any country name defined as middle or low income country according to the World Bank definition. Only published full economic evaluations were included.

3

This section is based in part on papers written for the committee by Stephen Jan and Alison Hayes and by Thomas Gaziano and Grace Kim.

4

The authors conducted a non-systematic search of the published and grey literature using PubMed and Google Scholar databases as well as hand-searches and snowballing. Search terms included “treatment gap and chronic diseases” and “treatment gap and cardiovascular disease.”

5

This section is based in part on papers written for the committee by Stephen Jan and Alison Hayes, by Marc Suhrcke et al., and by Thomas Gaziano and Grace Kim.

Copyright © 2010, National Academy of Sciences.
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