Assessing the Evidence on the Cost-Effectiveness of Interventions
Figures 2.2 and 2.3 display results gathered from other chapters on cost-effectiveness ratios. In some cases, interventions are grouped on the basis of their similarity and whether they were personal interventions or population-based interventions. For instance, all population-based programs to prevent HIV transmission via contaminated blood and needles were grouped as a single intervention. Note that the cost-effectiveness ranges should not be interpreted as statistical confidence intervals but rather as a range of "best estimates" of cost-effectiveness incorporating variation across interventions included in the cluster. Ranges for the cost-effectiveness ratios are also attributable to variations in the epidemiological settings in which these interventions were evaluated. For example, a population-based primary intervention in an area of low prevalence is likely to be less cost-effective than the same intervention in a region of high prevalence. Figure 2.2 reflects sets of interventions dealing with high-burden diseases, and figure 2.3 deals with relatively low-burden diseases.
[Figure
2.2]
[Figure
2.3]
Within each figure, intervention clusters are displayed in the order of increasing cost-effectiveness. Additional information on the setting, objective, and target population of each intervention cluster for which cost-effectiveness has been calculated is provided in annex 2.B. The tables in annex 2.B also provide information on the quality of the evidence on which the data presented are based. Furthermore, the annex tables present information on potentially avertable deaths and DALYs if the coverage of these interventions were expanded by a further 20 percentage points of the relevant population (scaling up from 62 percent means reaching 82 percent, not 74 percent, of the pertinent population). Care should be taken not to confuse this information with the current burden of the underlying disease, on which basis interventions were divided into high-burden and low-burden diseases (figures 2.2 and 2.3, respectively).5 For example, a cost-effective treatment for CVD has only limited scope for increased scale of intervention in countries with a low burden of this disease. At the same time, in many parts of Asia and Sub-Saharan Africa, even though HIV treatment is not a highly cost-effective intervention, it deserves attention because of its sizable potential for lowering the disease burden.
The tables in annex 2.C summarize information on intervention clusters for which cost-effectiveness was evaluated with a metric other than DALYs. For these interventions too, details of setting, objective, target population, and quality of the evidence have been provided. Given the difficulty in comparing these intervention clusters with those evaluated using DALYs, they are excluded from figures 2.2-2.5.
[Figure
2.5]
Observations about specific interventions follow. Ranges of cost-effectiveness estimates shown reflect geographical variations across regions.
Prevention and Control of Tuberculosis
The treatment of all forms of active tuberculosis (TB) using the directly observed treatment strategy based on short-course chemotherapy is among the most cost-effective of all interventions available to improve health in LMICs (US$5 to US$35 per DALY averted except in Europe and Central Asia) (box 2.1). The bacillus Calmette-Guerin (BCG) vaccination for children is also cost-effective (US$40 to US$170 per DALY averted), but its main effect is to reduce the burden of severe TB in children (TB meningitis and miliary TB). Because BCG has relatively little effect on the huge burden of pulmonary TB in adults—which constitutes the major cause of ill health resulting from Mycobacterium tuberculosis—development of a new vaccine that targets adults is highly desirable. The treatment of latent TB in patients uninfected with HIV is relatively cost-ineffective (US$4,000 to US$25,000 per DALY averted), but it is more cost-effective for groups of patients who are coinfected with TB and HIV. In the context of TB control, antiretroviral therapy for HIV/AIDS is likely to be useful in extending the lives of patients successfully treated for TB.
Multidrug-resistant TB is much more expensive to treat than drug-susceptible TB—2 to 10 times the cost of standard first-line regimens for drug-susceptible TB—and this is one reason why priority should be given to preventing its emergence and spread. The management of drug resistance through the use of a standardized regimen that includes second-line drugs costs roughly US$70 to US$450 per DALY averted. Individualized treatment regimens for multidrug-resistant TB—that is, with drug combinations adjusted to the resistance pattern of each patient—are more costly but usually yield higher cure rates. Individualized treatment is harder to implement on a large scale but may not be less cost-effective than standardized treatment with regimens that include second-line drugs. The set of interventions needed to manage drug-resistant TB and TB associated with HIV requires higher levels of investment than the basic directly observed treatment strategy, but its cost is still typically less than US$1 for each day of healthy life gained. Thus, a strong economic argument exists for integrating such interventions into an enhanced strategy for TB control.
Prevention and Treatment of HIV/AIDS
Despite the scale and relentless progression of the HIV/AIDS epidemic, important strides have been made in developing cost-effective interventions for both prevention and treatment.
Prevention
Although remarkably little rigorous evaluation has been conducted, population-based programs to prevent HIV/AIDS appear to be highly cost-effective approaches in countries with high HIV/AIDS prevalence where the epidemic is generalized. These programs include voluntary testing and counseling (US$14 to US$261 per DALY averted); peer-based programs to educate high-risk groups, including sex workers and injecting drug users (US$1 to US$74 per DALY averted); and social marketing, promotion, and distribution of condoms (US$19 to US$205 per DALY averted). Programs to improve blood and needle safety, while highly cost-effective (US$4 to US$51 per DALY averted), are limited in terms of the burden of disease they can avert.
Prevention of mother-to-child transmission using a single dose of nevirapine in generalized epidemic settings (US$6 to US$12 per DALY averted) stands out for its combination of well-documented high cost-effectiveness and significant avertable infections and deaths. Treatment of sexually transmitted infections to lower the risk of HIV transmission, although less well proven, also appears to be highly cost-effective (US$16 to US$105 per DALY averted).
Treatment
For care of people living with HIV/AIDS, treatment of most infectious opportunistic infections is cost-effective (US$10 to US$500 per DALY averted), with treatment becoming significantly more cost-effective for patients who also have access to antiretroviral treatment. Few studies evaluate the cost-effectiveness of providing antiretroviral treatment, and even these are limited to clinical trial settings and are not directly applicable to the resource-poor settings in which anti-retroviral treatment is being expanded. Economic evaluation of the cost-effectiveness of antiretroviral treatments based only on health outcomes for the treated patient is incomplete because of the large nonhealth impacts of HIV/AIDS and the effect of treatment on prevention of HIV transmission.
The cost-effectiveness of antiretroviral treatments is highly variable across settings as a function of drug prices and adherence rates. In low-cost settings with high adherence rates, anti-retroviral treatment is moderately cost-effective (US$350 to US$500 per DALY averted); however, it can be a significantly poor value for resources spent in low-adherence settings if drug resistance is allowed to emerge and proliferate. Little is known about how to achieve necessary adherence levels (80 to 90 percent) at large scale at an affordable cost in low-income settings. To this end, research on effective, low-cost interventions to achieve long-term adherence to antiretroviral treatments (using support groups and other complementary interventions) in resource-poor settings is an urgent priority.
Childhood Illnesses and Mortality among Children under Five
Neonatal mortality rates and mortality rates for children under five can be reduced by large margins, at an affordable cost, by using interventions proven effective in low-income settings. Improvements are likely to come from increasing the coverage of preventive measures, such as breastfeeding, and from expanding the scope of existing childhood vaccines beyond the traditional six antigens in areas where existing coverage is relatively high and where new antigens address diseases of significant burden, particularly pneumococcal vaccines. Curative interventions—including case management of acute respiratory infections, malaria, and diarrhea—hold promise for lowering the 6 million preventable deaths each year in this age group.
Neonatal Mortality
An estimated 4 million deaths occur during the first 28 days of life, accounting for 38 percent of all deaths of children under five. Causes include infections (36 percent, including neonatal sepsis, pneumonia, diarrhea, and tetanus), preterm birth (27 percent), and asphyxia (23 percent). Intensive care is not required to save most of these babies. Developed countries and some low-income countries—for instance, Sri Lanka—have achieved neonatal mortality rates of 15 per 1,000 without intensive care, which is less than a third of current neonatal mortality rates in Sub-Saharan Africa.
Adding a set of community-based interventions—including promoting healthy behaviors, such as breastfeeding, and providing extra care of moderately small babies at home through cleanliness, warmth, and exclusive breastfeeding, plus community-based management of acute respiratory infections—to the standard maternal and child health package is likely to be highly effective. The cost of a year of life saved using this approach could be as low as US$100 to US$257 in India (US$221 to US$568 per DALY averted) and US$100 to US$270 in Sub-Saharan Africa (US$183 to US$493 per DALY averted). Use of these approaches is feasible now in most countries. Adding a clinical package that includes essential newborn care (warmth, cleanliness, and immediate breastfeeding); neonatal resuscitation; facility-based care of small newborns; and emergency care of ill newborns to the maternal and child health package has been shown to be highly cost-effective in India (US$11 to US$265 per year of life saved, or US$24 to US$585 per DALY averted) and Sub-Saharan Africa (US$25 to US$360 per year of life saved, or US$46 to US$657 per DALY averted); however, clinical care will require significant initial investment to raise coverage.
Basic resuscitation of newborns using a self-inflating bag that is available for as little as US$5 in LMICs can save lives at low cost in areas where a midwife is available. Providing two tetanus toxoid immunizations costing less than US$0.20 each to all pregnant women would avert more than 250,000 deaths at low cost and is eminently achievable. Improving maternal and child health services delivered through a combination of family- and community-level care, outreach, and clinical care will improve the survival of newborns and children and reduce stillbirths and maternal deaths.
Vaccinations
Childhood vaccinations, long recognized as among the most cost-effective uses of limited health resources in low-income countries, prevented more than 3 million deaths in 2001. National immunization programs traditionally have included vaccines against TB, diphtheria, tetanus, pertussis, poliomyelitis, and measles at a cost per fully immunized child of US$13 to US$24, depending on coverage levels and type of delivery strategy. The total cost in developing countries for national programs in 2001 ranged from US$717 million to US$1.4 billion, with an estimated cost per death averted ranging by region from under US$275 (under US$10 per DALY averted) in Sub-Saharan Africa and South Asia to US$1,754 (US$20 per DALY averted) in Europe and Central Asia.
The cost-effectiveness of scaling up immunization coverage with the traditional Expanded Program on Immunization (EPI) vaccines is highly dependent on the underlying prevalence of illness, starting coverage levels and trajectories, and mix of delivery strategies (whether facility-based strategies, campaigns, or mobile and outreach modalities). The cost per death averted varies by region, from US$162 in Africa to more than US$1,600 in Eastern Europe. Cost-effectiveness ratios are less than US$20 per DALY averted in all regions other than Europe and Central Asia. The cost-effectiveness of the tetanus toxoid vaccine also varies widely by region from under US$400 per death averted and under US$14 per DALY averted in Sub-Saharan Africa and South Asia to more than US$190,000 per death averted and more than US$15,000 per DALY averted in Europe and Central Asia.
Adding additional antigens to national programs has been successfully accomplished in many countries. Expanding the vaccination schedule to include a second opportunity for measles through either routine or campaign-based approaches costs between US$23 and US$228 per death averted and under US$4 per DALY averted in regions other than Europe and Central Asia. Other new vaccines are less cost-effective because of their high unit costs per dose, but they may be worthwhile, especially in regions of high disease prevalence. For instance, the pentavalent vaccine (diphtheria, pertussis, tetanus, hepatitis B, and Haemophilus influenzae type B) was estimated to have a cost per death averted ranging from US$1,433 to greater than US$40,000 and cost-effectiveness of US$42 per DALY averted in Sub-Saharan Africa and greater than US$245 per DALY averted in other regions. The cost of adding a yellow fever vaccine ranges from US$834 per death averted and US$26 per DALY averted in Sub-Saharan Africa to US$2,810 per death averted and US$39 per DALY averted in Latin America and the Caribbean.
Because certain regions and countries contain the largest burden of disease, such as measles in India and Nigeria, targeting scarce public health resources to those geographic areas could potentially yield high returns to investment. Although immunization may have relatively low incremental cost-effective ratios, the total budget requirements for maintaining or increasing coverage rates, as well as for introducing new vaccines, can account for a large share of government health budgets.
The cost-effectiveness ratios of vaccination interventions presented here are based on estimates of their current costs and effectiveness; but they could change substantially with changing costs and the development of new interventions. For instance, multivalent pneumococcal conjugate vaccines have shown the potential to reduce the incidence of invasive pneumococcal disease while lowering the need for antibiotic use and the likelihood of drug resistance. The current price of these vaccines makes them expensive to most people in the developing world. However, with future price decreases, these vaccines could be adopted widely and could markedly lower the impact of the most common causes of morbidity and mortality in children under five (excluding the neonatal period). Moreover, new vaccines being developed could be included in the EPI schedule, including vaccines that protect against rotavirus, malaria, human papilloma virus associated with cervical cancer, HIV/AIDS, and dengue. With future demonstrations of reasonable cost-effectiveness, these vaccines could become a component of the set of attractive interventions.
Acute Respiratory Infections
Even though vaccination strategies can be cost-effective in lowering the disease burden related to acute respiratory infections, case management may also be an efficient use of financial resources, although more demanding of health system capacity. Moreover, community case management and case management at a health care facility may be of comparable cost-effectiveness. In fact, treating nonsevere pneumonia at health care facilities using a combination of oral antimicrobials and acetaminophen (US$24 to US$424 per DALY averted) is more cost-effective than a similar treatment administered at home by a health care worker (US$139 to US$733 per DALY averted). Treating severe pneumonia in a hospital facility is more expensive (US$1,486 to US$14,719 per DALY averted).
Diarrheal Disease
Among interventions against diarrheal disease during the first year of life, breastfeeding promotion programs (US$527 to US$2,001 per DALY averted), measles immunization (US$257 to US$4,565 per DALY averted), and oral rehydration therapy (US$132 to US$2,570 per DALY averted) are relatively cost-effective compared with rotavirus immunizations (US$1,402 to US$8,357 per DALY averted) and cholera immunizations (US$1,658 to US$8,274 per DALY averted). The cost-effectiveness of oral rehydration therapy is extremely sensitive to the cost of the package. The cost-effectiveness of this intervention can be as low as US$132 per DALY averted for an assumed cost per child of US$0.70. An important reason for the relatively unfavorable cost-effectiveness ratios for diarrheal disease is that significant reductions in mortality from this condition have already been achieved and further gains are likely to be more expensive.
Further improvements in water and sanitation (US$1,118 to US$14,901 per DALY averted from diarrheal disease) are generally less cost-effective in regions where access to these amenities is adequate and other interventions against diarrheal disease exist. However, in areas with little access to water and sanitation facilities, improving access can be highly cost-effective (US$94 per DALY averted for installation of hand pumps and US$270 per DALY averted for provision and promotion of basic sanitation facilities).
Inherited Disorders of Hemoglobin
Inherited hemoglobin disorders, including sickle cell anemia and the thalassemias, affect roughly 500,000 babies born each year and cause early death for many of them. Prenatal screening for sickle cell disease, which is expensive, can be replaced by much cheaper newborn screening. Antibiotic prophylaxis is moderately cost-effective at preventing death in the first few years (US$8,000 to US$12,000 per death averted, or US$300 to US$400 per DALY averted). Expensive interventions, such as bone marrow transplantation or repeated transfusions, are seldom needed. At US$10,000 or more per DALY averted, treatment for transfusion-dependent thalassemias is expensive and probably unaffordable to all but the rich in LMICs. A feasible strategy to deal with the thalassemias is to screen couples to determine their risk of having an affected child, followed by prenatal testing—a relatively expensive proposition—of couples at high risk. Information is then available to parents to help them determine whether to terminate the pregnancy. Such strategies appear to have worked in Cyprus, Greece, and Italy, all countries that formerly had a high incidence of thalassemias.
Ongoing Challenges: Malaria and Other Tropical Diseases
Despite health researchers' relative neglect of diseases predominantly found in the tropics, interventions to control—and in some cases even eliminate—these diseases rank among the most cost-effective of all available options.
Malaria
In countries where malaria is prevalent, both prevention and effective treatment of this disease are highly cost-effective and can result in large health gains. Prevention tools include insecticide-treated bednets (US$5 to US$17 per DALY averted) and indoor residual spraying where DDT, malathion, deltamethrin, or lambda-cyhalothrin is applied to surfaces inside homes as a spray or deposit for prolonged action (US$9 to US$24 per DALY averted for Sub-Saharan Africa).
Intermittent preventive treatment of malaria during pregnancy using sulfadoxine-pyrimethamine is a highly cost-effective intervention (US$13 to US$24 per DALY averted) to decrease neonatal mortality and reduce severe maternal anemia. Changing first-line treatment for malaria from chloroquine, a drug that is ineffective in many parts of the world, to artemisinin-based combinations offers the advantage of faster cures and potential reductions in transmission, with cost-effectiveness ratios of less than US$150 per DALY averted. Changing to sulfadoxine-pyrimethamine may be slightly more cost-effective initially because of the lower cost of this drug relative to artemisinin-based combinations; however, this advantage is likely to be eroded quickly because of the rapid expected growth of parasite resistance.
Lymphatic Filariasis, Onchocerciasis, and Chagas Disease
Annual mass drug administration to treat the entire population at risk for a period long enough to interrupt transmission is a cost-effective approach for eliminating lymphatic filariasis in areas of high prevalence (US$4 to US$8 per DALY averted). An alternative approach is to fortify salt with diethylcarbamazine (US$1 to US$3 per DALY averted) and to use ivermectin in countries where onchocerciasis is coendemic. Onchocerciasis control programs have been highly successful in West Africa: investigators have estimated the cost-effectiveness of community-directed ivermectin treatment programs at roughly US$6 per DALY averted when the drug has been provided free of charge. The cost of vector control to prevent—and perhaps eliminate—Chagas disease has been estimated at US$260 per DALY averted.
Leishmaniasis and African Trypanosomiasis
Feasible intervention opportunities exist even for tropical diseases for which control measures are relatively less effective. Improved case management and immunization (currently undergoing clinical trials) for dengue (US$587 to US$1,440 per DALY averted) are relatively cost-effective compared with environmental vector control (more than US$2,000 per DALY averted). Leishmaniasis treatment is also extremely cost-effective (US$315 per death averted and US$9 per DALY averted), as is treating African trypanosomiasis patients in the second stage of the disease using melarsoprol or eflornithine (US$10 to US$20 per DALY averted).
Helminthic Infections
Helminthic infections, although not a major contributor to deaths in tropical regions, have a significant effect on health, growth and physical fitness, school attendance, worker productivity, and earning potential. Mass school-based treatment of soil-transmitted helminths (Ascaris, Trichuris, and hookworm) using albendazole costs US$2 to US$9 per DALY averted. Although the cost of treating schistosomiasis with praziquantel is significantly greater (US$336 to US$692 per DALY averted), a combination of albendazole and praziquantel is extremely cost-effective (US$8 to US$19 per DALY averted).
Maternal and Neonatal Health
Given the hugely disproportionate burden of maternal and neonatal deaths in LMICs, identifying affordable, easy-to-implement interventions to prevent these deaths is a priority. Evidence from South Asia and Sub-Saharan Africa suggests that improved primary-level coverage with a package of interventions is extremely cost-effective (US$3,337 to US$6,129 per death averted and US$92 to US$148 per DALY averted). Improvements in the quality of prenatal and delivery care are of similar cost-effectiveness (US$2,729 to US$5,107 per death averted and US$82 to US$142 per DALY averted). An important finding is that improving the quality of care and expanding coverage are of comparable cost-effectiveness.
Improving Nutrition
The direct and indirect effects of undernutrition and micronutrient deficiencies account for a significant proportion of the overall burden of disease in LMICs. For the most part, interventions to provide micronutrient supplementation can prevent malnutrition in children at a fairly low cost. They include breastfeeding support programs (US$3 to US$11 per DALY averted and US$100 to US$300 per death averted) and growth monitoring and counseling (US$8 to US$11 per DALY averted). Specific micronutrient supplementation programs can be implemented either by distributing capsules or by fortifying sugar, salt, water, or other essentials. In addressing vitamin A deficiencies, capsule distribution (US$6 to US$12 per DALY averted) is more cost-effective than sugar fortification (US$33 to US$35 per DALY averted), especially in countries where the prevalence of vitamin A deficiency is low. However, fortification of salt, sugar, and cereal in the case of iron deficiency and fortification of water and salt in the case of iodine deficiency is less expensive than distributing supplements for mild deficiency, though pregnant women and severely anemic or iodine-deficient people may still require supplementation. Overall cost-effectiveness is US$66 to US$70 per DALY averted for iron fortification programs and US$34 to US$36 per DALY averted for iodine fortification programs.
Cancer Prevention and Treatment
Screening for breast cancer using clinical breast examination (CBE) is estimated to be cost-effective at US$552 per life year saved for biennial screening of women from age 40 to 60. This efficacy of CBE is related to the large percentage of tumors with a poor prognosis observed in developing countries. In this setting, CBE is estimated to be more cost-effective than mammography: mammograms every two years result in 10 percent more life years saved than annual CBE, but the cost is more than 100 percent greater. As with any screening program, cost-effectiveness is greater with higher underlying prevalence of disease.
In general, cancer prevention, when feasible, is far more cost-effective than treatment. The cost-effectiveness of initial treatment is between US$1,300 and US$6,200 per year of life saved for the more treatable cancers of the cervix, breast, oral cavity, colon, and rectum and between US$53,000 and US$163,000 per year of life saved for the less treatable cancers of the liver, lung, stomach, and esophagus. Postmastectomy radiation might be more cost-effective in developing countries, where the cost of radiation treatment can be relatively low compared to developed countries. Palliative care for terminally ill cancer patients can be a challenge in resource-constrained settings, where opioid drugs, a cost-effective option, may be in short supply. Studies from developed countries indicate that more advanced treatments to relieve pain and side effects of chemotherapy may be cost-effective under certain conditions.
Mental and Neurological Disorders
Mental disorders are a heterogeneous group of conditions with considerable variation in both the cost of the interventions and the burden reduction associated with such interventions. Interventions to treat depression, bipolar disorder, and schizophrenia rank among the least cost-effective of interventions considered in this volume. However, the potentially significant benefits to family members and to society as a whole are not captured by the DALY methodology and should be balanced against the relatively high cost of improving health of people with these disorders. For many disorders, drug treatment has been shown to be effective, especially when combined with psychosocial treatment that includes cognitive-behavioral approaches to managing symptoms and improving adherence to medications, group therapy, and family interventions.
Schizophrenia and Bipolar Disorder
Drug treatment accompanied by psychosocial treatment delivered through a community-based service was found to be the most cost-effective approach for severe mental disorders such as schizophrenia and bipolar disorder. Newer antipsychotic and mood-stabilizing drugs have recently become less expensive; even so, they are less cost-effective than drugs that have been available for many years. For example, family psychoeducation was much more cost-effective with haloperidol (US$1,743 to US$4,847 per DALY averted) compared with a newer anti-psychotic drug (risperidone) in treating schizophrenia (US$10,232 to US$14,481 per DALY averted). For bipolar affective disorder, the combination of family psychoeducation with the older medication lithium (US$1,587 to US$4,928 per DALY averted) is more cost-effective than the combination of family psychoeducation with the newer sodium valproate (US$2,765 to US$5,908 per DALY averted).
Depression and Panic Disorder
Treating the more common depressive and anxiety disorders was more cost-effective than treating the more severe disorders; the interventions were less expensive, and the reduction in disability was greater. For depression, drug therapy with tricyclic antidepressants (imipramine or amitriptyline) costs US$478 to US$1,288 per DALY averted. Managing depression as a chronic illness with case management to reduce relapses did not greatly decrease the cost-effectiveness (US$749 to US$1,760 per DALY averted). Using newer medications with fewer side effects and potentially greater compliance (an advantage if medications need to be taken long term)—for example, a generic selective serotonin reuptake inhibitor (SSRI) such as fluoxetine—increased the cost somewhat (US$1,229 to US$2,459 per DALY averted). Finally, the treatment of panic disorder using tricyclic antidepressants (US$305 to US$619 per DALY averted) and SSRIs (US$567 to US$865 per DALY averted) was more cost-effective than when combined with psychosocial treatment. Psychosocial treatment without drug treatment was of comparable cost-effectiveness (US$338 to US$927 per DALY averted).
The use of tricyclic antidepressants was more cost-effective than benzodiazepines, which are still commonly prescribed for anxiety disorders and produce dependence in many patients. Overall, the cost-effectiveness of a package of mental health interventions that addressed all four sets of disorders is between US$1,429 and US$2,902 per DALY averted, depending on the region.
Parkinson's Disease and Epilepsy
Ayurvedic treatment, a form of traditional medicine used in India, is relatively cost-effective in treating Parkinson's disease (US$750 per DALY averted). Less cost-effective interventions include a combination of levodopa and carbidopa (US$1,500 per DALY averted), which are used to treat the debilitating symptoms and delay the progress of the disease, and deep-brain stimulation (US$31,000 per DALY averted).
Cost-effective options for treating epilepsy are available, especially the use of phenobarbital to help control seizures (US$89 per DALY averted), but few eligible patients receive treatment. More expensive options, such as lamotrigine or surgery, are significantly less cost-effective than phenobarbital for first-line treatment; however, they are cost-effective for the small proportion of epilepsy patients who do not respond to phenobarbital.
Multipronged Strategy to Prevent and Treat CVD
CVD, including ischemic heart disease, congestive heart failure, and stroke, is the single most important cause of death worldwide; interventions to treat CVD are likely to account for increasingly greater proportions of health care expenditures in developing countries.
Population-based Primary Prevention
Interventions to modify lifestyles can effectively lower the risk of coronary artery disease and stroke without expensive health infrastructure. They include lowering the fat composition of the diet, limiting sodium intake, avoiding tobacco use, and engaging in regular physical activity. The costs and the effectiveness of these approaches vary widely with the socioeconomic and cultural context in which they are contemplated.
Replacing dietary trans fat from partial hydrogenation with polyunsaturated fat is likely to be extremely effective in populations in South Asia, where the intake of trans fat is high. If such replacement is done during manufacture at a relatively low cost rather than through changes in individual behavior, a cost-effectiveness ratio of US$25 to US$73 per DALY averted can be attained. Replacing saturated fat with monounsaturated fat in manufactured foods accompanied by a public education campaign is relatively expensive in the base case (US$1,865 to US$4,012 per DALY averted), although the cost per DALY averted is highly sensitive to both the relative risk reduction in CVD events as well as the cost per individual. Reducing salt in manufactured foods through a combination of legislation and education campaigns is also relatively expensive in the base case (US$1,325 to US$3,056 per DALY averted), but could be much more cost-effective in high-density populations with a high salt intake. Little evidence is available on the cost-effectiveness of programs to encourage exercise and other behavior changes by individuals.
Personal Interventions
Prevention strategies targeted at individuals at high risk for CVD—measured as a combination of nonoptimal blood pressure and cholesterol, lifestyle, and genetic risk factors—can be effective, especially when implemented in tandem with population-based measures. A previous cardiovascular event is a reliable predictor of a second event. The cost-effectiveness of primary prevention of CVD may vary greatly depending on the underlying risk factors, the age of the patient, and the cost of medications.
Single-pill combinations of blood pressure-lowering medications, statins, and aspirin offer the potential dual benefit of being highly effective at lowering the risk of CVD and facilitating patient compliance with the ongoing drug regimen. A hypothetical multidrug regimen that includes generic aspirin, a beta-blocker, a thiazide diuretic, an angiotensin-converting enzyme (ACE) inhibitor, and a statin may be implemented at a cost-effectiveness ratio of US$721 to US$1,065 per DALY averted compared with a baseline of no treatment in a population with an underlying 10-year CVD risk of 35 percent. The use of the multidrug regimen for prevention in patients with a lower underlying CVD risk improves health benefits, but costs increase more than proportionately.
Acute Management of CVD
The cost of treating acute myocardial infarction using aspirin and beta-blockers is less than US$25 per DALY averted in all regions. Relatively more expensive interventions that offer marginally greater effectiveness include the use of thrombolytics such as streptokinase (US$630 to US$730 per DALY averted) and tissue plasminogen activator (US$16,000 per DALY averted).
The combination of aspirin and the beta-blocker atenolol has been shown to be highly cost-effective in preventing the recurrence of a vascular event. The incremental cost-effectiveness ratio of sequentially adding an ACE inhibitor such as enalapril (US$660 to US$866 per DALY averted), a statin such as lovastatin (US$1,700 to US$2,000 per DALY averted), and coronary artery bypass graft (more than US$24,000 per DALY averted) to the baseline therapy is greater when hospital facilities are available. In regions with poor access to hospitals, the combination of aspirin and a beta-blocker is highly cost-effective (US$386 to US$545 per DALY averted). In all regions, treating congestive heart failure using enalapril and the beta-blocker metoprolol is also highly cost-effective (approximately US$200 per DALY averted).
Acute Management and Secondary Prevention of Stroke
The cost of treating acute ischemic stroke using aspirin is US$150 per DALY averted. Relatively cost-ineffective interventions involve the use of a tissue plasminogen activator (US$1,300 per DALY averted) and anticoagulants such as heparin or warfarin (US$2,700 per DALY averted). Aspirin is the lowest-cost option for secondary prevention of stroke (US$3.80 per single percentage point decrease in the risk of a second stroke within two years or US$70 per DALY averted). The combination of the antiplatelet medication dipyridamole and aspirin is equally cost-effective (US$93 per DALY averted). In contrast, carotid endarterectomy is expensive for secondary prevention (US$1,500 per DALY averted).
Strategies for Injury Prevention
Increasing economic development and use of motor vehicles has resulted in increases in traffic-related deaths and injuries; these events account for roughly a third of the burden from all unintentional injuries in LMICs.
Speed bumps appear to be the most cost-effective and cost less than US$5 per DALY averted in all regions if installed at the most dangerous junctions that account for 10 percent of junction deaths. Increased speeding penalties, media coverage, and enforcement of traffic laws are only slightly less cost-effective. Motorcycle helmet legislation (US$467 per DALY averted in Thailand), bicycle helmet legislation (US$107 per DALY averted in China), and improved enforcement of traffic codes through a combination of enforcement and information campaigns (US$5 to US$169 per DALY averted) are relatively more expensive but deserve greater attention, given the growing health burden associated with rising levels of vehicle ownership. Research has demonstrated that seat belts and child restraints are effective in the developed world, and lowering their costs and encouraging their routine use may improve their cost-effectiveness in LMICs.
Key interventions to reduce intentional violence, both self-inflicted (suicides) and interpersonal (homicides and war-related deaths), include changing cultural norms, reducing access to guns, and improving criminal justice and social welfare systems, but these interventions are difficult to evaluate using a cost-effectiveness framework, and a cost-benefit analysis is more appropriate. Studies of interventions targeting interpersonal violence in developed countries show that behavioral, legal, and regulatory interventions cost less than the money they save, in some cases by an order of magnitude. Providing shelters for victims of domestic violence in the United States has a benefit-cost ratio of 6.8 to 18.4. Implementing a gun registration law in Canada involved a one-time cost of US$70 million, compared with annual health-related costs of US$50 million for firearm-related injuries in that country. Interventions for troubled youths to reduce criminal activity include mentoring (with net benefits ranging from US$231 to US$4,651 per participant), family therapy (US$14,545 to US$60,721), and aggression replacement therapy (US$8,519 to US$34,071).
Policy Interventions to Lower Alcohol and Tobacco Use
The growing prevalence of smoking, especially among women in LMICs, is a serious threat to health. Interventions to reduce tobacco use are noteworthy not just because they are highly cost-effective but also because the burden of deaths and disability that they can avert is large. Tobacco control through tax increases often has dual benefits of increasing tax revenues as well as discouraging smoking initiation and encouraging smokers to quit. The cost-effectiveness of a policy to increase cigarette prices by 33 percent ranges from US$13 to US$195 per DALY averted globally, with a better cost-effectiveness ratio (US$3 to US$42 per DALY averted) in low-income countries. In comparison, nicotine replacement therapy (US$55 to US$751 per DALY averted) and nonprice interventions, including banning advertising, providing health education information, and forbidding smoking in public places, are relatively less cost-effective (US$54 to US$674 per DALY averted) in low-income countries but are still important components of any tobacco control program.
In regions with a relatively high prevalence of high-risk alcohol use—that is, Europe and Central Asia, Latin America and the Caribbean, and Sub-Saharan Africa—tax increases to lower alcohol use are extremely cost-effective (US$105 to US$225 per DALY averted). However, in regions with a lower prevalence of high-risk use—namely, East Asia and the Pacific and South Asia—tax-based policies can be among the least cost-effective interventions (more than US$2,500 per DALY averted). Advertising bans are among the most cost-effective (but least studied) of all interventions to reduce high-risk drinking in all regions (US$134 to US$280 per DALY averted). In East Asia and the Pacific, a comprehensive ban on advertising and reduced access to retail outlets are highly cost-effective interventions (US$123 to US$146 per DALY averted). Random breath testing is one of the least cost-effective interventions to reduce the alcohol-related disease burden (US$973 to US$1,856 per DALY averted). In Sub-Saharan Africa, however, averting the burden of disease associated with drunk driving is an important priority and is addressed effectively through such policies as random breath testing and stricter enforcement of drunk-driving laws (US$531 per DALY averted). Providing high-risk drinkers with brief advice from a physician in primary care settings is of intermediate cost-effectiveness (US$480 to US$819 per DALY averted) in all regions, but combining this intervention with a tax on alcohol increases cost-effectiveness (US$260 to US$533 per DALY averted) in all regions except Sub-Saharan Africa.
Packaging of Interventions and Services
This section examines the overall cost-effectiveness of a service level, including all conditions addressed as part of a package of services, rather than evaluating individual interventions separately.
Emergency and Hospital Care
The cost per death averted of training lay first responders and volunteer paramedics is between US$130 and US$283 (or US$5 to US$11 per DALY averted) depending on the region. Ambulances outfitted with trained paramedics can avert deaths at a cost of US$1,148 to US$3,479 (US$46 to US$137 per DALY averted) in urban settings and US$3,457 to US$10,449 (US$140 to US$410 per DALY averted) in rural settings. Although the evidence for the cost-effectiveness of district and referral hospitals is very limited, it does indicate that basic hospital care at the district level could be highly cost-effective (US$13 to US$104 per DALY averted).
Surgery
Some types of surgery are highly cost-effective as part of a country's health strategy. These include providing surgical care to injury victims, including those suffering from head trauma and burns; handling obstetric complications, such as obstructed labor or hemorrhage; and undertaking elective surgery to address conditions such as cataracts and otitis media that have a significant impact on the quality of life. In areas of high prevalence, cataract surgery can be extremely cost-effective at roughly US$100 per DALY averted.
Many of these surgical interventions—including improved resuscitation and airway management using relatively simple procedures such as chest tubes and tracheostomy, improved fracture management, and improved management of burns covering less than 30 percent of the body—require only the basic facilities offered by district hospitals. The quality of surgery and the risk of complications vary widely, and adequate health system capacity is an important consideration. For the typical surgical facility located in a district hospital in an LMIC, the average cost per DALY averted for a representative set of surgical procedures is between US$70 and US$230. General surgery at the district hospital is cost-effective relative to other interventions in South Asia and Sub-Saharan Africa because of the relatively low input costs related to infrastructure and the high level of the avertable disease burden. Examples of surgical interventions with poor cost-effectiveness include first-line treatment of epilepsy with surgery, which is useful only to patients who do not respond to drug treatment, and percutaneous transluminal coronary angioplasty for cardiovascular events.
Integrated Management of Childhood Illnesses
An intervention package consisting of exclusive breast feeding; vitamin A and zinc supplementation; screening for immunization; and case management of pneumonia, malaria, and diarrhea, including oral rehydration therapy, costs approximately US$4.10 per child in Sub-Saharan Africa and is a cost-effective approach (US$38 per DALY averted) to improving the health of children under five when program coverage is 50 percent.
Value of Doing Things Better
Intervention quality is an important determinant of cost-effectiveness, and improving quality can be an efficient way to use resources. Community health status tends to be correlated with the quality of health service facilities, which can be enhanced even in resource-constrained settings. Indeed, resource-poor settings have the greatest potential for improving quality at low cost. In the case of acute respiratory infections, for example, the cost-effectiveness of improving the quality of care by implementing an educational activity for providers ranges from US$132 to US$800 per life saved (US$4 to US$28 per DALY averted) when initial intervention quality is poor and infections are widespread. Quality improvements can cost between US$2,000 and US$5,000 per life saved (US$70 to US$176 per DALY averted) with improved baseline quality, low disease prevalence, or both. Educational interventions to improve the quality of diarrhea treatment can be extremely cost-effective (less than US$18 per DALY averted) depending on these two factors.
Regional Analyses for South Asia and Sub-Saharan Africa
Given the significant health burden borne by countries in South Asia and Sub-Saharan Africa, cost-effectiveness information for interventions related to high-burden health conditions is presented for these two regions. In South Asia (figure 2.4), CVD-related interventions, including tobacco taxes, treatment of acute myocardial infarction with aspirin and beta-blockers, and increasing coverage of the EPI program, rank among the most cost-effective interventions. Treatment of latent TB, coronary artery bypass graft for ischemic heart disease, treatment of depression, and cholera immunization to prevent diarrheal disease rank among the least cost-effective. Vitamin A deficiency, leprosy, and epilepsy are important conditions that impose a relatively lower burden of DALYs on this region, but a number of highly cost-effective interventions to deal with each of these conditions could be scaled up.
[Figure
2.4]
In Sub-Saharan Africa (figure 2.5), HIV/AIDS and malaria rank among the highest-burden conditions. Of the 16 most cost-effective interventions addressing high-burden diseases, 8 are associated with these two sources of ill health alone. Other interventions that are both cost-effective and address high-burden diseases include nutritional support (including breast-feeding advice for mothers) for children under the age of four, and increasing coverage of the EPI. Oral rehydration therapy for diarrheal disease can be cost-effective if the cost of the package is relatively low (that is, less than US$1 per child per treatment).
Table 2.2 identifies interventions relevant to South Asia and Sub-Saharan Africa that have been evaluated in this volume and have the greatest potential to reduce the burden of disease in those regions at an affordable price.6 The table also highlights interventions that address conditions that account for a moderate to high burden of disease but at a relatively high cost.
[Table .]
Personal versus Population-based Interventions
Figure 2.6 displays a histogram of intervention clusters categorized as either population based or personal (see annex 2.A for definitions). A greater number of personal intervention clusters than population-based intervention clusters are categorized as being highly cost-effective. Although this result may be partly an artifact of the way in which we have grouped interventions into clusters, it lends some support to the observation first made in the first edition of Disease Control Priorities in Developing Countries (Jamison and others 1993) that personal interventions are not necessarily less cost-effective than population-based interventions. Population-based interventions are cost-effective when effectively targeted to populations in which disease prevalence (or the potential prevalence and subsequent mortality if the interventions are not implemented) is high. For example, primary prevention of acute myocardial infarction using aspirin is not nearly as cost-effective as secondary prevention in patients who have already suffered a stroke or myocardial infarction, because this latter category has, by virtue of the first event, identified itself as being at higher risk than the general population. Similarly, malaria prevention programs will be highly cost-effective in areas where malaria is a serious problem but less so in countries where the burden of this disease is less and people are better served by treatment with an effective antimalarial.
[Figure
2.6]
