GAINS IN LIFE EXPECTANCY

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1 OPPORTUNITIES FOR MEDICAL RESEARCH Burden of Disease Implications for Future Research Catherine M. Michaud, MD, PhD Christopher J. L. Murray, MD, DPhil Barry R. Bloom, PhD GAINS IN LIFE EXPECTANCY worldwide were greater during the last century than at any other time in recorded human history. The rate of increase in life expectancies in the first half of the century was greatest in the United States, Europe, Australia, and New Zealand. For example, in the United States, life expectancy was 49 years in 1900 and 66 years by In developing countries, life expectancy increased the most between 1950 and 1990: from 40 to 63 years. 1 Tragically, life expectancy at birth has decreased in sub-saharan Africa as a result of the HIV/AIDS epidemic (human immunodeficiency virus/acquired immunodeficiency syndrome) and decreased to less than 40 years in 5 countries in The gap between highest and lowest life expectancy, women in Japan (84.3 years) and men in Sierra Leone (33.2 years), was 51.1 years (TABLE 1). In the new millennium, society faces difficult choices in the allocation of scarce resources to medical care and medical research. The challenge is to maintain and improve life expectancy and the quality of life that was achieved for most of the world s population during the 20th century. Estimates of life expectancy at birth are useful indices to assess trends and the distribution of life expectancy in the world. This type of assessment, however, masks large inequalities in life expectancy among different population groups within countries. For instance, a study of patterns of mortality in the United States One overall challenge for public health and medicine in the future is to allocate available resources effectively to reduce major causes of disease burden globally and to decrease health disparities between poor and affluent populations. The major risk factors for death and disability worldwide are malnutrition; poor water supply, sanitation, and personal and domestic hygiene; unsafe sexual behavior; tobacco use; alcohol use; occupational hazards; hypertension; physical inactivity; illicit drugs; and air pollution. The challenge for research in the 21st century is to maintain and improve life expectancy and the quality of life that was achieved for most of the world s population during the 20th century. JAMA. 2001;285: showed that life expectancy at birth for men in 1990 varied by 16.5 years from 61 to 77.5 years, and for women by 13 years from 70.5 to 83.5 years. 2 The gap is even larger when life expectancies are calculated for each race. For instance, the disparity between life expectancies of American Indian or Alaskan Native men in some counties in South Dakota and Asian women in New Jersey was 41.3 years in Life expectancy at birth is a critical index of human health and well-being, 3 and reflects the overall mortality in a population, but provides no information about the health of the population prior to death. Summary measures of population health that combine information on mortality and nonfatal health outcomes have been developed to fill this gap and to represent population health in a single number. While several summary measures have been developed, 4 the Global Burden of Disease (GBD) study in 1990 was a major landmark in the development and analysis of summary measures of population health. 5 The GBD study group developed a new system to assess fatal and nonfatal health outcomes the disability-adjusted lifeyear (DALY) making it possible to estimate the burden of major diseases, injuries, and risk factors in 8 regions of the world, and in many counties and county clusters in the United States. The DALY measures the gap between the actual health of a population and a hypothetical norm; namely, a life expectancy of 82.5 years for women and 80 years for men. DALYs for a disease or health condition are calculated as the sum of the years of life lost due to premature mortality in the population and the years of life lost due to disability. DALYs incorporate a discount rate for time preference and an age-weighting factor that take into account the higher social value given young adults in most societies. The rationale for inclusion of time preference and age weighting has been widely debated. 6-8 Although explicit, the assumptions may Author Affiliations: Department of Population and International Health, Harvard School of Public Health, Boston, Mass. Corresponding Author and Reprints: Catherine M. Michaud, MD, PhD, Center for Population and Development Studies, 9 Bow St, Cambridge, MA ( cmichaud@hsph.harvard.edu) American Medical Association. All rights reserved. (Reprinted) JAMA, February 7, 2001 Vol 285, No

2 be modified. 5 One important implication for policymaking is that DALYs weigh the burden of diseases of children less than those of adults. The DALY measure has been used by the World Health Organization, which publishes regular updates on the GBD as a statistical annex to the World Health Report, 9 and several countries, including the United States, have developed national burden of disease estimates These global, regional, and national assessments are useful for comparing the distribution of the burden of disease, quantifying the impact of major risk factors on health, and making projections about future disease burdens. They also provide the denominator for comparisons of cost-effectiveness of a wide array of preventive, palliative, and Table 1. Countries With the Highest and Lowest Life Expectancy in 1999* Life Expectancy Rating Probability of Dying (per 1000) Age 5 y Between Ages y Life Expectancy (Years) at Birth Country Boys Girls Men Women Men Women 1 Japan Sweden Australia Israel Canada Botswana Zambia Malawi Niger Sierra Leone *Reprinted with permission from the World Health Organization. 9 Table 2. Leading Causes of Disability-Adjusted Life-Years (DALYs) for the World in 1999* Rank Cause DALYs DALYs Deaths All conditions Lower respiratory tract infections Human immunodeficiency virus (HIV) Conditions arising during the perinatal period Diarrheal diseases Unipolar major depression Ischemic heart disease Vaccine-preventable diseases Cerebrovascular diseases Malaria Nutritional deficiencies Road traffic collisions Chronic obstructive pulmonary disease Congenital abnormalities Tuberculosis Falls Maternal conditions Self-inflicted Sexually transmitted diseases excluding HIV Alcohol use Bipolar disorder *Reprinted with permission from the World Health Organization. 9 Values are expressed in thousands. curative health interventions, and for setting priorities for health research. 9 One overall challenge for public health and medicine in the future is to allocate available resources effectively to reduce major causes of disease burden worldwide and to decrease health disparities between poor and affluent populations. This article summarizes findings from recent studies on burden of disease and discusses major implications for public health and future research. Burden of Disease Worldwide Burden of Disease in There were 56 million deaths worldwide in 1999, and 1.4 billion DALYs were lost to disease and injury. The burden of disease is not equitably distributed. For example, the burden of disease disproportionately affects people in sub-saharan Africa, which represents 10% of the total population but 26% of total DALYs. 13 The top 10 causes of disease burden are responsible for 46% of all DALYs (TABLE 2). Five of the top 10 causes of DALYs primarily affect children younger than 5 years (lower respiratory tract infections, conditions arising during the perinatal period, diarrheal diseases, childhood vaccine-preventable diseases, and nutritional deficiencies). Two of the top 10 causes malaria and HIV predominantly affect poor populations. These 7 causes are all part of what the World Health Organization has referred to as the unfinished agenda of infectious diseases, perinatal conditions, and nutritional disorders. The 3 remaining causes unipolar major depression, ischemic heart disease, and cerebrovascular diseases are chronic disorders. The fact that unipolar major depression ranks fifth as a source of DALYs even though it causes few deaths underscores how assessment of both fatal and nonfatal health outcomes affects the ranking of disease burden. Rankings based on DALYs differ substantially from rankings based on the number of deaths (TABLE 3). The importance of major depression worldwide was one of the key findings of the GBD study. 536 JAMA, February 7, 2001 Vol 285, No. 5 (Reprinted) 2001 American Medical Association. All rights reserved.

3 Although road traffic collisions, falls, and self-inflicted injuries account for 6.7% of total DALYs, prevention of injuries has not been a major part of the public health agenda in developing countries. In sub-saharan Africa, HIV accounted for 20% of the burden of disease in the region; malaria, tuberculosis, and vaccine-preventable childhood disease were responsible for another 20%. In 1990, malnutrition accounted for nearly 6 million deaths (11.7% overall) and 220 million DALYs (15.9% overall); poor water supply, sanitation, and personal hygiene accounted for 2.6 million deaths and 93 million DALYs; and tobacco use accounted for 3 million deaths and 36 million DALYs (TABLE 4). US Burden of Disease in Similar methods have been used to analyze the burden of disease in the United States. In 1996, 34.5 million DALYs were lost: 18.5 million for men and 16 million for women. The major causes of DALYs differ significantly between the United States and the rest of the world in that 9 of the top 10 causes include injuries and noncommunicable diseases. In the United States, ischemic heart disease ranked first for men and women, accounting for 17% of all DALYs lost, whereas HIV ranked fourth for men. Major depression caused the second largest loss of DALYs in women and road traffic collisions ranked second for men. Alcohol abuse and dependence, homicide and violence, and self-inflicted injuries were among the top 10 causes for men (Table 3). Projections of the Future of Global Burden of Disease. Projections of future burden of disease and risk factors are useful to inform policymaking. The DALYs metric can be projected on the basis of continuing secular trends to allow a prediction of the burden of disease at any future time. The ranking of major causes of burden worldwide is expected to change substantially over the next 20 years. The rank order of major disease burdens by the year 2020 is expected to be dominated by ischemic heart disease, unipolar major depression, and road traffic collisions (TABLE 5). Diseases affecting mostly children lower respiratory tract infections, diarrheal diseases, conditions arising during the perinatal period, and childhood vaccinepreventable diseases (eg, measles) are projected to decrease significantly as global immunization reaches essentially all countries. Human immunodeficiency virus infection was projected in 1990 to increase, but was still expected to rank only 10th by Regrettably, these projections were too optimistic, since HIV in 1999 ranked second as a cause of DALYs worldwide. The cause Table 3. Estimated Leading Causes of Disability-Adjusted Life-Years (DALYs) in the United States in 1996* Rank Cause DALYs DALYs Deaths Men All conditions Ischemic heart disease Road traffic collisions Lung, trachea, and bronchus cancers 4 HIV/AIDS Alcohol abuse and dependence Cerebrovascular disease Homicide and violence Chronic obstructive pulmonary disease 9 Self-inflicted Unipolar major depression Drug use Diabetes mellitus Osteoarthritis Congenital abnormalities Dementia and other degenerative and hereditary central nervous system disorders Women All conditions Ischemic heart disease Unipolar major depression Cerebrovascular disease Lung, trachea, and bronchus cancers 5 Osteoarthritis Breast cancer Chronic obstructive pulmonary disease 8 Dementia and other degenerative and hereditary central nervous system disorders Diabetes mellitus Road traffic collisions Alcohol abuse and dependence Congenital abnormalities Asthma Colon or rectum cancer Conditions arising during the perinatal period *Estimates presented here are from the ongoing collaborative study of the US Burden of Diseae and Injuries between the Centers for Disease Control and Harvard School of Public Health as of January 15, Final accounting may vary slightly. HIV/AIDS indicates human immunodeficiency virus/acquired immunodeficiency syndrome American Medical Association. All rights reserved. (Reprinted) JAMA, February 7, 2001 Vol 285, No

4 Table 4. Burden of Disease and Injury Attributable to Selected Risk Factors in the World in 1990* Risk Factor Deaths Deaths DALYs DALYs Malnutrition Poor water supply, sanitation, and personal and domestic hygiene Unsafe sex Tobacco use Alcohol use Occupational Hypertension Physical inactivity Illicit drug use Air pollution *Reprinted with permission from the World Health Organization. 13 Values are expressed in thousands. DALYs indicates disability-adjusted life-years. Table 5. Projected Change in Rank Order of Disability-Adjusted Life-Years for the 15 Leading Causes in 2020 Compared With 1990* Rank by Year Disease or Injury 1 5 Ischemic heart disease 2 4 Unipolar major depression 3 9 Road traffic collisions 4 6 Cerebrovascular disease 5 12 Chronic obstructive pulmonary disease 6 1 Lower respiratory tract infections 7 7 Tuberculosis 8 16 War 9 2 Diarrheal diseases Human immunodeficiency virus 11 3 Conditions arising during the perinatal period Violence Congenital anomalies Self-inflicted injuries Trachea, bronchus, and lung cancers *Reprinted with permission from Murray and Lopez. 5 of DALYs due to war is projected to rank among the top 10 causes. Implications for Research It is possible to analyze the burden of disease for any category by addressing (1) current methods; (2) potentially cost-effective ways to extend existing tools to more individuals (allocative efficiency); and (3) situations for which no cost-effective tools are available and for which research is required to develop new tools (technical efficiency). The key challenge for public health is to reduce major projected causes of burden by increasing allocative and technical efficiency of health systems so as to increase overall performance, and to define areas in which research is likely to have the greatest yield in the future. There is a strong case for the United States to invest in health research to reduce major causes of burden of disease that are not treatable or preventable with the current mix of interventions and health delivery systems, both nationally and globally. Gains in education and income have contributed to approximately half of the health gains during the past 50 years, and the other half is the result of the generation of new knowledge and the development of new tools (diagnostics, drugs, and vaccines). 9 First, there is a complex causal web involving socioeconomic determinants such as income, education, employment, social capital or income inequality, and proximal behavioral and environmental factors such as tobacco use, physical activity, diet, and health care; and physiological factors such as cholesterol levels, blood pressure, and genes that influence mortality or disability outcomes. 14 Research is needed to understand the contribution of proximal and distal risk factors to reduce the avoidable burden of disease and inequalities in health, as evidenced by the gaps in life expectancy within the United States. Second, the perception varies greatly from reality despite the enormous barrage of health information in the media, in advertisements, and on the Internet. For example, 1 survey found that public perceptions of major health risks for children were drug and child abuse, which contribute a minuscule fraction of the burden of childhood disease compared with poverty or lack of access to health care. 15 Interdisciplinary research is needed to further the understanding of how socioeconomic factors contribute to morbidity and mortality and how health professionals can make significant inroads to changing unhealthy behaviors. Third, research is also needed to improve the overall performance of the health system in the United States. The recent World Health Report evaluated health care systems with respect to attainment of good health, responsiveness to the expectations of the population, and fairness of financial contribution. While attainment of high level of care was unparalleled, the United States ranked 32nd on the basis of equity of distribution, and the US health care system overall was ranked 37th worldwide. 13 Despite evidence that investments in health research have been among the most cost-effective investments over the past decades, the great imbalance between investments in health research and the GBD first highlighted by the Commission on Health Research for Development in 1990 persists. 16 Global investments in health research in 1992 were estimated to be US $55.8 billion. Even though 85% of the global burden of disability and premature mortality occurs in the developing world, less than 4% of global research was devoted to communicable, maternal, perinatal, and nutritional disorders that dominate the burden of disease in developing countries. Funding for health research expressed as expenditures per DALYs in 1990 and 2020 illustrates low levels of funding for malaria, tuberculosis, acute respiratory tract infections, and diar- 538 JAMA, February 7, 2001 Vol 285, No. 5 (Reprinted) 2001 American Medical Association. All rights reserved.

5 rheal diseases, all of which disproportionately affect developing countries (TABLE 6). An increase in investments by the United States and other developed nations on major causes of burden of diseases that disproportionately affect the poor worldwide HIV, tuberculosis, and malaria is justifiable both on humanitarian grounds and also in the enlightened self-interest of people in these developed countries. The process of globalization that dominates the beginning of the 21st century has created a context of global health interdependence in which many health threats transcend national boundaries, such as the spread of reemerging and new infectious diseases, increased microbial resistance to currently available drugs, and bioterrorism, 17 and the challenges of financing the increasing demands of the public for better health. Past investments in health research have been very effective. The generation and application of new knowledge accounts for approximately half of all health gains worldwide over the last 50 years. 18 The 25-year increase in life expectancy in the United States and Table 6. Funding for Selected Health-Related Research Topics* Topic United States $ Value DALYs Expenditure per DALY, $ DALYs Expenditure per DALY, $ HIV/AIDS Tobacco use Asthma Blindness Cardiovascular epidemiology 100 NA NA NA NA Malaria Acute respiratory diseases Diarrheal diseases Road traffic collisions Tuberculosis *DALYs indicates disability-adjusted life-years; HIV, human immunodeficiency virus; and AIDS, acquired immunodeficiency syndrome. Expressed in millions. Values not available. the enormous gains in the quality of life over the past century confirm the value to human health of new knowledge deriving from biomedical and public health research. With the unfolding genomic and technological revolution, continuing investments in research offer unprecedented opportunities to understand disease processes, prevent intrinsic and environmental risks to health, and develop new treatments to improve the quality of life in the United States and worldwide. Funding/Support: The US Burden of Disease and Injury Study was supported by a cooperative agreement with the Centers for Disease Control and Prevention through the Association of Schools of Public Health. The Albert and Mary Lasker Foundation provided honoraria to Drs Michaud and Bloom for preparation of this article. REFERENCES 1. The World Bank. Investing in Health: World Development Indicators. New York, NY: Oxford University Press; Murray CJL, Michaud CM, McKenna MT, Marks JS. US Patterns of Mortality by County and Race: : The US Burden of Disease and Injury Monograph Series. Cambridge, Mass: Harvard Center for Population and Development Studies; Sen AK. The Standard of Living. Cambridge, Mass: Cambridge University Press; Summarizing Population Health: Directions for the Development and Application of Population Metrics. Washington, DC: National Academy Press; Murray CJL, Lopez AD. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 Projected to Cambridge, Mass: Harvard School of Public Health; Anand S, Hanson K. Disability-adjusted life years: a critical review. J Health Econ. 1997;16: Johanneson M, Johansson PO. Is the valuation of QALY s gained independent of age? some empirical evidence. J Health Econ. 1997;16: Murray CJL, Acharya A. Understanding DALY s. J Health Econ. 1997;16: World Health Organization. The World Health Report 2000: Health Systems: Improving Performance. Geneva, Switzerland: World Health Organization; Mathers C, Vos T, Stevenson C. The Burden of Disease and Injury in Australia. Canberra: Australian Institute of Health and Welfare; Victorian Burden of Disease Study: Mortality. Melbourne, Victoria: Victorian Government, Department of Human Services, Public Health and Development Division; Victorian Burden of Disease Study: Morbidity. Melbourne, Victoria: Victorian Government, Department of Human Services, Public Health and Development Division, WHO Ad Hoc Committee on Health Research Relating to Future Intervention Options. Investing in Health Research and Development. Geneva, Switzerland: World Health Organization; Murray CJL, Lopez AD. On the comparable quantification of health risks: lessons from the global burden of disease study. Epidemiology. 1999;10: Blendon RJ, Young JT, McCormick MC, Kropf M, Blair J. Americans view on children s health. JAMA. 1998;24: Commission on Health Research for Development. Health Research: Essential Link to Equity in Development. New York, NY: Oxford University Press; Howson CP, Fineberg HJ, Bloom BR. The pursuit of global health: the relevance of engagement for developed countries. Lancet. 1998;351: World Development Report 2000/2001: Attacking Poverty. New York, NY: Oxford University Press; American Medical Association. All rights reserved. (Reprinted) JAMA, February 7, 2001 Vol 285, No