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Cost-of-illness studies: fact or fiction?
Cost-of-illness studies: fact
or
fiction?
Cost-of-illness studies have been proliferating and doctors and policymakers often ask what the very large financial estimates mean and how useful and reliable they are. Different aspects of costs are measured, including losses to industry and business due to staff illness,’ lifetime costs,2 economic costs,3 and direct and indirect costs.4 One important issue is whether the estimates are based on prevalence or on incidence. Prevalence-based costs estimate the direct and indirect economic burden to society incurred during a period of time (the base period) as a result of the prevalence of the disease; the period is usually a year. This approach measures the value of resources used or lost during a specified period of time, irrespective of the time of disease onset. Incidence-based costs represent the lifetime costs resulting from a disease or illness, based on all cases with onset of disease in a given base year. The approach adopted depends on the purpose of the analysis. If the results are to be used for cost control, prevalence-based costing is appropriate; this method identifies the main components of current expenditures and foregone resources and identifies possible targets for economy. If the analysis is aimed at making decisions about which treatment or research strategy to implement, the incidence-based approach is more appropriate because it provides the basis for predictions about the likely savings from programmes that reduce incidence or
improve
outcomes.
Valuation of life is an important component of cost-ofillness studies. Economists generally adopt two for this approaches purpose: (a) the human capital approach, refined by me and my colleagues;4,5 and (b) the willingness-to-pay approach, first proposed by Schelling6 and Mishan.’ In the human capital approach, a person is regarded as producing a stream of output that is valued at market earnings, and the value of life is the discounted future earnings stream. Morbidity and mortality destroy labour, a valuable economic resource, by causing persons to lose time from work and other productive activities, or by bringing about premature death.8 This method has some disadvantages. Because life is valued in terms of market earnings, the technique yields very low values for children and the retired elderly. In addition, psychosocial costs-eg, pain and suffering-are components of the ’ burden of illness that are omitted from the human capital
approach. The willingness-to-pay approach values life according to what individuals are willing to pay for a change that reduces the probability of illness or death. This method could be helpful in indicating how individuals value health and life, in deriving social preferences regarding public policy, and in assessing the burden of pain and suffering. This technique is influenced by the wealth (thus ability to pay) of the individual involved and it suffers from circularity because the values. placed by individuals on government health programmes are clearly influenced by those policies.9 Willingness-to-pay measures in the USA approach$2 million per life, a much larger sum than that generated by human capital measures. Cost-of-illness studies are typically divided into two main categories: (a) core costs, those resulting directly from the illness; and (b) other related costs, including non-health
costs
of the illness. Within each category,
there are direct costs (for which payments are made) and indirect costs (for which resources are lost). Direct costs (expenditures for hospital and nursing home care, physician and other professional services, drugs, spectacles, and appliances) are generally estimated as the product of two components-number of services and unit prices or charges. For example, short-stay hospital days of care, by diagnosis, can be obtained in the USA from the National Hospital Discharge Survey conducted by the National Center for Health Statistics (NCHS), and expenses per patient day from the annual survey of the American Hospital Association. Nursing home costs are estimated by multiplying the numbers of residents with the diagnosis by the annual charge for all residents as reported by the National Nursing Home Survey conducted periodically by NCHS. Costs of outpatient care by office-based physicians can be based on visit data from the National Ambulatory Care Survey, also conducted periodically by NCHS, and charge data for physicians can be obtained from the American Medical Association annual report on physician practice. Other direct medical and related costs are calculated similarly from other data sources. Indirect costs include morbidity and mortality costs. Morbidity costs are the value of reduced or lost productivity due to the disease in question and are estimated as the product of (a) mean earnings an individual would have accrued had he or she not been affected by the disease, disaggregated by age and gender; and (b) the number of days lost from work for the employed population or days lost in performing their main activity for those keeping house. If an individual had not died prematurely from the disease, he or she would have continued to be productive in future years. Mortality costs are the product of the number of deaths from the disease and the expected value of an individual’s future earnings with gender and age taken into account. This method of derivation considers life expectancy for different age and gender groups, the changing pattern of earnings at successive ages, the varying labour force participation rates, an imputed value for house-keeping services, and the appropriate discount rate to convert a stream of earnings into its present worth. National surveys provide reasonably good information on the use of services for estimation of direct costs, but charge and cost data are less readily available and probably less reliable. Indirect costs depend on the discount rate used; the higher the discount rate, the lower the final costs. If the results of different cost-of-illness studies are compared, special attention should be paid to the techniques used, the discount rate, the reference years, and the scope and recency of the data. Cost-ofillness studies are used by policymakers to justify budgets, to set priorities for funding in biomedical research, and to develop intervention programmes to ameliorate or prevent a disease. Researchers in this area have an obligation to present the methods in considerable detail so that users will be better able to assess their accuracy and to evaluate whether the results are facts or fiction.
Dorothy P Rice Institute for Health and California, USA 1
Aging, University
of California, San Francisco,
Farnharn PG. Defining and measuring the costs of the HIV business firms. Public Health Rep 1994; 109: 311-18.
epidemic
to
1519
2
3
4
5
6
7 8
9
Rice DP, MacKenzie E, and associates. Cost of injury in the United States: a report to Congress. 1989. Produced by Institute for Health & Aging, University of California, San Francisco; Injury Prevention Center, School of Hygiene and Public Health, Johns Hopkins University; National Highway Traffic Safety Administration, US Department of Transportation; and Centers for Disease Control. Rice DP, Kelman S, Miller LS, Dunmeyer S. The economic costs of alcohol and drug abuse and mental illness. Rockville, MD: US Alcohol, Drug Abuse, and Mental Health Administration, 1990, publication no (ADM) 90-1694. Scitovsky AA, Rice DP. Estimates of the direct and indirect costs of acquired immunodeficiency syndrome in the United States: 1985, 1986, and 1991. Public Health Rep 1987; 102: 5-17. Rice DP. Estimating the cost of illness. Rockville, MD: US Department of Health, Education and Welfare, 1966, Health Economics Series, no 6. DHEW pub no (PHS) 947-6. Schelling TC. The life you save may be your own. In: Chase SB, ed. Problems in public expenditure analysis. Washington, DC: Brookings Institution, 1968. Mishan EJ. Evaluation of life and limb; a theoretical approach. J Polit Econ 1971; 79: 687-705. Hodgson TA, Meiners M. Cost of illness methodology: a guide to current practices and procedures. Milbank Memorial Fund Quart 1982; 60: 429-62. Robinson JC. Philosophical origins of the economic value of life. Milbank Memorial Fund Quart 1986; 64: 133-35.
Single-dose antibiotic treatment for travellers’ diarrhoea See page 1537
Diarrhoea is by far the most common ailment experienced by international travellers.’ 20-50% of those who travel to the tropics, whether for sun, sand, sex, or solitude, will be so afflicted. Although the illness is usually mild and selflimited, 30% of affected individuals will be bed-ridden and another 40% will have to curtail their activities.2 The overwhelming majority of those with travellers’ diarrhoea (at least 80%) are infected with bacterial enteropathogens-notably, enterotoxigenic Escherichia coli, Campylobacter jejuni, and species of salmonella and shigella. The bacterial aetiology of travellers’ diarrhoea accounts for the well-documented efficacy of antibiotics used for prophylaxis and therapy of this condition. However, antibiotic resistance has recently increased so strikingly in most areas of the world that only quinolones remain reliably effective. In several recent studies tetracycline resistance to shigella, salmonella, and E coli ranged from 59 to 91% of strains whereas co-trimoxazole resistance ranged from 35 to 76%/ Quinolone resistance has been increasing as well: in Thailand 50% of campylobacter strains were resistant to ciprofloxacin.5 Empirical self-treatment of travellers’ diarrhoea was pioneered by DuPont and his colleagues in the early 1980s.6 Numerous studies have subsequently shown that antibiotic therapy reduces the duration of diarrhoea from 50-93 h (untreated) to 16-30 h when treatment is given within 24 h of the onset of symptoms. Most regimens now consist of two antibiotic doses daily for 3-5 days, with or without an antimotility agent such as loperamide. The combination of loperamide with an antibiotic seems to be the most effective therapy for the majority of those with travellers’ diarrhoea, although not all controlled trials have shown increased benefit with the addition of the antimotility agent. A study of combination therapy for shigella dysentery in Thailand did not confirm the notion that loperamide is contraindicated in those with high fever and bloody diarrhoea, since no adverse effects-notably toxic megacolon-were detected in the loperamide group.’ However, this was a small study, so it is too early to
1520
the caution concerning the use of antimotility in drugs patients with severe dysentery. To reduce costs and improve compliance and convenience, several investigators have focused on singledose antibiotic therapy for the treatment of infectious diarrhoea. Single-dose therapy with norfloxacin 800 mg for the treatment of shigellosis was as effective as a 3-day course in Mexico and Thailand.8,9 However, the latter study showed that short-course quinolone therapy (1 dose or 3 days) did not consistently eliminate salmonella infection or lead to rapid resolution of symptoms. When a 750 mg dose of ciprofloxacin was compared with a 3-day course of therapy plus loperamide for travellers’ diarrhoea, those who took the combination had fewer liquid bowel movements. In a similar study of ciprofloxacin for shigellosis, a single 1 g dose was effective therapy for patients infected with species of shigella other than S dysenteriae type 1, but single-dose therapy was inferior to 5 days’ treatment for patients infected with S dysenteriae type 1.10 In this issue, Salam and colleagues report a study of single-dose 500 mg ciprofloxacin compared with placebo for the treatment of acute travellers’ diarrhoea in British soldiers in Belize. Mean duration of diarrhoea as assessed by the time to the last unformed stool was reduced from about 50 h to 24-8 h. Mean number of stools was reduced by more than 50% as well. These results confirm earlier work that single-dose therapy for travellers’ diarrhoea is in most cases an effective way to shorten the course of the illness. Discussion of the use of antibiotics for prevention of travellers’ diarrhoea is outside the scope of this commentary. However, a small international study group recently concluded that prophylaxis has a role in certain high-risk travellers." The advantages and disadvantages of prophylaxis were weighed against empirical therapy in three recent reviews.5,12,13 The issue of antibiotic prophylaxis aside, all travellers from the developed to the developing world, especially those taking short trips, are advised to carry a quinolone antibiotic and an antimotility agent; one or both should be taken at the first sign of diarrhoea.
remove
JS
Keystone
Tropical Disease Unit, Department of Medicine, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada 1
Steffen R, Rickenbach M, Wilhelm U, Helminger A, Schar M. Health problems after travel to developing countries. J Infect Dis 1987; 156: 84-91.
2
3
4
5 6
7
8
9
Gorbach SL. Travelers’ diarrhea. N Engl J Med 1982; 307: 881-83. Steffen R. Epidemiologic studies of travelers’ diarrhea, severe gastrointestinal infections and cholera. Rev Infect Dis 1986; 8 (suppl 2): S122-30. Tellier R, Keystone JS. Prevention of travelers’ diarrhea. Infect Dis Clin N Am 1992; 6: 333-54. Taylor DN. Quinolones as chemoprophylactic agents for travellers’ diarrhea. J Trav Med 1994; 1: 119-21. DuPont HI, Ericcson CD, Johnson PC. Chemotherapy and chemoprophylaxis of travelers’ diarrhea. Ann Intern Med 1985; 102: 260-61. Murphy GS, Bedhidatta L, Echeverria P, et al. Ciprofloxacin and loperamide in the treatment of bacillary dysentery. Ann Intern Med
1985; 102: 582-86. Gotuzzo E, Oberhelman RA, Maguina C, et al. Comparison of singledose treatment with norfloxacin and standard 5-day treatment with trimethoprim-sulfamethoxazole for acute shigellosis in adults. Antimicrob Agents Chemother 1989; 33: 1101-04. Petrucelli BP, Murphy GS, Sanchez JL, et al. Treatment of travelers’ diarrhea with ciprofloxacin and loperamide. J Infect Dis 1992; 165: 557-60.
or
fiction?
Cost-of-illness studies have been proliferating and doctors and policymakers often ask what the very large financial estimates mean and how useful and reliable they are. Different aspects of costs are measured, including losses to industry and business due to staff illness,’ lifetime costs,2 economic costs,3 and direct and indirect costs.4 One important issue is whether the estimates are based on prevalence or on incidence. Prevalence-based costs estimate the direct and indirect economic burden to society incurred during a period of time (the base period) as a result of the prevalence of the disease; the period is usually a year. This approach measures the value of resources used or lost during a specified period of time, irrespective of the time of disease onset. Incidence-based costs represent the lifetime costs resulting from a disease or illness, based on all cases with onset of disease in a given base year. The approach adopted depends on the purpose of the analysis. If the results are to be used for cost control, prevalence-based costing is appropriate; this method identifies the main components of current expenditures and foregone resources and identifies possible targets for economy. If the analysis is aimed at making decisions about which treatment or research strategy to implement, the incidence-based approach is more appropriate because it provides the basis for predictions about the likely savings from programmes that reduce incidence or
improve
outcomes.
Valuation of life is an important component of cost-ofillness studies. Economists generally adopt two for this approaches purpose: (a) the human capital approach, refined by me and my colleagues;4,5 and (b) the willingness-to-pay approach, first proposed by Schelling6 and Mishan.’ In the human capital approach, a person is regarded as producing a stream of output that is valued at market earnings, and the value of life is the discounted future earnings stream. Morbidity and mortality destroy labour, a valuable economic resource, by causing persons to lose time from work and other productive activities, or by bringing about premature death.8 This method has some disadvantages. Because life is valued in terms of market earnings, the technique yields very low values for children and the retired elderly. In addition, psychosocial costs-eg, pain and suffering-are components of the ’ burden of illness that are omitted from the human capital
approach. The willingness-to-pay approach values life according to what individuals are willing to pay for a change that reduces the probability of illness or death. This method could be helpful in indicating how individuals value health and life, in deriving social preferences regarding public policy, and in assessing the burden of pain and suffering. This technique is influenced by the wealth (thus ability to pay) of the individual involved and it suffers from circularity because the values. placed by individuals on government health programmes are clearly influenced by those policies.9 Willingness-to-pay measures in the USA approach$2 million per life, a much larger sum than that generated by human capital measures. Cost-of-illness studies are typically divided into two main categories: (a) core costs, those resulting directly from the illness; and (b) other related costs, including non-health
costs
of the illness. Within each category,
there are direct costs (for which payments are made) and indirect costs (for which resources are lost). Direct costs (expenditures for hospital and nursing home care, physician and other professional services, drugs, spectacles, and appliances) are generally estimated as the product of two components-number of services and unit prices or charges. For example, short-stay hospital days of care, by diagnosis, can be obtained in the USA from the National Hospital Discharge Survey conducted by the National Center for Health Statistics (NCHS), and expenses per patient day from the annual survey of the American Hospital Association. Nursing home costs are estimated by multiplying the numbers of residents with the diagnosis by the annual charge for all residents as reported by the National Nursing Home Survey conducted periodically by NCHS. Costs of outpatient care by office-based physicians can be based on visit data from the National Ambulatory Care Survey, also conducted periodically by NCHS, and charge data for physicians can be obtained from the American Medical Association annual report on physician practice. Other direct medical and related costs are calculated similarly from other data sources. Indirect costs include morbidity and mortality costs. Morbidity costs are the value of reduced or lost productivity due to the disease in question and are estimated as the product of (a) mean earnings an individual would have accrued had he or she not been affected by the disease, disaggregated by age and gender; and (b) the number of days lost from work for the employed population or days lost in performing their main activity for those keeping house. If an individual had not died prematurely from the disease, he or she would have continued to be productive in future years. Mortality costs are the product of the number of deaths from the disease and the expected value of an individual’s future earnings with gender and age taken into account. This method of derivation considers life expectancy for different age and gender groups, the changing pattern of earnings at successive ages, the varying labour force participation rates, an imputed value for house-keeping services, and the appropriate discount rate to convert a stream of earnings into its present worth. National surveys provide reasonably good information on the use of services for estimation of direct costs, but charge and cost data are less readily available and probably less reliable. Indirect costs depend on the discount rate used; the higher the discount rate, the lower the final costs. If the results of different cost-of-illness studies are compared, special attention should be paid to the techniques used, the discount rate, the reference years, and the scope and recency of the data. Cost-ofillness studies are used by policymakers to justify budgets, to set priorities for funding in biomedical research, and to develop intervention programmes to ameliorate or prevent a disease. Researchers in this area have an obligation to present the methods in considerable detail so that users will be better able to assess their accuracy and to evaluate whether the results are facts or fiction.
Dorothy P Rice Institute for Health and California, USA 1
Aging, University
of California, San Francisco,
Farnharn PG. Defining and measuring the costs of the HIV business firms. Public Health Rep 1994; 109: 311-18.
epidemic
to
1519
2
3
4
5
6
7 8
9
Rice DP, MacKenzie E, and associates. Cost of injury in the United States: a report to Congress. 1989. Produced by Institute for Health & Aging, University of California, San Francisco; Injury Prevention Center, School of Hygiene and Public Health, Johns Hopkins University; National Highway Traffic Safety Administration, US Department of Transportation; and Centers for Disease Control. Rice DP, Kelman S, Miller LS, Dunmeyer S. The economic costs of alcohol and drug abuse and mental illness. Rockville, MD: US Alcohol, Drug Abuse, and Mental Health Administration, 1990, publication no (ADM) 90-1694. Scitovsky AA, Rice DP. Estimates of the direct and indirect costs of acquired immunodeficiency syndrome in the United States: 1985, 1986, and 1991. Public Health Rep 1987; 102: 5-17. Rice DP. Estimating the cost of illness. Rockville, MD: US Department of Health, Education and Welfare, 1966, Health Economics Series, no 6. DHEW pub no (PHS) 947-6. Schelling TC. The life you save may be your own. In: Chase SB, ed. Problems in public expenditure analysis. Washington, DC: Brookings Institution, 1968. Mishan EJ. Evaluation of life and limb; a theoretical approach. J Polit Econ 1971; 79: 687-705. Hodgson TA, Meiners M. Cost of illness methodology: a guide to current practices and procedures. Milbank Memorial Fund Quart 1982; 60: 429-62. Robinson JC. Philosophical origins of the economic value of life. Milbank Memorial Fund Quart 1986; 64: 133-35.
Single-dose antibiotic treatment for travellers’ diarrhoea See page 1537
Diarrhoea is by far the most common ailment experienced by international travellers.’ 20-50% of those who travel to the tropics, whether for sun, sand, sex, or solitude, will be so afflicted. Although the illness is usually mild and selflimited, 30% of affected individuals will be bed-ridden and another 40% will have to curtail their activities.2 The overwhelming majority of those with travellers’ diarrhoea (at least 80%) are infected with bacterial enteropathogens-notably, enterotoxigenic Escherichia coli, Campylobacter jejuni, and species of salmonella and shigella. The bacterial aetiology of travellers’ diarrhoea accounts for the well-documented efficacy of antibiotics used for prophylaxis and therapy of this condition. However, antibiotic resistance has recently increased so strikingly in most areas of the world that only quinolones remain reliably effective. In several recent studies tetracycline resistance to shigella, salmonella, and E coli ranged from 59 to 91% of strains whereas co-trimoxazole resistance ranged from 35 to 76%/ Quinolone resistance has been increasing as well: in Thailand 50% of campylobacter strains were resistant to ciprofloxacin.5 Empirical self-treatment of travellers’ diarrhoea was pioneered by DuPont and his colleagues in the early 1980s.6 Numerous studies have subsequently shown that antibiotic therapy reduces the duration of diarrhoea from 50-93 h (untreated) to 16-30 h when treatment is given within 24 h of the onset of symptoms. Most regimens now consist of two antibiotic doses daily for 3-5 days, with or without an antimotility agent such as loperamide. The combination of loperamide with an antibiotic seems to be the most effective therapy for the majority of those with travellers’ diarrhoea, although not all controlled trials have shown increased benefit with the addition of the antimotility agent. A study of combination therapy for shigella dysentery in Thailand did not confirm the notion that loperamide is contraindicated in those with high fever and bloody diarrhoea, since no adverse effects-notably toxic megacolon-were detected in the loperamide group.’ However, this was a small study, so it is too early to
1520
the caution concerning the use of antimotility in drugs patients with severe dysentery. To reduce costs and improve compliance and convenience, several investigators have focused on singledose antibiotic therapy for the treatment of infectious diarrhoea. Single-dose therapy with norfloxacin 800 mg for the treatment of shigellosis was as effective as a 3-day course in Mexico and Thailand.8,9 However, the latter study showed that short-course quinolone therapy (1 dose or 3 days) did not consistently eliminate salmonella infection or lead to rapid resolution of symptoms. When a 750 mg dose of ciprofloxacin was compared with a 3-day course of therapy plus loperamide for travellers’ diarrhoea, those who took the combination had fewer liquid bowel movements. In a similar study of ciprofloxacin for shigellosis, a single 1 g dose was effective therapy for patients infected with species of shigella other than S dysenteriae type 1, but single-dose therapy was inferior to 5 days’ treatment for patients infected with S dysenteriae type 1.10 In this issue, Salam and colleagues report a study of single-dose 500 mg ciprofloxacin compared with placebo for the treatment of acute travellers’ diarrhoea in British soldiers in Belize. Mean duration of diarrhoea as assessed by the time to the last unformed stool was reduced from about 50 h to 24-8 h. Mean number of stools was reduced by more than 50% as well. These results confirm earlier work that single-dose therapy for travellers’ diarrhoea is in most cases an effective way to shorten the course of the illness. Discussion of the use of antibiotics for prevention of travellers’ diarrhoea is outside the scope of this commentary. However, a small international study group recently concluded that prophylaxis has a role in certain high-risk travellers." The advantages and disadvantages of prophylaxis were weighed against empirical therapy in three recent reviews.5,12,13 The issue of antibiotic prophylaxis aside, all travellers from the developed to the developing world, especially those taking short trips, are advised to carry a quinolone antibiotic and an antimotility agent; one or both should be taken at the first sign of diarrhoea.
remove
JS
Keystone
Tropical Disease Unit, Department of Medicine, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada 1
Steffen R, Rickenbach M, Wilhelm U, Helminger A, Schar M. Health problems after travel to developing countries. J Infect Dis 1987; 156: 84-91.
2
3
4
5 6
7
8
9
Gorbach SL. Travelers’ diarrhea. N Engl J Med 1982; 307: 881-83. Steffen R. Epidemiologic studies of travelers’ diarrhea, severe gastrointestinal infections and cholera. Rev Infect Dis 1986; 8 (suppl 2): S122-30. Tellier R, Keystone JS. Prevention of travelers’ diarrhea. Infect Dis Clin N Am 1992; 6: 333-54. Taylor DN. Quinolones as chemoprophylactic agents for travellers’ diarrhea. J Trav Med 1994; 1: 119-21. DuPont HI, Ericcson CD, Johnson PC. Chemotherapy and chemoprophylaxis of travelers’ diarrhea. Ann Intern Med 1985; 102: 260-61. Murphy GS, Bedhidatta L, Echeverria P, et al. Ciprofloxacin and loperamide in the treatment of bacillary dysentery. Ann Intern Med
1985; 102: 582-86. Gotuzzo E, Oberhelman RA, Maguina C, et al. Comparison of singledose treatment with norfloxacin and standard 5-day treatment with trimethoprim-sulfamethoxazole for acute shigellosis in adults. Antimicrob Agents Chemother 1989; 33: 1101-04. Petrucelli BP, Murphy GS, Sanchez JL, et al. Treatment of travelers’ diarrhea with ciprofloxacin and loperamide. J Infect Dis 1992; 165: 557-60.