EDITORIAL * EDITORIAL
Universal hepatitis B vaccination: the economics of prevention Murray D. Krahn, MD, FRCPC; Allan S. Detsky, MD, PhD, FRCPC a major worldwide public health problem. About 300 million people, more than 5% of the world's population, are chronic carriers.' Of carriers with a life expectancy of more than 30 years 25% to 30% will die from complications of hepatitis B.2 Those who live with the disease often suffer for decades. Universal vaccination programs, many of which have been administered through the World Health Organization's Expanded Program on Immunization, have been instituted in highly endemic regions.3 Only recently, however, have universal programs been contemplated in areas of low endemicity, such as North America. Two factors account for this change in the direction of clinical policy. The first is the inexorable rise in the apparent burden of the disease in North America. Over the past 15 years the reported incidence and death rates have more than doubled in Canada,4 and similar trends have been observed in the United States.5 Even though the reported incidence rate is only remotely related to the true incidence rate (owing to subclinical illness, underreporting and misreporting) the increase in causespecific death rates4 implies that the true burden of hepatitis B is probably increasing. The second factor is the failure of the targeted "high-risk" vaccination strategy. Like acquired immunodeficiency syndrome hepatitis B has been labelled as a disease of people at high risk. Thus, apart from recently introduced prenatal screening programs in both Canada and the United States prevention efforts have been aimed solely at these people. This approach has shown at best mixed results. The reported incidence rate continues to rise, even though a vaccine has been available since 1982. Data from the four counties in Washington, Colorado, Alabama and Florida where the US Centers for
pepatitis B is
H
Disease Control maintain an intensive surveillance (no such Canadian program exists) have shown that the incidence rate among health care workers and homosexual men has fallen dramatically between 1982 and 1988;5 the decrease in the latter group most likely occurred more because of changes in high-risk behaviour than because of vaccine usage. But the rate among injection drug users nearly doubled, from 15% to 27% of reported cases. Moreover, the continuing increase in the number of reported cases due to heterosexual transmission has called into doubt the viability of the targeted approach. Various authors6'7 and advisory bodies, such as the National Advisory Committee on Immunization (NACI) (see page 36 of this issue), the Canadian Paediatric Society (see pages 25 to 28 of this issue) and the Advisory Committee on Immunization Practices,8 now advocate universal vaccination as the only feasible means of controlling hepatitis B. Are the rising burden of hepatitis B and the failure of current policies sufficient grounds for the introduction of a new technology or, in this case, the broad diffusion of an existing technology? After all, hepatitis B is still relatively rare and is not perceived to be a major public health burden in Canada, and the vaccine is expensive. How should this intervention be measured against cholesterol screening, coronary artery bypass surgery, organ transplantation and similar worthy interventions that compete for increasingly scarce health care resources? A rigorous accounting of the potential costs and benefits of a universal vaccination program (i.e., an economic evaluation or cost-effectiveness analysis performed in a manner that would allow comparison with other, unrelated health care programs) is required. We have completed such an analysis.9 The preliminary results were presented at the national meeting of the American Federation of Clinical program
From the departments of Medicine and Health Administration, University of Toronto, and the Division of General Internal Medicine and Clinical Epidemiology, Toronto Hospital, Toronto, Ont.
Reprint requests to: Dr. Allan S. Detsky, Rm. EN G-246, Toronto Hospital (General Division), 200 Elizabeth St., Toronto, ON M5G 2C4 JANUARY 1, 1992
CAN MED ASSOC J 1992; 146 (1)
19
Research on May 1 1, 1991, and have been reviewed by NACI. Many preliminary observations can be made about the components of the evaluation. The cost of vaccination, of which the vaccine price is the main component, is clearly a critical factor. Although prices have decreased in recent years a single pediatric dose still costs between $13 and $30 in Canada, depending on the manufacturer, the dose and whether vial splitting was used. The vaccine price is lower elsewhere in the world: in the United States it has been as little as $7 US per dose, and for mass vaccination programs in highly endemic areas it is less than $1 per dose. Our preliminary findings9 demonstrate that a universal vaccination policy could be economically attractive, but only at substantially lower vaccine prices. Because the pricing strategy of pharmaceutical companies is linked to sales, high-volume sales engendered by a universal strategy could lead to a substantial reduction in the price of the vaccine. On the other hand, it may be difficult to proceed without lower prices. Cooperation between funding agencies and vaccine manufacturers on the issues of volume and price is essential if the program is to be economically attractive. Just as important is the duration of vaccine efficacy. In North America hepatitis B is a disease of young adulthood, the incidence rate peaking among people 25 to 29 years of age.4 Unless a series of neonatal vaccinations provides protection for decades it is unlikely that universal vaccination will either be economically attractive or result in a significant reduction in the burden of the disease. The duration of immunity provided by vaccination is still uncertain; 5 years after vaccination 7% to more than 38% of adults may lose immunity (conventionally defined as a level of antibody to hepatitis B surface antigen [anti-HBs] of more than 10 mIU/mL).'0"' Vaccine responses in infants are less well characterized, but evidence suggests that neonates have lower peak anti-HBs titres and protective levels for shorter periods than adults.'2 '3 Finally, there is the issue of "immunologic memory." Many believe that protection against infection, especially against conversion to the carrier state (the most important function of the vaccine), extends far past the period of detectable anti-HBs levels. Because of the uncertainty surrounding the duration of vaccine effectiveness long-term monitoring of the immune status of vaccinated infants would be an important component in ensuring the effectiveness of a universal vaccination program. Should booster vaccinations become necessary, however, the program's economic attractiveness would be substantially reduced. The cost of long-term monitoring, the booster doses and the administration of such 20
CAN MED ASSOC J 1992; 146 (1)
doses would have to be included. The need for booster doses would mean some combination of additional physician visits and a new infrastructure for delivering the vaccine. Higher administrative costs and lack of an effective means of delivering the vaccine to adolescents and adults are the main reasons for vaccinating newborns in the first place, despite the probable greater efficacy of vaccinating adolescents. Finally, there is the issue of time and its effect on economic attractiveness via the discounting of future resources compared with present ones. Most health care programs have a time frame of 5, 10 or at most 20 years. Hepatitis B dictates a multidecade, intergenerational perspective, which is unusual, even for preventive health care programs. Incurring the costs of vaccination today results in savings in the future by preventing infection in 20 years and chronic liver disease, hepatoma and death in 60 years. Universal vaccination of infants would have virtually no impact on the disease for 15 to 20 years. Although some speak of universal programs as a means of eradicating the disease, analogous to the situation with smallpox, such a goal may well be overly ambitious. The passage of time will have other effects as well. Within the anticipated time frame many things may change. The cost of health care is going up, and innovative and ever more costly ways of caring for those with chronic liver disease from hepatitis B (e.g., liver transplantation and interferon therapy) continue to be developed. The exogenous burden of hepatitis B may rise because of increased emigration from countries of medium and high endemicity. Finally, the cost of vaccination will almost certainly fall. These changes will probably make universal hepatitis B vaccination increasingly attractive in the medium to long term. As mentioned earlier both NACI and the Canadian Paediatric Society now support a policy of universal childhood vaccination against hepatitis B. Given the current data our analysis9 suggests that a universal program appears to be an economically attractive use of resources if vaccine prices can be substantially reduced. It is essential, though, that the implementation of such a program be coupled with a means of monitoring the long-term effectiveness of the vaccine. Only then can we close the loop,'4 determine the ongoing effectivneess of the program and ensure a substantial reduction in the burden of hepatitis B. The cost-effectiveness analysis referred to in this editorial was funded by SmithKline Beecham Canada. Dr. Detsky was supported by a scholarship from the National Health Research and Development Program, Department of National Health and Welfare. LE 1 er JANVIER 1992
References 1. Maynard JE: Control of hepatitis B by immunization: global perspectives. In Zuckerman AJ (ed): Viral Hepatitis and Liver Disease, Liss, New York, 1988: 967-969 2. Szmuness W, Harley EJ, Ikram HI: Sociodemographic aspects of the epidemiology of liver disease. In Vyas GN, Cohen SN, Schmid R (eds): Viral Hepatitis, Franklin Inst Pr, Philadelphia, 1978: 17-21 3. Hepatitis Surveillance (rep 52), Centers for Disease Control, US Dept of Health and Human Services, Public Health Service, Atlanta, 1989 4. Hepatitis B in Canada: surveillance summary, 1980-1989. Can Dis Wkly Rep 1991; 17: 166-171 5. Alter MJ, Hadler SC, Margolis HS et al: The changing epidemiology of hepatitis B in the United States. Need for alternative vaccination strategies. JAMA 1990; 263: 12181222 6. Blumberg BS: Feasibility of controlling or eradicating the hepatitis B virus. Am J Med 1989; 87 (suppl 3A): 2S-4S 7. Hoofnagle JH: Toward universal vaccination against hepatitis B virus. NEnglJMed 1989; 321: 1333-1334
Conferences continuedfrom page 18
Other Conferences * Conferences diverses Jan. 6-10, 1992: Art Therapy Workshops for Depression and for Sexually Abused Individuals Toronto Art Therapy Institute Gilda Grossman, Toronto Art Therapy Institute, 216 St. Clair Ave. W, Toronto, ON M4V 1 R2; (416) 924-6221 Feb. 6-8, 1992: National Forum on Health Care EthicsDecision Making that Values Differences Westin Hotel, Ottawa Freda Fraser, director of communications, Catholic Health Association of Canada, 1247 Kilborn P1., Ottawa, ON K1H 6K9; (613) 731-7148 Feb. 6-10, 1992: International Conference of Dermatology and Venerology
8. Marwick C: Hepatitis B vaccine appears headed for pediatric immunization schedule. JAMA 1991; 265: 1502 9. Krahn M, Detsky AS: Universal vaccination against hepatitis B in North America: a cost effectiveness analysis [abstr]. Clin Res 1991; 39: 379A 10. Horowitz MM, Ershler WB, McKinney WP et al: Duration of immunity after hepatitis B vaccination: efficacy of a low dose booster vaccine. Ann Intern Med 1988; 108: 185-189 11. Couroce AM, LaPlanche A, Benhamou E et al: Long-term efficacy of hepatitis-B vaccination in healthy adults. In Zuckerman AJ (ed): Viral Hepatitis and Liver Disease, Liss, New York, 1988: 1002-1005 12. Wainwright RB, McMahon BJ, Bulkow LR et al: Duration of immunogenicity and efficacy of hepatitis B vaccine in a Yupik Eskimo population. JAMA 1989; 261: 2362-2366 13. Coursaget P, Yvonnet B, Chotard J et al: Seven-year study of hepatitis B vaccine efficacy in infants from an endemic area (Senegal). Lancet 1986; 2: 1143-1145 14. Tugwell P, Bennett K, Sackett D et al: The measurement iterative loop: a framework for the critical appraisal of need, benefits and costs of health interventions. J Chronic Dis 1985; 38: 339-351
Feb. 10-16, 1992: Sudden Infant Death Syndrome International Conference Sydney K. Fitzgerald, Sudden Infant Death Research Foundation Inc., 1227 Malvern Rd., Malvern, VIC 3144, Australia
Feb. 11-14, 1992: Asia-Pacific Burns Conference
Singapore Secretariat, Academy of Medicine, 16 College Rd., 01-01 College of Medicine Building, Singapore 0316 Feb. 11-14, 1992: 2nd International Conference on Recent Advances in Crisis Intervention and Community Mental Health Krishna Oberoi Hotel, Hyderabad, India International Conference Secretariat, 63 Nabcroft Lane, Crosland Moor, Huddersfield HD4 5DU, England; telephone 011-44-0484-658054, fax 011-44-0484654777
Cairo Meetings coordinator, Jefferson Center for International Dermatology, 1020 Locust St., Philadelphia, PA 19107; (215) 955-5785
Feb. 14-16, 1992: Asian Congress of Plastic Surgery
Les 7 et 8 fev. 1992: ler Congres international de lipoplastie H6tel Concorde Palm Beach Marseille Langue officielle:francais; traduction simultanee: anglais,
Feb. 16-20, 1992: International Congress on Cardiovascular Research Antwerp, Belgium Sr. S. De Nollin, Te Boelaerlei 23, 2140 Borgerhout, Belgium
italien Societe francaise de lipoplastie, 149, ave. du Prado, 13008 Marseille, France; telephone 01 1-33-91-25-46-66, fax 01 1-33-91-25-41-81 Feb. 9-16, 1992: Congress of the International Society of
Gynecological Endocrinology Madonna di Campiglio, Italy Prof. A.R. Genazzini, Universita di Modena, via dei Pozzo 71, 41100 Modena, Italy JANUARY 1, 1992
Singapore Secretariat, Academy of Medicine, 16 College Rd., 01 -01 College of Medicine Building, Singapore 0316
Feb. 19-22, 1992: Child Health 2000: World Congress and Exposition on Child Health Vancouver Trade and Convention Centre Child Health 2000, 200-1190 Melville St., Vancouver, BC V6E 3W1; (604) 684-3663, fax (604) 689-4806
continued on page 28 CAN MED ASSOC J
1992; 146 (1)
21
Universal hepatitis B vaccination: the economics of prevention Murray D. Krahn, MD, FRCPC; Allan S. Detsky, MD, PhD, FRCPC a major worldwide public health problem. About 300 million people, more than 5% of the world's population, are chronic carriers.' Of carriers with a life expectancy of more than 30 years 25% to 30% will die from complications of hepatitis B.2 Those who live with the disease often suffer for decades. Universal vaccination programs, many of which have been administered through the World Health Organization's Expanded Program on Immunization, have been instituted in highly endemic regions.3 Only recently, however, have universal programs been contemplated in areas of low endemicity, such as North America. Two factors account for this change in the direction of clinical policy. The first is the inexorable rise in the apparent burden of the disease in North America. Over the past 15 years the reported incidence and death rates have more than doubled in Canada,4 and similar trends have been observed in the United States.5 Even though the reported incidence rate is only remotely related to the true incidence rate (owing to subclinical illness, underreporting and misreporting) the increase in causespecific death rates4 implies that the true burden of hepatitis B is probably increasing. The second factor is the failure of the targeted "high-risk" vaccination strategy. Like acquired immunodeficiency syndrome hepatitis B has been labelled as a disease of people at high risk. Thus, apart from recently introduced prenatal screening programs in both Canada and the United States prevention efforts have been aimed solely at these people. This approach has shown at best mixed results. The reported incidence rate continues to rise, even though a vaccine has been available since 1982. Data from the four counties in Washington, Colorado, Alabama and Florida where the US Centers for
pepatitis B is
H
Disease Control maintain an intensive surveillance (no such Canadian program exists) have shown that the incidence rate among health care workers and homosexual men has fallen dramatically between 1982 and 1988;5 the decrease in the latter group most likely occurred more because of changes in high-risk behaviour than because of vaccine usage. But the rate among injection drug users nearly doubled, from 15% to 27% of reported cases. Moreover, the continuing increase in the number of reported cases due to heterosexual transmission has called into doubt the viability of the targeted approach. Various authors6'7 and advisory bodies, such as the National Advisory Committee on Immunization (NACI) (see page 36 of this issue), the Canadian Paediatric Society (see pages 25 to 28 of this issue) and the Advisory Committee on Immunization Practices,8 now advocate universal vaccination as the only feasible means of controlling hepatitis B. Are the rising burden of hepatitis B and the failure of current policies sufficient grounds for the introduction of a new technology or, in this case, the broad diffusion of an existing technology? After all, hepatitis B is still relatively rare and is not perceived to be a major public health burden in Canada, and the vaccine is expensive. How should this intervention be measured against cholesterol screening, coronary artery bypass surgery, organ transplantation and similar worthy interventions that compete for increasingly scarce health care resources? A rigorous accounting of the potential costs and benefits of a universal vaccination program (i.e., an economic evaluation or cost-effectiveness analysis performed in a manner that would allow comparison with other, unrelated health care programs) is required. We have completed such an analysis.9 The preliminary results were presented at the national meeting of the American Federation of Clinical program
From the departments of Medicine and Health Administration, University of Toronto, and the Division of General Internal Medicine and Clinical Epidemiology, Toronto Hospital, Toronto, Ont.
Reprint requests to: Dr. Allan S. Detsky, Rm. EN G-246, Toronto Hospital (General Division), 200 Elizabeth St., Toronto, ON M5G 2C4 JANUARY 1, 1992
CAN MED ASSOC J 1992; 146 (1)
19
Research on May 1 1, 1991, and have been reviewed by NACI. Many preliminary observations can be made about the components of the evaluation. The cost of vaccination, of which the vaccine price is the main component, is clearly a critical factor. Although prices have decreased in recent years a single pediatric dose still costs between $13 and $30 in Canada, depending on the manufacturer, the dose and whether vial splitting was used. The vaccine price is lower elsewhere in the world: in the United States it has been as little as $7 US per dose, and for mass vaccination programs in highly endemic areas it is less than $1 per dose. Our preliminary findings9 demonstrate that a universal vaccination policy could be economically attractive, but only at substantially lower vaccine prices. Because the pricing strategy of pharmaceutical companies is linked to sales, high-volume sales engendered by a universal strategy could lead to a substantial reduction in the price of the vaccine. On the other hand, it may be difficult to proceed without lower prices. Cooperation between funding agencies and vaccine manufacturers on the issues of volume and price is essential if the program is to be economically attractive. Just as important is the duration of vaccine efficacy. In North America hepatitis B is a disease of young adulthood, the incidence rate peaking among people 25 to 29 years of age.4 Unless a series of neonatal vaccinations provides protection for decades it is unlikely that universal vaccination will either be economically attractive or result in a significant reduction in the burden of the disease. The duration of immunity provided by vaccination is still uncertain; 5 years after vaccination 7% to more than 38% of adults may lose immunity (conventionally defined as a level of antibody to hepatitis B surface antigen [anti-HBs] of more than 10 mIU/mL).'0"' Vaccine responses in infants are less well characterized, but evidence suggests that neonates have lower peak anti-HBs titres and protective levels for shorter periods than adults.'2 '3 Finally, there is the issue of "immunologic memory." Many believe that protection against infection, especially against conversion to the carrier state (the most important function of the vaccine), extends far past the period of detectable anti-HBs levels. Because of the uncertainty surrounding the duration of vaccine effectiveness long-term monitoring of the immune status of vaccinated infants would be an important component in ensuring the effectiveness of a universal vaccination program. Should booster vaccinations become necessary, however, the program's economic attractiveness would be substantially reduced. The cost of long-term monitoring, the booster doses and the administration of such 20
CAN MED ASSOC J 1992; 146 (1)
doses would have to be included. The need for booster doses would mean some combination of additional physician visits and a new infrastructure for delivering the vaccine. Higher administrative costs and lack of an effective means of delivering the vaccine to adolescents and adults are the main reasons for vaccinating newborns in the first place, despite the probable greater efficacy of vaccinating adolescents. Finally, there is the issue of time and its effect on economic attractiveness via the discounting of future resources compared with present ones. Most health care programs have a time frame of 5, 10 or at most 20 years. Hepatitis B dictates a multidecade, intergenerational perspective, which is unusual, even for preventive health care programs. Incurring the costs of vaccination today results in savings in the future by preventing infection in 20 years and chronic liver disease, hepatoma and death in 60 years. Universal vaccination of infants would have virtually no impact on the disease for 15 to 20 years. Although some speak of universal programs as a means of eradicating the disease, analogous to the situation with smallpox, such a goal may well be overly ambitious. The passage of time will have other effects as well. Within the anticipated time frame many things may change. The cost of health care is going up, and innovative and ever more costly ways of caring for those with chronic liver disease from hepatitis B (e.g., liver transplantation and interferon therapy) continue to be developed. The exogenous burden of hepatitis B may rise because of increased emigration from countries of medium and high endemicity. Finally, the cost of vaccination will almost certainly fall. These changes will probably make universal hepatitis B vaccination increasingly attractive in the medium to long term. As mentioned earlier both NACI and the Canadian Paediatric Society now support a policy of universal childhood vaccination against hepatitis B. Given the current data our analysis9 suggests that a universal program appears to be an economically attractive use of resources if vaccine prices can be substantially reduced. It is essential, though, that the implementation of such a program be coupled with a means of monitoring the long-term effectiveness of the vaccine. Only then can we close the loop,'4 determine the ongoing effectivneess of the program and ensure a substantial reduction in the burden of hepatitis B. The cost-effectiveness analysis referred to in this editorial was funded by SmithKline Beecham Canada. Dr. Detsky was supported by a scholarship from the National Health Research and Development Program, Department of National Health and Welfare. LE 1 er JANVIER 1992
References 1. Maynard JE: Control of hepatitis B by immunization: global perspectives. In Zuckerman AJ (ed): Viral Hepatitis and Liver Disease, Liss, New York, 1988: 967-969 2. Szmuness W, Harley EJ, Ikram HI: Sociodemographic aspects of the epidemiology of liver disease. In Vyas GN, Cohen SN, Schmid R (eds): Viral Hepatitis, Franklin Inst Pr, Philadelphia, 1978: 17-21 3. Hepatitis Surveillance (rep 52), Centers for Disease Control, US Dept of Health and Human Services, Public Health Service, Atlanta, 1989 4. Hepatitis B in Canada: surveillance summary, 1980-1989. Can Dis Wkly Rep 1991; 17: 166-171 5. Alter MJ, Hadler SC, Margolis HS et al: The changing epidemiology of hepatitis B in the United States. Need for alternative vaccination strategies. JAMA 1990; 263: 12181222 6. Blumberg BS: Feasibility of controlling or eradicating the hepatitis B virus. Am J Med 1989; 87 (suppl 3A): 2S-4S 7. Hoofnagle JH: Toward universal vaccination against hepatitis B virus. NEnglJMed 1989; 321: 1333-1334
Conferences continuedfrom page 18
Other Conferences * Conferences diverses Jan. 6-10, 1992: Art Therapy Workshops for Depression and for Sexually Abused Individuals Toronto Art Therapy Institute Gilda Grossman, Toronto Art Therapy Institute, 216 St. Clair Ave. W, Toronto, ON M4V 1 R2; (416) 924-6221 Feb. 6-8, 1992: National Forum on Health Care EthicsDecision Making that Values Differences Westin Hotel, Ottawa Freda Fraser, director of communications, Catholic Health Association of Canada, 1247 Kilborn P1., Ottawa, ON K1H 6K9; (613) 731-7148 Feb. 6-10, 1992: International Conference of Dermatology and Venerology
8. Marwick C: Hepatitis B vaccine appears headed for pediatric immunization schedule. JAMA 1991; 265: 1502 9. Krahn M, Detsky AS: Universal vaccination against hepatitis B in North America: a cost effectiveness analysis [abstr]. Clin Res 1991; 39: 379A 10. Horowitz MM, Ershler WB, McKinney WP et al: Duration of immunity after hepatitis B vaccination: efficacy of a low dose booster vaccine. Ann Intern Med 1988; 108: 185-189 11. Couroce AM, LaPlanche A, Benhamou E et al: Long-term efficacy of hepatitis-B vaccination in healthy adults. In Zuckerman AJ (ed): Viral Hepatitis and Liver Disease, Liss, New York, 1988: 1002-1005 12. Wainwright RB, McMahon BJ, Bulkow LR et al: Duration of immunogenicity and efficacy of hepatitis B vaccine in a Yupik Eskimo population. JAMA 1989; 261: 2362-2366 13. Coursaget P, Yvonnet B, Chotard J et al: Seven-year study of hepatitis B vaccine efficacy in infants from an endemic area (Senegal). Lancet 1986; 2: 1143-1145 14. Tugwell P, Bennett K, Sackett D et al: The measurement iterative loop: a framework for the critical appraisal of need, benefits and costs of health interventions. J Chronic Dis 1985; 38: 339-351
Feb. 10-16, 1992: Sudden Infant Death Syndrome International Conference Sydney K. Fitzgerald, Sudden Infant Death Research Foundation Inc., 1227 Malvern Rd., Malvern, VIC 3144, Australia
Feb. 11-14, 1992: Asia-Pacific Burns Conference
Singapore Secretariat, Academy of Medicine, 16 College Rd., 01-01 College of Medicine Building, Singapore 0316 Feb. 11-14, 1992: 2nd International Conference on Recent Advances in Crisis Intervention and Community Mental Health Krishna Oberoi Hotel, Hyderabad, India International Conference Secretariat, 63 Nabcroft Lane, Crosland Moor, Huddersfield HD4 5DU, England; telephone 011-44-0484-658054, fax 011-44-0484654777
Cairo Meetings coordinator, Jefferson Center for International Dermatology, 1020 Locust St., Philadelphia, PA 19107; (215) 955-5785
Feb. 14-16, 1992: Asian Congress of Plastic Surgery
Les 7 et 8 fev. 1992: ler Congres international de lipoplastie H6tel Concorde Palm Beach Marseille Langue officielle:francais; traduction simultanee: anglais,
Feb. 16-20, 1992: International Congress on Cardiovascular Research Antwerp, Belgium Sr. S. De Nollin, Te Boelaerlei 23, 2140 Borgerhout, Belgium
italien Societe francaise de lipoplastie, 149, ave. du Prado, 13008 Marseille, France; telephone 01 1-33-91-25-46-66, fax 01 1-33-91-25-41-81 Feb. 9-16, 1992: Congress of the International Society of
Gynecological Endocrinology Madonna di Campiglio, Italy Prof. A.R. Genazzini, Universita di Modena, via dei Pozzo 71, 41100 Modena, Italy JANUARY 1, 1992
Singapore Secretariat, Academy of Medicine, 16 College Rd., 01 -01 College of Medicine Building, Singapore 0316
Feb. 19-22, 1992: Child Health 2000: World Congress and Exposition on Child Health Vancouver Trade and Convention Centre Child Health 2000, 200-1190 Melville St., Vancouver, BC V6E 3W1; (604) 684-3663, fax (604) 689-4806
continued on page 28 CAN MED ASSOC J
1992; 146 (1)
21
