The highest attainable standard: Ethical issues in AIDS vaccines

Science

Volumn 279, Issue 5348, 1998, Pages 186-188

  Bloom, Barry R ^a,b  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b UNAIDS   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

HUMAN IMMUNODEFICIENCY VIRUS VACCINE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; HUMAN; IMMUNIZATION; INFECTION PREVENTION; MEDICAL ETHICS; MEDICAL RESEARCH; PRIORITY JOURNAL; SHORT SURVEY;

BIOMEDICAL AND BEHAVIORAL RESEARCH; CODES OF ETHICS; COUNCIL FOR INTERNATIONAL ORGANIZATIONS OF MEDICAL SCIENCES; DECLARATION OF HELSINKI; HEALTH CARE AND PUBLIC HEALTH; INTERNATIONAL ASPECTS; INTERNATIONAL ETHICAL GUIDELINES FOR BIOMEDICAL RESEARCH INVOLVING HUMAN SUBJECTS; STANDARDS; THERAPEUTIC RESEARCH; UNAIDS; UNITED NATIONS; WORLD HEALTH ORGANIZATION;

AIDS VACCINES; ANTI-HIV AGENTS; CLINICAL TRIALS; CODES OF ETHICS; CONTROLLED CLINICAL TRIALS; DEVELOPED COUNTRIES; DEVELOPING COUNTRIES; ETHICAL REVIEW; ETHICS, MEDICAL; HIV INFECTIONS; HUMAN EXPERIMENTATION; HUMANS; INTERNATIONALITY; PLACEBOS; PRACTICE GUIDELINES; THERAPEUTIC HUMAN EXPERIMENTATION; UNITED NATIONS;

HUMAN IMMUNODEFICIENCY VIRUS;

EID: 0032498209     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.279.5348.186     Document Type: Short Survey

References (24)

1. Trials can create a demand by proving to the local community that an effective treatment or vaccine is available. For example, although Hemophilus influenzae B and hepatitis B vaccines are highly effective and are recommended by WHO for universal immunization, they are currently used in only a minority of national vaccine programs.
2. M. Angell, N. Engl. J. Med. 337, 847 (1997); P. Lurie and S. M. Wolfe, ibid., p. 853; H. Varmus and D. Satcher, ibid., p. 1003.
3. M. Angell, N. Engl. J. Med. 337, 847 (1997); P. Lurie and S. M. Wolfe, ibid., p. 853; H. Varmus and D. Satcher, ibid., p. 1003.
4. M. Angell, N. Engl. J. Med. 337, 847 (1997); P. Lurie and S. M. Wolfe, ibid., p. 853; H. Varmus and D. Satcher, ibid., p. 1003.
5. J. W. Mellors et al., Ann. Intern. Med. 126, 12946 (1997).
6. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research [U.S. Government Printing Office (GPO 887-809), 1988]; Code of Federal Regulations, Regulations on the Protection of Human Subjects, Title 45, Part 46 (45CFR46), Title 21, Parts 50 and 56 (21CFR50, 21CFR56); U.S. Public Health Service, Consultation on International Collaborative Human Immunodeficiency Virus (HIV) Research (Assistant Secretary for Health, Department of Health and Human Services, Washington, DC, (1990).
7. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research [U.S. Government Printing Office (GPO 887-809), 1988]; Code of Federal Regulations, Regulations on the Protection of Human Subjects, Title 45, Part 46 (45CFR46), Title 21, Parts 50 and 56 (21CFR50, 21CFR56); U.S. Public Health Service, Consultation on International Collaborative Human Immunodeficiency Virus (HIV) Research (Assistant Secretary for Health, Department of Health and Human Services, Washington, DC, (1990).
8. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research [U.S. Government Printing Office (GPO 887-809), 1988]; Code of Federal Regulations, Regulations on the Protection of Human Subjects, Title 45, Part 46 (45CFR46), Title 21, Parts 50 and 56 (21CFR50, 21CFR56); U.S. Public Health Service, Consultation on International Collaborative Human Immunodeficiency Virus (HIV) Research (Assistant Secretary for Health, Department of Health and Human Services, Washington, DC, (1990).
9. For Europe, see Council of Europe, Convention on Human Rights and Biomedicine (Strasbourg, 1997); M. A. M. deWachter, Hastings Center Report 27, 13 (1997); and F. W. Dommel and D. Alexander, Kennedy Inst. Ethics J. 7, 259 (1997).
10. For Europe, see Council of Europe, Convention on Human Rights and Biomedicine (Strasbourg, 1997); M. A. M. deWachter, Hastings Center Report 27, 13 (1997); and F. W. Dommel and D. Alexander, Kennedy Inst. Ethics J. 7, 259 (1997).
11. For Europe, see Council of Europe, Convention on Human Rights and Biomedicine (Strasbourg, 1997); M. A. M. deWachter, Hastings Center Report 27, 13 (1997); and F. W. Dommel and D. Alexander, Kennedy Inst. Ethics J. 7, 259 (1997).
12. Declaration of Helsinki [World Medical Association, Ferney-Voltaire, France, 1964 (revised 1974, 1983, 1989, and 1996)].
13. CIOMS, in collaboration with WHO, International Ethical Guidelines for Biomedical Research Involving Human Subjects [CIOMS, Geneva, Switzerland, 1982 (revised in 1993)].This document contains 15 guidelines that address fundamental ethical principles relating to the need for informed consent and freedom to withdraw from studies; the use of children, prisoners, and vulnerable populations in research; undue inducements to participate in trials; indemnification for injuries suffered as a consequence of the research; and mechanisms for ethical review, among others.
14. C. C. Carpenter et al., J. Am. Med. Assoc. 277, 1962 (1997). A draft set of revised Centers for Disease Control guidelines is currently under review. British HIV Association Guidelines, Lancet 349, 1086 (1997). Early initiation of treatment with combination chemotherapy including protease inhibitors is recommended in the U.S. guidelines prepared by the International AIDS Society-USA Panel. In contrast, the U.K. guidelines recommend treatment initially only with anti-reverse transcriptase drugs and inclusion of protease inhibitors in therapy only at later stages of disease.
15. C. C. Carpenter et al., J. Am. Med. Assoc. 277, 1962 (1997). A draft set of revised Centers for Disease Control guidelines is currently under review. British HIV Association Guidelines, Lancet 349, 1086 (1997). Early initiation of treatment with combination chemotherapy including protease inhibitors is recommended in the U.S. guidelines prepared by the International AIDS Society-USA Panel. In contrast, the U.K. guidelines recommend treatment initially only with anti-reverse transcriptase drugs and inclusion of protease inhibitors in therapy only at later stages of disease.
16. Povl Riis, chairman of the Central Scientific-Ethical Committee of Denmark, a member of the committee that drafted the Helsinki Declaration in 1974 and a co-author of the "best proven therapeutic method" sentence in the declaration, has indicated that "In the seventies we focused mainly on clinical-pharmacological trials in developed countries. During the last 15 years, the Danish Committee System has interpreted the above sentence" as implicitly qualified by ". . . in accordance with national accessibility," and "with the indispensable condition that the project is of great importance to the developing country and consequently is not intending to test drugs or methods of primary interest to the donating country." (P. Riis, personal communication).
17. D. Greco et al., N. Engl. J. Med. 334, 341 (1996); L. Gustafsson et al., ibid., p. 349 (1996). Another example is the cholera vaccine trials in Bangladesh in the 1960s, in which children in the unvaccinated experimental groups, if not protected by the vaccine, were at risk for rapid death from dehydration. A system was put in place for the trial to allow rapid oral rehydration to any child in the trial contracting cholera. That system remains in place. W. E. Van Heyningen and J. Seale, Cholera: The American Scientific Experience, 1947-1980 (Westview, Boulder, CO, 1983).
18. D. Greco et al., N. Engl. J. Med. 334, 341 (1996); L. Gustafsson et al., ibid., p. 349 (1996). Another example is the cholera vaccine trials in Bangladesh in the 1960s, in which children in the unvaccinated experimental groups, if not protected by the vaccine, were at risk for rapid death from dehydration. A system was put in place for the trial to allow rapid oral rehydration to any child in the trial contracting cholera. That system remains in place. W. E. Van Heyningen and J. Seale, Cholera: The American Scientific Experience, 1947-1980 (Westview, Boulder, CO, 1983).
19. D. Greco et al., N. Engl. J. Med. 334, 341 (1996); L. Gustafsson et al., ibid., p. 349 (1996). Another example is the cholera vaccine trials in Bangladesh in the 1960s, in which children in the unvaccinated experimental groups, if not protected by the vaccine, were at risk for rapid death from dehydration. A system was put in place for the trial to allow rapid oral rehydration to any child in the trial contracting cholera. That system remains in place. W. E. Van Heyningen and J. Seale, Cholera: The American Scientific Experience, 1947-1980 (Westview, Boulder, CO, 1983).
20. The World Bank, World Development Report 1993, Investing in Health (Oxford Univ. Press, 1993).
21. UNAIDS Programme, Geneva, Switzerland.
22. C. J. W. Murray and A. Lopez, Eds., The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries and Risk Factors in 1990 and Projected to 2020, Vol. 1. (Harvard Univ. Press, Cambridge, MA, 1996).
23. UNAIDS, Ethical Considerations in Clinical Trials of Preventive HIV Vaccines, proceedings of a meeting held 23 to 24 September 1997 (UNAIDS, Geneva, Switzerland, 1997).
24. Many of the ideas in this article derive from discussions with the participants at the UNAIDS meeting (12). I thank R. Macklin for her critical reading of the manuscript; P. Riis for permission to quote from his letter to me; J. Esparza, D. Guenter, and S. Kalibala of UNAIDS for current AIDS statistics; J. Weber for guidelines for care in the United Kingdom; R. Glass for information on the cholera vaccine trials; and J. LaMontagne for information on the acellular pertussis vaccine trials. I thank D. Baltimore, M. L. Clements Mann, M Johnston, P. Fast, A. Fauci, C. Grady, D. Ho, J. Mann, D. Richmond, P. Smith, and H. Varmus for thoughtful comments on the manuscript and R. Levine, M. Sommerville, and E. Mbidde for helpful discussions.