Post-Trial Access To Antiretrovirals: Who Owes What To Whom?

Bioethics

Volumn 25, Issue 3, 2011, Pages 145-154

  Millum, Joseph ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

Antiretrovirals; ART; HIV AIDS; Post trial access

Indexed keywords

ANTIRETROVIRUS AGENT;

ARTICLE; BIOETHICS; CLINICAL TRIAL (TOPIC); ETHICS; HEALTH CARE DELIVERY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; RESEARCH SUBJECT;

ANTI-RETROVIRAL AGENTS; BIOETHICAL ISSUES; CLINICAL TRIALS AS TOPIC; HEALTH SERVICES ACCESSIBILITY; HIV INFECTIONS; HUMANS; RESEARCH SUBJECTS;

EID: 79551551489     PISSN: 02699702     EISSN: 14678519     Source Type: Journal    
DOI: 10.1111/j.1467-8519.2009.01736.x     Document Type: Article

References (57)

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6. World Medical Association. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects: Paragraph 33. 2008.
7. C. Slack et al. Provision of HIV Treatment in HIV Prevention Trials: A Developing Country Perspective. Soc Sci Med 2005; 60: 1197-1208 Assessment of the soundness of these arguments has been attempted elsewhere, and so, for the most part, I do not replicate it here. For some comprehensive critical evaluations see
8. C. Weijer & G.J. LeBlanc. The Balm of Gilead: Is the Provision of Treatment to those Who Seroconvert in HIV Prevention Trials a Matter of Moral Obligation or Moral Negotiation? J Law Med Ethics Winter 2006: 793-808.
9. I note other critical work as I consider particular arguments.
10. See Section 3.
11. J. Ananworanich et al. Creation of a Drug Fund for Post-Clinical Trial Access to Antiretrovirals. Lancet 2004; 364: 101-102.
12. E. Bass. Raising Hopes and Many Questions: Vaccine Trial Sponsors' New Approaches to Providing Antiretrovirals for Trial Volunteers. IAVI Report September 2003-January 2004.
13. S. Berkley. Thorny Issues in the Ethics of AIDS Vaccine Trials. Lancet 2003; 362: 992
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15. Lo et al. op. cit. note 2
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18. Examples include the President's Emergency Plan for AIDS Relief (PEPFAR), and the Global Fund To Fight AIDS, Tuberculosis and Malaria. This approach is mooted in Lo et al. op. cit. note 2.
19. R. Hogg et al. Life Expectancy of Individuals on Combination Antiretroviral Therapy in High-income Countries: a Collaborative Analysis of 14 Cohort Studies. Lancet 2008; 372: 293-299.
20. Lo et al. op. cit. note 2, 1229.
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22. US Department of Health and Human Services. 2005. Questions and Answers Regarding Guidance for Addressing the Provision of Antiretroviral Treatment for Trial Participants Following their Completion of NIH-Funded HIV Antiretroviral Treatment Trials in Developing Countries. [Accessed 2 July 2008]: Answers 1 and 5.
23. E.g., Council for International Organizations of Medical Sciences, World Health Organization. International Ethical Guidelines for Biomedical Research Involving Human Subjects. Geneva: CIOMS: Guideline 19. 2002.
24. Schüklenk & Ashcroft, op. cit. note 2, 168.
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26. Subsequent analysis of the data from the STEP vaccine trials suggested that the group at increased risk of HIV infection was uncircumcised men with pre-existing immunity to adenovirus type 5 (Ad5), the virus used as the carrier for the HIV genes in the vaccine (National Institute of Allergy and Infectious Diseases, NIH. 2008. NIAID Will Not Move Forward With The Pave 100 HIV Vaccine Trial. Bethesda, MD: NIH. Available at: [Accessed 12 Jan 2009]).
27. G. Jourdain et al. Perinatal HIV Prevention Trial Group. Intrapartum Exposure to Nevirapine and Subsequent Maternal Responses to Nevirapine-based Antiretroviral Therapy. N Engl J Med 2004; 351: 229-240.
28. S. Sungkanuparph et al. HIV-1 Genotype after Interruption of Non-nucleoside Reverse Transcriptase Inhibitor-based Antiretroviral Therapy and Virological Response after Resumption of the Same Regimen. Int J STD AIDS 2007; 18: 832-834.
29. A.N. Phillips et al. Interruption of Antiretroviral Therapy and Risk of Cardiovascular Disease in Persons with HIV-1 Infection: Exploratory Analyses from the SMART Trial. Antivir Ther 2008; 13: 177-187.
30. For analysis of the data on the risk-taking behavior of participants in HIV-prevention trials see Slack et al. op. cit. note 4. They conclude that there is no good evidence that overall risk behavior of trial participants increases, and that it is possible to identify specific individuals who may engage in more risky behavior. Schüklenk and Ashcroft address the implications of this analysis in U. Schüklenk & R. Ashscroft. HIV Vaccine Trials: Reconsidering the Therapeutic Misconception and the Question of What Constitutes Trial Related Injury. Dev World Bioeth 2007; 7(3): ii-iv.
31. J.F. Childress. Compensating Injured Research Subjects: I. The Moral Argument. Hastings Cent Rep, 1976; 6 6: 21-27.
32. H.S. Richardson, L. Belsky. The Ancillary-care Responsibilities of Medical Researchers. Hastings Cent Rep 2004; 34: 25-33. They define ancillary care as 'that which goes beyond the requirements of scientific validity, safety, keeping promises, or rectifying injuries'. (p. 26). Though their theory was developed to help determine the obligations of researchers during a trial, it is clear from Richardson's later uses that it applies to post-trial obligations as well.
33. N. Dickert et al. Ancillary-care Responsibilities in Observational Research: Two Cases, Two Issues. Lancet Space does not permit critical assessment of the account here (some critical reflections can be found in 2007; 369: 874-877
34. It is worth noting that the account incorporates a number of moral considerations - such as reciprocity and the duty of rescue - that I also consider separately in this paper. It is therefore unclear exactly what difference the relationship alone makes.
35. S. Richardson. Gradations of Researchers' Obligation to Provide Ancillary Care for HIV/AIDS in Developing Countries. Am J Public Health 2007; 97: 1956-1961.
36. For example, treatment trials sponsored by the National Institute of Allergy and Infectious Diseases at the US NIH vary in length from 12 weeks to 5 years (Seema Shah, personal communication).
37. Lo et al., op. cit. note 2
38. Macklin, op.cit. note 2.
39. I leave this idea of voluntary engagement vague, since there is not space for proper analysis of the precise limits of reciprocal duties here. It should not affect my central point.
40. Or people at risk for acquiring HIV/AIDS in the case of prevention studies.
41. F. Berger. Gratitude. Ethics 1975; 85: 298-309. For a classic analysis of duties of gratitude see
42. Space constraints and the relative weakness of duties of gratitude preclude my giving them serious consideration as an independent ground for an obligation to supply post-trial ART.
43. M. Merritt & C. Grady. Reciprocity and Post-Trial Access for Participants in Antiretroviral Therapy Trials. AIDS 2006; 20: 1791-1794 for a detailed analysis of whether and when it would be permissible to prioritize research participants for treatment, on the assumption that they are owed reciprocation by their compatriots.
44. For reasons of space I omit some of these considerations. For example, I have not considered the difficult question of how to measure someone's contribution, nor the relative merits of different sorts of contribution.
45. The relevant contribution for assessing desert is the ex ante contribution. This means that, in general, each participant in any particular trial will make the same sized contribution, and so deserve the same reward. In particular, in HIV prevention trials there is no difference in the contribution made to scientific knowledge by those who sero-convert and those who do not - each is equally important for assessing the effects of the study intervention (see Weijer and LeBlanc, op. cit. note 4, pp. 802-803 for a more complete argument to this effect). Note, however, that even if every participant deserves an equal benefit, it may still be appropriate to supply it by giving care just to those who are infected. The benefit supplied here would be the equivalent of giving each participant HIV-related health insurance. Finally, it is worth noting that if a trial enrolled different types of participants (e.g. healthy volunteers and patients) this might make a difference to their expected contributions and so to what they were owed as a matter of reciprocity.
46. Merritt & Grady, op. cit. note 30, 1792.
47. 2007. Human Development Report 2007/2008. United Nations Development Programme. New York: Palgrave Macmillan: 219-384.
48. 2007. Ethical considerations in biomedical HIV prevention trials. UNAIDS/WHO. Geneva: UNAIDS: 48.
49. K. Shapiro & S.R. Benatar. HIV Prevention Research and Global Inequality: Steps Towards Improved Standards of Care. J Med Ethics 2005; 31: 39-47
50. Treating People with Intercurrent Infection in HIV Prevention Trials: Report from a WHO/UNAIDS Consultation, Geneva July 17-18, 2003. AIDS 2004; 18: W4.WHO-UNAIDS Report.
51. I. Kant. 1996. The Metaphysics of Morals. Practical philosophy / Immanuel Kant. [1797] Mary J. Gregor, trans & ed.; general introduction by Allen Wood. Cambridge; New York: Cambridge University Press.
52. The duty of rescue is called a duty of 'specific beneficence' by Beauchamp and Childress, who give a more comprehensive list of the conditions under which it applies (T.L. Beauchamp & J.F. Childress. 2001. Principles of Biomedical Ethics 5th edn. New York: Oxford University Press: 171).
53. General duties are possessed by moral agents just in virtue of their agency, and owed to moral patients just in virtue of their moral status.
54. One important debate concerns the extent to which considerations of justice apply internationally. Some argue that the requirements of distributive justice that apply to the basic structure of a nation state are much more stringent than those that apply to the global order (e.g. J. Rawls. 1999. The Law of Peoples; with 'The Idea of Public Reason Revisited'. Cambridge, Mass.: Harvard University Press). Others think that justice applies globally just as much as it applies nationally (e.g. C.R. Beitz. 1979. Political Theory and International Relations. Princeton, NJ: Princeton University Press).
55. Indeed, if they are conducting research that responds to the health needs of poor communities, researchers may be already playing their part in correcting injustice (cf. Weijer & LeBlanc, op. cit. note 4, p. 804).
56. Similar considerations would apply if the justification cited historical instead of present injustices. For example, rich countries might owe poorer countries reparations for the harms of colonialism. Again, however, these reparations would not be owed to research participants in particular.
57. Whatever the reason for the obligations being acquired, the cost of doing so should be shared fairly among the citizens. Except in the case where a fair share would mean burdening only those citizens with HIV/AIDS, this implies that whatever the costs imposed on citizens with HIV/AIDS, they would be outweighed by the increase in provision of ART.