ARTICLES

The protection of participants in clinical research in Africa: Does domestic human rights law have a role to play?

Annelize Nienaber

Senior Lecturer, Faculty of Law, University of Pretoria, South Africa

SUMMARY

This article investigates the protection of clinical research participants in sub-Saharan Africa by domestic human rights instruments. It assesses the weaknesses in the existing regulatory framework in the form of international and national ethical guidelines, and surveys domestic human rights law in selected African countries to ascertain whether domestic human rights law may be used to augment and enhance the existing system of protection. It concludes that domestic human rights law has an important (if hitherto unutilised) role to play in the protection of clinical research participants in sub-Saharan Africa.

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* BA (Hons) (Wits) LLB, LLM, LLD (Pretoria); annelize.nienaber@up.ac.za The article draws on sections of the writer's unpublished doctoral thesis, entitled 'Ethics and human rights in HIV-related clinical trials in Africa with specific reference to informed consent in preventative HIV vaccine efficacy trials in South Africa', University of Pretoria, 2007.
1 Also known a 'mother-to-child-transmission' or MTCT.
2 See M Angell 'The ethics of clinical research in the Third World' (editorial) (1997) 337 The New England Journal of Medicine 847;         [ Links ] H Varmus & D Satcher 'Ethical complexities of conducting research in developing countries' (1997) 337 The New England Journal of Medicine 1003;         [ Links ] P Lurie & SM Wolfe 'Unethical trials of interventions to reduce perinatal transmission of the Human Immunodeficiency Virus in developing countries' (1997) 337 The New England Journal of Medicine 854.         [ Links ] The controversy concerned the use of a placebo in the trial where a known effective treatment exists. Such a trial would not have been allowed in the developed world, as it would have violated various principles of research ethics, such as art II.3 of the Declaration of Helsinki.
3 A 'placebo' is a dummy treatment or no treatment at all. Usually sugar tablets are given to the placebo or control group in a clinical trial, instead of the medication that is being studied.
4 Angell (n 2 above) 847. The Declaration of Helsinki, issued by the World Medical Association (WMA), is an international code of ethics overseeing biomedical research involving human participants. The Declaration of Helsinki was adopted by the WMA's 18th Assembly, held in Helsinki, Finland, in 1964, and has been revised several times, most recently in October 2000.
5 R Bayer 'The debate over maternal-fetal HIV transmission prevention trials in Africa, Asia, and the Caribbean: Racist exploitation or exploitation of racism?' (1998) 88 American Journal of Public Health 568.         [ Links ] Such a trial would be considered unethical because it is not trying to find an intervention that is at least as effective as, or better than the prevailing standard of care (the 076 regimen of AZT). Several authors have subsequently commented upon the views expressed by Angell in her editorial. See eg H Vermus & D Satcher 'Ethical complexities of conducting research in developing countries' (1997) 337 The New England Journal of Medicine 1003.         [ Links ] Varmus and Satcher argue that placebo-controlled trials alone are able to provide definitive and clear answers about whether the interventions have worked and maintain that no clear answer would be gained by testing two or more interventions of unknown benefit against each other as it would not become clear whether either intervention would be more effective than no intervention. A more recent response to Angell is presented by EJ Emanuel 'The ethics of placebo-controlled trials - A middle ground' (2001) 345 The New England Journal of Medicine 915.         [ Links ]
6 Angell (n 2 above) 848. See also the sources referred to in n 26 below.
7 See A Nienaber 'The protection of clinical research participants in Africa by the African regional human rights system' (forthcoming).         [ Links ]
8 UNAIDS (2006) AIDS epidemic update 6; 58% of them are women.
9 See below.
10 UNAIDS (n 8 above) 20. See Table A below.
11 Nuffield Council on Bioethics The ethics of research related to healthcare in developing countries (2002) 20.         [ Links ]
12 Information in both tables from WHO (2007) World Health Statistics 2007. These are the same countries that are included in the study of constitutional provisions of countries in sub-Saharan Africa (para 4 below).
13 Of the population.
14 Of the population.
15 Gross Domestic Product. The figure is that of 2004.
16 Nuffield Council on Bioethics (n 11 above) 21.
17 SR Benatar 'The HIV/AIDS pandemic: A sign of instability in a complex global system' in AA van Niekerk & LM Kopelman (eds) Ethics and AIDS in Africa: The challenge to our thinking (2005) 75.         [ Links ]
18 Benatar (n 17 above) 83.
19 The Nuffield Council on Bioethics was established by the Trustees of the Nuffield Foundation in 1991 to identify, examine and report on the ethical questions raised by recent advances in biological and medical research. Since 1994, if has been funded jointly by the Nuffield Foundation, the Medical Research Council and The Wellcome Trust http://www.nuffieldbioethics.org/go/print/aboutus/page_2.html (accessed 15 January 2008).
20 CRD Health research: Essential link to equity in development (1990).         [ Links ]
21 Nuffield Council on Bioethics (n 11 above) 22.
22 As above.
23 As above.
24 n 21 above.
25 It is also self-evident that, despite the prevailing circumstances, research sponsored by developed countries and carried out in developing countries need not, by definition, be exploitative.
26 See eg R Macklin Double standards in medical research in developing countries (2004) chs 1, 3 & 4;         [ Links ] DB Resnik 'Exploitation in biomedical research' (2003) 24 Theoretical Medicine 233;         [ Links ] DM Carr 'Pfizer's epidemic: A need for international regulation of human experimentation in developing countries' (2003) 35 Case Western Reserve Journal of International Law 15.         [ Links ]
27 J Ford & G Tomossy 'Clinical trials in developing countries: The plaintiff's challenge' (2004) 1 Law, Social Justice and Global Development 3.         [ Links ]
28 As above; eg Malawi, Tanzania and Zambia lack legally binding informed consent procedures (see BM Meier 'International protection of persons undergoing medical experimentation: Protecting the right of informed consent' (2002) 20 Berkeley Journal of International Law 533,         [ Links ] fn 124).
29 Kelleher writes: 'Because their impoverished governments would otherwise be unable to provide medical treatment to their citizens, host countries - African nations in particular - have no legislative protection for subjects of clinical trials. Researchers in such countries, faced with dire medical conditions, understaffed hospitals, language and cultural barriers, and research subjects who would otherwise have no access to medical treatment, thus find it expedient to violate the minimum ethical standards for the protection of human subjects' (F Kelleher 'The pharmaceutical industry's responsibility for protecting human subjects in clinical trials in developing nations' (2004-2005) 38 Columbia Journal on Law and Society 67).         [ Links ]
It should be noted that Kelleher's statement does not present the whole truth. In several African countries, local ethical guidelines exist over and above international guidelines. As well, in many instances a great deal of effort has been put into educating researchers about the content of ethical guidelines and into building the capacity of research ethics committees. Rather, the problem lies with enforcing these guidelines - see below.
30 Meier (n 28 above) 532.
31 Meier (n 28 above) 533.
32 See RJ Levine Ethics and regulation of clinical research (1986) 12-13;         [ Links ] 425-427 for more on the history and promulgation of these codes of ethics.
33 Meier (n 28 above) 531.
34 As above.
35 Kenya is included in the survey, although its Constitution may be suspended in the light of recent events in that country.
36 Constitutional Law of the Republic of Angola, adopted 25 August 1992; http://www.chr.up.ac.za/hr_docs/constitutions/ docs/Angola%20Constitution(rev).doc (accessed 31 January 2008).         [ Links ]
37 Arts 18 & 20 Constitutional Law of the Republic of Angola.
38 Art 47 Constitutional Law of the Republic of Angola.
39 Art 30 Constitutional Law of the Republic of Angola.
40 Arts 18 & 29(2) Constitutional Law of the Republic of Angola.
41 Constitution of the Republic of Benin, adopted 2 December 1990; http://www.chr.up.ac.za/hr_docs/constitutions/ docs/BeninC(englishsummary)(rev).doc (accessed 31 January 2008).         [ Links ] Interestingly, the Benin Constitution incorporates the human rights guaranteed by the African Charter in its Bill of Rights (see art 7 Constitution of the Republic of Benin).
42 Art 26 Constitution of the Republic of Benin.
43 Constitution of Botswana, adopted in 1966, last amended in 1999; http://www.chr.up.ac.za/hr_docs/constitutions/docs/Botswana (summary)(rev).doc (accessed 31 January 2008).         [ Links ]
44 Art 9 Constitution of Botswana. However, the right to privacy is limited by, amongst others, anything that is 'reasonably required in the interests of public health'.
45 This article may be relied upon by proponents of mandatory or 'opt out' HIV testing in public hospitals in Botswana.
46 Constitution of Burundi, 2004; http://democratie.francophonie.org/article.php37id_ article=368&id_rubrique=94 (accessed 31 January 2008).         [ Links ]
47 Constitution of the Republic of the Congo, 1992; http://www.chr.up.ac.za/hr_docs /constitutions/docs/CongoC%20(english%20summary)(rev).doc (accessed 31 January 2008).         [ Links ]
48 Art 8 Constitution of the Republic of the Congo.
49 Art 14 Constitution of the Republic of the Congo. This provision may be limited to privacy of the home.
50 Art 20 Constitution of the Republic of the Congo.
51 Art 30 Constitution of the Republic of the Congo.
52 Art 31: 'The state has the obligation to assist the family in its mission as guardian of the morality and the traditional values recognised by the community. The rights of the mother and the child are guaranteed.'
53 Art 34 Constitution of the Republic of the Congo.
54 Constitution of Eritrea, adopted by the Constituent Assembly on 23 May 1997; http://www.chr.up.ac.za/hr_docs/constitutions/docs/EritreaC.pdf (accessed 31 January 2008).         [ Links ]
55 Constitution of the Federal Democratic Republic of Ethiopia; http://www.chr.up.ac.za/hr_docs/constitutions/docs/ EthiopiaC(rev).doc (accessed 31 January 2008).         [ Links ]
56 Constitution of the Republic of Ghana, 1991; http://www.chr.up.ac.za/hr_docs/constitutions/docs/GhanaC.pdf (accessed 31 January 2008).         [ Links ]
57 Constitution of Kenya, adopted in 1963 and amended in 1999; http://www.chr.up.ac.za/hr_docs/constitutions/docs/KenyaC(rev).doc (accessed 31 January 2008).         [ Links ]
58 Art 76(1) Constitution of Kenya.
59 Art 82 Constitution of Kenya.
60 Art 82(4)(b) Constitution of Kenya.
61 Art 37 Proposed New Constitution of Kenya, 2005.
62 Art 38 Proposed New Constitution of Kenya.
63 Constitution of Lesotho, adopted in 1993, amended 1996, 1997, 1998 and 2001; http://www.chr.up.ac.za/hr_docs/constitutions/docs/ LesothoC(summary)(rev).doc (accessed 31 January 2008).         [ Links ]
64 Art 18(3) Constitution of Lesotho.
65 Arts 4(b) & (c) Constitution of Lesotho.
66 So-called 'directive principles of state policy' and 'fundamental objectives of state policy' (see the Constitution of Nigeria below) are not justiciable human rights. Rather, they serve as a guide to the executive or legislature in the exercise of their functions. They are often used by the judiciary as a guide to the interpretation of the Constitution and other laws.
67 Constitution of the Republic of Malawi, entered into force on 18 May 1994; http://www.chr.up.ac.za/hr_docs/constitutions/docs/MalawiC.pdf (accessed 31 January 2008).         [ Links ]
68 Arts 23 & 24 Constitution of Malawi.
69 Constitution of the Republic of Mali, adopted in 1992; http://www.chr.up.ac.za/hr_docs/constitutions/docs/ MaliC(rev).doc (accessed 31 January 2008).         [ Links ]
70 Art 17 Constitution of the Republic of Mali.
71 Constitution of Mozambique 2005;http://www.chr.up.ac.za/hr_docs/constitutions/docs /Mozambique.doc (accessed 31 January 2008).         [ Links ]
72 Art 35 Constitution of Mozambique.
73 Constitution of Namibia, adopted in February 1990, amended on 24 December 1998; http://www.chr.up.ac.za/hr_docs/constitutions/docs/Namibia C(rev).doc (accessed 31 January 2008).         [ Links ]
74 Constitution of the Federal Republic of Nigeria, entered into force on 29 May 1999; http://www.nigeria-law.org/ConstitutionOfTheFederalRepublicOfNigeria.htm#Chapter_1 (accessed 31 January 2008).         [ Links ]
75 See n 66 above.
76 My emphasis.
77 Constitution of the Republic of Senegal, adopted on 7 January 2001; http://www.chr.up.ac.za/hr_docs/constitutions/docs/ SenegalC%20(english%20summary)(rev).doc (accessed 31 January 2008).         [ Links ]
78 Constitution of the Republic of South Africa 1996.
79 Constitution of the Kingdom of Swaziland, 2005; http://www.chr.up.ac.za/hr_docs/constitutions/docs/Swaziland.doc (accessed 31 January 2008).         [ Links ]
80 Art 20(1)(2) Constitution of the Kingdom of Swaziland 2005.
81 Arts 22(1)(a) & 22(2)(a) Constitution of the Kingdom of Swaziland 2005.
82 Art 27(4) Constitution of the Kingdom of Swaziland 2005.
83 Constitution of the United Republic of Tanzania, 1998, incorporates and consolidates all amendments made in the Constitution since its enactment by the Constituent Assembly in 1977 up to 1998; http://www.chr.up.ac.za/hr_docs/constitutions/docs/TanzaniaC.pdf (accessed 31 January 2008).         [ Links ]
84 Constitution of the Republic of Uganda, 1995; http://www.chr.up.ac.za/hr_docs/constitutions/docs/Uganda C(rev).doc (accessed 31 January 2008).         [ Links ]
85 Art 33(6) Constitution of the Republic of Uganda 1995.
86 Constitution of Zambia, as amended by Act 18 of 1996; http://www.chr.up.ac.za/hr_docs/constitutions/docs/ZambiaC (rev).doc (accessed 31 January 2008).         [ Links ]
87 Draft Constitution of Zambia Cap 1.
88 Art 41(5) Draft Constitution of Zambia.
89 Constitution of the Republic of Zimbabwe, as amended to no 16 of 20 April 2000 (amendments in terms of Act 5 of 2000 (Amendment 16) are at sections 16, 16A (Land Acquisition) and 108A (Anti-Corruption Commission)); http://www.chr.up.ac.za/hr_docs/constitutions/docs/ ZimbabweC(rev).doc (accessed 31 January 2008).
90 Such benefit may take many forms, such as increased access to anti-retrovirals, antinatal health care or cancer treatment only available at the research site.
91 In this regard, see the South African case of NM & Others v Smith & Others (Freedom of Expression Institute as Amicus Curiae) 2007 7 BCLR 751 (CC), which affirms the notion that the unauthorised disclosure of research participants' HIV status during a preventive HIV-related clinical trial or thereafter constitutes a violation of participants' rights to privacy, dignity and psychological integrity.
92 See eg SMC Smith 'Misinforming the uninformed? Issues of informed consent in the multicultural context of HIV vaccine trials' unpublished BHons dissertation, University of the Witwatersrand, 2004.         [ Links ] Also see NJ Ives et al 'Does an HIV clinical trial information booklet improve patient knowledge and understanding of HIV clinical trials?' (2001) 2 HIV Medicine 241,         [ Links ] who conclude that, while participants' general knowledge and understanding of clinical trials improved over time, this was not improved by the informed consent process and information booklet and that their recollection of the details of the trial protocols remained poor.
93 This omission may be ascribed to a variety of reasons which are explored in a different context; see AG Nienaber 'Ethics and human rights in HIV-related clinical trials in Africa with specific reference to informed consent in preventative HIV vaccine efficacy trials in South Africa' unpublished LLD thesis, University of Pretoria, 2007 478-482.         [ Links ]
94 Here open-ended constitutional provisions on equality, such as those including the words 'other status', were taken to indicate a possibility of 'reading in' the protection of people living with HIV/AIDS, or people perceived to be living with HIV/AIDS. This study surveys only constitutional provisions; no account is given of protections provided by other legislation in force in those countries.
95 Art 21 Constitution of Eritrea.
96 Art 27 Constitution of the Republic of South Africa 1996.
97 See para 2 above.
98 There are further, non-legal, consequences in a rights-based approach. Human rights may be used to question the status quo, the established way in which things are done; F Viljoen 'The obligations of governments in a time of HIV and AIDS' (2005) 15 Interights Bulletin 47).         [ Links ] Viljoen speculates that a rights-based approach, as an alternative way of seeing and thinking about experience, extends outside the courtroom; that human rights discourse is 'a language of moral authority that may be used in many ways, such as lobbying for reform or mobilising and strengthening social movements' (Viljoen 47-48).