Abstract
At present, considerable numbers of research projects are conducted on a multinational basis. Teams of researchers based in different States may participate in a single project. Furthermore, internationally-based organizations may be able to choose the country in which a particular research project that they are conducting or funding is carried out. This has led to concerns being expressed about the possibility of fundamentally different standards of protection for participants being applied in different countries. The issue of double standards has increasingly become part of regulatory frameworks in biomedical research. This paper reviews and compares the 2008 version of the WMA Declaration of Helsinki with existing guidelines and rules on research in developing countries adopted by intergovernmental (UNESCO, WHO, Council of Europe, EU) and non-governmental (CIOMS, WMA) organisations. The paper concludes with some reflections on the issues which need to be addressed in the future to achieve solidarity, in line with the EU Charter of Fundamental Rights which proclaims in its preamble that:
The Union is founded on the indivisible and universal values of human dignity, freedom, equality and solidarity. (EU Charter of Fundamental Rights 2009)
Therefore, research activities involving human subjects cannot exclusively be assimilated to an economic activity subject to market rules. On the contrary, in the context of solidarity, regarding health as a public good rather than a commodity, it needs to be regulated according to fundamental principles.
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Notes
- 1.
There are several explanations of this trend to transfer clinical trials (mainly Phase III-IV) to developing countries. First of all, drug companies can obtain substantial cost savings by conducting trials in developing countries. A first-rate academic medical centre in India, for instance, charges between $ 1,500 and $ 2,000 per case report, less than one tenth of the cost at a second-tier centre in the US. According to the FDA registry as of January 2011, approximately 30% of the clinical trials of the biggest US pharmaceutical companies are carried out in developing countries (Sub-Saharan Africa, South America, South East Asia) and in States of Eastern Europe (www.fda.gov/).
- 2.
United Nations, General Assembly Resolution 55/2 of 8 September 2000.
- 3.
The right to health is foreseen in several international treaties and declarations. The Preamble of the WHO Constitution underlines that the enjoyment of the highest attainable standard of health is a fundamental human right. The ICESCR establishes in Article 12 the right to enjoy the highest attainable standard of health through steps including: (1) Provisions for reducing stillbirth rate, childhood mortality, and development of the child; (2) improvement of environmental and industrial hygiene; (3) prevention, treatment and control of epidemic, endemic and other diseases; and (4) creation of conditions assuring all medical services and attention. The African Charter on Human and Peoples’ Rights of 1981 foresees in Article 16 the “right to enjoy the best attainable state of health through necessary measures to protect health and ensure medical attention to the sick”. Similar provisions are also contained in the American Declaration of the Rights and Duties of Man of 1948 (Article XI), the European Social Charter of 1961 (Article 11), the Additional Protocol on Economic, Social and Cultural Rights to the Inter-American Convention of 1988 (Article X), the UN Convention on the Rights of the Children of 1989 (Article XXIV), the Council of Europe Convention on Human Rights and Biomedicine of 1997 (Article III), and the UN Convention on the Rights of People with Disabilities of 2006 (Article XXV).
- 4.
All four Geneva Conventions of international humanitarian law of 12 August 1949 list among the grave violations, which all parties are required to punish, “wilful killing, torture or inhuman treatment, including biological experiments”. The 1998 Rome Statute of the International Criminal Court defines “war crimes” in Article 2 as: “Grave breaches of the Geneva Conventions of 12 August 1949, namely, any of the following acts against persons or property protected under the provisions of the relevant Geneva Convention: […] Torture or inhuman treatment, including biological experiments; [and] wilfully causing great suffering, or serious injury to body or health”. In addition, Article 2(b) lists the following as serious violations of the laws and customs applicable in international armed conflict: “Subjecting persons who are in the power of an adverse party to physical mutilation or to medical or scientific experiments of any kind which are neither justified by the medical, dental, or hospital treatment of the person concerned, nor carried out in his or her interest, and which cause death to or seriously endanger the health of such person or persons.”
- 5.
SG/SM/11004/GA/10595 AIDS/131 of 21 May 2007. See, also, Report of the Secretary-General, Uniting for Universal Access: Towards Zero New HIV Infections, Zero Discrimination and Zero AIDS-Related Deaths, 28 March 2011, A/65/797.
- 6.
The right to health care is a social right from which stem some duties the States have towards their citizens. It must not be confused with the right to health that, as outlined by Roscam Abbing in 1979, can never be obtained, as it implies the right of everybody to a given god which cannot be formulated objectively.
- 7.
The term “standard of care” can be defined as “the nature of the care and treatment that will be provided to participants in research”. See National Bioethics Advisory Commission (NBAC) (2001), Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries. Volume I: Report and Recommendation of the NBAC.
- 8.
With reference to HIV/AIDS, according to the UN General Committee on Economic, Social and Cultural Rights (General Comment no. 14 of 11 May 2000), Article 12.2 (C) of the ICESCR “requires the establishment of prevention and education programs for behavioural-related health concerns such as sexually transmitted diseases, in particular HIV/AIDS and those adversely affecting sexual and reproductive health, and the promotion of social determinants of good health and the promotion of social determinants of good health, such as environmental safety, education, economic development and gender equity. […]. The control of disease refers to States’ individual and joint efforts to, inter alia, make available relevant technologies, using and improving epidemiological surveillance and data collection on a disaggregated basis, the implementation or enhancement of immunization programs and other strategies of infectious diseases control”.
- 9.
See, for instance, the Preamble of the Universal Declaration on Bioethics and Human Rights.
- 10.
Article 5 of the Convention on Human Rights and Biomedicine provides that: “An intervention in the health field may only be carried out after the person concerned has given free and informed consent to it”; articles 13 and 14 of the Additional Protocol to the Biomedicine Convention on Biomedical Research establish further safeguards concerning the information and the consent of research participants, respectively.
- 11.
Judgement no. 438 of 2008, para. 4: “Informed consent, understood as an expression of the informed acceptance of the medical treatment proposed by the doctor, has the status of a full-scale right of the person and is grounded in the principles expressed in Article 2 of the Constitution, which protects and promotes fundamental rights, and Articles 13 and 32 of the Constitution which provide, respectively, that ‘personal freedom is inviolable’ and that ‘nobody may be forcefully submitted to medical treatment except as provided by law.’”
- 12.
See the UNESCO Declaration on Bioethics, COE Additional Protocol on Biomedical Research, CIOMS Guidelines, WMA Declaration of Helsinki.
- 13.
See, for example, Paragraph IV (3e) of the Brazilian Resolution No. 196/96 on Research Involving Human Subjects, which states that “in communities with a different culture, including Indigenous communities, prior consent must be obtained from the community through its leaders, without foregoing, however, efforts to obtain individual consent.”
- 14.
Camp and Bourini v. The Netherlands, n. 28369/95, ECHR 2000-X, para. 37.
- 15.
Thlimmenos v. Greece [GC], no. 34369/97, § 44, ECHR 2000-IV.
- 16.
Pretty v. United Kingdom, Final, 2346/02, ECHR, 2002, para. 32.
- 17.
This is clearly established in the Fed Reg April 28, 08, 22800-16, 27/X/08.
- 18.
Guideline 8 establishes that: “Before undertaking research involving subjects in underdeveloped communities, whether in developed or developing countries, the investigator must ensure that persons in underdeveloped communities will not ordinarily be involved in research that could be carried out reasonably in developed communities.”
- 19.
Clinical trials are conducted in four phases: Phase I, carried out with healthy volunteers, phase II performed on a limited number of patients, phase III, performed on a large number of patients, and phase IV, performed after the product has been commercialized.
- 20.
See, for example, Article 3 of the Universal Declaration on Bioethics, and Article 2 of the ECB. Article 22 of its Explanatory Report states: “The whole Convention, the aim of which is to protect human rights and dignity, is inspired by the principle of the primacy of the human being, and all its articles must be interpreted in this light.”
- 21.
Nevertheless, the Explanatory Report to the ECB has lowered the concrete application of this principle, specifying that the interest of the human being must “in principle” take precedence over science and society in the event of a conflict between them.
- 22.
Article 29 of the 2000 version of the DH provided that: “The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists.” The previous version also contained the reference to investigation for a “minor condition”, that, combined with the minimal harm principle, would have implied the use of placebo only in trials with some analgesics, hypnotics, antihistamines, and antiemetics where the disease would have been minor.
- 23.
UNAIDS “Ethical Considerations in HIV Preventive Vaccine Research (2000)”. Guidance Point 11 states: “As long as there is no known effective HIV preventive vaccine, a placebo control arm should be considered ethically acceptable in a phase III HIV preventive vaccine trial”. Guidance Point 16 specifies that: “Care and treatment for HIV/AIDS and its associated complications should be provided to participants in HIV preventive vaccine trials, with the ideal being to provide the best proven therapy, and the minimum to provide the highest level of care attainable in the host country in light of…circumstances listed. These circumstances include: the level of care and treatment available in the sponsor country, the highest level of care available in the host country, the highest level of treatment available in the host country (including the availability of antiretroviral therapy outside the research context in the host country), the availability of infrastructure to provide care and treatment in the context of research, potential duration and sustainability of care and treatment for the trial participant. In addition, UNAIDS/WHO Guidance 2007 establishes that the use of a placebo control arm is ethically acceptable in a biomedical HIV prevention trial only when there is no HIV prevention modality of the type being studied that has been shown to be effective in comparable populations (Article 15).”
- 24.
ICH, 2000, para. 2.1.3 establishes: “Where an available treatment is known to prevent serious harm (…) it is generally inappropriate to use a placebo control. Whether a particular placebo controlled trial of a new agent will be acceptable (…) when there is known effective therapy (…) is a matter of judgement.” The guideline on “The Choice of a Control Group” (E10) affirms that “Whether a particular placebo-controlled trial is ethical may in some cases, depend on what is believed to have been clinically demonstrated and on the particular circumstances of the trials.” “It should be emphasised that use of placebo or no-treatment control does not imply that the patient does not get any treatment at all.”
- 25.
CIOMS Guidelines for Biomedical Research (1993) state that: “If there is already an approved and accepted drug for the condition that a candidate drug is designed to test, placebo for controls usually cannot be justified.” (Commentary on Guideline 14).
- 26.
COE, 2005, Articles 23.2 and 23.3 state: “The use of placebo is permissible where there are no methods of proven effectiveness.”.
- 27.
The Directive 2001/83/EC on the Community Code relating to Medicinal Products for Human Use, specifies that: “In general clinical trials placebo shall be done as controlled clinical trials and if possible, randomised; any other design shall be justified. The control treatment of the trials varies from case to case and will also depend on ethical considerations; thus, it may, in some instances, be more pertinent to compare the efficacy of a new medical product with that of an established medicinal product of proven therapeutic value rather than with the effect of a placebo”.
- 28.
According to WHO data, 5.25 million people (36%) of those in need in 2009 had access to ART in low- and middle-income countries.
- 29.
According to WHO Constitution, “Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.”
- 30.
Article 2.1. of the ICESCR provides that: “Each State Party to the present Covenant undertakes to take steps, individually and through international assistance and cooperation, especially economic and technical, to the maximum of its available resources, with a view to progressively achieving the full realization of the rights recognized in the present Covenant by all appropriate means, including particularly the adoption of legislative measures.”
- 31.
Commentary on Guideline 21 specifies the content and scope of the moral obligation contained in the Guidelines. The Commentary states that obligations of external sponsors to provide health-care services will vary with the circumstances of particular studies and the needs of host countries. The sponsors’ obligations in particular studies should be clarified before the research is begun. The research protocol should specify what health-care services will be made available, during and after the research, to the subjects themselves, to the community from which the subjects are drawn or to the host country, and for how long. The details of these arrangements should be agreed by the sponsor, officials of the host country, other interested parties, and, when appropriate, the community from which subjects are to be drawn. The agreed arrangements should be specified in the consent process and document. It is evident that the communities concerned are involved in the negotiation process with the drug company “when appropriate”, and it is the State that should represent their interests. In the reality of developing countries, where governments are often corrupt, a more incisive disposition concerning the role of the research participants in the deal should have been provided.
- 32.
In Brazil, the National Health Council issued a Resolution (No. 251/1997) which expressly refers to post-trial obligations. The research sponsor or other specified groups have a legal duty to provide post-trial treatment at least to research participants in clinical trials carried out in Brazil. In Kenya, there are the 2004 National Council for Science and Technology (NCST) “Guidelines for Ethical Conduct of Biomedical Research Involving Human Subjects in Kenya” (“human subjects guidelines”) and the 2005 Ministry of Health (MoH) “Kenya National Guidelines for Research and Development of HIV/AIDS Vaccines” (“vaccines guidelines”), and in South Africa, the Department of Health (DoH) “Ethics in Health Research: Principles, Structures and Processes”, which was drawn up by members of both the Department and the Interim National Health Research Ethics Committee, appointed under the National Health Act of 2003.
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Pavone, I.R. (2012). Biomedical Research in Developing Countries and International Human Rights Law. In: Schildmann, J., Sandow, V., Rauprich, O., Vollmann, J. (eds) Human Medical Research. Springer, Basel. https://doi.org/10.1007/978-3-0348-0390-8_7
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