Principles and practices: The implementation of ethical guidelines for research on HIV
WHO, Department of HIV/AIDS
2-3 June 2003
The changing context of ethics debate on HIV
In recent years, a number of controversies have drawn attention to difficult ethical dilemmas arising from HIV/AIDS research and intervention activities and to the issues that emerge as guidelines developed in the context of countries of the North are implemented in developing countries. Key players have made major investments in formulating guidelines and providing training, and numerous sources are available regarding ethical principles, guidelines, and training. There is, however, little evidence about what actually happens with the implementation of ethical guidelines in real situations, and researchers have few opportunities to exchange ideas with others who are similarly struggling to apply ethical principles to HIV research. A major question underlying ethical debates is the extent to which context needs to be taken into account when defining principles for the protection of human subjects and applying them in different settings.
Several factors make it urgent to turn our attention to this topic. The first is the rapid increase in HIV research in different countries, and the stricter standards that are being applied in the wake of controversial cases. As a result, the process of ethical review and clearance has become lengthier, more complex, and more expensive in terms of time and resources; this sometimes translates into insurmountable hurdles which in turn can delay or discourage needed research. Another factor is the availability of antiretrovirals and the duty to provide treatment to participants, which has changed the way in which projects are assessed from an ethical point of view. A related development is that the domain of research now expands to include treatment provision, which raises new questions regarding eligibility for care, coverage, standards of care, and sustainability. With the blurring of the distinction between research and practice, each traditionally defining a different approach to ethical oversight, it is at times difficult to balance the protection of individual rights against the interests of the public. The pervasive disparity in resources and knowledge between researchers and participants puts the question of researchers’ responsibilities in sharper focus, in particular how far duties for the ethical conduct of research ought to extend, beyond the protection of participants in specific projects. These cross-cutting issues recur in discussions of various topics, and remind researchers of the connections between the specific problems they face and broader trends in research ethics.
Bringing together evidence from the field in order to inform discussions about the applicability of principles and the implementation of guidelines is thus an especially timely task. To this end, the Department of HIV at WHO held a two-day meeting entitled “Principles and Practices: The Implementation of Ethical Guidelines in HIV Research.” The meeting brought together a mutidisciplinary group of 21 participants from a dozen countries. It was designed to facilitate discussions of these issues in a way that is informed by evidence on the influence of culture and context, and by case studies illustrating problems and their possible solutions.
The goals of the workshop were to:
- present evidence on the implementation of guidelines in different settings to show the diversity of problems and highlight the common themes that confront researchers;
- give concrete examples of the difficulties encountered, their consequences for research and interventions, and the ways in which they are addressed;
- identify areas where further work is needed in order to improve the process of implementation.
The ethical review process: constraints and current efforts
Surveys and audits conducted with international researchers, national research agencies, and local research ethics committees, highlight the many constraints that Institutional Review Boards (IRBs) face. Even though there is consensus on the need for ethical review, and institutional mechanisms may be in place, numerous problems limit the performance of ethics committees, and presenters reviewed several examples that illustrate these problems. Other difficulties with ethical review stem from a discrepancy between the values of autonomy and informed choice that committees must uphold, and the continuing paternalism which characterizes the practice of medicine and medical research in many countries.
Progress in the institutional review of research ethics is dependent both on investing resources and on the growth of a “culture of ethical review”. Participants examined current efforts at the regional and country level to improve the review process, noted that capacity is gradually building, and discussed case studies from different regions. These examples illustrate ways to address the problems that stem from the scarcity of human and financial resources, the lack of ethics training, and the heavy burdens that members have to shoulder. Participants at the meeting also underscored the need to improve he composition of ethics committees, and possible ways to deal with the limited pool of potential IRB members and to increase representation from women or the lay community.
Informed consent: how to reduce dissonance
While it is recognized as an essential requirement of ethical research, the application of informed consent is often challenging. Meeting participants reviewed studies on the understanding of consent and examined obstacles to consent in resource poor settings. Language problems and the lack of familiarity with scientific terminology and concepts often limit volunteers’ understanding of the research project. Forms tend to be lengthy and legalistic, and in practice, fieldworkers do not always follow the consent procedures as laid out by review committees because of practical and social constraints. In addition, the goals of research can be misunderstood. Misconceptions about illness and treatment, and beliefs that care will be adversely affected if study participation is refused, can affect motivations to participate. All presenters noted that the procedural requirements of consent (for example, obtaining signatures, isolating the volunteer) should be secondary to the rationale for consent, i.e. ensuring that consent is truly obtained, fully informed, and genuinely voluntary.
Comparisons across settings indicate that even where consultation is not explicitly recognized to happen, potential participants may first need to get advice from trusted individuals. Hence, the process of obtaining consent will be enhanced where it is separated from, but facilitates, the prior step of informal consultation. Another innovation presented at the meeting is based on the recognition that the notion of isolating each individual during the process of information and consent may not be optimal; thus, in some settings, a group process may be more effective in conveying information and allowing participants to raise questions. Discussions of experiences in diverse contexts help clarify the social, ethical, and cultural issues that arise and suggest ways to improve the implementation of informed consent.
Standards of care: negotiating fair treatment
In reviewing standards of care, the emphasis was on how specific trials have negotiated the care question, and the multiple arrangements for post trial care that have been made. Against the background of debates on justice, sustainability of care, and drug access, and the threat that ethical clearance will delay or block research, different groups have come up with innovative approaches to the provision of care for research participants. Some of these responses have focused on developing criteria to establish eligibility for care, while others have focused on methods to secure drug access to trial participants, including co-payments, pharmaceutical donations, patient roll over designs, and drug funds. The negotiation of care standards in multi-site studies, particularly those joining researchers from the developed world with those in the developing world, was highlighted, stressing the dynamic nature of care. Concerns were voiced over the influence of corporate or political interests in the research design, and attempts made by interest groups to control the study design. The justice considerations in different studies were also examined, including determining who qualifies for ART access, ensuring sustainability of care, and incorporating community guidance into the study design process.
Examining the community dimension of HIV research raises number of questions with implications both for ethics and for the feasibility of research: how to increase the motivation of individuals to participate, how best to seek consent from groups of people residing in particular communities, and what is the effect of a research project on the community in which it takes place. Discussions at the meeting covered the role of governments and communities in the research oversight process, particularly in resource poor settings. Examples were discussed of different approaches to incorporate community voices into ethics debates about standards of care or the obligations of sponsors and investigators. Multiple methods of engaging communities in the research process were discussed, such as bringing “lay” representatives onto IRBs, consulting with community advisory boards as a study is designed, employing community liaisons to dialogue with communities during the course of a study.
The rich discussions at the workshop served to demonstrate that many of the difficulties in ensuring the ethical practice of HIV research are shared across sites. They also highlighted practical solutions and strategies. Contributions from those in the field help provide some balance to ethical discussions, which all too often take the form of principled debates unconstrained by the reality of particular situations. Comparisons across sites help distinguish core principles from their expression in particular settings, and to share innovative responses to ethical dilemmas.
Much more however needs to be done. Participants agreed that more evidence would help define better practices regarding the informed consent process, standards of care, the representation of communities, and the social implications of research. They also acknowledged the need to take into account the increased burdens faced by researchers, and to help build the capacity for ethical review. Participants noted that HIV often brings into sharper focus issues that are shared with other diseases, and that advances in HIV research ethics can help raise ethical standards across health research more broadly.
- Welcome -- Ties Boerma (WHO)
- General introduction to the workshop: Global Concerns Local Implementations -- Carla Makhlouf Obermeyer (WHO)
- Disease Surveillance and Public Health Research: Duties, Rights and the Ethics of International Guidance -- Ron Bayer (Columbia University)
- Standards of care issues in research on HIV -- Charlie Gilks (WHO)
Principles and their applicability
Session I: How are the principles that define current practice regarding the protection of human subjects adapted to different contexts?
- Ethical guidelines for HIV vaccines: Generic vs. specific issues and the question of exceptionalism -- Jose Esparza (WHO)
- Applying international guidelines to local settings: the case of voluntary counseling and testing in HIV prevention trials -- Reidar Lie (National Institutes of Health)
- Audit and research: A study of Mexican research ethics committees -- John Porter (London School of Hygiene and Tropical Medicine)
Session II: How have the key concepts that ensure informed consent been understood and applied across cultures?
- Ethical challenges to informed consent in resource-poor settings -- Patricia Marshall (Case Western Reserve University)
- Informed consent and the WICRAM initiative -- Alex Capron (WHO)
- Seeking informed, voluntary and confidential participation in population based surveys -- Stan Yoder (MACRO International)
Session III: How have the issues related to standards of care been addressed in research?
- Ethical considerations for HIV research in Thailand: the HIVNAT as a case study -- Praphan Phanupak (Thai Red Cross AIDS Research Centre)
- Standards of care and end of trial issues: the DART trial in Africa -- Paula Munderi (Medical Research Council, Uganda)
- The Adult AIDS Clinical Trial Group International Initiative -- Thomas Campbell (University of Colorado Health Sciences Center)
- Providing and sustaining care during and after MTCT-prevention research: Case study from the Kesho Bora multinational study -- Tim Farley (WHO)
Building on Innovative Solutions
Session IV: Institutions and communities
- The practical implementation of ethical principles in South African HIV Research -- William Pick (Medical Research Council, South Africa)
- Developing guidelines for HIV AIDS in India: concerns, needs, bottlenecks, and solutions -- Vasantha Muthuswamy (Indian Council of Medical Research)
- Local culture and institutional culture in Latin America -- Fernando Lolas (PAHO)
- Back to the rough ground: Community participation and ethics guidance in HIV prevention trials -- Kathleen McQueen (Family Health International)
Session V: From principles to better practices
Group discussions around the two topics of informed consent and standards of care: key issues, problems and potential solutions. In addition to general discussions, topics to be covered include:
- Next steps & conclusion
- Potential for collaborations to gather better data and identify “best practices”
- Further work needed
List of Presentations
General introduction to the workshop: global concerns local implementations -- Carla Makhlouf Obermeyer
Disease surveillance and public health research: duties, rights and the ethics of international guidance -- speech notes-- Ron Bayer
Standards of care issues in research on HIV -- Charlie Gilks
Ethical guidelines for HIV vaccines: generic vs. specific issues and the question of exceptionalism -- Jose Esparza
Applying international guidelines to local settings: the case of voluntary counseling and testing in HIV prevention trials -- Reidar Lie
Audit and research: a study of Mexican research ethics committees -- John Porter
Ethical challenges to informed consent in resource-poor settings -- Patricia Marshall
Informed consent and the WICRAM initiative -- Alex Capron
Seeking informed, voluntary and confidential participation in population based surveys -- Stan Yoder
Ethical considerations for HIV research in Thailand: the HIVNAT as a case study -- Praphan Phanupak
Standards of care and end of trial issues: the DART trial in Africa -- Paula Munderi
The Adult AIDS Clinical Trial Group International Initiative -- Thomas Campbell
Providing and sustaining care during and after MTCT-prevention research: case study from the Kesho Bora multinational study -- Tim Farley
The practical implementation of ethical principles in South African HIV Research -- William Pick
Developing guidelines for HIV/AIDS in India: concerns, needs, bottlenecks, and solutions -- Vasantha Muthuswamy
Local culture and institutional culture in Latin America -- Fernando Lolas
Back to the rough ground: community participation and ethics guidance in HIV prevention trials -- Kathleen McQueen
List of Participants
Joseph L. Mailman School of Public Health
New York, USA
Thomas B. Campbell
Associate Professor of Medicine, Division of Infectious Diseases
University of Colorado Health Sciences Center
Department of Clinical Bioethics
National Institutes of Health
Director, Regional Program on Bioethics
Family Health International
Associate Professor, Department of Bioethics
Case Western Reserve University School of Medicine
DART Project Leader
Medical Research Council Programme on AIDS, Uganda
Senior Deputy Director General and Chief
Division of Basic Medical Sciences
Indian Council of Medical Research
New Delhi, India
Thai Red Cross AIDS Research Centre
Cape Town, South Africa
Departments of Infectious and Tropical Diseases and Public Health and Policy
London School of Hygiene and Tropical Medicine
London, United Kingdom
Demographic and Health Surveys
Ties Boerma, Coordinator, SRM, Department of HIV/AIDS
Charlie Gilks, SRM, Department of HIV/AIDS
Carla Makhlouf Obermeyer, SRM, Department of HIV/AIDS
George Schmid, SRM, Department of HIV/AIDS
Alex Capron, Ethics, Office of the Director-General
Jose Esparza, Initiative for Vaccine Research
Tim Farley, Reproductive Health
Effy Vayena, Reproductive Health
Johannes Sommerfeld, TDR
Miriam Maluwa, Law, Human Rights and Ethics Adviser