Important note: Information in this article was accurate in September/ November 2000. The state of the art may have changed since the publication date. IAVI Report - September / November 2000
Bob Huff
The ethics of clinical research in developing regions was the official topic of just four sessions at the Durban meeting. Yet the questions addressed there pervaded many other issues discussed at the conference, and are sure to come to the forefront as clinical studies of AIDS vaccines, microbicides and treatments move ahead internationally.
What emerged was an affirmation of the fundamental prin-ciple that successful and ethical collaborations in developing country settings must begin early in the research process and continue as an ongoing partnership among equals.
In his plenary address, the president of South Africa's Medical Research Council, Malegapuru William Makgoba, stressed that a true collaborative process is crucial as research relationships develop among parties with unequal power. Past collaborations have often been characterized by the mentality that "he who pays the piper chooses the tune," Makgoba said, so that the priorities of the more powerful partner dominated. Moving towards genuine partnerships and developing an ethical framework should not be done by imposing guidelines from the outside but by "engaging civil society in an open and transparent process." Makgoba noted that, during the past fifty years, the quality of clinical research has been vastly improved by greater attention to ethics. As this process continues, he said, we have a responsibility to "practice the best ethics within our constraints."
Finally, addressing concerns about the commitment of the South African leadership to international collaboration, Makgoba assured the audience that "in our government you have a partner."
At a slide talk the following day, bioethicist Robert Levine of Yale University outlined some key points covered by the UNAIDS guidance document on HIV vaccine trials in developing regions. These include:
Engaging these issues, he said, requires a mutual understanding of the cultural context and scientific requirements of the study. For example, if no other proven vaccine exists, a placebo may be ethical. A better alternative, though, might be to give an unrelated vaccine as a control. Also, the terms of access to the test vaccine (if proven effective) and to knowledge gained from the trial should be discussed among all stakeholders in advance. By engaging the community in designing the protocol, informed consent process, and risk-reduction interventions, the scientific and ethical quality of the research is strengthened. Further-more, community acceptance is fostered and the capacity of the host country is enhanced. Levine concluded that "to ensure the scientific and ethical conduct of the trial, to support meaningful self-determination, and to strive for a partnership among equals is the foundation of ethical research."
One of these issues, that of providing "best proven" treatment to trial participants, was the subject of a heated debate on the proposition: "Research participants in developed and developing countries should receive the same standard of care." Speaking in favor was Jorge Beloqui of Brazil, a University of S‹o Paulo mathematics professor, a member of the PWA advocacy organization GIV-SP, and an outspoken critic of international trade agreements that restrict access to affordable HIV treatments. Against the proposition was Solomon Benatar, professor of medicine and director of the Bioethics Centre at the University of Cape Town.
Beloqui argued that accepting different standards of care between poor and rich countries simply entrenches inequality as a principle and perpetuates the notion of two worlds-one that benefits from the best available care and one that must suffer. He also pointed out that failure to provide the best possible care is a breach of the doctor/patient relationship and violates the commitment to research subjects described in paragraph 11.3 of the Helsinki agreements. "How can an ethical physician knowingly provide suboptimal treatment for a patient?" he asked.
Beloqui believes that commercial interests are responsible for the conflict between the doctor/patient and researcher/volunteer relationships. Yet, since commercial sponsors have so much to gain in profit, he sees no reason for them not to provide the best standard of care to the individuals who sustain the risks of proving the drugs. "Clinical trials in developing countries are the first step to opening new markets," he said, yet he fears that the products tested will be unaffordable in the host countries. "Guarantees must be in place to insure future availability," Beloqui argued.
Solomon Benatar responded by questioning the meaning of "same standard of care," with its paternalistic implication that developed country standards represent the optimum. For example, a Western trial that failed to provide social support, continuing access to drug treatments initiated during the trial and adequate follow-up might be unacceptable by his criteria. For Benatar, "same standard" is not a clear-cut criterion; its meaning depends on who is speaking and where. Certainly, some standards set by developing countries have been mediocre and can be improved, but holding out for conditions equal in every way to those in rich countries would preclude research from ever being done in these settings. The solution, he feels, is to provide the highest attainable standard of care for the research setting in the host country. After all, Benatar noted, "we all come from developing countries," since even most wealthy nations have aspects of their health care provision that could be improved.
Benatar recommended that researchers have knowledge of the local social and economic situation, including an awareness of how the host country has historically been treated by the sponsor country. A point made by several speakers during the week-long conference was that Africans often emphasize community values and may understand their individual rights as emanating from membership in a community. Such a world view can be difficult to understand for Westerners, who give primacy to individual rights. This can result in paternalistic and insulting notions, such as the idea that home country institutional review boards (IRB) are necessary to protect host country subjects. Benatar also believes that the benefits of research conducted in a particular region should be seen to flow into the lives of the local people. In his experience, research participants in South Africa care less about access to antiretroviral drugs than that their participation contributes to a stronger community.
Benatar concluded that ethics should not mean policing researcher compliance to a disembodied set of international agreements. Rather, it should be about guiding people who want to work together to achieve ethical and excellent results.
Most of the arguments for and against the debate proposition are encompassed by the UNAIDS guidance document. For example, Beloqui's concern that host countries may never benefit from the test vaccine or drug is addressed by the principle that trial sponsors and hosts should negotiate the distribution of benefits beforehand. Benatar's willingness to trust local scientific and ethical oversight is supported by the guideline that clinical research should only be performed in countries with the capacity to provide that oversight.
Ultimately, Levine conceded, we all recognize that the distribution of wealth in the world is inequitable. But this fact should not "impede the efforts of the developed world to help low resource countries develop treatments and prevention that they can afford."
Bob Huff works at the American Foundation for AIDS Research (amfAR) in New York as editor of their HIV/AIDS Treatment Directory. He has been a community advocate for ethical HIV clinical research for twelve years.
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