Developing and testing a vaccine capable of halting the spread of AIDS is a bigger job than any single institution — or even any single country — can tackle alone. That's why the Fred Hutchinson-based HIV Vaccine Trials Network (HVTN) unites the expertise of almost 30 clinical-trial sites in 13 countries on four continents, involving researchers and volunteers from many of the developing countries hardest hit by the epidemic.
But the benefits of an international clinical-trials network like the HVTN come with a major challenge: how to ensure that every individual who volunteers to take part in the trials receives ethical protections mandated by U. S. federal research agencies. Now, a new collaborative venture of HVTN staff and the center's Institutional Review Office (IRO) promises to help countries with limited resources strengthen their ability to comply with these requirements.
During a two-week trip in May to southern Africa, Karen Hansen, IRO director; Renee Holt, HVTN's regulatory manager; and Danna Flood, HVTN training manager; co-hosted an ethics-training conference in Malawi attended by research-ethics committee members from 12 countries in sub-Saharan Africa. In addition, they provided personalized training for ethics committees of HVTN sites in Botswana. This fall, they will travel to Haiti and the Dominican Republic to offer similar activities for the HVTN's Caribbean partners. At each international site, their goal is to provide tools that enable the center's far-flung research partners to develop self-sustaining ethics programs of their own.
"This is more than providing a single training experience for these institutions," Hansen said. "Our commitment to following through is very important to us."
As the center prepares to forge new international collaborations through its International Research Initiative — which aims to develop and deliver new preventive measures for many of the world's major public-health problems — Hansen expects these outreach efforts to be expanded to other international locales.
The HVTN outreach efforts are funded by a Human Subjects Research Enhancement grant from the National Institutes of Health awarded to the center in 2003. Such grants are intended to strengthen oversight of human-subjects research at institutions like Fred Hutchinson that receive significant NIH support for clinical research, as well as foster partnerships that will help strengthen ethics programs at institutions with less experience in this area, Hansen said.
"During our second year of funding, we were to collaborate with organizations that wouldn't qualify for this kind of grant," she said. "With all of the HVTN's international activity, this seemed like a perfect fit."
By signing on as an HVTN partner site, an overseas institution agrees to abide by ethical requirements mandated by the NIH, Holt said.
"This isn't always a commitment that their government is equipped to support," she said.
"The challenge for ethics-committee members in developing countries is to take the U.S.-mandated ethical principles and interpret them in a meaningful way in their own culture," Flood added. "This will help ensure research is conducted in harmony with local ethical standards."
To help their partners in developing nations build strong ethics programs of their own, Holt and Flood approached Hansen, a nationally recognized leader in developing training materials to educate scientists and research administrators on protection of human subjects.
The team designed a three-phase outreach project. First, they sent members of four international ethics committees and institutional review boards to the 2003 annual meeting of the Applied Research Ethics National Association/Public Responsibility in Research and Medicine in Washington D.C. The organization promotes high standards in research ethics.
The May trip to Africa was the second phase of the project. During the visit, the team provided training for ethics-committee members at HVTN partner sites, for some participating sites of the HIV Prevention Trials Network, a group dedicated to conducting nonvaccine HIV prevention interventions, such as microbicides, and for other research networks supported by the National Institute of Allergy and Infectious Diseases. Hansen, Holt and Flood also collaborated with NIH's Division of AIDS (DAIDS) to sponsor a five-day meeting in Malawi at which ethics-committee members and researchers from 12 African nations attended training sessions and presented talks on issues relevant to their settings.
Joseph Mfutso-Bengo, the head of the University of Malawi College of Medicine's research-ethics committee, chaired the conference. The agenda included review of U.S. requirements for ethical review of research, information on how to document committee work, small-group discussions on the challenges faced by ethics committees, mock reviews of research protocols, and a poster session in which committees shared their unique processes and approaches. Conference presenters — more than half of which were from Africa — offered perspectives on the major ethical principles of autonomy, beneficence, respect and justice. Discussions initiated at the conference are continuing through a list-serve created specifically for the attendees.
Hansen said the meeting was a major success. "By the end of the five days, we could see leaders from each country emerging as the participants discussed ideas and future directions," she said.
After they conduct ethics training in Haiti and the Dominican Republic this fall, the team will implement phase three of the project: on-site assessments for the ethics committees at each of the participating HVTN sites.
In addition, follow-up support will be provided through a Web site to be established by DAIDS as well as through existing Web-based training tools that Hansen has helped to design. Hansen said that members of five African research institutions have already offered to write modules for the online training site.
"These will enable U.S. collaborators to learn more about country-specific requirements, which will be very helpful to researchers at the center who are establishing new research partnerships," she said.
"The new links with institutions in resource-poor nations also help to heighten sensitivity to cultural issues associated with international research," Holt said.
"There are some unique needs for training among U.S. researchers who are conducting research in regions of the world with very different cultures," she said. "Many of these countries have a history of oppression by wealthier countries and need to know how the research will benefit their population as a whole, not just address a disease prominent in wealthy countries."
Different cultures, same dilemmas
"This conference went a long way toward helping the U.S. attendees better understand African perspectives on research and ways that U.S. research partners can enhance their collaboration with African ethics committees," Flood said.
The visit to Africa brought to light not only the differences between those nations and her own, but also many similarities, Hansen said.
"When all was said and done, we could see that they are grappling with the very same ethics issues that we face right here," she said.