The establishment of research ethics committees (REC) in El Salvador will enhance the ability of that country to undertake clinical trials aimed at improving cure rates of pediatric catastrophic diseases, according to investigators from St. Jude Children's Research Hospital who helped to establish the committees.
The new programs not only ensure rigorous ethical oversight of research involving human participants, but also serve as a model for other institutions in high-income countries to create or strengthen existing RECs in low-income countries, the investigators said. A report on the establishment of these RECs in El Salvador appears in the December issue of Lancet Oncology. Once formed, RECs provide oversight while guiding clinical trials designed to reverse the relatively low cure rates of many adult and pediatric diseases in low-income countries compared to those in high-income nations, the authors said.
The establishment of the REC in El Salvador is important because investigators in low-income countries often have little or no access to such groups, said Miguela A. Caniza, M.D., assistant member of the St. Jude Infectious Diseases Department and director of its Infectious Diseases International Outreach Program. Research institutions in high-income countries require that a REC be in place before they collaborate with international partners, she noted.
"The absence of such RECs either restricts or prevents just the collaborative research needed to help improve medical care in countries with limited resources," Caniza explained. "Existing hospital ethics committees usually can offer only general ethical oversight of difficult cases in patient management in the hospital and do not have the expertise needed to take on the ethical requirements required by collaborative research sponsored by high-income countries." Caniza is lead author of the report in Lancet Oncology. Establishing the REC also addressed a mandate from the Council for International Organizations of Medical Sciences, in collaboration with the World Health Organization, which directed that externally sponsored collaborative research, sponsors and investigators have an ethical obligation to strengthen the ethical review of medical research in the host country.
The El Salvador REC enabled the Hospital Nacional de Niños Benjamin Bloom (Hospital Bloom) in San Salvador to collaborate with St. Jude on two projects: research into the effect of nutrition on the immune systems of Salvadoran children and their susceptibility to dengue hemorrhagic fever (a potentially deadly virus infection); and the training of 100 Salvadoran nurses to care for patients with HIV/AIDS.
As part of the collaboration, a clinical investigator from Hospital Bloom received training at St. Jude, which included learning how to obtain a Federal Wide Assurance from the Office for Human Research Protections of the U.S. Department of Health and Human Services. An assurance document is required for research by U.S. investigators at international sites; it is awarded following demonstration that proper ethical oversight committees are in place so research will be conducted according to ethical guidelines.
The initial success of the REC approach encouraged other institutions in El Salvador to imitate the Hospital Bloom model and prompted the Salvadoran government to form a national committee to guide ethical research throughout the country.
"The collaboration with St. Jude gave us an opportunity to do an exhaustive review of the issue of research ethics as it impacts our country," said José Ernesto Navarro Marin, vice minister of health in the Ministry of Public Health and Social Assistance in El Salvador. "We concluded that we must ensure the proper use of ethics in research; and such a law is now being formulated by a committee set up for that purpose." Building on the success in El Salvador, the St. Jude team is currently guiding the establishment of RECs in Paraguay as a first step in building infrastructure for collaborative clinical studies in that country, according to Caniza.
The establishment of such RECs in low-income countries should reflect a true collaboration and not be imposed by high-income countries, Caniza said. Such a partnership makes possible the transmission of a vast amount of experience on RECs available to low-income countries while allowing collaborative research projects to proceed. "The collaboration also challenges researchers in high-income countries to improve communication with colleagues in low-income countries," she added.
The authors reported that the success of such collaborations requires a methodical, strategic approach that begins with identifying both individuals and organizations that are interested in improving ethical oversight of human research. One participant must have ample experience in human research ethics and the resources to develop or strengthen REC at the partner institution. This requires buy-in from the government in the low-income country's government, research institutions and clinical investigators, the authors said. In addition, investigators in the high-income country must identify, support and train local leaders in the low-income country.
Collaboration also allows high-income countries to offer guidance and support to local investigators whose governments place a low priority on RECs and provide only limited resources to them, Caniza said. And while online training courses allow participants to work at their own pace at work or at home, some daily issues regarding human research ethics require additional practical training and guidance from more experienced partners that only collaboration can offer, she noted. Once underway, the burden of running an REC effectively can be eased if the local investigators have a relationship with an existing hospital ethics committee that already handles administrative procedures, such as recording minutes of meetings and producing follow-up reports.
In order to promote the continuity of REC collaboration in El Salvador, the researchers exchange of information and offer ongoing mentoring of members of the RECs.
"Ongoing communication also helps the collaborating institutions to understand how ethical standards in low-income countries differ from those of high-income countries," said Raymond Barfield, M.D., Ph.D., assistant member of the St. Jude Division of Bone Marrow Transplantation and chair of the hospital's ethics committee. "There is no international standard of fairness appropriate for all cultures, so standards should be flexible enough to reflect what is appropriate in each setting."
The collaboration between St. Jude and El Salvador has also raised the question of whether it might be possible to simplify the requirements for protecting human participants, Caniza said. Currently, the requirements are so elaborate that they might interfere with efforts to protect human participants in clinical trials, she noted. For example, the consent documents used to obtain parental consent to treat leukemia and solid tumor treatments or to perform bone marrow transplantation at St. Jude are usually 20 to 30 pages.
"Our experience with El Salvador has prompted us to consider whether we could communicate the required information for ethical consent more simply and concisely in low-income countries," Caniza said. "And if so, whether that would that help us to improve the informed consent process used in high-income countries. But the most important basis for establishing ethically responsible international clinical research is the fund of good relations that builds up during these collaborations."
Other authors include Scott C. Howard (St. Jude); Wilfrido Clara and Gabriela Maron (Hospital Bloom); Jose Ernesto Navarro-Marin (Ministry of Health and Social Assistance, El Salvador); Roberto Rivera (Family Health International, Research Triangle Park, N.C.); and Jonathan Camp (Center for the Study of Rhetoric and Applied Communication FedEx; University of Memphis, Tenn.).
This work was supported in part by ALSAC.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization. For more information, please visit www.stjude.org.
The Lancet Oncology