Organization updates international guidelines
Recently updated guidelines for human subjects biomedical research highlight the international research community’s concerns that studies conducted in poor nations may give too little attention to the health and well-being of participants who have few options and fewer medical resources. The International Ethical Guidelines for Biomedical Research Involving Human Subjects, developed by the Council for International Organizations of Medical Sciences (CIOMS) of Geneva, have been extensively revised and updated since the last version was published in 1993.
The changes, published in October 2002, highlight how the research community has changed in the past decade, says Juhana E. Idanpaan-Heikkila, PhD, MD, secretary-general for CIOMS. "Since 1993, we see more and more new challenges and these huge changes in international research," Idanpaan-Heikkila says. "More and more clinical research is taking place in resource-poor countries with very little tradition and experience in research."
This often means the nations lack well-organized oversight institutions for clinical trials, and they may not have ethics committees, he says. "They may not be experienced in dealing with very complicated scientific issues, and the research sponsors are more and more anxious to go to these countries because they don’t need to be on waiting lists for trials," Idanpaan-Heikkila says. "The case certainly is different in western nations today where most institutions are overloaded with research activities."
Plus, the world has seen an emergence of new and older deadly diseases, such as the HIV/AIDS epidemic in sub-Saharan Africa and tuberculosis following on its heels. These epidemics have created a need for new medications and treatments, all of which are being studied among populations in both the industrialized world and in resource poor nations, he says.
One of the ethical issues that arose has to do with how unbalanced the health options are for clinical trial participants in poor nations. If they are enrolled in a clinical study they may receive cutting edge medical treatment, but if they are not they may receive no treatment at all. "In western countries people are already getting something, and so you have to change and manipulate existing treatments," Idanpaan-Heikkila says. However, in poor nations, the study participants may have no treatment to which to return once the study concludes.
Also, there is the issue of whether this research holds any realistic potential benefit for the public in poor nations. For example, suppose a new antiretroviral drug is being studied to treat HIV. Even if this drug proves to have very potent activity against the virus and eventually is brought to the international market, how likely is it that the general public of a nation as poor as Zambia will be able to purchase and distribute the drug to its HIV-infected population when even aspirin often proves too expensive for general use? "Does this research really benefit these countries, and what remains after the study when the scientist collects instruments and goes home?" Idanpaan-Heikkila asks.
So one of the ethical challenges of international research is deciding how to make a balanced evaluation of the research from both the sponsor’s and the host nation’s perspectives, he says. "These countries are very happy to receive these studies and not the least because of the experience, training, and money they bring," he notes. "All of this has caused new problems."
These issues have led to CIOMS adding a new first guideline of the "Ethical justification and scientific validity of biomedical research involving human subjects" and to the organization extending the third guideline, which is "Ethical review of externally sponsored research."
"Our guidelines clearly are saying that it’s not enough if the sponsoring country does its best in ethics evaluation because they don’t know local circumstances," Idanpaan-Heikkila says. "They don’t know if the study addresses the health needs of that country or not, so therefore it has to be a double evaluation with the sponsoring country doing this and the host country doing something, too."
Researchers and IRBs need to address some unique issues regarding research in poor nations, and these include deciding in advance whether and how long treatment will be provided research participants after the trial ends, if the treatment is apparently safe and apparently effective, Idanpaan-Heikkila says. "I think it’s not ethically right to start people on treatment for six months and then leave and let them die," he says. "You have to provide treatment, and the first option is to have it organized in advance that they may continue on this medication."
Also, placebo studies pose ethical dilemmas that need to be resolved in advance because this is an issue that never has received a full consensus of opinion and standard for care. The guidelines suggest that when there is no treatment for a certain disease, then the comparison of the investigational treatment and placebo may be appropriate, and the same may be true in the case of trials in which the subjects have a mild condition.
However, although placebo trials require fewer subjects to be enrolled in a study, this may or may not be a good reason for using a placebo study arm, Idanpaan-Heikkila says. "If you use placebo you can cut down on the number of people you need for a study by nine-tenths," he says. "So instead of 600, you may need 60 people; and so now the IRB may view any unnecessary exposure to risky treatment to be dangerous, so it will require the study to limit to a minimum the number of people required."
On the other hand, a particular disease may have an acceptable treatment that is available, and investigators will want to study a treatment they believe to be more efficacious. In this case, it may be unethical to compare the potentially better therapy with a placebo, when the comparison could be between the new therapy and the existing therapy, Idanpaan-Heikkila says.
CIOMS has tried to address all of these complicated issues, and the organization has added more requirements and recommendations for how informed consent should be obtained, he adds. "We also have tried to extend guidelines regarding vulnerable groups in research, including pregnant women, children, immigrants, nomads, people in nursing homes, military service people, medical students, nurses, and members of hierarchical groups," Idanpaan-Heikkila says.
Recently updated guidelines for human subjects biomedical research highlight the international research communitys concerns that studies conducted in poor nations may give too little attention to the health and well-being of participants who have few options and fewer medical resources.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content