As international research trials increase, new problems crop up

Basic subjects protection regs often are missing

As the number of international research protocols increase, the problems faced by reviewing IRBs increase. "International research is taking more and more IRB time," says Howard Guenther, PhD, MBA, associate vice chancellor for research and interim executive secretary of the Institutional Review Board at the University of Illinois at Urbana-Champaign.

"As federal regulations become tighter and more inclusive, then we of course adhere to that," he says. "Just by the policies the federal government is implementing, we see increased workload."

Partly what has contributed to this increase is the global economy, which has made it easier for investigators to conduct studies overseas, Guenther adds.

The other reason for the increase is federal requirements that put a greater burden on domestic IRBs in the cases where the international site does not have an IRB of its own.

"In the case where a foreign institution does not have an agreement already on file with the National Institutes of Health, then we work with the foreign institution to establish that agreement with them directly," Guenther says. "And in many cases, that would involve training and at least some kind of awareness of what our policies and U.S. policies involve." (See table.)

Another problem is the lack of basic human subjects protection regulations. While some nations, including China, have human subjects protection regulations, there are many others that do not, says Laszlo Szabo, CIP, sponsored programs administrator of the research integrity and compliance unit of the Office of Research and Sponsored Programs at Rutgers, The State University of New Jersey in New Brunswick.

International sites must have an international federalwide assurance (FWA) when they’re engaged in research funded by the U.S. government, he notes.

IRBs will have an easier time handling those international sites that already have their international FWA, as well as their own IRB and human subjects protection laws, Szabo says.

Unfortunately, it’s becoming more common to deal with sites that have none of the above, he notes.

"The issue that has come up with us, and I suspect it must be coming up across this country, is that now we’re dealing with institutions that are engaged in research but don’t have international federalwide assurance and, in most cases, have never heard of the international FWA and often don’t have an IRB," Szabo says. "Great examples of this are in central European countries and former USSR republics, including Latvia and Estonia."

These places have very limited human subjects protection but are improving, he adds.

Cultural differences 

This deficit places an onus on the IRB to make certain that human subjects are adequately protected within the context of the communities in which they live, and this can be quite challenging, Szabo and Guenther note.

For example, suppose a research project is conducted in an Eastern European country and the site has no access to a local IRB. This means that the international federalwide assurance must list the U.S. IRB as its designated IRB, Szabo explains.

"This sounds like a good solution on the surface, but the problem is the Common Rule and that this federal guidance asks for an IRB to have knowledge of the local research context," he says. "Wherever the research is being conducted, the IRB should have knowledge of that community."

It’s not always easy to identify and handle the cultural considerations of foreign countries, Guenther notes.

"You may need leaders of a tribe to approve of a project, and people in the community need to be informed of what they’re doing," he says.

"Many times human subjects research projects in the U.S. offer some sort of compensation for participating in the project, and many times you have to make sure that compensation is consistent with native culture," Guenther says.

For instance, cash compensation that appears to be minimal in the United States might be considered coercive in other parts of the world and, instead, it might be appropriate to provide noncash incentives such as soaps or perfumes, he explains.

At the minimum, it would appear that the U.S. IRB will need to work with a consultant from that international community, but finding a suitable person is not easy, Szabo notes.

"If we hire a consultant, is it fine to get anybody in the country, or should we go a step further and get someone with scientific knowledge for the type of research conducted there?" he asks. "The answer so far, from what I’m finding, is it depends on the level of risk involved in the procedure."

One potential solution to finding the appropriate consultant and to learning more about a particular research site’s culture and human subjects protection regulations would be to contact that nation’s embassy for information, Szabo suggests.

"If it comes down to finding written documents, regulations, and if it’s greater than minimal risk research, we’d ask the embassy’s assistance in providing human subjects protections in that country," he says. "Dealing with the embassy will take a while, but I think the embassy is the best source besides finding information on the web."

Sometimes graduate students from foreign countries work on these international research projects and returning to their native nations, helping the IRB with the cultural issues that arise, Guenther says.

"They can pick up the research fundamentals and principles here and then take those back to their country of origin for implementation of the actual project," he explains. "We are always open to feedback and talk with researchers on a daily basis as they bring back stories and reports from the field in international countries, and we always incorporate those into our future policies."

However, even if the level of risk typically is considered benign, there could be unanticipated problems within the local context, Guenther and Szabo say.

Suppose, for example, the research protocols calls for a blood draw, he says.

There could be religious issues that conflict with having a man draw blood from a woman subject, or there could even be an aversion on the part of subjects to sign an informed consent document for that blood draw, Szabo points out.

In the former Soviet Union, there are many people who may be afraid to sign any documents, even if they are told that it is something standard or benign, he says.

"My grandfather in Hungary spent 20 years in the gulag in Russia, and he’s not someone to sign anything no matter how benign it is," Szabo says. "He says, Shouldn’t you trust me if it’s benign enough?’"

Another example of cultural clash involved an anthropological study conducted internationally, Guenther notes.

"For an anthropological study, a researcher approached a female in the household and did everything by the book as far as the study goes," he explains. "But it turns out that the cultural norms in that society required that any type of activity of this sort needed to go through the head of the household."

If a domestic IRB has no knowledge about these types of cultural issues, then there will be unanticipated problems with the research and human subjects protection, Guenther and Szabo say.