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"Minimal risk" poses ethical issues to IRB, investigators
Expert discusses interpretation problems
The federal regulations leave the job of interpreting "minimal risk" up to IRBs, which can lead to challenges for ethics boards and investigators.
"There is language in the regulations that everyone knows, and they're widely agreed upon as an appropriate standard, saying that minimal risk is the risk experienced by a normal child in everyday life," says John Lantos, MD, a professor at the University of Chicago, division of biological sciences in the department of medicine in Chicago, IL. Lantos is a former IRB associate chair, and he published a paper about minimal risk in the American Journal of Bioethics earlier this year.
"But no one knows how to operationalize that definition when they're trying to use it as a criteria for acceptability for a particular protocol," Lantos says. "What happens is that both individuals and IRBs come up with their own interpretation of this, and their interpretations seem to differ quite wildly from one IRB to another."
For example, IRB members often have difficulty evaluating the risks of surveys, Lantos says.
"How stressful is it to ask people questions about sex or drugs or school performance, and the answer is that no one really knows," Lantos says. "The follow-up question is, 'How do those risks compare to risks of everyday life?' and it becomes a fairly subjective standard."
Investigators involved in multi-center protocols, which have to go through many different IRB protocol reviews, experience the arbitrariness of IRB decisions first-hand, Lantos says.
"Some will approve the protocol, some will reject it, and some will ask for specific changes," Lantos says. "There's no real recourse or appeals process when that happens."
Even medical procedures can have multiple layers of risk, depending on how deeply an IRB chooses to delve into the issue, he notes.
"Most IRBs would consider a needlestick to be of minimal risk," Lantos says. "But the question of what is going to be done with the blood is more complicated."
Would the IRB consider it greater than minimal risk if the investigator planned to test someone for certain genes that are known to predispose a person to diabetes, for instance?
"Some people say that's minimal risk, but others say, 'No, that's a completely unforeseen potential harm that puts it above minimal risk,'" Lantos explains.
The solution is not to have regulators or a committee come up with more precise standards because any regulation has to be written in such a way that you can apply it to a wide range of studies, from an interventional cancer protocol to a survey to an epidemiological study, Lantos says.
"So, there's no way the regulation will precisely cover all of those in a way that doesn't lead to variation," he adds. "But the question is whether people see the variation as a problem."
To Lantos, this variation is a problem, and the sensible solution would be to have an appeals process so that investigators who disagree with an IRB's decision can appeal it to a separate body.
"So if one IRB says, 'Oh this questionnaire clearly has greater than minimal risk,' and another one says, 'No, it does not,' then an appeals body could resolve the issue," Lantos says.
"Right now, the decisions are sealed and confidential, and no one knows the basis for their decision-making, and no one can appeal the decision," Lantos says.
"It seems like it would be a much better system if investigators could appeal it to a higher court and have them publish a written decision," he adds. "You may not like the decision, but at least they can explain why they reached it."
Any oversight body would have to be based outside the institution that represents the IRB and researchers, and depending on funding, it could be created to work like a federal appeals court or a district court, Lantos suggests.
"You can imagine one housed in the Office for Human Research Protection which is comprised of experts in research ethics and health law," he says.
This idea would no doubt have its detractors, he says.
"One of the things that makes this proposal so radical is that right now IRB deliberations are treated as confidential," Lantos says.
Confidentiality does not serve human subjects protection, he says.
"The only reason to keep them confidential is to protect investigators and institutions," Lantos says.
Besides serving on an IRB, Lantos has experienced the IRB from the other side of the aisle, and it's these experiences that have led him to his proposal of an appeals process.
For example, Lantos was working with a community theater group that performed original musicals in high schools, focusing on topics such as teen pregnancy, drug use, and gang violence.
"They were taking the show around to schools and performing it, and the actors would stay afterward and have discussions with the kids about how they make decisions about joining a gang and those sorts of social issues," Lantos explains.
"In one show, one of the kids brings his policeman dad's gun to school, and someone else ends up with the gun and a kid gets shot," Lantos says. "It was a dramatic scene, and a researcher wanted to evaluate it."
The researcher took the proposal to an IRB, which decided that the scene might traumatize some kids, so it would be above minimal risk, and the IRB rejected the protocol, he says.
"I pointed out that the kids already are watching the show, and the study was just about the researchers evaluating it," Lantos explains. "You could argue whether or not this was below or above minimal risk, but once the IRB said 'No,' there was nothing else to do."
The play continued to be performed with the violent and dramatic scene, but it couldn't be studied, he adds.
In another example, Lantos was involved in a project with community health workers in a Chicago neighborhood containing Mexican immigrants.
"The health workers were lay health workers — not doctors and nurses — and the project was to see whether they could go into people's homes and do assessments of asthma risk factors, working with parents of children with asthma to reduce home triggers, such as dust, pets, carpets, etc.," Lantos explains.
"Most of the people we wanted to study spoke only Spanish, and the community health workers spoke Spanish," he adds. "So we developed an informed consent form that spoke in a simple and colloquial language, explaining what the health workers would do, and we took that to the IRB."
The IRB said the informed consent form was inadequate because it didn't have the standard boilerplate language, and they required investigators to revise it according to their standards and then use a certified translator to translate it into Spanish, Lantos says.
"This meant we basically came up with a form that was unintelligible to the people we wanted to study because it was full of legal jargon and things about the university not providing emergency care if they were harmed in the study that were inapplicable to this particular project," Lantos says.
Investigators used the revised form, and the community health workers told them that when they presented it to the participants, they basically told them that the form was meaningless, and instead, explained what the study was about, Lantos recalls.
"If there had been an appeals process, we would have gone through it, and who knows what they would have said," Lantos says.
The problem is that while IRBs are meant to be an independent board of peers, many institutions now have so many rules and legal considerations that the IRB's independent discretion has been eroded, Lantos says.
Institutions fear that if an IRB makes a mistake and violates federal rules, then the government might shut down the institution's research program, and so they interpret the rules conservatively, he says.
"But if all you're doing is deciding whether or not something meets the rules, then all you need is one lawyer or bureaucrat to evaluate it — the way someone does a contract for employment — and you don't need an ethics committee," Lantos adds.