Incidental findings in genomic research
Researchers, IRBs differ on how to handle them
As the technology that enables genetic research becomes more sophisticated, it opens a kind of Pandora's box to researchers — telling us information about subjects that they weren't looking for and may not necessarily want to know.
These genomic incidental findings (GIFs) can take many forms: Evidence that a subject has a genetic predisposition for a particular condition — which may or may not be preventable or treatable. Evidence that someone is not biologically related to a parent. News that a person has a racial ancestry he or she isn't aware of.
Investigators and IRBs still are trying to catch up to the technology, figuring out when, how, or even if they should give these results to participants. So far, few guidelines exist to help make these decisions, which can be highly dependent on factors such as the validity of the test, how conclusive it is and whether the subject has expressed an interest in knowing it.
A recent survey of genomic researchers and IRB chairs underscores the lack of set policies in this area. While 42% of researchers had encountered GIFs in the previous year and 68% of IRB chairs had discussed GIFs with their boards during that time, the groups took different approaches when discussing how they should be handled, says Janet K. Williams, PhD, RN, FAAN, a professor of nursing at the University of Iowa in Iowa City.
The findings from this survey were published in a recent issue of the journal Genetic Testing and Molecular Biomarkers.1
Researchers generally did not express a need for general disclosure policies, except in rare circumstances. They argued that their research rarely turns up something that is useful to participants, and that the purpose of research is generalizable knowledge, rather than providing information to individuals. They noted that most of their research was not conducted in labs that meet federal CLIA standards, and so would have to be confirmed in another lab, at a cost.
IRB chairs, meanwhile, said that there should be consistent policies established and laid out in informed consent, rather than figuring out what to do with individual cases after data collection has begun.
"It did not surprise us that the IRB chairs had one set of assumptions and that the researchers had a different set of assumptions," Williams says. "That would be very logical based on the roles that each of those groups have in the conduct of research."
Having the conversation
Williams is both a researcher who studies the psychosocial effects of genetic testing and the chairwoman of a social-behavioral IRB at her own institution. She says her experience on both sides of that divide leads her to think that there needs to be a conversation between IRBs and genetic researchers about how to handle GIFs.
Handling individual cases as they come up "takes a lot of time and resources," she says. "As investigators, we came to the realization that these kinds of questions will not be as unique as one might have formerly thought.
"Conversations between IRB programs and chairs and researchers need to happen so that the surprise and urgency of what to do when faced with this situation are laid to rest."
Some institutions skirt the question by simply stating up front that researchers will give individual results to subjects. But in the survey, researchers themselves reported finding an occasional result that they felt compelled to disclose because of its importance.
Williams says that in these days of direct-to-consumer genetic testing, it's clear that people are interested in their genetic makeup.
"Making a statement to the public who would participate in research that there is nothing for them to decide [about whether to receive incidental findings] I think is very narrow," she says. "I don't know that that is the best approach."
IRBs and researchers contemplating this issue have to consider a number of factors, Williams says:
• Medical importance: Is it clear what the finding means, and what it will mean for the participant? Williams says different people can interpret that in different ways.
"Probably the most conservative definition is that it's something that's life-threatening and it's treatable," she says. "It's pretty hard to argue against that."
But there are other areas that might be important to participants. Is the condition in question one that can be passed down to a person's children? Should a person be told that they're of an ethnic group they didn't know about, particularly if it has health implications?
"What is the kind of information that would make the IRB say, 'We really need to be thinking about this'?" Williams says. "Researchers will have views and IRBs will have views about what we're talking about. That's one of the biggest challenges."
Having a choice
• Subject preference: In some studies, subjects are asked whether they want to be contacted with incidental findings, or asked what kind of findings they'd wish to know about. Williams says IRB chairs in the study were not universally in favor of giving subjects this choice.
"Putting it into language that's appropriate and accessible for research subjects, regardless of their literacy level, that's going to be an issue for IRBs," she says. Williams says she'd like to see national guidelines that address this issue and come up with suggested language.
And how should an IRB handle things if a participant does not want to be contacted, but information comes back about a life-threatening and treatable condition?
"Do they honor that, or do they override? It's a topic they may want to consider."
• Test validity: If the original test that turns up a disclosable result did not come from a CLIA-approved lab, what must be done to validate the findings? And who pays for that?
• Who discloses? Williams says one reason researchers give for not wanting to disclose results is that it's unclear who would be best to do it. If the researcher is not the subject's physician, and is not trained in having that kind of conversation, who should do so?
"They thought that people like a genetic counselor, a medical geneticist, or sometimes they'd talk about the local provider," she says. "Those individuals need to be considered as part of this plan for disclosure. And what would be the cost to the participants?"
• Time limit: Biobanks can keep samples for years, complicating disclosure plans. Findings that may not be considered definitive now may take on added importance as the technology for interpreting them improves.
"These samples may have a lot of use," Williams says. "At what point are the obligations completed as far as contacting subjects?"
• State laws: IRBs and researchers must be aware of local laws regarding reporting of genetic findings.
• Potential misunderstanding: Any communications with subjects would need to be clear about what the finding shows and what it means. A genomic finding may not mean that a person definitely will develop a condition, and Williams says this can often be difficult for subjects to understand.
There's also the potential for a type of therapeutic misunderstanding as a result of genetic testing, she says.
"If you ask people to consent to be informed if there's an incidental finding and they hear nothing, will they conclude they have a clean bill of health?" she says. "The other concern we heard is that people may want to do this as a back door way of getting genomic health information about themselves, without going through a proper clinical evaluation."
While IRB chairs and researchers had different perspectives on the idea of disclosing GIFs, Williams says both groups surveyed were very thoughtful about the issue, and really struggled with its implications.
"It goes again to our point that if there were opportunities for them to be talking with each other about them, I think that would really be a good place to start," she says.
Reference
- Williams JK, Daack-Hirsch S, Driessnack M, et al. Researcher and Institutional Review Board Chair Perspectives on Incidental Findings in Genomic Research. Genet Test Mol Biomarkers. 2012 Feb 21 (epub).
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