Handling incidental findings in age of genetic research
Ethics and pragmatism intersect
Clinical research teams and investigators may find that their traditional strategies for handling incidental findings during a trial are inadequate in this age of genetic research.
"As we become more involved in working in areas of the human genome, it's more likely and foreseeable that we're going to be obtaining information about our patients that goes beyond the scope of research studies," says Lynn G. Dressler, DrPH, assistant professor in the school of pharmacy at the University of North Carolina at Chapel Hill.
This is a new era for researchers, Dressler says.
What do clinical trial teams do if they receive incidental information that they think might be useful clinically but there is nothing definitive about how to handle the findings she asks.
"What kind of processes do we need to think about when we come across this kind of information in a research study?" Dressler asks.
For example, there is one genetic variation recently discovered that could have two different medical implications: One mutation might mean a person is prone to heart disease, and another mutation could mean the person might be susceptible to Alzheimer's disease, Dressler explains.
"There is an association between the genetic variation and the development of Alzheimer's disease, but there still is a degree of uncertainty," she says. "It's not a clear-cut association, and there's not a standard of care or standard test we do for this finding."
Suppose there is a clinical research study being conducted about heart disease, and this genetic marker is looked at in context of that study. But for some volunteers, investigators find the Alzheimer's disease marker, Dressler says.
To tell or not to tell
The question then is: Does the clinical research team tell the participants about the findings related to Alzheimer's disease?
"Some of the advocacy groups I have talked with take the position that you should disclose any research results to a subject except when the information is not analytically valid or clinically validated," Dressler says. "The National Bioethics Advisory Committee takes the position of most academic researchers that the research should not be disseminated routinely to research subjects."
When the incidental findings are not well understood or are not applicable to the population in general, then they should not be disclosed, she adds.
"There needs to be some process by which we evaluate the clinical validity and analytical validity of this information before we can say, 'Yes, this is important to impart to the individual,'" Dressler says.
Those who favor disclosing information to subjects base their opinion on the ethical principle of respect for a person, Dressler says.
"If you have information about someone, this information should be communicated to the individual so he or she can utilize it and make lifestyle decisions or reproductive decisions about it," she says.
Those who disagree about disclosing information to subjects base their opinion on the position that research results are not intended for individual use, but are for [public] information, Dressler says. "Their position is: 'We've done this study, and we're trying to make some kind of statement that we can generalize to the public about this genetic abnormality and gene mutation and human response to a treatment.'"
To provide information to specific people goes against the concept of what research is all about, she adds.
Another factor is that research is by nature dynamic, and findings that seem relevant today may not be as relevant tomorrow.
"The nature of research is that three or four years down the road, we'll learn something else, and what we initially thought is not the same as what we know now," Dressler says.
Going back to the Alzheimer's disease genetic marker example, this could mean that further research reveals that the association discovered earlier is invalid and doesn't mean that an individual is at any greater risk of developing Alzheimer's disease.
Since this future scenario is a possibility, is it even ethical to disclose the genetic finding to an individual research volunteer?
"So what level of certainty do we need to have to say this is information we should communicate to an individual or family?" Dressler says. "That's where the ethical discussion is heading."
And this is where genetic research incidental findings differ from radiological research and other areas, she notes.
When a radiological scan reveals a mass, for example, there's a clear clinical course of action that can be taken, including confirming the finding.
But this is not at all true with genomic findings.
'How' just as important as 'what'
The final ethical consideration is how to communicate the findings to research participants.
Even when researchers decide to give volunteers the results, how they do so is problematic.
Many research institutions and sponsors do not have standard operating procedures (SOPs) for how and when to give study subjects the final results of a study — let alone incidental findings.
"One thing we haven't done a good job of is disseminating aggregate results to research subjects in a language that is accessible and understandable," Dressler says. "What kind of information are people able to access on the web or elsewhere about what is learned from this study?"
Some areas of research are starting to communicate study results more consistently to study participants, but overall this remains a problem, she notes.
"It's not a funded part of most studies to disseminate or communicate information about an entire study by newsletter or Internet site to study participants," Dressler says.
Research sites, institutions, and sponsors should develop a process for assessing what needs to be communicated to research participants and how to do so, she suggests.
Someone needs to decide whether the assay from the research laboratory provides valid results that can be trusted and effectively communicated to an individual volunteer.
"What are the standards that need to be met?" Dressler asks. "Are there different standards for different tests, and are there some that have more risks associated with them?"
For example, any information that might hold clues about a person's future reproductive health would be considered valuable information to share, she says.
"But if it's information then someone might hold it in the back pocket and say, 'Mmmm, that's interesting. I don't know what I'll do with it, but maybe I'll be more careful about doing regular exercise.' Then it may not be considered as high a priority to disclose," Dressler says. "It's hard to know what threshold of evidence or certainty is appropriate before you communicate findings and still do no harm to the research subject."
From the perspective of many patients, all incidental findings are important. Even if the findings involve an association for a disease such as Alzheimer's, for which there is no cure, some people would say that this information they would want, Dressler says.
So the key is for investigators and research sites to anticipate these kinds of findings and make policies and procedures, accordingly.
"Even if you can't foresee some findings, then you should at least be asking researchers to say which incidental findings they are likely to find, and what kind of plan they have in place to address these," Dressler says. "They could give the information to a committee that reviews it on a case-by-case basis, or they could give the information to an IRB."
Finally, if there are any incidental findings to be disclosed, the person who communicates the information to the research volunteer should be a professional, she notes.
"This shouldn't just be a lab researcher who finds the information, but someone who is an expert in genetic counseling or another professional," Dressler says. "Also, most people agree that the person being told the information should have counseling before the finding is communicated to them."
Before data collection begins, the counselor could offer the volunteer the choice of hearing or not hearing the incidental findings.
"Then when you call them to give them the information, you could ask if they still want the information," Dressler suggests. "So it's a matter of being sensitive to the fact that there are rights both to know and not know information, and people need to know the pros and cons on either side so they're in the best position to say what they want to know."