Handling incidental findings in genomic research

Biobanks face particular challenges

An issue that can frequently arise in the area of genomic research is what to do with incidental findings (IFs) — discoveries concerning a research subject that are beyond the scope of the study, but could have potential health importance for the subject. The findings can arise during the collection or analysis of research data, such as unexpected discoveries in neuroimaging (such as a mass or aneurysm) or genetic studies (unexpected genetic variation).

The debate, says Jeffrey Kahn, PhD, MPH, lies in whether to disclose the incidental findings, and which are appropriate to disclose. “The key question is whether the results are clinically meaningful,” says Kahn, Levi Professor of Bioethics and Public Policy, Johns Hopkins Berman Institute of Bioethics in Baltimore.

Reports state that incidental findings occur in 13-40% of research MRI subjects and up to 84% of scans, Kahn says.

Questions that researchers will encounter with incidental findings include: What should researchers do when they encounter IFs? With whom should researchers consult? What, if anything, should be disclosed? What should the researcher tell that subject? “There is almost no way to do this in a way that won’t worry them [the subjects] a lot,” Kahn says. As far as disclosing IFs that are not life-threatening or clinically significant, “you may be creating more morbidity than you help treat,” he says. For example, a study subject could end up undergoing unnecessary surgery due to an incidental finding, and would have to then deal with associated risks and recovery of the surgery.

There is a proposed duty of reciprocity to subjects, that “they put themselves in harm’s way for science, so we give them a little bit to compensate for it,” Kahn says. “Some would argue that we owe them [subjects] more than that and if something is incidental, we would tell them and do something about it.”

Biobank challenges

Biobanks face particular challenges with incidental findings, Kahn says. “Advancing technologies will increase incidental findings — stronger magnets in imaging and longer DNA strands will make things worse,” he says. “Researchers and biobanks should establish a pathway for handling suspected IFs. IRBs and biobanks should oversee compliance with IF-related obligations. Guidance should be developed by funders as part of research guidance.”

The four key responsibilities of biobanks are referred to as CARR:

Clarify the criteria to determine what kinds of findings are returnable, and the roster of returnable IFs and individual research results.

Analyze the finding to decide whether it should be offered to the individual contributor.

Re-identify the contributor.

Re-contact the contributor and offer the finding along with genetic counseling or other appropriate counseling.

Researchers should establish a pathway for handling suspected incidental findings, and IRBs should oversee compliance with the guidelines, Kahn suggests. Consent forms and study protocols should include a section on IFs and what researchers intend to do if any are discovered. “Whatever the answer is, tell them [the IRB] what you’re going to do, and tell the subjects as well.” There should also be language detailing how IFs will be handled if discovered in reanalysis of archived patient samples.