When sequencing an individual’s DNA for a particular medical issue uncovers genetic variants that may suggest that the patient may develop other health problems, it presents laboratories and clinicians with a dilemma: should patients be told?
Today a prominent group of geneticists and clinicians weighed in by releasing recommendations that advise laboratories to report such incidental findings to physicians if they involve a subset of conditions for which patients may derive a benefit from being told. The recommendations specify that the patient’s physician should be the one to deliver the news and provide context about the finding in relation to the individual’s medical history.
As genome sequencing has become less expensive, its use for clinical testing has become more common. However, screening large swaths of the genome can lead to the discovery of genetic variants that are potentially harmful but that are not related to the intended target of the screening. Whether to share these incidental findings with patients has been a hotly debated subject, with arguments swirling about a patient’s right to know about potential genetic risks and the benefits of such findings as well as potential harms, including psychological distress, additional costs, and adverse effects that might be associated with additional testing.
To provide some guidance on the issue, the American College of Medical Genetics and Genomics convened a working group to develop recommendations on what laboratories and clinicians should do with incidental findings. Although the group found “insufficient evidence about benefits, risks, and costs of disclosing incidental findings to make evidence-based recommendations,” it reached consensus that reporting incidental findings about a specific subset of genetic variants may offer medical benefits to patients and their families.
The list of genetic variants includes those that predispose individuals to a higher risk of breast and ovarian cancer, variants associated with Marfan syndrome and other conditions that may lead to aortic dissection, variants associated with other cardiac problems, and certain other cancers. Because most of these conditions are rare, only about 1% of the individuals who undergo sequencing will likely receive an incidental finding as a result of the recommendations, according to the recommendation.
Those patients who do receive such findings “will learn unexpected but potentially life-saving information about an illness they may have never suspected they were at risk for,” said Leslie G. Biesecker, MD, co-chair of the working group and chief of the genetic disease research branch at the National Human Genome Research Institute.
The recommendations are likely to generate considerable controversy. For example, the working group opposed seeking patient consent to deliver incidental findings before testing. The group argued that practical considerations would make such consent difficult in the setting of genome screening and that the potential clinical benefit of receiving results about the specified conditions outweighed a patient’s “right not to know.”
But Anne Townsend, PhD, a research associate at the University of British Columbia W. M. Young Centre for Applied Ethics, said that ethically there is a need for patients to give properly informed consent. She argued that ideally, patients should have a voice in developing such recommendations.
Practical barriers should not stand in the way of consent, she said, and new approaches to consent using digital technology should be considered. “In the new digital health era, we need to be looking at more creative ways to interact and offer information,” she said.
Several committee members also disclosed financial or other relationships with laboratories that offer sequencing or companies that profit from sequencing, which may raise questions about whether these relationships pose conflicts of interest that can be problematic for persons making policy recommendations.
The committee members acknowledged the recommendations would likely change as new information became available, a point echoed by Townsend. “Guidelines will change as knowledge and technologies evolve,” she said. But it’s important to decide, she added, if the starting point in building those guidelines will be based on the older paternalistic model in which a clinician decides for the patient or whether it will be informed by the newer approach of respecting the patient’s autonomy and, ultimately, the patient’s right to know or not to know results.