Tracy Vence GEN
Critics say the American College of Medical Genetics and Genomics’ recent recommendations for reporting incidental clinical sequencing results undermine patient autonomy.
You’ve done some reading, really thought it through, spoken with your doctor, talked it over with your family and friends, and decided to have your exome sequenced. You’d like to know more about your risk of developing the breast cancer that looms within your family’s history. But, before learning this, consider: Do you also want to know whether you have a heightened risk of developing colorectal cancer later in life?
That patients who opt to have their genomes sequenced—in part or whole—in a clinical setting would not be able to ignore such a so-called incidental finding is the major implication of guidelines issued by an American College of Medical Genetics and Genomics (ACMG)-appointed working group in March. In a dramatic shift away from the patient’s “right-not-to-know” message pervading clinical genetics since the field’s inception, the new ACMG guidelines suggest that anyone undergoing genome sequencing for any reason should also be screened for dozens of variants associated with life-threatening but treatable conditions.
“Clinicians and laboratory personnel have a fiduciary duty to prevent harm by warning patients and their families about certain incidental findings…. This principle supersedes concerns about autonomy, just as it does in the reporting of incidental findings elsewhere in medical practice,” the group behind these new recommendations wrote. Last week, ACMG issued a statement to clarify some of the more hotly debated issues related to its recommendations, including prediction of disease likelihood, returning results to pediatric patients and their families, and billing and reimbursement considerations, among other things.
In a blog entry over at the Huffington Post, report co-author Robert Green, associate professor of medicine at Brigham and Women’s Hospital and Harvard Medical School, elaborated on his team’s position, calling the recommendations “a controversial but necessary step towards genomic medicine.”
Scanning for additional disease-associated variants when searching an exome sequence for some other anomaly, he said, is much like a radiologist scrutinizing an entire chest x-ray, even if it was ordered to be interpreted with respect to a particular anatomical focus.
“The search for rare incidental findings is routine in medical practice,” Green wrote at HuffPost. “Exceptionalizing the incidental information discovered through genetics has no rational basis except to maintain traditions that are becoming increasingly impractical as genomics [sic] medicine arrives,” he added.
Depending upon who you ask, genomic medicine has arrived. Already, researchers and oncologists are routinely scanning genomic sequences in tumor-normal pairs, seeking to match cancer patients with the right treatments at the right time. Every day, genetic counselors help parents-to-be navigate the murky waters of prenatal genetic testing.
For most people, this may not all mean much just yet—the number of patients who have had their genomes or exomes scanned for medical reasons is still small. But for some, clinical sequencing is right now being used to great effect.
As sequencing costs fall and clinical utility expands beyond rare diseases, cancer, and prenatal considerations, more and more physicians will be ordering more and more genomic testing.
But ethicists and geneticists are concerned that a lack of genomics training within the broad medical community could spell disaster when it comes to informed consent.
It is generally acknowledged among patients scheduled for, say, a routine CT scan, that there is a slim possibility the test might pick something unexpected up. “When it comes to genetics, we cannot necessarily make the same assumptions about what our patients understand,” Tanya Eble, manager of adult genetics at Baylor College of Medicine’s department of molecular and human genetics tells GEN. “It is incumbent on the genetic counselor or medical geneticist to educate the patient about the possible risks, benefits, and limitations of testing.”
According to Maegan Roberts, genetic counselor and instructor of medical genetics at the Mayo Clinic in Jacksonville, FL, “the most important step in this process is the initial counseling session—prior to ordering whole-exome—and the consent process.”
“My personal concern is that physicians who are not trained in medical genetics will start ordering this testing and not take the needed steps to educate and consent the patient appropriately,” Roberts tells GEN. “We all know that physicians are way too busy to spend an hour or two with each patient discussing the ins and outs of genetic testing.”
Should clinical labs choose to heed the ACMG working group’s recommendations, “the additional burden on genetic counseling services [would be] a huge factor,” Megan Allyse, a postdoctoral research fellow at the Stanford School of Medicine, tells GEN. “ACMG recommends that clinicians should be responsible for providing pre- and post-test genetic counseling, while recognizing that many physicians will not have the sufficient expertise and will need to refer for genetic counseling.”
Problem is, Allyse notes, “there is already a significant shortage of qualified genetic counselors in the U.S. and it is by no means clear that the existing supply could meet this additional demand.”
At press time, the American Board of Genetic Counselors counts 3,026 certified professionals among its ranks. For the sake of comparison, the U.S. National Cancer Institute estimates that 232,340 women will be diagnosed with breast cancer this year.
Experts on both sides of recent debates over the working group’s guidelines and patient autonomy agree: It is imperative, they say, that patients are made fully aware of the potential for unforeseen genetic anomalies to pop up in exome or whole-genome sequencing in order to decide for themselves whether they indeed wish to be tested. But there are some idiosyncrasies in the issue of patient autonomy.
“We can’t control whether we see an incidental finding, but we can certainly control whether we purposefully look for genetic variants,” Allyse says. “There’s really no reason not to give the patient the ability—ahead of time—to decide what information they do or do not want to receive.”
In a Trends in Biotechnology article published today, Allyse and her colleague Marsha Michie, also at Stanford, say that by following ACMG’s recommendations as outlined, clinicians would be overstepping their boundaries with respect to patients’ rights to decide what they’d like to know for themselves. Despite perhaps the best of intentions, Allyse and Michie write, scanning for additional mutations would make a physician’s diagnostic foray into clinical genomics “forcing a patient to learn about a future disease risk.”
But the National Human Genome Research Institute’s Leslie Biesecker, who co-chairs the ACMG working group, says medical practitioners routinely order nongenetic testing without first fully explaining all of the potential implications to their patients.
“Patient autonomy is always important. Patients should have the option, after being fully informed about what this testing necessarily involves, as to whether or not they wish to undergo that testing. That’s how we handle every other similar situation in medicine,” Biesecker tells GEN. But, he says, a primary care physician is unlikely to outline every possible condition he or she may eventually diagnose an asymptomatic individual with at the outset of every visit. “Why is it so necessary, in genetics, to give patients a choice and a menu of what they wish to learn and what they don’t wish to learn when we don’t do that for a physical exam?” Biesecker asks.
To Roberts’ mind, “as long as the patient is fully educated on what whole-exome [sequencing] is, the chance for an incidental finding, is given examples of possible incidental findings and how it would impact their medical management, and they still agree to proceed, then patient autonomy is not a problem,” she says.
“I find it paradoxical that we would be less enthusiastic about finding a disease manifestation before it occurs than we are about finding it when it is occurring, because, for almost all diseases, and essentially every disease on this [ACMG] list, knowing about it before the patient has any consequences gives that patient and their physician the best potential opportunity to keep them healthy and alive,” Biesecker says. “So, when people say, with genetics, ‘Gosh, you shouldn’t be doing that—it’s predictive, it’s pre-symptomatic,’ I say: ‘Hallelujah!’ That’s exactly what I want because I have the best opportunity to help my patient in that scenario.”