At ACMG, Concern About Patients' Choice in Genetic Testing

By Allison Proffitt 

March 28, 2014 | The American College of Medical Genetics and Genomics hosted its 2014 Annual Clinical Genetics Meeting in Nashville this week. Incidental findings dominated many conversations and sessions. 

In a Wednesday morning session, conversation centered on best practices in clinical sequencing, specifically the return of incidental findings and collaboration with treating physicians who are not geneticists.

The public's perception of incidental findings is still mixed, reported James Evans, the Bryson Distinguished Professor of Genetics and Medicine at UNC School of Medicine. In a small cohort of sequenced patients, 15 of 18 said they would like to receive incidental findings discovered during their sequencing. But when faced with a small barrier to gaining the information – patients were required to call and receive their data over the phone – only a third followed through.

Gail Jarvik, head of the Division of Medical Genetics at University of Washington, reported some of the reasons why patients said they did or did not want the additional information. Some said their attention was taken up with their current diagnosis and they didn't need more to worry about. Others expressed interest in learning more if the findings were fairly conclusive, but did not want a high level of uncertainty. Only a few patients said they wanted all of their data, with no “sugar coating.”

Jarvik also had the opportunity to observe how patients shared their data. In a larger study, 33 patients were sequenced at the end stages of their disease. The researchers offered to pass the eventual incidental findings on to a family member if the patient died before the analysis could be completed. Of the 33, 31 asked for the findings to be passed on; the two who declined had no living relatives. Most chose to release the data to a spouse, but 12 chose another relative. Jarvik pointed out that interestingly, 11 of the chosen relatives were women – mothers, sisters, and daughters. She wondered if this was telling in terms of where and how family medical data is passed down.

In order to observe how genetic data is disclosed and used, the BASIC3 study at Texas Children's Hospital enrolled pediatric cancer patients, their parents, and their primary oncologists all as study subjects, Christine Eng, Senior Director of the Baylor College of Medicine Medical Genetics Laboratories reported.

122 patients, 176 of their parents, and their oncologists all enrolled and agreed to participate in the study and receive their genetic data, including incidental findings. After sequencing and analysis, researchers held private pre-disclosure meetings with the treating oncologists before meeting with the patients, their families, and genetic counselors.

The findings, Eng reported, were particularly interesting in terms of how the treating oncologists responded.

Treating oncologists had mixed levels of comfort with, and interest in, the genetic findings. Training is needed across the board, Eng said, but even many trained oncologists preferred to let genetic counselors return the results. There was general discomfort explaining Mendelian inheritance to patients.

Many of the physicians were unfamiliar with the term “damaging” in a genetic context and most asked that it be removed from the report. They were extremely uncomfortable communicating findings regarding variants of unknown significance, or introducing incidental findings that dealt with conditions new to the patients and their families. They chose, if possible, to avoid protocols that included incidental findings or variants of unknown significance.

The genetic counselors involved in the study, on the other hand, were more inclined to push for more testing – of additional family members and additional genes of interest.

The BASIC3 study revealed a need for an established plan for additional testing or the testing of family members, and an in-place referral protocol for when incidental findings did necessitate medical follow-up

The Debate on Incidental Findings 

Eng also joined a panel on Thursday afternoon debating the ACMG's year-old decision to recommend returning results for 56 genes.

Based on Baylor's experience, Eng reported that about 3% of patients had findings among the ACMG's 56 genes. Including an additional several genes that Baylor deems medically actionable, the number rises to 5% of patients with incidental findings.

The problem is admittedly not large, but it is important, said Robert Nussbaum, Chief of the Division of Medical Genetics at UC San Francisco. James Evans agreed. In a minority of cases, he said, there will be “nuggets of great medical consequence.”

Nussbaum stressed that the ACMG recommendations were meant to inform testing labs which gene results they should return to the ordering clinician. The recommendations were not specific instructions for which findings to return to patients.

The debate continues, however, on how patients should be able to interact with those data. In a live poll at the session, nearly 70% of respondents called for some changes to the recommendations, and 88% of the responding audience supported an opt-out option.

Wylie Burke, a bioethicist from the University of Washington, and Susan Wolf, the McKnight Presidential Professor of Law, Medicine & Public Policy at the University of Minnesota, agreed that there is no reason patients should not be offered the choice to opt out of receiving the incidental findings report. Patients can choose to opt out of medically-necessary treatments, Wolf pointed out; these findings should be no different.

Designing an opt-out process, however, requires further choices to be made. Evans argued that opting out must take place before testing, so that if patients choose not to receive results, the results aren't even generated.

If the results are collected and entered into the medical record, Evans says it's impossible to ensure that the patient doesn't get that information. Because so many providers – physicians, nurses, and others – have access to the records, it's very likely that the information will slip out. He likened it to a pregnant couple who chose not to know the sex of their unborn baby. For some couples, an unwary provider is bound to congratulate them on the expected baby boy.

Burke agreed. If patients don't want the results, we shouldn't be generating them, she said, as a matter of respect.

But what if they want some of the results?

At Baylor, Eng said patients can't opt out of any of the ACMG 56 results, although they can opt out of seeing results for the additional genes Baylor has deemed actionable.

It's a position Burke says is “defensible.” Consenting patients on all 56 genes would be a monumental task, and she supports groups that take an all-or-none approach.

On the other hand, many can imagine situations in which patients would choose to have some of the data but not all of it. A commonly cited example was results linked to adult-onset diseases for pediatric patients. Do the parents of these patients need to know about adult-onset diseases?

92% of the responding audience members said parents should be able to opt out of adult-onset data for their children, focusing instead on the more immediately relevant findings.

A proposed solution is “binning” or grouping the findings into smaller groups of similar conditions, allowing patients to opt out of adult-onset findings, for instance, or cancer findings.

That sort of “checklist” approach would be challenging for labs, Eng said, but not insurmountable. On Twitter, audience members scoffed at the idea that logistical challenges overrode the patient’s right to choose.

Nussbaum challenged Burke on the concept of the patient’s ultimate autonomy. Does it always trump the physician’s recommendation?

We have an obligation of beneficence, Burke said, to offer anything that would be helpful. But there's also a communication issue; physicians are responsible for explaining the rationale for the 56 genes tested and why they believe it’s a worthwhile test.

Physician communication can make all the difference. It’s an unusual patient that opts out after being consented, said Evans.

But Wolf again stressed that the patient’s values must govern the choices made, even if the menu of choices offered is up to the physician. Part of a physician’s duty of beneficence is to respect the patient’s decision, she said.



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