January 1, 1970 (Vol. , No. )

Presidential panel, ACMG, and experts struggle with what patients should learn, and how.

Sarah Hilgenberg, M.D., was a self-described “hard-working, high achieving, strong willed, Type A 20-something” who wanted to help a friend and earn $40 for herself when she volunteered in 2002 for an MRI scan of her brain.

During her third scan, doctors found an anomaly. Originally thinking it was a tumor, her friend and others studied the results further, and found she instead had an arteriovenous malformation. She followed the advice of her physicians and underwent two embolizations, then the resection of her frontal AVM, scheduling the procedures around her studies at Stanford School of Medicine.

“I am grateful that Matt decided to tell his superiors about my scan,” Dr. Hilgenberg, now a clinical instructor at Stanford’s Lucile Packard Children’s Hospital, recently told a White House advisory panel. “A part of me thinks he had no obligation to do this. I am not sure I would be here today to speak to you if he had not acted.”

The Presidential Commission for the Study of Bioethical Issues heard Dr. Hilgenberg, another patient and others address what should be done with information from data gleaned from medical procedures or laboratory tests beyond their stated goals, “incidental findings”? How differently should investigators handle incidental findings in basic research? In clinical trials? And in direct-to-consumer genetic testing?

Setting Some Standards

Commission spokeswoman Hillary Viers told GEN that members will likely deliberate their recommendations at the panel’s next public meeting August 19–20 in Philadelphia: “The Bioethics Commission expects to submit a report on incidental findings to the President in the fall.”

No consensus exists on incidental findings. Responsibilities for returning results to patients have yet to be established in each setting. The sequencing that generates findings is only now inching into clinical practice. Furthest along in suggesting answers is the American College of Medical Genetics and Genomics (ACMG). In its “Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing,” ACMG developed a minimum list of 57 genes it suggested be sequenced for mutations for any of 24 disorders “where early intervention is likely to reduce or prevent serious morbidity or early mortality.”

Michael S. Watson, Ph.D., FACMG, ACMG’s executive director, told GEN the group’s primary considerations in developing the list were that conditions be severe in their risks of mortality and morbidity, that a long asymptomatic period be present in people with pathogenic mutations, and that the intervention significantly impact morbidity and mortality.

“We find that about 5% of the causes of common diseases are the rare Mendelian forms, which are the forms on which we are focused. And, within these Mendelian forms, we focus on the known or highly likely pathogenic variants as incidental findings (IFs) only. We anticipate that ~1% of cases will have one of the reportable IFs. Our focus is on prevention,” Dr. Watson said.

For the genes on its minimum list, ACMG recommended that lab should, regardless of patient preference, return incidental findings to the doctor ordering the sequencing to discuss with patients. Genes should be sequenced no matter the age of the patient, and no matter the indication that triggered the sequencing. Patients who decline to give consent should not be sequenced.

“We felt that clinicians and laboratory personnel have a fiduciary duty to prevent harm by warning patients and their families about certain incidental findings and that this principle supersedes concerns about autonomy,” the ACMG stated. “We recognize that this may be seen to violate existing ethical norms regarding the patient’s autonomy and ‘right not-to-know’ genetic risk information.”

A Right Not to Know?

Indeed it does, argues the PHG Foundation, a genomics and health policy think tank in Cambridge, U.K. PHG opposes ACMG’s suggestion that patients not consenting to its minimum list of tests be denied screening for their primary complaint: “This is an example of coercive and paternalistic behavior that is no longer the norm for clinical practice,” Philippa Brice, Ph.D., PHG’s communications director, told GEN.

PHG also faults ACMG for failing to require explicit consent for screening beyond the primary complaint, while acknowledging that detailed explanations of each test, and consequences of positive results, are not required. Dr. Brice also said giving discretion to physicians whether and how to communicate positive findings to patients “places an unreasonable burden on the referring physician, given that it was not necessary to have carried out the analysis in the first place.”

ACMG defends its stance, saying it envisions clinical practices will evolve toward the multi-specialty practices of sequencing centers. “The practice model could boil down to having a lab representative, a clinical geneticist who understands the genetics of the variant and the clinical issues in the patient, and their primary care and specialty care provider,” Dr. Watson said.

In an “Incidental Findings Clarification” released May 2, ACMG said it will work in coming months to develop an “open and transparent” means to nominate additional conditions for the list. “We are defining the pieces of information that need to be presented and referenced that inform the various criteria or principles we have been using to identify the conditions that go on such a list of IFs,” Dr. Watson said.

Two bioethicists contend ACMG’s recommendations should balance the benefits with risks from disclosing incidental findings.

“The drafters ignore all the negative potential consequences of giving people additional information. They or their family members might have follow-up testing. There may be additional procedures, even including invasive procedures,” Mark A. Rothstein, J.D., director of the Institute for Bioethics, Health Policy and Law at University of Louisville School of Medicine, told GEN. “It may be expensive. It may be not particularly revealing, and not actionable. These people may then be committed to sort-of a lifetime of medical surveillance of questionable utility. There may be psycho-social harms. There may be economic harms.”

Jeremy Gruber, J.D., president and executive director of the Council for Responsible Genetics, told GEN the presidential commission should not promote increased physician use of genetic tests without accompanying privacy standards: “It’s incumbent upon the presidential commission to be much more specific and detailed about what privacy framework would govern the use of all these new technologies.” In October, the commission recommended better data security and access, and a process for fully informed consent in clinical whole-genome sequencing, but didn’t offer details.

Yet ACMG deserves credit for wrestling with incidental findings ahead of groups representing researchers, physicians, lab professionals, and patients. Until they weigh in, there’s no basis for stakeholders to collectively address the issue. What’s needed is a consensus solution that combines some form of ACMG’s minimum screening with greater patient consent sought by critics, and additional testing as envisioned by PHG, namely serious yet actionable conditions.

What One Patient Says

Absent that, patients will continue to gamble on treating or ignoring incidental findings of potential serious illness. Addressing the commission April 30, Carol Krucoff, a yoga instructor/therapist with Duke Integrative Medicine, discussed how she has held off surgery for a brain tumor discovered in 2004, during an MRI while hospitalized for severe hyponatremia.

Her acoustic neuroma on the eighth cranial nerve was small. She experienced no symptoms. And the Acoustic Neuroma Association website’s discussion board offered both tales of botched treatments and excellent results. Rather than undergo treatment, Krucoff opted to watch and wait over the past nine years, during which she has had nine MRIs.

“As a health journalist, I had always thought there was great benefit in early detection. However, my experience has made me question the wisdom of learning about an abnormality if all it offers is anxiety, as well as potential harm from treatments for something that might never affect my health,” said Krucoff, founding editor of The Washington Post’s health section.

Krucoff’s advice to the commission should be part of the consensus solution: “Please keep me informed in simple, direct language of what’s been found and its implications for my health. Train providers with good communication skills to ensure that they present this information compassionately and clearly with patience and honesty. Consider adding a support person to the health care team, such as a social worker or psychologist, to help the patient and their family process the information and decide on a course of action.”

And finally: “Unless it’s clearly a medical necessity, don’t rush to treatment.”

For more on the topic, be sure to check out our Insight & Intelligence™ article “Your Genes, Your Choice?

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