As exemplified this week by Angelina Jolie’s soul-baring op-ed in the New York Times, in which she revealed her mutation in the BRCA1 gene and subsequent double mastectomy, clinical genetic testing, and how we act on the information that stems from such testing, remains a complex, emotional, and controversial topic.
Not all clinicians agree with these recommendations. In two Policy Forum papers published this week in Science, arguments on both sides were aired (1,2). The opposing physicians call the ACMG’s paper a “startling statement” and that “rather than reconfirming well-established principles of patient autonomy and informed consent ... ACMG recommends an abrupt change.”
“Whole genome and whole exome sequencing is starting to get fairly rapidly integrated into clinical practice,” said Amy McGuire, director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine and a co-author on both the ACMG recommendations and the supportive Policy Forum piece. “But there are not a whole lot of standards or guidelines for laboratories in terms of what they should be looking for and how they should be setting up their analysis pipeline.”
So the ACMG gathered together a working group to address these concerns and create standards to guide the field. McGuire’s Policy Forum paper asserts that the ACMG set the bar high, listing 57 well-studied genes in which mutations almost always cause disease and for which existing treatment interventions exist. She and her co-authors further state that “Laboratories have an obligation to report clinically beneficial incidental findings.” The ACMG suggests this reporting of incidental or secondary findings could pinpoint diseases earlier.
But those who oppose the ACMG’s position believe that the policy is a “profound departure from prevailing law and norms” because it ignores a patient’s right to informed consent. They argue that it turns genetic testing into a deliberate hunt for genes, not an accidental finding like spotting an unexpected tumor on an X-ray. Furthermore, ACMG lists as a rationale for requiring testing in children that their family members could benefit from knowledge of a familial genetic abnormality. This is a huge departure from the consensus that testing in kids should be focused on the child’s best interests, writes Susan Wolf at the University of Minnesota and colleagues in the opposing Policy Forum paper.
Another issue raised by opposing physicians is that the ACMG policy seems more concerned with protecting its members than with protecting the patient.
“If it is thought to be best for the patients—then there should be no problem getting consent to sequencing from patients,” said George Annas, chair of Health Law, Bioethics, and Human Rights at Boston University and co-author of the opposing Policy Forum paper. “But it seems like the group is trying to provide legal protection from lawsuits for both clinical labs and ordering physicians.” His paper states that if physicians are so worried about liability, they should document the patient’s refusal, not strip them of the right to decide.
But McGuire disagrees, claiming that getting informed consent for the analysis of results is a departure from medical standards. “It treats the analysis aspect of the test as itself a separate test, I think it is not really how testing is done in this area or in other areas of medicine.”
1. McGuire, A. L., S. Joffe, B. A. Koenig, B. B. Biesecker, L. B. McCullough, J. S. Blumenthal-Barby, T. Caulfield, S. F. Terry, and R. C. Green. 2013. Ethics and genomic incidental findings. Science (May).
2. Wolf, S. M., G. J. Annas, and S. Elias. 2013. Patient autonomy and incidental findings in clinical genomics. Science (May).