When dealing with the findings that having your genome sequenced brings, patients have predominantly been given the choice of either all the information or none at all.
In March 2013, the American College of Medical Genetics and Genomics (ACMG) released recommendations on how to handle incidental findings (IFs) for the clinical application of whole exome or whole genome sequencing (WES/WGS). The ACMG recommended that clinical laboratories “actively search,”evaluate, and report pathogenic or likely pathogenic variants in 56 genes and report these findings to the ordering clinician, who could then “contextualize any incidental findings for the patient in light of personal and family history, physical examination, and other relevant findings.”
The 2013 recommendations did not provide guidance for laboratories to offer patients of any age the ability to opt out from the reporting of IFs. The 56 genes are associated with 24 genetic cardiovascular disorders or predisposition to cancers for which confirmatory diagnostic approaches are available as well as some preventive or treatment measures that can be offered. The ACMG recommended further that those who did not agree to learn of these IFs could choose to forego the entire test. These recommendations generated much controversy, most of which focused on patients’ ability to opt out of receiving unwanted results.
“Patients say that being able to have a say in what they learn or don’t learn is really kind of important,” said Jennifer McCormick, from the Bioethics Program at the Center for Individualized Medicine.
Much is known about how individuals respond to learning about genetic risk information, but the bulk of those data is from individuals undergoing single-gene testing. These experiences with single-gene testing may not be a fair comparison to WES/WGS testing. With the former, a person knows what is being tested and has sought the test to determine his or her risk for carrying genetic variants causing the disease.
In contrast, WES/WGS is not selective, and the results may reveal much more information than originally desired or anticipated. The landscape has changed appreciably, and it is no longer clear what it means to be well prepared to get results from clinical WES/WGS. These issues require additional study in well-designed clinical trials to understand more about the risks and benefits of receiving information on IFs. This is especially true for the release of IFs to children and their parents.
The vibrant discussions that have ensued since the release of the 2013 ACMG recommendations are encouraging, including those that the ACMG itself has hosted. It is important that these ongoing updates of the recommendations continue and that the discussions have input from all stakeholders including, but not limited to, patient advocacy groups, regulatory agencies, geneticists and genetic counselors, oncologists, hematologists, pediatricians and pediatric subspecialists, bioethicists, sequencing experts, and industry partners.
The recent revisions to the ACMG’s recommendations place greater weight on the diversity of patient interests and the importance of individual autonomy. As many have acknowledged, we need to develop new ways to assist patients in making informed choices that best fit their individual needs and better understand how individual patients perceive actionability. We believe an individualized, patient-centered approach to WES/WGS is necessary and attainable to realize the full potential of sequencing techniques to improve medical care.
Read more at the Star Tribune.
Article featured on Mayo Clinic Proceedings.