By Diane Allingham-Hawkins, PhD, FCCMG, FACMG, Senior Director, Genetic Test Evaluation Program
On Thursday, March 27, I presented our poster about our evidence-based assessment of whole exome sequencing (WES) for rare and undiagnosed genetic conditions. During the poster session, I had the opportunity to speak to a number of genetics colleagues about Hayes’ work on the evidence-based assessment of genetic and genomic tests. It has been truly gratifying to see the transformation in opinion regarding the need for evidence in the use of genetic and genomic tests over the last few years. When Hayes began evaluating these tests in 2008, there was virtually no acceptance in the genetics community that evidence was important in determining how to use these tests. However, in the last 2 to 3 years, I have witnessed a definitive shift in mindset such that many colleagues now acknowledge that evidence that genetic and genomic tests change patient outcomes is needed in order to justify the use of these tests in clinical care.
The highlight of Thursday’s sessions was what can only be described as a rousing panel debate about the controversial ACMG guidelines regarding the reporting of “incidental findings” in WES or whole genome sequencing (WGS). A year ago, ACMG published these guidelines, which recommended that variants in a list of 56 genes deemed to be “medically actionable” MUST be reported to patients undergoing WES or WGS, regardless of the indication for testing and regardless of the patient’s wishes to receive this information. The guidelines have been divisive, at best. Mandatory reporting of findings that are unrelated to the reason for testing flies in the face of the traditional non-directive approach to genetic testing, which has always given the patient the final say in what is done and what is reported. Incidental or unintended results are nothing new in genetics—one of the big challenges we faced in the 1990’s when I was first doing diagnostic genetic testing was the issue of non-paternity. Some 15% of planned pregnancies are not fathered by the named father and it has always been a challenge to address such controversial issues. The key, however, is in the pretest genetic counseling such that patients can understand the risks, benefits, and limitations—including the fact that sometimes you get information your aren’t expecting—before agreeing to be tested. This is another basic tenet in genetics, that of informed consent. It is notable that there was no genetic counselor on Thursday’s panel, an unfortunate oversight.
As technology has advanced, we can now find variants for cancer, heart disease, and other conditions that may not be clinically important to the patient for many years—or even decades—or may never be important. The ACMG stance is that these results have such potentially important implications for patients and their families that the patients’ own preferences should be ignored, and this has created a rift in the membership. At the beginning of Thursday’s session, 4 polling questions clearly demonstrated that the majority of ACMG members present feel that patients should be allowed to decide which results to receive and which they do not want to receive. Despite a very spirited exchange, there was no real difference in the audience opinion following the session. As one panelist expressed, it is time for the ACMG to “take the bull by the horns,” listen to its members, and make modifications to these guidelines such that they are more acceptable to ACMG members and the patients they serve. It will be very interesting to see the response to the feedback received during this session.
Stay tuned for more updates from the 2014 ACMG annual meeting!