What to do with “incidental findings” Some genomic labs offer panels with more than 50 analytes, and oth-
ers focus on offering a broader range of smaller, focused panels. Large panels increase the probability of incidental findings (IF), where one notices something that was not part of the target set or lab order. Many payers insist that test results be limited to relevancy to the presenting complaint. But frequently a focused request will be performed most economically as part of a larger panel. Or, in the case of whole genome sequencing (WGS), the interpretation report will contain “incidental findings” often for “variants of unknown significance” (VUS).
IF and VUS are not welcome by payers since they may lead to added expense. Indeed, several reported that payers favor labs that ignore IF and VUS. Others report that some oncologists desire reports responding to only what was specifically ordered, even if the assays leading to IF are run as a subset of a larger panel. Some clinicians want even a narrower report of only actionable diagnoses. Only a small fraction of clinicians self-report as being comfortable and confident with broad results from genetic assays, particularly whole genome sequencing.
Prof. David Magnus, Director of the Stanford Center for Biomedical Ethics (Stanford, CA), offered that failure to report IF could be a basis for medi- cal malpractice litigation. As a patient I want to know about IF since some could emerge as serious as our knowledge of genomics expands.
However, not all patients feel the same way. Some want to protect other family members, especially progeny, from having genomic data freely available. Yes, discrimination on the basis of genomics is prohibited, but the nature of discrimination often makes detection nearly impossible. And, yes, data are often “de-identified,” but the protection is far from perfect.
The business segment of clinical genomics is in conflict. So how about the technical side? Conflicts abound here, too. But these are more inter- esting to chemists, and probably more solvable.
The technical side of clinical genomics
Exome vs whole genome sequencing Dr. Pfeifer’s keynote was the first of many lectures to compare the cost and merits of exome sequencing, primarily with arrays on chips, with sequencing the entire genome (WGS). New technologies from several firms have reduced the cost of the analytics to $5000 or less, some much less. Interpretation is not included and can be much more expensive. Dr. Pfeifer explained that WGS has a cost advantage in his lab when the question at hand involves more than 2 kilobases. Below that, focused exome sequencing (ES) with arrays is lower in cost.
Dr. Elizabeth Worthey’s (Medical College of Wisconsin, Milwaukee) lec- ture presented a powerful, data-filled rebuttal. For her lab, they do WGS simply because it avoids the issue of “Are we missing something by using focused arrays?” She reported that with WGS, you will consistently find more, but this raises the issue of incidental findings above. She also explained that about 2% of patients at the Medical College present with more than one disorder. Without WGS, the clinical team would stop with the first positive result, and probably miss the second and subsequent. Dr. Worthey feels that patients and society are best served when full
AMERICAN LABORATORY • 31 • SEPTEMBER 2014
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