NEW YORK — As whole-genome sequencing becomes a more common testing option, a panel of genetic counselors and others participating in the virtual annual meeting of the National Society of Genetic Counselors this week discussed whether healthcare providers and payors are ready for its use as a first-line test.

Whole-genome sequencing has increasingly been used in pediatric populations to diagnose children with rare disease. Such pediatric patients often face long diagnostic odysseys, but as panel moderator Molly McGinniss, staff market development manager, global marketing at Illumina, noted, there is increasing evidence that next-generation sequencing may cut those odysseys short as well as bring down healthcare costs.

But whether the field is ready for broader adoption of whole-genome sequencing as a testing option is unclear, the panel noted. In particular, the panelists examined the utility of whole-genome sequencing as well as what policies are in place for reimbursing for sequencing tests and what educational initiatives may be needed to keep clinicians up to date.

“I think there’s a lot of unanswered questions as it relates to the types of patient indications, the technical capabilities … as well as just general readiness from a provider standpoint and also key decision makers like payor communities,” McGinniss said.

Clinical testing has progressed from single-gene tests to panel tests to focused exome testing to whole exomes and now to whole genomes, PerkinElmer CSO Madhuri Hegde, one of the panelists, said. While she noted that testing has recently focused on exome sequencing, she said whole-genome sequencing offers a more unbiased approach and can provide diagnoses where other approaches cannot.

For instance, Hegde said that whole-genome sequencing was able to diagnose a five-year-old boy with Thiamine Metabolism Dysfunction syndrome 5 by uncovering two different types of changes — a missense alteration and a CNV — in the TPK1 gene. Likewise, whole-genome sequencing was able to uncover a de novo deletion in an 11-year-old girl, leading to a diagnosis of Cornelia de Lange syndrome 6.

Additionally, she added that more and more genes have been tied to various diseases, which could make it more difficult to select a few for analysis. As an example, she said that within muscular dystrophy, four years ago there were 10 genes linked to the condition and now there are 60.

“I think that is a classic example of why a whole-genome sequencing approach is very useful,” Hegde said.

HudsonAlpha Chief Medical Officer David Bick further noted that in the clinic, he’s sometimes faced with a patient who presents with a range of phenotypic features, such as autism and seizures. In those cases, he said that rather than doing an autism and a seizure panel, it may make more sense to do whole-genome sequencing, especially as that can be revisited when new genes are found to be involved in certain conditions.

Whole-genome sequencing is moving beyond rare diseases, Bick added, into the realm of elective genome testing where testing is sought without a clinical indication. 

However, Hegde added that there are instances where sequencing may not be able to provide a diagnosis. Still, she noted that her lab has begun to see a slow shift from exome sequencing to whole-genome sequencing.

One challenge to the broader adoption of whole-genome sequencing is reimbursement, but Jessie Conta, a genetic counselor at Seattle Children’s, noted there is some movement there, in part driven by some recent studies that have found cost savings.

For instance, Project Baby Bear, which was funded with $2 million from the California Medical Assistance Program (Medi-Cal), studied the impact of offering rapid whole-genome sequencing to 178 critically ill infants. The study found whole-genome sequencing led to diagnoses for 76 babies, as well as to $2.5 million in healthcare savings. According to Conta, these findings led BlueShield of California to cover rapid and ultra-rapid whole-exome or whole-genome sequencing, though it does not yet cover standard genome sequencing.

However, she pointed out that some payors in the US are less likely to see the economic value of sequencing, as people tend to change providers every few years.

Still, Conta said that once a policy such as one covering exome sequencing is in place, it is easier to expand upon it. She added that some payors have begun to cover pediatric whole-exome sequencing, despite what they see as a lack of evidence, because of the value in available interventions and ending the diagnostic odyssey.

“It’s reasonable to expect that expanded coverage for genome sequencing, probably starting in the rapid [genome sequencing] space, really will spread and it will see increasing utilization by providers,” Conta added. 

However, some non-genetics healthcare professionals feel ill-prepared to discuss sequencing results, suggesting that more education is needed. According to Kimberly LeBlanc, associate director of research operations for the Undiagnosed Diseases Network Coordinating Center at Harvard Medical School, about half the healthy adults from the PeopleSeq Consortium, who had undergone genome sequencing either through a commercial provider or a research effort, shared their results with a healthcare provider, most typically a primary care provider.

But a survey by the eMERGE network of primary care physicians and subspecialty physicians found such providers often felt unprepared to handle sequencing results, especially if they had not ordered the test themselves, she noted. She added that the physicians highlighted the need for clinical decision support tools, including consultants and patient materials. LeBlanc noted that this finding was in line from what a survey of investigators in the IGNITE network found, namely that provider education and clinical decision support are barriers to the adoption of genomic medicine.  

Those survey respondents, LeBlanc said, suggested adding genomics training into medical school curriculum and continuing education programs. She noted there are a number of education initiatives aimed at non-genetics providers, including one being put together by the American College of Medical Genetics and Genomics. 

The panelists added that there are numerous ways genetic counselors could help close these gaps. LeBlanc, for instance, said that genetic counselors are well poised to help educate other healthcare professionals, and Bick added genetic counselors could serve as consultants and introduce the utility of genome sequencing to physicians.

“I think educating different types of providers about what genome sequencing can offer, what is detected by genome sequencing, what’s not detected by genome sequencing, when is it an appropriate test for a patient, I think those are all really important pieces,” LeBlanc said. “As well as this potential consulting relationship between genetic counselors and other types of providers.”

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