Whole-Genome Sequencing Is Here, But Clinical Utility Remains Unproven

Multiple firms are racing to develop an affordable whole-genome sequencing product as a marketable diagnostics tool, but clinicians and genetics experts told a government advisory panel last week that the practice is not yet ready for clinical application.

More evidence on clinical utility has to be collected and physicians need to be better educated in how to apply whole-genome information before the practice should be adopted, speakers noted June 15 at a meeting of the Health and Human Services Secretary's Advisory Committee on Genetics, Health and Society (SACGHS) in Washington, D.C.

"The intersection of personalized medicine and genomes and evidence-based medicine, at this point in time, is actually quite small, and I think this is a huge barrier to whole genome sequencing," said William "Greg" Ferro, director of the Maine-Dartmouth Family Medicine Residency Program.

The committee agreed at the conclusion of the meeting to form a task force that would monitor developments in whole-genome sequencing and keep HHS informed of the rapidly developing space.

SACGHS provides advice intended to inform policy within all HHS agencies including FDA regulations, Medicare reimbursement and research funding priorities.

Costs Could Be Under $1,000 In Two Years

Sequencing tools have rapidly evolved in the past seven years since the Human Genome Project was completed. That project cost $3 billion (Also see "IBM Edges Toward A Bargain DNA Sequencer, With Dx Applications In Sights" - Medtech Insight, 12 Oct, 2009.).

Today, it costs about $10,000 to sequence an individual's entire genome. And within two years, the price is expected to drop to between $500 and $1,000 as a growing "convergence" is reached between accuracy and affordability, said Dietrich Stephen, CEO of the Ignite Institute, a non-profit organization that advocates and supports research for genomic and personalized medicine technologies.

First generation sequencing tests, performed with Applied Biosystems' capillary electrophoresis technology, are mostly "unaffordable" but provide diagnostic accuracy, he told the panel.

Second generation tests sequencers, including Life Technologies'/Applied Biosystems' SOLiD system, Illumina's HiSeq and Dover Systems' Polonator G.007 are "barely affordable" and accurate enough for research, but not for clinical use.

Third- and fourth-generation products now in development will be the "most affordable and accurate" tests, bringing whole-genome sequencing within the reach of more patients, he said.

Physicians, Counselors Will Need A Lot More Data

But while affordability is one important threshold, other speakers at the meeting stressed that physicians, genetic counselors and other stakeholders of the information will need to see much better data on the applicability of a whole genome scan to their patients prior to adoption.

Charis Eng, who chairs the Genomic Medicine Institute at the Cleveland Clinic Foundation, said that the genetic counseling and bioethicist community remains cautious about the practice.

Genome-wide association studies differ in their interpretations of what each genetic variation means and sequencing itself is not 100 percent accurate, she noted. Eng also pointed out the steep challenges of educating physicians and patients about test results.

Whole-genome sequencing will be affordable well before physicians "understand the clinical importance of all the data," concluded Emily Edelman, a genetic counselor with the National Coalition for Health Professional Education in Genetics.

Richard Sharp, Director of Bioethics Research for Cleveland Clinic, told the committee that even if he had access to genetic counseling, and an affordable way to be tested, that he still would not have genetic testing performed on himself.

Most physicians are "still out of touch with the leading edge of research on genetics," and are simply not comfortable counseling patients about currently available gene tests, "let alone whole-genome sequencing," Sharp said.

Ferro, from Maine-Dartmouth, agreed. Primary care physicians "don't wrap their minds in thoughts of genomics. They wrap their minds in the bread and butter things, which they know are most useful in health care systems," he said.

In addition to a general push for more studies addressing clinical utility, speakers at the meeting recommended more whole genome sequencing investigations of entire families as well as research into how best to educate the physicians on whole genomic sequencing.

SACGHS Chairman Steven Teutsch, chief science officer for Los Angeles County Public Health, agreed with the cautious mindset.

Teutsch noted that while the potential advantages of predicting a disease well in advance are not insignificant, there are many potential downsides to the screening in terms of negative health benefits or unnecessary costs and treatments.

Besides straightforward false negatives and false positives, which have clear consequences for health, other potential outcomes include whether the screening correctly predicts the patient will develop a disease, but the patient will not experience morbidity and mortality from the disease even without treatment, or if existing treatments for a disease are no more effective if initiated prior to symptoms manifesting than if given after symptoms have surfaced, Teutsch explained.

There needs to be "a lot more discussion about what the evidentiary standards should be" for whole-genome sequencing and the cost-effectiveness of individual tests, he said.

New Task Force Will Keep HHS Updated

To assist with that discussion and ensure that HHS is informed of progress, the committee elected to establish a task force on whole-genome sequencing.

The task force will hold a session at SACGHS' next meeting in October.

Eric Green, Director of the National Human Genome Research Institute and a SACGHS advisor, suggested that the group put together a framework for what issues they could brief the Secretary on in the short term, since the field is advancing so quickly.

Sitting on the task force will be James Evans, professor of genetics and medicine at the University of North Carolina, Chapel Hill; Andrea Ferreira-Gonzalez, professor of pathology at Virginia Commonwealth University; Janice Bach, state genetics coordinator for Michigan Department of Community Health; and Charmaine Royal, a professor at Duke University's Institute for Genome Sciences and Policy.

-Sue Darcey ([email protected])

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