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Many Concerned About Safety, True Value of Sequencing Tests

Tony Hagen @oncobiz
Published: Tuesday, Jul 28, 2015
Richard L. Schilsky, MD

Richard L. Schilsky, MD

Next-generation sequencing—the rapid analysis of genetic biomarkers that may be triggers for cancer—is an advance in medicine that has many physicians and researchers excited, but substantial concern remains about the usefulness of the data generated.

A big question mark hovers over the clinical utility of the information that comes back from the testing laboratory, and there is also concern about physicians’ ability to interpret these reports accurately and act appropriately when treating their patients.

Lack of clinical evidence, lack of standards in reporting, lack of physician education, the danger of acting on genetic variants of unknown significance, industry hype, and the variety of the tests on the market were all cited as hurdles by oncologists and others interviewed by OncLive.

“There are many concerns, and also great excitement,” says Richard L. Schilsky, MD, chief medical officer of ASCO. “NGS can reveal the entire portrait of a tumor, and in doing so identify treatment options that might not have been immediately obvious from other forms of testing.”

With little standardization and huge volumes of data, the reports that come back from labs are confusing for doctors to understand, Schilsky said. It’s unclear how reliable the information is, and because tumor characteristics can vary inside the same patient, a single biopsy sent to a lab for NGS testing may not yield a true picture of a patient’s disease, he says.

Nevertheless, the US genomics testing market was estimated at $5.9 billion in 2011 by research firm Booz Allen Hamilton, with nearly 2900 different tests available in that year.1 A subsequent study released in June by Grand View Research predicted growth would continue and that the US genomics testing market would measure $27.87 billion by 2022.2

With this scale of growth and marketing in mind, the FDA has been working to develop a set of standards and processes to ensure that the tests are reliable. The agency is also working also to develop clinical databases that will help physicians to make better decisions about what to do based on the information they get from these tests, says Elizabeth Mansfield, PhD, director of personalized medicine for the FDA.

“There are a lot of ways to make errors in sequencing, and our concept is to develop a set of process and material standards that will, we hope, allow us to essentially be confident that a lab that develops a test will do it in a manner that generates a test that is accurate and reliable,” Mansfield told OncLive.

She says the FDA aims to publish a report on these activities by the end of the year.

In a public forum held early this year by the FDA to discuss the issues involved in this process, David Litwack of the FDA’s Office of In Vitro Diagnostics and Radiological Health talked about the importance of producing tests that measure what they purport to measure and do it accurately; and further, of the need to ensure that what manufacturers and labs say about their tests is true.3 “We recognize that NGS is incredibly important.…We want to allow it to continue while we still perform our mission of protecting patients, making sure that it is used in a safe and effective way.”

The standards the FDA is developing will help to inform manufacturers and laboratories that the tests they are offering work right and are accurate and reliable, Mansfield says. “We’re not necessarily attempting to standardize the results,” she says.

Mansfield says doctors are very much in the catch-up mode as they try to understand how to use these tests and what to make of the information they produce, adding that “We’re trying to address the interpretation part through the clinical validity database building side of our project that will provide clinical evidence for given variants.”

From that point on, doctors will be on their own, she says. “We can’t tell doctors what to order. That’s their practice of medicine. We hope that people over time will catch up to the technology and understand what they should order.”

What doctors know already is that NGS tests offer far more information than is useful, says Schilsky. “Roughly 40% of the time, NGS tests reveal an abnormality that’s defined as being actionable. That’s a definition in the eye of the beholder—something that the doctor might be able to act on. Only in half of those cases can the doctor get access to therapy that is thought to be beneficial, and in less than half of those cases is there evidence that the patient actually benefits from the treatment, so we’re still at a point where NGS testing is more of a promissory note than it is a highly accurate predictive test,” he says.


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