Concerns Raised Over Pharmacogenetic Tests

Two issues include lack of training for doctors to order and interpret tests correctly and fraud

CEO SUMMARY: Some executives at pharmacogenetic testing companies are criticizing the federal Food and Drug Administration for its recent actions to exercise oversight over PGx testing. But there is more to the story, said one expert who is a past adviser to the FDA on clinical laboratory testing. One issue is how to educate physicians to understand how to order PGx tests and use the results appropriately. Another challenge is how to curb fraud involving pharmacogenetic tests.

EVIDENCE ACCUMULATES that the federal Food and Drug Administration (FDA) wants it increase oversight of laboratory-developed tests—including pharmacogenetic tests. The result is that criticism of such increased oversight has come from the clinical laboratory industry.

Opposition to the FDA’s attempts to assert more regulatory authority over pharmacogenetic (PGx) testing is expected, given that executives and investors in PGx lab companies prefer lighter regulation of these tests.

Physicians Need Training

But there is another perspective to consider. Serious concerns are associated with some pharmacogenetic tests and whether physicians have the training and knowledge needed to use this genetic test data appropriately in patient care.

In an interview with THE DARK REPORT, Roger D. Klein, MD, JD, said the FDA is reacting to a lack of understanding among treating physicians about how to use these tests appropriately. “One problem in the area of pharmacogenetic testing is that, in general, physicians have been slow to embrace such testing except in some clearly-defined settings,” stated Klein. “Physicians have been slow to adopt these tests because it’s not been clear what exactly they should do with the information they get from PGx testing.

“Just because a variant shows there’s a potential relationship doesn’t necessarily mean you understand what to do with that information in particular patients,” added Klein, a pathologist, attorney, and expert in precision medicine.

A past advisor to the FDA and other federal regulatory agencies and policy-makers, Klein said one of the problems for laboratories that develop PGx tests is the lack of adequate direction in the clinical literature about how to use these tests.

“That’s because the field of pharmacogenetics is in a nascent stage,” he commented. “In this stage, the medical specialties have not yet embraced pharmacogenetic testing to a significant degree.

“There are some specific instances where good clinical evidence demonstrates that these PGx tests work and that physicians know what to do with the information,” he explained. “But outside of those few areas, there is limited clinical evidence supporting the use of these tests. Most pharmacogenetic tests in use today are for changes that theoretically affect how patients metabolize drugs.

Uptake in Psychiatry

“One specialty that has been receptive to PGx testing is psychiatry,” explained Klein. “These physicians may use pharmacogenetic tests to identify patients who will respond well to certain medications—such as antidepressants—based on their PGx test results.”

An issue seldom addressed by executives at many PGx labs is the lack of data supporting the utility of identifying genetic markers and the lack of studies demonstrating the results PGx tests provided to physicians and how that information can help them improve patient care. More specifically, many PGx tests offered in the market today don’t provide adequate data to support their clinical usefulness.

Asked about this problem, Klein said, “Some labs have promoted such testing on the basis that these assays help certain patients. Other labs may have promoted pharmacogenetic tests based on little or no evidence that testing will benefit patients.”

Fraud within the PGx Sector

Also, the potential for fraud exists when PGx labs promote tests that are unsupported by adequate data. Cases of alleged fraud have been reported widely in the field of drugs of abuse testing, for example.

“In the past, we’ve seen instances where there has been significant uptake of some PGx tests, but that increase in usage was related to fraud and abuse,” Klein observed. Such fraudulent behavior taints reputable labs, he added.

“Most of the fraud cases have been related more to a lab’s ability to scam Medicare than anything else,” he said. “Therefore, I am skeptical the FDA would be any help in preventing it. In some cases, it’s possible the tests involved were FDA-cleared. While fraud is a big problem in Medicare, those cases relate more to the ability of the Medicare agency to police fraud than to the FDA status of a test.”

Inevitably, any FDA action to regulate pharmacogenetic testing raises concern among lab directors and pathologists that the FDA will require all labs to submit applications for laboratory-developed tests (LDTs). When the FDA has raised the issue of lab-developed tests, the lab industry has pushed back.

The FDA has asserted that it has the authority to regulate all diagnostic tests and can require companies to remove tests from the market if they do not meet FDA’s standards. In 2014, the FDA proposed a complex framework to regulate LDTs. (See “Public Comment Started on FDA LDT Regulations,” TDR, Nov. 3, 2014.)

LDT Oversight

The FDA later pulled back from that proposal and since then has left oversight of the lab testing industry to the federal Centers for Medicare and Medicaid Services under the Clinical Laboratory Improvements Amendments of 1988.

Meanwhile, since 2014, several proposed bills have surfaced in Congress that are intended to guide how clinical laboratory tests, including LDTs, are regulated. Each of these bills have different proponents and advocates from the in vitro (IVD) diagnostics industry and the clinical laboratory profession.

Lab directors and pathologists have long asserted that clinical lab tests are not medical devices and so are not subject to FDA regulations. However, lab industry leaders often fail to recognize the fraud and abuse problem. Also, they seldom offer recommendations on how federal regulators can curb fraud while still allowing ethical labs to offer clinically-useful tests.

Contact Roger Klein, MD, JD at 216-896-0568 or


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