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Mental Health Advocacy Groups Appeal to FDA to Reconsider PGx Enforcement Activity

NEW YORK - A group of mental health advocacy organizations have sent a letter to the US Department of Health and Human Services and the US Food and Drug Administration, imploring FDA to reconsider its recent actions curtailing the activities of pharmacogenomic test providers.

Addressing HHS Secretary Alex Azar, and FDA Acting Commissioner Normal Sharpless yesterday, representatives of the National Alliance on Mental Illness (NAMI), the National Council for Behavioral Health (NCBH), the Depression and Bipolar Support Alliance (DBSA), and the Mental Health Alliance (MHA) cited "serious concern" over FDA's actions, on behalf of patients, caregivers, and provider organizations that the various organizations represent.

"Although we appreciate the FDA's mission to protect the public health, in this case we believe the agency's actions may in fact inflict greater harm on patients and impede innovation," the letter authors wrote.

"Given the public mental health crisis confronting our nation, we believe health care providers should have access to more innovative tools and treatments, not less. The FDA actions against laboratories offering pharmacogenomic testing will cause a dramatic scientific and clinical setback for the treatment of mental illness," they added.

Last October, FDA issued a safety communication cautioning patients and providers against changing drugs based on PGx tests not approved by the agency. This April, it followed that up with a warning letter to PGx firm Inova telling the company to stop reporting information linking gene variants with drugs in ways that have not been recognized by FDA labeling. Inova subsequently stopped providing PGx testing all together.

In the months since, FDA has gone on to initiate interactions with several other labs, advising some that if they chose to continue to offer testing outside of FDA approval, they must not describe the clinical implication of their genetic findings unless those implications are reflected in FDA drug labeling.

The letter from the four mental health advocacy groups follows a similar missive sent last week by the American Clinical Laboratory Association. ACLA raised some of the same concerns: that the FDA's actions would "negatively impact patient care and increase medical costs" by taking from doctors information that could help guide drug prescribing decisions. But the association also positioned the current PGx issue as part of a larger dispute around FDA's authority to regulate laboratory-developed tests more generally, arguing that agency's actions "amount to an inappropriate form of backdoor regulation of LDTs."

While the FDA has long exercised enforcement discretion, avoiding regulating most LDTs on the market, the agency has consistently maintained that such tests do fall within its purview should it choose to address them.

In their letter yesterday, NAMI, DBS, MHA and the NCBH wrote that they are worried specifically that preventing labs from directly discussing medications and medication classes on PGx test reports prevents psychiatrists and other doctors from personalizing their care of patients with major depressive disorder.

"Today's standard of care for depression is unfortunately trial and error of medication selection with patients responding to the first treatment only [half] of the time. This long and frustrating journey rarely leads to remission and can instead lead to symptomatic decline, relapse, and potentially … to treatment resistant depression," the groups wrote, adding that "Extensive studies [have shown] that failure on just one antidepressant medication increases both the chances of a second failure and raises the concomitant risk of suicide."

As a result, mental illness physicians are in "desperate need" of personalized, or precision medicine tools, the groups argued.

The groups' plea highlights a recurring theme in the debate over FDA's various moves toward enforcing its authority over lab tests — the difficulty of weighing the potential benefit of new technologies against their possible harm when not held to strict standards for both analytical and clinical validity.

When asked to cite the public health issues that spurred the agency to take action against PGx providers, an FDA spokesperson said that healthcare providers may have inappropriately changed patients' medications based on PGx tests that claim to inform dosing or regimens of some antidepressants, but did not provide specifics beyond that. Some experts in the field have echoed this concern.

In their letter, the mental illness advocates describe the application of personalized medicine to mental illness as an "exciting scientific area," and argue that PGx tests that guide prescription of depression medications are provide "more than hope."

"Clinical studies have shown that physicians using genetic information as part of the treatment decision process are seeing more patients achieve remission than treatment as usual," the authors wrote.

Myriad Genetics is one company that has been able to demonstrate this type of result, reporting in a conference presentation last year that patients tested using its GeneSight test had significant improvements in remission and drug response rates compared to a control group receiving standard psychiatric care.

But not all psychiatric or other PGx tests on the market have such data to support their utility. Various marketed test panels also include different sets of genes, for which gene-drug interactions may be more or less scientifically well-established.

In their letter, NAMI, DBS, MHA and the NCBH argued that FDA "should not stand in the way of this emerging and exciting field of science," and that "physicians must be able to continue to receive information about the impact a patient's genetics may have with medication choices."

FDA's position has remained that it is in the public's best interest that it require that emerging science prove its validity before it can be performed, and sold, clinically.

As the agency has become more active in the PGx testing space this last year, various professional groups have announced their own efforts to try to bring possible bad actors into line. The Clinical Pharmacogenetics Implementation Consortium, for example, recently indicated that it may start issuing guidelines for non-actionable pharmacogenes that lack evidence and shouldn't be used in clinical decision-making.

And in its own response to the FDA's actions against PGx labs, the Association for Molecular Pathology issued a position statement earlier this month outlining best practices to which PGx labs should adhere. These include reporting only drug-gene associations that are backed by "well-established clinical validity" data from the peer-reviewed literature, practice guidelines like CPIC, or FDA-approved drug labeling.

The association further advised how the test results should be communicated to healthcare providers to best represent the meaning and limitations of the results.