Dive Brief:

• Physicians asked the Food and Drug Administration Thursday to revoke its recent approval of Autogenomics’ AvertD genetic test for opioid addiction. 
• The Physicians for Responsible Opioid Prescribing (PROP) said the test is based “on old genetic studies that have largely been abandoned.” They said the test could exacerbate the opioid crisis by leading to overprescribing in patients who falsely test negative, or could wrongly label people as prone to opioid use disorder, causing them to face discrimination or not receive treatment.
• PROP sent another letter to the Centers for Medicare and Medicaid Services (CMS). Quoting the same evidence they submitted to the FDA, the physicians asked the CMS to deny coverage to the test.

Dive Insight:

AvertD detects 15 single nucleotide polymorphisms (SNPs) to show if a person may have an elevated risk of opioid use disorder (OUD). An FDA advisory committee voted overwhelmingly against an earlier version of the test in October 2022. However, the FDA then worked with Autogenomics as it modified the test based on the committee’s feedback, culminating in the approval of AvertD last December.

PROP contends the FDA erred in approving the test. The letters to the agencies are signed by around 30 physicians and researchers from Johns Hopkins University, Stanford University School of Medicine and other academic institutions, and outline the perceived problems with AvertD.

“This test is based on an approach that has been abandoned by mainstream genetics,” PROP wrote. “The largest well-powered and state-of-the-art genome-wide studies of OUD to date demonstrate that even a full genome’s worth of markers (roughly 6,000,000) is not sufficient to predict OUD in a clinically useful way.”

PROP cited a peer-reviewed paper of an independent evaluation of a similar approach to OUD prediction to argue that AvertD test is flawed. The study looked at five machine learning algorithms trained on 16 SNPs. None of the algorithms could predict OUD when ancestry was balanced. 

The researchers found their algorithms were vulnerable to ancestral confounding, leading PROP to contend the test “fell into known pitfalls of genetic prediction that give the appearance of predicting genetic risk, without being a true measure of genetic risk.” PROP outlined the implications of inaccurate OUD test results.

“The harmful consequences of an invalid genetic test for OUD are clear. Patients who test negative, and their clinicians, may have a false sense of security about use of opioids,” PROP wrote. “Positive test results may also result in harmful consequences. For example, clinicians might refrain from prescribing opioids to patients who test positive, even in situations where opioids are beneficial.”

PROP is trying to stop the use of AvertD by pushing the FDA to revoke the approval. If that fails, the nonprofit could still limit its use if the CMS decides to deny coverage of the test.

Jeff Shuren, director of the FDA's Center for Devices and Radiological Health, acknowledged the risks of false positives and negatives when the agency approved AvertD. Shuren said the risks “can be mitigated, in part, through accurate, transparent product labeling and a health care provider training program.”

Autogenomics was acquired by Prescient Medicine Holdings in 2019, which then changed its name to SOLVD Health in December 2020.