An FDA advisory committee on Thursday voted strongly against AvertD, a prescription genetic risk assessment tool for opioid use disorder (OUD).
In an 11-2 decision, the Clinical Chemistry and Clinical Toxicology Devices Advisory Committee said the probable benefits of the AvertD device did not outweigh its probable risks, taking into account risks and benefits of currently available alternative forms of detecting OUD risk.
AvertD detects the presence of 15 single nucleotide polymorphisms (SNPs) to help identify people who may have an increased risk of OUD. It's intended to be used in combination with clinical evaluations and patient assessments when oral prescription opioids are being considered to treat acute pain.
Currently, no FDA-cleared or -approved devices are indicated for identifying genetic risk for OUD. SOLVD, maker of the AvertD device, submitted an initial de novo classification request for AvertD, which the FDA declined in August 2021. In June 2022, the company resubmitted its request after collecting additional information to address the agency's concerns.
But for many advisory committee members, questions about the device lingered. "My vote was really based on my concerns about the clinical validity of this test," said Laura Bierut, MD, of Washington University School of Medicine in St. Louis, who voted no. "I am concerned about the validity of these 15 SNPs really being able to differentiate people with opiate use disorder."
At the meeting, SOLVD presented results of an that demonstrated an 82.76% sensitivity and a 79.23% specificity for detecting OUD among 385 adults exposed to prescription oral opioids for 4 to 30 days. Slightly more than half (57%) of the sample population were men, and 92% were white.
"There was no safety evaluation of this device, which I thought was a really odd omission," noted panelist Adam Gordon, MD, MPH, of the University of Utah in Salt Lake City, who voted no.
"We have no idea what the prescribing patterns would be after the test was implemented," Gordon pointed out. "We have no patient-level outcomes. We have no assessment of both providers and patients of how they would approach receiving results of this test. And I think that's a really important point because I'm really worried about the false positives."
"I believe 100% of the risk associated with this test is with false positives and false negatives -- both people being untreated or poorly treated because somehow it came back as a positive result, or being given inappropriate treatment because it said negative," observed Timothy Ness, MD, PhD, of the University of Alabama at Birmingham, who also voted no.
For some panelists, the demographic makeup and sample selection of the study helped sway their decision. "I have a lot of concerns about the demographic population that was sampled in the testing, that it's not reflective of the population that would actually be treated out there," noted Sherif Zaafran, MD, president of the Texas Medical Board, who voted no.
And at least one committee member who voted yes did so with reservations. "I voted in favor of approval clearance," said Wilson Compton, MD, MPE, deputy director of the NIH's National Institute on Drug Abuse. "I would have preferred not to be able to answer yes or no but to give sort of a balance, and I just barely kicked into the yes area."
"I heard lots of concerns expressed today about potential risks," Compton acknowledged. "I expressed a number of those myself."
"But the part of the question that tipped the balance for me was the second half where it asked for risks and benefits in comparison to current available technology," he noted. "And to my mind, I think genetic tests are likely to add benefit compared to the currently used risk profile test that clinicians have available at this time."