A group of scientists and experts are calling on the FDA to rescind their approval of a controversial DNA test that claims to predict genetic risk of opioid addiction.
In a letter sent to the public health agency last week, 31 experts in genetics, addiction, psychiatry, public health and device regulation say AvertD, the genetic test, is based on an approach that has been abandoned by mainstream genetics.
“Current scientific knowledge about opioid use disorder genetics is strong enough for us to state that AvertD does not predict genetic risk of opioid use disorder,” the experts write in the letter.
Aimed at patients who may be prescribed opioids for the first time following a surgery or procedure, AvertD was approved by the FDA on Dec. 19, 2023 as the first test to use DNA to assess if an individual is at an “elevated” genetic risk of developing opioid use disorder. The test does this by detecting 15 single nucleotide polymorphisms (SNPs), and then running the results through an algorithm trained on genetic data from over 7,000 people—some of whom were diagnosed with opioid use disorder.
However, the experts say accepted literature to date demonstrates that even a full genome’s worth of markers—roughly 6,000,000—is not sufficient to predict opioid use disorder in a clinically useful way. Additionally, the geneticists in the group conducted an independent evaluation using a methodology resembling the one used by AvertD’s sponsor, Solvd Health. Their findings, published in the peer-reviewed journal Drug and Alcohol Dependence, found that the algorithm used for AvertD “fell into known pitfalls of genetic prediction that give the appearance of predicting genetic risk, without being a true measure of genetic risk.”
This led the experts to conclude: “With proper controls for ancestry, genetic predictors from the 15 variants used in AvertD did not predict risk of opioid use disorder any better than chance.”
This is not the first time the reliability of AvertD has been questioned, either. In October 2022, an FDA advisory group voted 11-2 against approval of the test, saying the probable benefits of the device did not outweigh the risks. Panelists expressed multiple concerns, including the validity of 15 SNPs, the lack of safety evaluation, and demographic makeup of the study. The main concern, however, was the risk of false positives—a sentiment the letter-writing experts also expressed.
“The harmful consequences of an invalid genetic test for opioid use disorder are clear. Patients who test
negative, and their clinicians, may have a false sense of security about use of opioids,” writes the group of experts. Additionally, those wrongly—and correctly—identified as prone to opioid use disorder could face discrimination and other negative health and social consequences.
Positive test results may also lead clinicians to refrain from prescribing opioids to high-risk patients, even in situations where the medication would be beneficial.
“The FDA has touted its approval of AvertD as a step toward addressing the opioid crisis. We believe AvertD may make the opioid crisis worse by contributing to overprescribing in patients who falsely test negative,” the experts conclude in their letter. “We urge you to personally review the peer-reviewed publications cited in this letter. We are hopeful that after careful review you will agree with the expert consensus that that the decision to approve AvertD was a mistake, and that the approval should be rescinded.”
On the same day, the group sent a similar letter to Chiquita Brooks-LaSure, Administrator at the Centers for Medicare and Medicaid Services, urging the insurance programs to deny coverage of AvertD.
“As the administrator of an agency with the responsibility of providing high quality medical care to more than 100 million people, we urge you to carefully consider the expert consensus on AvertD and deny coverage of this test,” reads the letter.