FDA Approves Genetic Test for Opioid Addiction Risk

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has approved a controversial genetic test that uses a patient’s DNA to assess whether they are at risk of developing opioid use disorder (OUD).  

Although the test is only intended for patients with short-term acute pain who have not used opioids before, there is concern about the test’s accuracy and whether it will be used “off-label” to assess addiction risk in chronic pain patients – who could potentially lose access to opioids as a result.

In approving the AvertD test, the FDA stipulated that it only be available by prescription to patients who consent to its use and have no prior history of using an oral opioid for pain relief.

The test is administered by a provider swabbing the cheek of a patient to collect a DNA sample, which will then be tested in a laboratory to see if the patient has 15 genetic markers that puts them at elevated risk of OUD.

According to the FDA, the test will help patients “make better informed decisions” about opioids, such as a patient facing surgery who wants to know what analgesic to use for acute post-operative pain.

AUTOGENOMICS IMAGE

"AvertD may help patients who are concerned about being treated with an opioid for acute pain,” Jeff Shuren, MD, director of the FDA's Center for Devices and Radiological Health, said in a statement. “The test is not intended to be used in patients being treated for chronic pain.”

But given the history of opioid guidelines being mistakenly applied to all kinds of patients, regardless of their condition, some worry the test will be misused.

“I’m sure it would be used for anyone who may be considered for opioid therapy,” says Lynn Webster, MD, a pain management expert and Senior Fellow at the Center for U.S. Policy. “I am all for gathering more data to help clinicians make better decisions, but we must exercise caution with such tests. Otherwise, the test may be over-read or misinterpreted. Some patients may be deprived of access to an opioid if they test positive or there can be a false sense of harmlessness from opioids if the test is negative. 

“I am most concerned that providers will see the results as binary. Either a patient will or won’t develop OUD, depending on the result. That would be a big mistake. Any such device or test must be used along with other clinical and personal information to help mitigate harm from using, or being denied, opioids.”

80% Accuracy

As part of its approval order, the FDA is requiring AutoGenomics – the company that makes AvertD – to provide training to healthcare providers on the proper use of the test and to conduct a post-market study of its performance and accuracy.

In 2022, an FDA advisory committee voted 11-2 against recommending an earlier version of AvertD, primarily because of concerns about false-negative and false-positive results. An observational study found the test was about 80% accurate in detecting genes associated with OUD.

"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," said Timothy Ness, MD, an anesthesiologist and Professor Emeritus at the University of Alabama at Birmingham, an advisory panel member who voted no.

After the advisory committee vote, the FDA worked with AutoGenomics to modify the test and improve its accuracy. The company then submitted a premarket approval application for the modified test, which the FDA granted without going back to the advisory committee for further review.

“The FDA recognizes that in premarket decision-making for devices, there generally exists some uncertainty around benefits and risks. Given the totality of available evidence and the urgent need for medical devices that can make a positive impact on the overdose crisis, and specifically devices that can help assess the risk of developing OUD, the FDA determined that there is a reasonable assurance of AvertD's safety and effectiveness,” said Dr. Shuren.

But no test is foolproof in either its accuracy or implementation, as Dr. Webster learned when he developed a questionnaire that assesses addiction risk by asking patients about their family history and other potential risk factors. Webster was disappointed to learn his questionnaire was “weaponized” by some providers to deny opioid therapy to patients, particularly women with a history being sexually abused.

Webster says the risk of OUD can’t be measured by a genetic test alone.

“We should not think it is a diagnostic tool or a crystal ball. Having an increased risk due to genetics does not mean that, if exposed to an opioid, an individual necessarily will develop an opioid addiction,” Webster told PNN. 

“We have known for a long time that about fifty percent of the risk of developing an opioid addiction is due to genetics. The other fifty percent is due to environmental factors and life’s experience. Furthermore, people can develop OUD without genetic risks. OUD risk is dynamic, meaning it changes over time with adverse events in life and often co-morbid conditions. For example, there was a surge in all forms of drug abuse, including OUD, during the pandemic because of isolation and loneliness. This is not detected by a genetic test.”

Although the risk of a surgery patient misusing opioids or becoming addicted is low – less than one percent -- the parent company of AutoGenomics has a more stark assessment, calling surgery “a gateway to addiction” that puts another 7 million Americans at risk every year.