DNA test says it can predict opioid addiction risk. Skeptics aren’t so sure.
Using a swab inside the cheek and a sophisticated computer algorithm, a DNA test recently approved by federal regulators promises to assess genetic risk of opioid addiction. The test’s maker says results give doctors and patients a crucial tool when considering use of the very pain pills that ignited the nation’s opioid crisis.
But as the company, SOLVD Health, prepares to roll out AvertD in coming months, skeptics remain unconvinced. They worry that patients shown to have a low risk of addiction may feel emboldened to pop pain pills - then get hooked. Or that doctors will deny painkillers to patients errantly deemed at elevated risk.
Above all, some geneticists and public health experts say AvertD relies on unsound science. The Food and Drug Administration approved the AvertD cheek-swab test in December, despite an agency committee of experts voting overwhelmingly, 11-2, against recommending approval.
Andrew Kolodny, an opioid researcher at Brandeis University, blasted the test as a “sham.”
“You’ve got an alignment: profiteering by industry and federal agencies that feel they’re under the gun to do something about the problem, even if that something is counterproductive,” said Kolodny, president of Physicians for Responsible Opioid Prescribing, which aims to educate prescribers and patients.
The FDA says it approved the test because the severity of the opioid crisis “calls for innovative measures” to prevent addiction and save lives. The agency said it worked with SOLVD Health to address concerns raised by the advisory committee.
The company and the FDA stress that AvertD does not predict whether a person will develop opioid use disorder. They say doctors should use the test - which is available by prescription - only as part of an in-depth evaluation of adults who may experience pain or will undergo surgery and have no history of using opioids, not those already grappling with addiction. Patients identified by AvertD as having an elevated risk are 18 times more likely to develop an addiction after taking an opioid compared with people who take the test and are shown not to have an elevated risk, according to research cited by the company.
“We are extremely focused on informing and empowering a patient to understand their risk prior to taking that medication,” said Keri Donaldson, CEO of SOLVD Health, based in Carlsbad, Calif.
To use the test, a doctor swabs the inside of a patient’s cheek, then sends the sample overnight to the company. Its lab analyzes DNA for 15 genetic markers it says are associated with opioid use disorders. The data is run through an algorithm trained on genetic data from more than 7,000 people, some of whom were diagnosed with opioid use disorder. The computer generates a score of between zero and one. Someone who scores 0.33 or higher is considered at elevated genetic risk of getting hooked on an opioid medication.
“We felt that was important information that providers and patients should have access to,” William Maisel, director of the office of product evaluation and quality at the FDA’s Center for Devices and Radiological Health, said in an interview.
“You could argue that it’s unethical to withhold that type of product and that type of information from people. … We recognize the potential shortcomings of the test. But there are also great benefits,” Maisel said.
The FDA has long been criticized for approving certain drugs despite concerns about their safety or effectiveness. The agency has also come under scrutiny for not doing enough to regulate increasingly popular lab tests.
AvertD was developed by SOLVD subsidiary AutoGenomics. The company has yet to set prices for the test, which could be covered by Medicare and Medicaid.
The FDA advisory committee that reviewed AvertD was composed of independent experts who raised questions about the validity of the test during an Oct. 20, 2022, meeting. While their vote was not binding, committee members cited worries about algorithm bias, uncertainty about how much of a role the genetic variations play in addiction and the design of the clinical trial.
The committee and speakers such as Kolodny and patient representative Elizabeth Joniak-Grant were troubled by how AvertD might be used in the real world - and how results will be understood by consumers.
Patient advocates wonder if time-strapped doctors, despite FDA-mandated labeling, will lean too heavily on results instead of asking probing questions of patients. Will doctors prescribe the test off-label? Could a test indicating a risk for addiction be memorialized in medical records and used against a patient years later - in a custody dispute in court, or by an employer? Will someone with an elevated test come to believe they are prone to addictions of all sorts?
Joniak-Grant, a North Carolina sociologist, worries about all of those questions - and whether pain patients might be treated unfairly if they decline to use AvertD. “Refusing the test could be interpreted by clinicians as a patient being drug-seeking,” she said.
FDA officials approved the test with conditions. The agency added a “black-box” label warning patients about the test’s limitations. Such warnings are rare for products newly approved by the FDA, said Michael Abrams, a senior researcher at Public Citizen, a nonprofit consumer advocacy group.
“Somehow, they justified approval based on putting on these warnings,” Abrams said. He said he fears that despite the warnings, the test could provide “very high cover for irresponsible opioid prescribing.”
In response to concerns raised by the advisory committee, the company also changed the wording of test results - patients now have an elevated, not “high,” risk of developing an opioid use disorder. Patients and doctors will need to undergo education programs such as videos, online classes or reading materials. The FDA is requiring the company to study how patients and doctors use the test. Donaldson, the company’s CEO, said SOLVD is committed to educating clinicians and patients about how the test results should be viewed responsibly.
“This type of information should be empowering, not fear inducing, and it should not be misinterpreted,” Donaldson said.
Products such as AvertD reflect hope that cutting-edge science can ease a drug epidemic killing more than 100,000 people in the United States each year, mostly from opioids. The crisis was kick-started by the proliferation of legal - and highly addictive - prescription pain pills in the late 1990s. Regulators and law enforcement cracked down on unscrupulous prescribers. Doctors began writing fewer prescriptions. Users switched to cheaper street heroin, now largely replaced by dangerous illicit fentanyl. Opioid use disorder affects at least 6 million Americans.
Genetic testing is playing an increasing role in identifying health risks. Tests for general wellness and low-risk medical purposes do not require FDA approval. In 2017, the FDA authorized 23andMe to market the first agency-approved direct-to-consumer genetics test that examines predisposition to diseases such as Parkinson’s and blood clotting disorders; the agency has approved several others since.
AvertD is the first FDA-authorized polygenic risk test. Such genetic tests analyze small variations in an array of genes to predict risk for chronic diseases or other traits. While insignificant on their own, these genetic variations combined may influence susceptibility to certain diseases.
Such testing isn’t supposed to be a definitive prediction of heart disease, diabetes or hypertension. Rather, the tests provide a risk score that can guide patients into changing their lifestyles, implementing preventive care and testing for diseases earlier. In most cases, genetics alone doesn’t determine likelihood of illness. Environmental and social factors such as poverty, clean air and access to healthy food play a significant role.
Well-known companies such as Ancestry and 23andMe offer direct-to-consumer reports that rely on polygenic risk scores and predict the probability of inheriting or passing down a certain disease, developing insomnia or even having an aversion to cilantro.
AvertD is intended for use in a medical setting, but critics fear that the imprimatur of the doctor’s office may lead patients and clinicians to assign too much weight to test results.
They note that substance use disorders are complex to ascertain through such testing because tiny genetic variations - say, ones affecting the reward center in the brain - may overlap with ones affecting other behavioral health disorders. Several researchers said they are concerned that AvertD’s analysis of 15 genetic mutations and the sample size of 7,000 people used to develop the test aren’t large enough to deliver meaningful information about risk for addiction to opioids.
“There should be hundreds or thousands of genetic variants going in that risk score, not 15,” said Danielle M. Dick, director of the Rutgers Addiction Research Center, who is part of a team developing a genetics test that would examine the broader risk of addiction by analyzing genetic data from more than 1.5 million people compiled by researchers during many years.
White people of European ancestry are overrepresented in most genetic data. Even algorithms using smaller, more diverse data sets primed to predict for opioid use disorders may be confounded by ancestry, potentially skewing results for African Americans and people of mixed heritage from different parts of the world, researchers say.
In a 2021 study, algorithms attempting to predict opioid addiction using 16 genetic markers performed “no better than a coin flip” after correcting for geographic ancestry, said lead author Alexander S. Hatoum, a researcher at Washington University in St. Louis. Hatoum said genetic testing remains less effective than a clinician asking simple questions about family history of drug use.
“It’s just an underdeveloped technology at this point,” Hatoum said.
Donaldson, of SOLVD Health, said about 30 percent of the people whose information shapes the algorithm identified as Black or African American, and that most volunteers hailed from the United States. He said the data was “purposely very diverse” and pointed to a clinical trial he asserts backs up the test’s validity.
Initially, AvertD won’t be available nationwide. Instead, the company will partner with institutions in five to 10 locations.
The test has drawn attention from families touched by the opioid crisis.
Ken Daniels, a play-by-play announcer for the Detroit Red Wings, lent his support to the test at the advisory committee meeting. His 23-year-old son, Jamie Daniels, died of an overdose in 2016 after a long struggle with addiction that started with prescription pills. In an interview, Ken Daniels said his son might have avoided taking that medication had he been able to access a test such as AvertD.
“If there is anything out there than can be done to give people more knowledge, I’m all for it,” said Daniels, who started an advocacy foundation in his son’s name.
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