A group of researchers urged US regulators to revoke the approval of a test marketed for predicting risk for opioid addiction and said government health plans should not pay for the product.
The focus of the request is AdvertD (SOLVD Health), which the US Food and Drug Administration (FDA) approved in December as the first test to use DNA to evaluate if people have an elevated risk for opioid use disorder (OUD). A sample obtained through a cheek swab is meant to help guide decisions about opioid prescriptions for patients not previously treated with these drugs, such as someone undergoing a planned surgery, the FDA said.
But Michael T. Abrams, MPH, PhD, senior health researcher for Public Citizen’s Health Research Group, and 30 other physicians and researchers sent an April 4 letter to the Food and Drug Administration calling on the government to reconsider.
Abrams and fellow signers of the letters, including longtime opioid watchdog Andrew Kolodny, MD, of Brandeis University, said the algorithm used in creating AvertD “fell into known pitfalls of genetic prediction that give the appearance of predicting genetic risk, without being a true measure of genetic risk.”
“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,” the letter states.
The letter adds that false-positive test results may result in harmful consequences, with clinicians refraining from prescribing needed opioids, a problem that may be magnified in minority populations.
Among the signers of the letter is Alexander Hatoum, PhD, of Washington University, who conducted an independent evaluation of AdvertD, which he and his colleagues published in 2021 in Drug and Alcohol Dependency.
Hatoum said many patients may not fully understand the limit of genetic testing in predicting conditions like risk for OUD, where many factors are at play. The availability of a test may lend the impression that a single DNA trait makes the difference, as happens with conditions like Huntington’s disease and cystic fibrosis, he said.
“But it’s just not reality for most diseases,” Hatoum told Medscape Medical News.
The FDA declined to comment on the letter and said its approval of the test was “another step forward” in efforts to prevent new cases of OUD.
In 2021, a little more than three quarters of people who died by overdose in the United States involved opioids, or more than 80,000 people, according to the US Centers for Disease Control and Prevention. This figure includes prescription opioids, heroin, and fentanyl.
While deaths from overdoses with prescription opioids peaked in 2017 at 17,029 people, that figure has decreased steadily. Meanwhile, synthetic opioids other than methadone — primarily fentanyl — were the main driver of drug overdose deaths with a nearly 7.5-fold increase from 2015 to 2021.
The FDA agency said it had “a reasonable assurance of AvertD’s safety and effectiveness, taking into consideration available alternatives, patients’ perspectives, the public health need and the ability to address uncertainty through the collection of post-market data.”
Slow RolloutIn a separate letter to the Centers for Medicare and Medicaid Services, Abrams, Kolodny, Hatoum, and the other signers repeated their arguments against the use of AdvertD and asked that the government not use federal funds to pay for the test.
SOLVD is not yet selling AdvertD in the United States, and it has not yet set a price for the product. The Carlsbad, California-based company told Medscape Medical News in an email exchange that it is working with both Medicare and private insurers on questions of future coverage.
AvertD correctly identified an elevated risk for OUD in about 82.8% of cases, equating to a false-negative rate of 18.2% of patients, the FDA said in its summary of on the data supporting the application. This measure is known as sensitivity, meaning it shows how often an individual has the condition addressed in the test.
Meanwhile, the false positive rate was 20.8%, the FDA said.
SOLVD published similar study results in 2021.
The company failed to impress the FDA’s Clinical Chemistry and Clinical Toxicology Devices Panel, which in October 2022, said the probable risks of the test likely outweighed its benefits.
Then, in November 2022, the FDA and National Institutes of Health (NIH) held a public workshop meeting to consider the challenges and possibilities in developing tools to predict the risk of developing OUD. At that meeting, Keri Donaldson, MD, MSCE, the chief executive officer of SOLVD, said the company planned to conduct a controlled rollout of AdvertD on FDA approval.
Donaldson said a “defined set” of clinicians would first access the test, allowing the company to understand how results would be used in clinical practice.
“Once a test gets into practice, you have to be very purposeful and thoughtful about how it’s used,” he said.
The FDA approved the test in December 2023, saying it had worked with the company on modifications to its test. It also said that the advisory committee’s feedback helped in the evaluation and ultimate approval of AdvertD.
Even beyond the debate about the predictive ability of genetic tests for OUD are larger questions physicians need time to ask patients in assessing their potential risk for addiction when prescribing narcotic painkillers, said Maya Hambright, MD, a physician in New York’s Hudson Valley who has been working mainly in addiction in response to the overdose crisis.
Genetics are just one of many factors at play in causing people to become addicted to opioids, Hambright said.
Physicians must also consider the lasting effects of emotional and physical trauma experienced at any age, but particularly in childhood, as well as what kind of social support a patient has in facing the illness or injury that may require opioids for pain, she said.
“There is a time and place for narcotic medications to be prescribed appropriately, which means we have to do our due diligence,” Hambright told Medscape Medical News. “Regardless of the strides we make in research and development, we still must connect and communicate safely and effectively and compassionately with our patients.”
Kerry Dooley Young is a freelance journalist based in Washington, DC.
Source : Medscape