Scientists urge FDA to rescind approval of test for opioid addiction risk

April 24, 2024

The Washington Post 

By David Ovalle

April 5, 2024 

A group of public health experts and scientists is calling on the Food and Drug Administration to rescind its controversial approval of a DNA test that promises to predict genetic risk of opioid addiction.

In a letter sent to the agency on Thursday, 31 experts in genetics, addiction, psychiatry and medical-device regulation called the approval of AvertD a mistake that relied on faulty science and puts patients at risk. The group sent a separate letter to the Centers for Medicare and Medicaid Services urging theagency, which oversees government health insurance programs, to deny coverage for the prescription-only test.

The Washington Post last month highlighted concerns about the test’s reliability and the unintended consequences of false results. The letters said a negative test could give patients a false sense of security, or lead doctors to “refrain from prescribing opioids to patients who test positive, even in situations where opioids are beneficial.”

“The harmful consequences of an invalid genetic test for [opioid use disorder] are clear,” the experts wrote.

The test’s developer, SOLVD Health, said in a statement Thursday it was reviewing the letters and that the FDA’s approval “represents a significant step forward” in helping doctors and patients discuss alternatives to opioids. “In the hands of physicians, the test results can be a critical tool to help combat opioid use disorder,” the company said.

The FDA, in a statement, declined to comment on the letters. But it stressed that the agency found reasonable assurance of the test’s safety and effectiveness “given the totality of available evidence and the urgent need for medical devices that can make a positive impact on the overdose crisis.”

CMS, in a statement, said it “has received the letter and will respond directly to the experts.”

The FDA authorized AvertD in December against the backdrop of a crushing overdose crisis killing more than 100,000 people in the United States each year, mostly from illicit synthetic opioids such as fentanyl. The unprecedented public health crisis began in the late 1990s as doctors increasingly prescribed addictive pain pills aggressively marketed by pharmaceutical companies.

The test is aimed at patients who may be prescribed opioids before surgeries. SOLVD Health and the FDA have stressed that the test doesn’t predict if someone will develop an opioid addiction but instead shows if someone is at an “elevated” genetic risk. They say doctors should use the test as part of a comprehensive evaluation of a patient’s risk.

SOLVD Health, in its statement, emphasized thatthe test was validated by a clinical trial consistent with regulatory guidelines and standards.

Questions about the reliability of AvertD were publicly raised in October 2022 when an FDA advisory committee composed of independent experts met. The panel voted 11-2 against recommending approval, prompting the FDA to require more analysis of study data, add strict labeling and impose requirements to educate doctors and patients about the test’s limitations.

The letter writers echoed concerns raised at that committee meeting about the science underpinning AvertD, the first FDA-approved test that relies on polygenic genetic testing, which analyzes small variations in multiple genes that might affect susceptibility to a disease.

The company analyzes swab samples from inside a patient’s cheek, evaluating DNA for 15 genetic markers associated with opioid use disorders, then runs the results through an algorithm trained on genetic data from more than 7,000 people, some of whom were diagnosed with opioid use disorder. The result is a score of between zero and one, with 0.33 or higher considered elevated genetic risk.

“This test is based on an approach that has been abandoned by mainstream genetics,” the scientists wrote in the letters, posted Thursday on the website of Physicians for Responsible Opioid Prescribing, a group that educates about the dangers of the prescription medications.

The scientists say the sample size of the data used by AvertD to predict opioid risk is not large enough to predict opioid use disorder in a “clinically useful way,” and the genetic data can potentially skew results for minority populations or those of mixed heritage from different parts of the world. Controlling for ancestry means the algorithm doesn’t predict opioid addiction “any better than chance,” they wrote.

The company “fell into known pitfalls … that give the appearance of predicting genetic risk, without being a true measure of genetic risk,” the letters states.


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