April 13, 2024

DNA testing says it can predict risk of opioid addiction. 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 the genetic risk of opioid dependence. The test’s creator says the results give doctors and patients a crucial tool when considering the use of the same painkillers that triggered the country’s opioid crisis.

But as the company SOLVD Health prepares to launch AvertD in the coming months, skeptics remain unconvinced. They worry that patients who are at low risk for addiction may be encouraged to take painkillers — and then become addicted. Or that doctors will deny painkillers to patients mistakenly considered high 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, even though a committee of agency experts voted overwhelmingly, 11-2, against recommending approval.

Andrew Kolodny, an opioid researcher at Brandeis University, called the trial a “scam.”

“There is an alignment: profit from industry and federal agencies who feel they are under gun to do something about the problem, even if it 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 “requires innovative measures” to prevent addiction and save lives. The agency said it worked with SOLVD Health to respond to concerns raised by the advisory committee.

The company and the FDA Emphasize that AvertD does not predict whether a person will develop opioid use disorder. They say doctors should use the test – which is available with a prescription only as part of an in-depth assessment of adults who may experience pain or are undergoing surgery and who have no history of opioid use, nor those already struggling with addiction. Patients identified by AvertD as being at elevated risk are 18 times more likely to develop an addiction after taking an opioid compared to people who take the test and are shown not to be at elevated risk, according to research cited by the company.

“We are extremely focused on informing and empowering a patient to understand their risk before taking this medication,” said Keri Donaldson, CEO of SOLVD Health, based in Carlsbad, California.

To use the test, a doctor swabs the inside of a patient’s cheek and sends the sample overnight to the company. His lab analyzes DNA for 15 genetic markers it says are associated with opioid use disorders. The data is analyzed using an algorithm trained on genetic data from more than 7,000 people, some of whom have been diagnosed with opioid use disorder. The computer generates a score between zero and one. Someone with a score of 0.33 or higher is considered to be at elevated genetic risk of becoming addicted to an opioid medication.

“We felt this was important information that providers and patients should have access to,” said William Maisel, director of the office of product evaluation and quality in the FDA’s Center for Devices and Radiological Health. in an interview.

“You could argue that it is unethical to withhold this type of product and this 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 taken steps to increase regulation of increasingly popular laboratory tests, following previous scrutiny over limited oversight.

AvertD was developed by AutoGenomics, a subsidiary of SOLVD. The company has not yet set prices for the test, which may be covered by Medicare and Medicaid.

The FDA advisory committee that reviewed AvertD was made up of independent experts who raised questions about the validity of the test during a meeting on October 20, 2021. Although their vote was not binding, committee members cited concerns about algorithm bias, uncertainty about the role genetic variations play in addiction and the design of the clinical trial.

The committee and speakers like Kolodny and patient representative Elizabeth Joniak-Grant were concerned about how AvertD could be used in the real world — and how the results would be understood by consumers.

Patient advocates wonder whether time-strapped doctors, despite FDA-mandated labeling, will rely too much on results rather than asking probing questions of patients. Will doctors prescribe the test off-label? Could a test that indicates an addiction risk be recorded in medical records and used against a patient years later – in a custody dispute in court or by an employer? Will someone with a high test believe they are prone to all types of vices?

Joniak-Grant, a sociologist from North Carolina, worries about all of these questions — and whether pain patients might be treated unfairly if they refuse to use AvertD. “Testing refusal could be interpreted by doctors as a patient seeking drugs,” 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 recently approved by the FDA, said Michael Abrams, senior researcher at Public Citizen, a nonprofit consumer advocacy group.

“Somehow they justified the approval based on these warnings,” Abrams said. He said he fears that despite the warnings, the test could provide “too high coverage for irresponsible opioid prescribing.”

In response to concerns raised by the advisory committee, the company also changed the wording of test results – patients are now at increased risk, not “high,” of developing an opioid use disorder. Patients and doctors will need to go through educational programs such as videos, online classes or reading materials. The FDA requires the company to study how patients and doctors use the test. Donaldson, the company’s CEO, said SOLVD is committed to educating doctors and patients about how test results should be viewed responsibly.

“This type of information should be empowering, not fear-inducing, and should not be misinterpreted,” Donaldson said.

Products like AvertD reflect the hope that cutting-edge science can alleviate a drug epidemic that is killing more than 100,000 people in the United States every year, mainly from opioids. The crisis was triggered by the proliferation of legal – and highly addictive – prescription painkillers in the late 1990s. Regulators and authorities cracked down on unscrupulous prescribers. Doctors began writing fewer prescriptions. Consumers have 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 genetic test that examines predisposition to diseases such as Parkinson’s and blood clotting disorders; the agency has approved several more since then.

AvertD is the first FDA-authorized polygenic risk test. These genetic tests analyze small variations in a set of genes to predict the risk of chronic diseases or other characteristics. Although insignificant by themselves, these combined genetic variations can influence susceptibility to certain diseases.

These tests should not be a definitive predictor of heart disease, diabetes, or high blood pressure. Instead, the tests provide a risk score that can guide patients in changing their lifestyles and implementing preventative measures. care and testing for illnesses earlier. In most cases, genetics alone do not determine the likelihood of disease. Environmental and social factors such as poverty, clean air and access to healthy foods play a significant role.

Well-known companies like Ancestry and 23andMe offer direct-to-consumer reports that are based on polygenic risk scores and predict the likelihood of inheriting or transmitting a certain disease, developing insomnia, or even having an aversion to cilantro.

AvertD is intended for use in a medical setting, but critics worry that the doctor’s office endorsement could lead patients and doctors to place too much weight on test results.

They note that substance use disorders are complex to determine through these tests because small genetic variations — say, those that affect the reward center in the brain — can overlap with ones that affect other behavioral health disorders. Several researchers said they were concerned that AvertD’s analysis of 15 genetic mutations and the sample size of 7,000 people used to develop the test were not large enough to provide meaningful information about the risk of opioid addiction.

“There should be hundreds or thousands of genetic variants in this risk score, not 15,” said Danielle M. Dick, director of the Rutgers Addiction Research Center, who is part of a team developing a genetic test that would look at broader risk. of addiction by analyzing genetic data from more than 1.5 million people compiled by researchers over many years.

Whites of European descent are overrepresented in most genetic data. Same algorithms using prepared smaller and more diverse datasets The prediction of opioid use disorders can 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 that attempted to predict opioid dependence using 16 genetic markers performed “no better than a coin toss” after correcting for geographic ancestry, said lead author Alexander S. Hatoum, a researcher at the U.S. of Washington in St. Hatoum said genetic testing continues to be less effective than a doctor asking simple questions about family history of drug use.

“It’s just an underdeveloped technology at this point,” Hatoum said.

SOLVD Health’s Donaldson said that about 30% of the people whose information shapes the algorithm identify as black or African-American, and that the majority of volunteers came from the United States. He said the data was “intentionally very diverse” and pointed to a clinical trial that he says supports the test’s validity.

Initially, AvertD will not be available nationwide. Instead, the company will partner with institutions in five to ten locations.

The test caught the attention of families affected by the opioid crisis.

Ken Daniels, broadcaster for the Detroit Red Wings, threw his support behind 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 began with prescription medication. In an interview, Ken Daniels said that his son could have avoided taking this medication if he had been able to get a trial like AvertD.

“If there’s anything that can be done to give people more knowledge, I’m all for it,” said Daniels, who created an advocacy foundation in his son’s name.

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