On Thursday, members of the FDA's Clinical Chemistry and Clinical Toxicology Devices Advisory Committee to discuss AvertD, a prescription genetic risk assessment tool for opioid use disorder (OUD).
AvertD detects the presence or absence of 15 single nucleotide polymorphisms (SNPs) to help identify adults with an increased genetic risk of OUD. It's intended to be used in combination with clinical evaluations and patient assessments when oral prescription opioids are being considered to treat acute pain.
The device currently is and is paid for either by insurance or by the patient directly at $199.
Currently, no FDA-cleared or approved devices are indicated for identifying genetic risk for OUD. A version of AvertD with 11 of the 15 SNPs now included in the device was granted FDA breakthrough device designation in March 2018.
More recently, the device was assessed in a multi-site that evaluated 385 people after their initial exposure to prescription oral opioids.
The FDA declined device maker SOLVD's initial request for AvertD in August 2021. That decision was upheld on appeal in January. In June, SOLVD resubmitted a de novo request after collecting additional information about study participants to respond to the FDA's concerns.
Now, the FDA is seeking input from its advisory committee before rendering its final decision.
SOLVD reported overall study results demonstrating a sensitivity of 82.76% (95% CI 76.31-88.05) and specificity of 79.23% (95% CI 73.06-84.54). "However, numerous factors impact the interpretation of test performance and raise uncertainty about the applicability of the observed clinical study test results to the intended use population," the FDA wrote in its ahead of the meeting.
"A device that detects genetic variants that may be associated with OUD could be potentially beneficial in combating the opioid epidemic," the agency observed.
But genetic risk may not be the biggest factor in predicting OUD risk, the FDA pointed out, noting that "the genetic associations of individual candidate genes identified so far explain only a small portion of OUD risk." In addition, many individuals with risk factors may never develop the disease, the FDA said.
Unlike risk assessment tools for chronic pain that include routine screening like patient history questionnaires and urine drug tests, genetic tests may have different emotional ramifications and stigmas associated with them, the FDA noted. Risks associated with false-positive and false-negative results also need to be considered, the agency said.
Research studies have indicated that the 15 SNPs detected by the AvertD are not specific to OUD and may be associated with several other disorders of addiction and mood, the FDA added.
But the over-arching question for the advisory panel on Thursday will focus on the clinical study and whether study participants adequately represent the intended-use population. The FDA voiced a number of potential concerns, including variances in the case report forms used to collect study data, confidence that the study fully excluded people whose index oral opioid exposure was either illicit or for treatment of chronic pain, and the demographic makeup -- race, ethnicity, age, and sex -- of participants.
In SOLVD addressed these points and provided additional analyses to support that AvertD study results apply to the intended-use population.
SOLVD also noted that prescribing guidelines call for individual benefit-risk assessments to determine whether opioids are appropriate to manage acute pain.
"Thus, AvertD would fit into current clinical flow, with the principal benefits being providing information to patients and providers to make more informed choices about prescribing opioids for acute pain," the company wrote.