Amy Carpenter Aquino
September 2018—Qualitative or quantitative testing. Hydrolyze or don’t hydrolyze. Use or don’t use standard cutoffs. These and other decisions in toxicology testing have taken on new urgency amid the opioid crisis, which is driving laboratories to change test methods to assess prescription drug compliance and illicit drug use.
“From a provider’s perspective, it’s difficult to provide adequate pain control while avoiding the risk for abuse,” said Athena Petrides, PhD, director of toxicology and assistant director of chemistry at Brigham and Women’s Hospital, in a session at the AACC annual meeting in July. Dr. Petrides, who is also an assistant professor of pathology at Harvard Medical School, told attendees that more than 40 percent of chronic pain patients report feeling inadequately treated for pain.
At Brigham and Women’s Hospital, the laboratory responded to the increased demand for pain toxicology testing—which rose from approximately 750 tests in 2005 to approximately 3,500 tests in 2017—by developing a new assay to assess pain medication compliance.
“It is straight-to-LC-MS/MS definitive testing. We eliminated the immunoassay,” said co-speaker Stacy Melanson, MD, PhD, associate director of clinical laboratories and co-director of chemistry at Brigham and Women’s Hospital. “There are several guidelines, including one from us as laboratory scientists, that support mass spectrometry as the best methodology to assess medication compliance.”
The new assay is the result of the laboratory’s efforts to adapt urine drug testing to provide more guidance to clinicians and to help manage the opioid crisis, said Dr. Melanson, an associate professor of pathology at Harvard Medical School. “We’ve had a journey with urine drug testing and many changes” coinciding with the opioid crisis.
The speakers framed their AACC session as a friendly back-and-forth discussion on best practices for assessing prescription opioid compliance and illicit drug use. Dr. Petrides took the stance that urine is the preferred specimen for testing while Dr. Melanson defended oral fluid as the specimen of choice. The speakers also argued the merits of quantitative versus qualitative testing, hydrolysis, and standard cutoff limits. “These are all issues that are up for debate,” Dr. Petrides said.
Recent guidelines recommend urine drug testing as a risk assessment tool to detect the presence of prescribed medication as evidence of regimen adherence and to identify unauthorized substances, Dr. Petrides said. “Urine is considered to be the specimen type of choice due to the wider window of detection and the noninvasive way to collect a specimen,” she said, adding: “Oral fluid, however, is increasingly discussed as an alternative to urine.”
The stakes have never been higher for those who manage chronic pain patients. CDC data show that between 59,000 and 65,000 drug overdose deaths occurred in 2016, outnumbering peak deaths from car crashes, HIV, or firearms in any other year, Dr. Petrides said. At least half of all opioid-related overdose deaths reported in 2016 involved a prescription opioid.
One bright spot in the CDC’s prescription opioid overdose data—the decrease in prescription opioid medication rates between 2006 and 2016—was overshadowed by the increase in average days of supply from 13 in 2006 to 18 in 2016, an overall increase of 35.7 percent. “So that means that patients now have more pills in their house,” Dr. Petrides said.
The laboratory at Brigham and Women’s detected significant levels of prescription opioid diversion and illicit drug abuse in its patient population. “We saw 14.7 percent of patients that were potentially diverting their medication, and 28.7 percent of patients were positive for non-prescribed or illicit drugs,” Dr. Petrides said. The synthetic opioid fentanyl is a growing concern. U.S. Drug Enforcement Agency data showed more than 30,000 fentanyl seizures in 2016, almost double the number in 2015, she said. “We’re getting a high positivity rate for fentanyl in our patient population.”
Requests for pain toxicology panels from pain management physicians at Brigham and Women’s declined in recent years while requests from non-pain management physicians were on the rise. “Anecdotally, what we’ve heard is that testing is shifting to the primary care physicians because they see the patient more frequently and are taking over their management,” she said. The clinicians who regularly order pain toxicology tests and interpret the results are “no longer the population we had at the beginning of this epidemic.” Clinicians with less experience in interpreting pain toxicology results may require more guidance from the laboratory.
The previous toxicology panel offered at Brigham and Women’s was a hybrid, Dr. Petrides said. Amphetamines, buprenorphine, cocaine metabolite, fentanyl, THC, barbiturates, tramadol, 6-acetylmorphine, EDDP, and methadone were tested by immunoassay, which offered a large test menu and fast turnaround time.
The platform’s advantages did not overcome its challenges when testing for benzodiazepines and opioids. The lack of specificity in the immunoassay for these classes of drugs in particular required definitive testing by liquid chromatography tandem mass spectrometry (LC-MS/MS). “We were doing immunoassay for some drugs and sending out the positive results to a reference laboratory for confirmation and upfront definitive testing for opioids and benzodiazepines,” Dr. Petrides said.
Data showed a high false-positive rate for many drugs screened by immunoassay, specifically for 6-acetylmorphine, amphetamines, fentanyl, and buprenorphine. “We had an issue,” she said.