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Urine drug testing debate: How best to test compliance and manage opioid crisis

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The laboratory’s solution was to “create one big definitive testing panel” and test for all prescribed and illicit substances in-house by mass spectrometry. The panel reflected a compromise between the speakers’ positions on the critical components of a definitive testing panel, which Dr. Petrides described as quantitative versus qualitative testing, hydrolysis, and cutoff levels.
“For the sake of this debate, I am going to support reporting qualitative results, performing the hydrolysis step, and using standard cutoffs,” Dr. Petrides said, noting that the views she and Dr. Melanson were going to express during the session were for debate purposes only.

Dr. Petrides presented the case of a 37-year-old female patient prescribed Dilaudid (hydromorphone) for chronic pain. After three months of tracking the patient’s urine hydromorphone levels to assess compliance, the provider called the lab to confirm a suspicion that the patient was not taking her medication. The patient’s urine creatinine levels varied as well. “The results are going up and down, and the clinician is thinking that the patient isn’t really taking it as prescribed,” Dr. Petrides said.

Asked if the test results could be used to determine whether the patient was taking her medication as prescribed, most in the session said no. Dr. Petrides agreed. “Urine drug testing has many variables to determine what the measured drug response is going to be,” she said. “Drug interactions is one; you could be competing for binding to enzymes with these drugs, so the metabolism of that drug isn’t happening as rapidly as you would expect.” Adherence, which is the question in this case, is another.

Other factors to consider: urine adulteration caused by drinking large amounts of water to dilute the urine and mask the presence of the drug; genetic variation if the patient has alterations in the cytochrome P450 enzymes or glucuronosyltransferases (UGT) that cause a different metabolic pattern or conjugation of the drugs; a clinical diagnosis, such as a kidney or liver disease, which could affect results; dose management; and the half-life of the drug—“the most important thing here.”

“I think qualitative testing is the way to go in this case to avoid confusion,” Dr. Petrides said. “You want to avoid the misinterpretation and assumption that you can use these results to determine dose and timing, which is what the physicians are trying to do.” If the question is one of compliance, “why do you need those quantitative numbers? Isn’t the fact that the drug is there evidence enough?”

Qualitative testing requires fewer calibrators, and assay validation is less laborious, she added.
Dr. Petrides made the case for performing the hydrolysis step, which involves incubating the sample to remove the glucuronide group, and sometimes the sulfate group, in order to measure total drug levels instead of the different metabolites—conjugated metabolites—and the primary drug. “You increase your detection sensitivity because you have a larger pool now and it avoids false-negatives,” she said.

Adding the hydrolysis step also results in fewer drugs and their metabolites in the testing panel. “If you have all the results listed for the different glucuronides, it’s going to be a gigantic list and it will be very difficult for clinicians to go through and read every single one,” she said. By using a panel with appropriate metabolites, “you will make interpretation for clinicians easier and allow them to better assess compliance.”

In the past, for example, noroxycodone was not included in their panel. “It was difficult to assess whether the oxymorphone result was due to oxycodone ingestion or oxymorphone ingestion. It can be either one. By having noroxycodone, you’re able to differentiate that,” Dr. Petrides said.

With oxycodone and oxymorphone in the panel, if the patient is prescribed oxycodone, “in our patient population that would be 31 percent of the positive results.” Adding noroxycodone raised the positivity rate to 36 percent, “and you’re definitely sure that that comes from oxycodone metabolism.”

“This is showing the confidence in your interpretation.”

Dr. Petrides shared another example from her laboratory to support the use of standard cutoffs. “We have an assay that detects benzoylecgonine down to 5 ng/mL—you can go that low—and we had a positive result. The clinician called us and said, ‘My patient is adamantly saying they did not take cocaine. Please send it to another lab.’” Brigham and Women’s sent the specimen to another lab, which had a cutoff of 50 ng/mL, and the result came back negative. “That causes some suspicion of how accurate our results are in our lab. If we all use standard cutoffs, we can consistently assure clinicians that these methods are actually valid for testing their population.”

Scientific data exist defining detection windows with use of standard cutoffs, she said. “Although that can vary between individuals, at least you have a ballpark of when the patient might have taken this drug,” which helps the laboratory answer a common question from providers: Was the cocaine strongly or weakly positive? “We can’t answer those questions if we have very, very low cutoffs that we don’t have any data around.”

Laboratories with standard cutoffs would be able to use the accepted detection windows for the different types of drugs, Dr. Petrides said.

Dr. Melanson argued that laboratories should report results quantitatively, not hydrolyze, and use the lower limit of quantitation.

She presented the case of a 54-year-old chronic pain patient with a history of substance abuse managed with methadone. The provider ordered the pain toxicology panel to assess compliance, and results showed that methadone and EDDP (methadone metabolite) were detected, reported qualitatively. Urine creatinine was normal. “If you had those results and your clinician called, would you say this patient is compliant?” Dr. Melanson agreed with the majority of session attendees who answered yes.

But what if the laboratory provided quantitative results? Dr. Melanson asked. “Same patient, but the methadone was sky high, greater than the reporting limit of your assay. There was EDDP there, but it was right at the cutoff, about 5 ng/mL, so both were detected but the parent compound was significantly higher. The creatinine was still normal. If you have these quantitative results in front of you and the clinician called, would you assume this patient is compliant with their medication?”

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