Charna Albert
May 2025—When a physician or health care professional isn’t sure how to interpret a urine drug test result, Christine Snozek, PhD, codirector of clinical chemistry at Mayo Clinic in Arizona, always hopes they’ll call the laboratory for help—especially if the alternative is paging Dr. Google.
But sometimes, she admits, she finds their questions concerning. “It’s things like, ‘My patient is prescribed codeine. Why are they positive for morphine?’” she says, noting it’s a major metabolite and a question that gives her pause. “You would hope they would recognize the basic metabolic pathway, but we’re getting calls asking for that simple interpretation, which lets you know they don’t know how to interpret the results.”
Dr. Snozek coauthored a recently published study that assessed knowledge and educational needs in urine drug test interpretation among health care professionals (Snozek CLH, et al. Am J Clin Pathol. 2025;163[1]:69–79). Most respondents, with the exception of MD toxicologists and PhD laboratory scientists, displayed significant knowledge gaps.
“I’m glad they call,” she says of those who reach out for interpretive help. “But the concern is there are probably people out there who also don’t know what they’re doing when it comes to interpreting results but don’t think to call.”
Or they turn elsewhere for help. In the study, Dr. Snozek and her coauthors surveyed clinical professionals about where they would seek information if they had a question about urine drug testing. Of 540 respondents to this question, 37 percent said they would contact the laboratory, 23 percent said they would ask a specialist health care professional and 15 percent a colleague in the same specialty, 22 percent said they would search the internet, and three percent would do none of the above. “It was a pretty low percentage who said they would reach out to the laboratory,” says study coauthor Stacy Melanson, MD, PhD, vice chair of clinical laboratories at Brigham and Women’s Hospital.
Dr. Melanson has seen a lack of awareness of testing methods and their pros and cons. “I’ve been in meetings where they think we’re doing radioimmunoassay for these tests, which we haven’t done in the lab for 20-plus years,” she says. She too has seen confusion around metabolism. “We’re reporting definitive results by mass spectrometry a lot of the time, which has the drug and the metabolites,” she says. “You have to understand the metabolism to be able to interpret the results.”
Though there is published evidence that many clinicians and trainees have difficulty interpreting urine drug test results accurately, the literature on the subject was limited, with most studies that evaluated proficiency in urine drug test interpretation focusing on one clinical specialty or institution. No study had evaluated how well a variety of health care professionals as well as pathologists and laboratory professionals were interpreting urine drug test results, Dr. Snozek says, explaining what led her and Dr. Melanson and others to conduct a survey gauging such expertise. “We wanted to do a broader study,” she says. “We also wanted to make sure we incorporated lab staff.”
To capture a broad swath of clinical specialties and levels of education, they enlisted professional societies in the U.S. and Canada to distribute the survey, which instructed respondents to answer six interpretive questions without consulting other sources. Additional questions captured respondents’ educational and professional backgrounds related to interpreting urine drug test results. In all, 911 clinical and laboratory professionals responded. “The misinterpretations we would see on a daily basis sparked the questions we put together,” Dr. Snozek says. She and her coauthors analyzed the responses to identify knowledge gaps.
Toxicologists and laboratory PhD scientists had means of 4.82 and 4.63 questions (of the six) answered correctly, respectively.
Physicians specializing in pathology (4.19), emergency medicine (4.26), and primary care and internal medicine (3.66) had more difficulty, as did laboratory professionals with nondoctoral degrees (laboratory bachelor’s/master’s: 3.70; laboratory associate degree: 3.03). Being able to identify simulated compliance, as well as understanding opioid exposure, metabolism, and immunoassay cross-reactivity, were among the most notable knowledge gaps, Dr. Snozek and her coauthors write in their article.
The question that received the fewest correct responses overall (39.5 percent) presented respondents with urine confirmation results of 10,000 ng/mL buprenorphine, 50 ng/mL norbuprenorphine, and 2,500 ng/mL naloxone in a patient prescribed Suboxone (buprenorphine/naloxone). The correct interpretation was that the patient adulterated the sample with Suboxone to simulate compliance.
It’s possible that simulated compliance is a blind spot for primary care physicians and other non-addiction medicine specialists tasked with monitoring medication-assisted treatments, Dr. Snozek says. “These are clinicians who want to have a trusting relationship with their patients, and simulated compliance is essentially providing the result they want to see, even though it’s not the accurate result.” It’s not their specialty, “and they’re asked to do this for a lot of people,” she notes, “along with everything else primary care physicians are tasked with.” Respondents in behavioral and addiction medicine did well on the question. “That’s the realm they live in, so they have a higher threshold for following up on results,” she says.
Then again, simulated compliance has puzzled the laboratory on more than one occasion, Dr. Melanson says. “If you only see the parent compound and none of the metabolite, it’s pretty straightforward,” she says. Borderline cases, though, where the metabolite is present at a low level and the parent compound at a high level, raise the question: What ratio should be interpreted as simulated compliance? “It gets even more complicated because there are so many factors that go into what the concentrations are in urine, and mass spec assays are not standardized between labs,” she says.
With the opioid epidemic often in the news, Dr. Snozek was surprised respondents didn’t fare better on the questions that addressed opioid exposure. “We did a question related to cannabidiol and folks in the U.S. answered spot-on, I think because there was so much emphasis on it in the lay press that people recognize the potential for THC [an active compound in marijuana] to be present in cannabidiol,” she says. “I would have thought that the emphasis on opioids, with the opioid epidemic and overdoses for the last however many years now, would have contributed to a more solid base in that area.”
On the other hand, she’s sympathetic to the reasons why many physicians didn’t do well on those questions. For example, 12 percent of respondents answered incorrectly that fentanyl could be detected by a urine opiate immunoassay screen, which, though incorrect, isn’t an unreasonable choice from the standpoint of a physician. “They’re thinking about drugs as, ‘What kind of effect am I trying to create by giving them?’” Dr. Snozek says. “They might think, well, it causes the same effect, without recognizing the chemical structure is different.”
“They’re doing a lot,” Dr. Melanson adds. “This is one small piece of how they practice medicine, and it’s hard to keep up with all these things, especially at sites that are not as academic.”
One question posed a scenario in which a patient prescribed Ativan has a negative urine immunoassay screen for benzodiazepines. Sixty-seven percent of respondents recognized the need for confirmatory testing. Common incorrect responses were that negative screening results proved noncompliance (14.8 percent) and that no available immunoassay screen can detect lorazepam (11.9 percent).
Until recently, Dr. Melanson says, benzodiazepine assays didn’t cross-react well with newer drugs like Ativan. “That said, there have been newer benzodiazepine assays coming on the market which add a beta glucuronidase and have had improved cross-reactivity for the newer metabolites.” Many of the toxicology assays are on the older side, she says. “The antibodies were designed to detect drugs that aren’t as common anymore. We see this with quite a few assays out there, that the antibodies haven’t been updated to improve cross-reactivity, and that’s a knowledge gap of the clinicians.”
Adds Dr. Snozek: “Maybe it’s an issue of the field moving quickly. Yes, there are old assays out there, but that doesn’t mean the information is completely static, and that’s a gap we’re seeing.”
Respondents displayed a somewhat better grasp of the concept of detection windows. One survey question asked for the most likely explanation after a test detected THC metabolites in a patient’s urine two weeks after the patient was asked to cease his regular marijuana habit pre-surgery. The patient had a body mass index above 40. Though 59.5 percent of respondents answered correctly that the testing was within the THC detection window for an obese patient, 37.2 percent answered that THC metabolites remain detectable for several months.
Case reports have documented longer than average detection windows in certain people, Dr. Snozek says. “I think that tends to get inflated into ‘this can happen for everyone,’ when these are case reports because they’re exceptions to the general rule.” And interpreting based on exceptions, she says, comes with risks. “You want to be able to recognize the typical expected pattern and then investigate further if something doesn’t seem to fit the pattern.”
Other survey findings are, in part:
- Fifty-five percent answered correctly the following question: A patient prescribed oxycodone is positive on her urine confirmation test for oxycodone (40,000 ng/mL) and hydrocodone (5,000 ng/mL). What is the best interpretation? Answer: Hydrocodone and oxycodone were both ingested; she is noncompliant.
- Forty-seven percent answered this question correctly: A patient on OxyContin (oxycodone) says he ate a pastry with poppy seed filling for breakfast. If he is compliant, which drugs might reasonably be expected to be detected in his urine? Answer: oxycodone, codeine, and morphine.
- 73.5 percent answered the following question correctly: Your patient has a history of heroin use. A urine opiate screen is positive, and confirmation shows 250 ng/mL morphine; 6-monoacetylmorphine (6-AM) is undetectable. Correct response: 6-AM is a specific heroin metabolite but is not always present after remote use.
- 71.5 percent answered this question correctly: An ED patient arrived with miosis and respiratory depression, waking after several doses of Narcan (naloxone). An immunoassay drug screen was positive only for fentanyl. However, confirmation was negative for fentanyl and norfentanyl. Most likely reason? Patient used a fentanyl analog(s).
All respondent groups had mean scores below the maximum possible six correct answers, “suggesting there is room for improvement throughout all educational backgrounds and clinical specialties,” the authors write.
About 55 percent of pathologists reported having little to no training and experience in urine drug test interpretation, with the rest reporting moderate to extensive training and experience. The training for clinical chemists is “a bit more robust” in this area, Dr. Melanson says, with most reporting moderate to extensive training and experience.
She’s in favor of incorporating urine drug test interpretation in the pathology curriculum, or potentially as a Pathology Milestone. Interpretive questions on the pathology board exams, too, would help. “I think you have to attack it from multiple angles,” she says. One hurdle: A number of training sites likely don’t have mass spectrometry for toxicology or an expert to teach it. This is where professional organizations like the CAP and others could step in to offer educational material and other support, she suggests.
The 100 respondents who received the survey through the American College of Medical Toxicology had the best overall performance (mean, 4.91). Education on toxicology testing—“and specifically the flaws in toxicology testing, the limitations of it,” Dr. Snozek says—is a regular offering of organizations like the ACMT and Association for Diagnostics and Laboratory Medicine. “It’s that gentle exposure over time that seems to have an effect,” she says.
At Brigham and Women’s Hospital, an internal study yielded findings similar to those of the survey (Chua I, et al. J Gen Intern Med. 2020;35[1]:283–290). Although the study had a different format—it was a retrospective chart review of 160 urine drug test results and whether the results documented in the medical record were concordant with the expert laboratory toxicologist’s interpretation—the concepts providers missed were similar. In this study, too, “they missed simulated compliance quite frequently,” Dr. Melanson says. Overall, only 88 of the 160 had any documented provider interpretations, of which 28 percent were discordant with the laboratory toxicologist’s interpretation.
In a follow-up study, Dr. Melanson and her colleagues experimented with including interpretations with the laboratory results (Chua IS, et al. Pain Physician. 2021;24[2]:E191–E201), something she sees as a potential fix for the problem. The challenge is deciding how liberally to apply such comments. “You could make the argument that for almost every test there could be some nuance that you’d want to alert the clinician on how to interpret,” Dr. Melanson says. “And then it could clutter up the medical record.”
The interpretations did not significantly improve laboratory-clinician interpretation concordance, interpretation documentation frequency, or opioid-prescribing behavior. Still, the clinicians reported at six-months post-intervention that the interpretive service was easy to use, improved results comprehension, and helped them interpret results more accurately and confidently. In time, Dr. Melanson and colleagues intend to make the interpretive comments a regular feature of the laboratory’s toxicology reports. “We’re hoping, as a next step, to develop an algorithm where we pull active medications from Epic and in conjunction with our laboratory results develop a software tool that will interpret results.” A pathologist or chemist would then review the interpretation, she says.
Encouraging one’s patient-facing colleagues to use the laboratory as a resource means ensuring there’s always someone in the laboratory who can take those calls. “Not everybody in the laboratory scored well on the quiz,” Dr. Snozek says, “particularly bench-level staff. And that’s okay—it’s not part of routine medical technologist training, especially when you start getting into the complications of interpreting confirmations and things like that.” Yet every laboratory would do well to identify “at least one or two people who do have the information,” she says. “It’s a little bit of burden on the lab to identify expert level staff,” or train staff to help physicians locally.
Dr. Snozek and her coauthors are conscious that their findings could be viewed as a delicate matter. They took care not to direct blame toward anyone; in a field like toxicology, “the knowledge gaps are exacerbated by the nature of the testing itself,” she says. “The technology changes, the drugs themselves change, the metabolites that are identified change, and our ability to test for broader and broader panels has grown in recent years.” Still, “We did see when we were trying to publish the data that it got a lukewarm reception the first few places we submitted it to,” she says.
Says Dr. Melanson, “We didn’t want to call out different groups.” Rather, they attempted to frame the problem in a constructive light.
“There’s a knowledge gap that’s not anyone’s particular fault,” she says. “How do we improve that?”
Charna Albert is CAP TODAY associate contributing editor.
The CAP was among the organizations that participated in disseminating the survey online. Other participating laboratory professional societies were the ADLM (then AACC), Academy of Clinical Laboratory Physicians and Scientists, Canadian Society of Clinical Chemists, and Canadian Society for Medical Laboratory Science. In addition to the American College of Medical Toxicology, the participating clinical professional societies were the American Academy of Emergency Medicine, American College of Occupational and Environmental Medicine, American Society of Addiction Medicine, Medical Review Officer Certification Council, and Substance Abuse Program Administrators Association. Survey responses were acquired between August 2020 and May 2023.