Although urine drug tests can be used to identify potential misuse concerns in patients with an opioid prescription for chronic pain, their use in mitigating harms requires further research, according to research results published in the Journal of General Internal Medicine.

Using data from the Transforming Opioid Prescribing in Primary Care (TOP-CARE; ClinicalTrials.gov Identifier: NCT01909076) cluster-randomized trial, researchers determines the prevalence of urine drug test results that may correctly identify substance misuse in patients prescribed opioids for chronic pain.

The study was conducted between 2014 and 2016 at 4 safety-net clinics in Boston, MA. Fifty-three primary care clinicians were randomly assigned to the intervention arm, which included nurse care management, an electronic registry, academic detailing, and web-based decision support tools, or a control arm which only included web-based decision support tools.


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Patients evaluated were between 18 and 89 years of age, had a primary care clinician assigned to the intervention arm, were receiving long-term opioid therapy for chronic pain, and received at least 1 urine drug test in the year after their provider was randomized. 

The sample included all urine drug tests from patients who met study inclusion criteria in the 1 year after provider randomization. Researchers included 9 common immunoassay tests: amphetamines, barbiturates, benzodiazepines, buprenorphine, cocaine, methadone, opiates, and oxycodone. The primary study outcome was categorization of urine drug test results as not concerning, uncertain, or concerning, through expert adjudication.

Adjudication was carried out in a 2-stage process. Actual results were compared with expected results based on prescription history. If results were discordant, it was flagged for further review. The second stage included a review of abstracted clinical data from the patient chart, including the result of urine drug test immunoassays, the date, strength, quantity, and number of days supplied of up to 2 prescriptions on or 180 days prior to the urine drug test date, data on all other medications, and follow-up notes and discussions on urine drug test results.

A total of 638 patients met inclusion criteria (49% older than 55 years; 48% women). The sample was both racially and ethnically diverse, including 42% non-Hispanic White patients, 39% non-Hispanic Black patients, and 8% Hispanic patients. Most patients—60%—had mental health diagnoses; 17% had a substance use diagnosis and 14% had an alcohol use diagnosis. Patients were primarily enrolled in Medicaid (39%) or Medicare (38%).

In the 90 days before the study period, 12.4% of patients received more than 100 mg mean daily morphine milligram equivalents (MEDs). During the intervention, oxycodone was the most commonly prescribed opioid (82% of patients), followed by morphine and hydrocodone (16% and 14%). Patients also received benzodiazepines (27%), amphetamines (1.6%), barbiturates (1.6%), or buprenorphine (0.2%).

A total of 2218 urine drug test samples were analyzed, with a median of 3 samples per patient. Overall, 1009 samples—45%—with a discordant result were identified and flagged for further review. Of these, definitive urine drug test results and time of the last opioid dose were available for 25% and 38% of adjudicated drug tests. 

Interrater adjudication reliability was moderate or better for 14 of 17 immunoassay test/result combinations, while interrater reliability was weak for negative opiate and oxycodone tests.

During the study period, 37% of patients had at least 1 concerning urine drug test and 35% had at least 1 uncertain urine drug test. Similar proportions of patients had concerning positive tests that detected a nonprescribed substance and concerning negative tests that did not detect a prescribed substance (24% vs 23%).

Outcomes varied by both immunoassay and immunoassay test result. For cocaine and immunoassays targeting amphetamines, barbiturates, buprenorphine, and methadone, more than 95% of tests were not concerning. The majority of test results were negative and more than 99% of test results were not concerning.

For immunoassays targeting oxycodone, opiates, and benzodiazepines, results were mixed; only 3% of positive oxycodone test results were concerning, while 32% of negative oxycodone tests were concerning.

Results of a multivariable analysis showed that several patient characteristics were associated with concerning urine drug test results. These included patients aged 18 and 34 (adjusted odds ratio [aOR], 4.8; 95% CI, 1.9-12.1), those with mental health diagnoses, and those with substance use disorder (aOR, 1.6 and 2.3; 95% CI, 1.1-2.3 and 1.5-3.6, respectively).

Study limitations include a lack of prospective data collection, no access to Prescription Drug Monitoring Program data, and a lack of generalizability of findings to other clinical settings or geographic areas.

“In a large cohort of patients receiving opioids for chronic pain, 1 in 3 patients had [urine drug test] results concerning for misuse or diversion in a year-long period,” the researchers concluded. “An additional 1 in 3 patients had 1 or more [urine drug test] results adjudicated as uncertain, highlighting the clinical uncertainty associated with [urine drug tests].”

“From these data, [urine drug tests] appear to provide actionable data for monitoring patients prescribed opioids for chronic pain,” they concluded. “However, their effectiveness in mitigating opioid-related harms is yet to be determined.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Larochelle MR, Cruz R, Kosakowski S, et al. Do urine drug tests reveal substance misuse among patients prescribed opioids for chronic pain? J Gen Intern Med. Published online August 17, 2021. doi: 0.1007/s11606-021-07095-8