Urine Drug Screen and When to Order More Tests
It takes years to develop relationships of trust with patients yet only seconds to destroy those relationships with false accusations. How to deftly handle abnormal urine drug tests (UDTs), therefore, becomes a critical skill when working in pain management.
Three general principles are important when interpreting results from UDTs:
- Seek definitive results to guide any decisions that will alter treatment.
- Plan in advance how abnormal results will be handled, and stick to your plan.
- When aberrant behavior is identified, do not ignore it; address it immediately, and document the medical record accordingly.
Unfortunately, sending all UDTs for confirmation testing to obtain definitive results may result in steep penalties from Medicare and Medicaid for unnecessary or fraudulent lab orders.1 Spurring the recent scrutiny is the high cost of UDTs—10 to 20 times that of immunoassay tests. Litigation and hefty fines have been used in egregious cases of overuse. Reimbursement rates have also been reduced. Therefore, sending every test for confirmation is not the standard of care, and ordering the right initial test requires forethought and knowledge of drug-specific tests.
There are two general types of UDTs routinely used in clinical practice—immunoassay testing and confirmation testing. Understanding their unique features and limitations is critical.
Immunoassay is often referred to as “in-office,” “point-of-care (POCT),” or “dipstick” testing. The test’s results are typically fast, inexpensive, and sensitive, but its lack of specificity can result in false positives. Extensive lists of common false positives are available and should be readily accessible when interpreting unexpected results. Apps and algorithms are also available to guide practitioners through this process. A UDT positive for cocaine is almost never a false positive because it specifically tests for benzoylecgonine, a metabolite unique to cocaine. Amphetamines, however, have a very high false positive rate, with numerous structurally similar prescription drugs triggering a positive UDT. Benzodiazepines and cannabinoid tests vary significantly between labs and with the specificity of the assay used. However, in general, they too have a documented potential for false positives.
A standard opiate immunoassay screen does not detect all opioids equally. It is designed to detect morphine, as well as drugs metabolized to morphine, including opium (concentrated morphine), heroin (metabolized to morphine and 6-Monoacetylmorphine), and codeine (metabolized to morphine by CYP2D6). It will also include other structurally similar opioids at higher concentrations, by default, but may result in false positives or negatives. While labs vary in detection thresholds for hydrocodone and other synthetic opioids compared to morphine, a substantial dose of oxycodone is required to trigger a positive result on an opiate screen (Table 1). Many labs overcome this issue by including a separate oxycodone screen (100 ng/mL) to ensure it is detectable at low doses.
An opiate screen is not designed to detect opioids from different pharmacologic classes, such as fentanyl or methadone, or even most synthetic dehydroxylated phenanthrenes with unique chemical structures, such as levorphanol or buprenorphine. Separate specialty immunoassay tests for many of these are available. While some labs offer comprehensive immunoassay tests that include every specialty screen, many do not. Practitioners must be familiar with available tests and make an informed choice. Of note, most labs keep urine samples for a limited period of time—some only 7 days—so if test results are unexpected, practitioners should determine if the correct test has been requested for the prescribed medications and, if necessary, reorder in a timely manner.
The second type of UDT is confirmation testing, which has both high sensitivity and high specificity and is usually performed with either gas or liquid chromatography-mass spectrometry. Confirmation testing takes longer than for an immunoassay test, and is more expensive, but its accuracy provides definitive results. Unlike immunoassays that provide only a positive or negative qualitative result, confirmatory tests specify which drug was present along with metabolites and their respective quantitative concentrations. The threshold required for detection is substantially less, which ensures that the test will more likely capture the substance if it is present. Correct interpretation of a confirmation test requires an understanding of the metabolites in commonly prescribed medications so as to not misinterpret results to mean a patient is taking medications that are not prescribed (Table 2).
In 2016, the Centers for Medicare and Medicaid Services (CMS) replaced previous drug testing codes with dedicated The Healthcare Common Procedure Coding System (HCPCS) “G” codes. The codes differentiate between presumptive testing (Is a drug present?) and definitive testing (to provide a positive identification of the substance in question). Presumptive codes are eligible for reimbursement when testing is performed in an office, laboratory, or facility setting.
The definitive tests must be both more sensitive and specific than the initial screen. Definitive tests are performed in a laboratory or by a provider with Certificate of Registration, Compliance of Accreditation, or Medical Test Site Categorized License, or Accredited License. The tests are able to quantify the amount of drug or metabolite present in the urine sample. Definitive tests can be used to confirm the presence of a specific drug identified by a screening test and can identify drugs that cannot be isolated by currently available presumptive testing. Results are reported as specific levels of substances detected in the urine sample.
Occasionally, assistance is required in interpreting unexpected UDT results, and discussing them with another provider, clinical pharmacist, or laboratory toxicologist may be helpful. Result 1 on Table 2 could lead providers to believe the patient is on multiple benzodiazepines and opioids, but this result should be interpreted as a patient taking diazepam (oxazepam and temazepam are metabolites) and hydrocodone (hydromorphone is a minor metabolite).
Result 2 indicates a patient taking fentanyl (norfentanyl is the major metabolite) and lorazepam, as well as using marijuana. With most immunoassay tests, lorazepam and clonazepam won’t trigger a positive UDT. They require either a specific immunoassay or confirmation testing. The presence of cannabinoids in a confirmation test is definitive, so without question it was in the patient’s system in this example. A patient’s previous response regarding this result and the patient’s history, as well as clinic policy or state law, may then influence the decision to continue treatment.