History of Urine Drug Testing

To assure a drug-free workplace, the Mandatory Guidelines for Federal Workplace Drug Testing Programs came about as a result of the Federal Drug Free Workplace Act established in the 1980s. The five drugs tested for in a federal urine drug test (UDT) include opiates, marijuana, cocaine, phenylcyclohexyl piperidine (PCP), and amphetamine/methamphetamine. Eventually, urine drug testing as a means of deterring and detecting illicit drug use expanded to nonfederal workplaces, sports organizations, schools, forensics, and the health care arena. Unfortunately, the type of urine drug testing performed and method of testing employed by federal testing is suboptimal for the health care setting. With federal testing, thresholds for the detection of opioids and illicit substances are higher as determined by statutes, the testing panel is limited with a fewer number of opioids tested, specimen collection may be witnessed, there is a strict chain of custody, and there is no therapeutic relationship between the individual and testing entity.

Bodily Specimens That Can Be Tested

Why test urine as opposed to other bodily specimens, such as blood, hair, sweat, or saliva? Unless a patient has a neurogenic bladder requiring intermittent catheterization, urine is an easily obtainable noninvasive specimen, is cheap to analyze, can be analyzed with in-office point-of-care (POC) tests, is detectable for days, has higher concentrations of the parent drug and/or metabolites than serum, and has the most extensively published information and evidence for adherence testing. The disadvantages of urine specimens include ease of adulteration or substitution, a short to intermediate window of detection, and difficulty of same patients to spontaneously provide a specimen. Other bodily specimens possess apparent advantages, but limitations currently override widespread use as part of an adherence-monitoring program.

Measuring a drug’s serum concentrations is useful in the setting of the anuric patient or for detecting recent substance use, such as in the intoxicated patient seen in an Emergency Department setting. There are established testing methods for serum. The disadvantages of serum specimens are the cost, the narrow window of detectability (hours), and invasiveness. Because drawing blood requires a trained professional, use of this specimen in the workplace setting is not practical or economically feasible.

Saliva concentrations reflect serum concentrations since the salivary gland is highly perfused. In addition to being noninvasive, testing saliva offers more potential advantages compared to testing urine: ease of specimen collection, ability to witness collection in a less embarrassing manner than a urine specimen, low likelihood of adulteration, ability to target the parent drug instead of the metabolite, and availability as a POC test. Saliva testing, however, has limitations: salivary concentration is influenced by salivary pH, with basic drugs being found in a higher concentration; low concentrations of a drug may be difficult to detect if the salivary volume is low; elution solvent must adequately remove the drugs adsorbed to the collection device; drug-interference patterns, cross-reactivity, and impact of potential adulterants are not as well studied; and because it reflects serum concentrations, the window of detectability is only hours.

Hair testing presents a number of advantages: minimally invasive; specimen is easy to store and transport; collection can be observed with minimal embarrassment or risk of substitution; and, depending on the length of the hair sample, the window of detectability expands from days to months. Clinical application of hair testing is challenged by a number of factors: unclear relationship to timing and dosing of the drug versus hair length; difficulty detecting low-level use and low drug concentrations; difficulty obtaining a sufficient hair sample from those who shave or who otherwise have minimal body hair; hair can be adulterated by using dyes or other stylistic treatments; a drug is more readily identified in naturally occurring dark-colored hair versus lighter colored or white hair, thereby inherently biasing test results; and costly and time-consuming sample preparation. Ultimately, hair analysis is really useful from a forensics standpoint as it is most reliable for detecting chronic drug use as opposed to recent and infrequent drug use.

Sweat testing presents a number of advantages as it is minimally invasive, difficult to adulterate, and has a window of detectability that allows detection of drug that has been used within 24 hours (using a sweat wipe) or up to weeks (using a sweat patch worn for 1 to 2 weeks), which is ideal for monitoring in a chemical dependency or probation program. Sweat patch testing requires two visits for application and removal of the patch. Drug detection depends on the drug’s diffusion from the vasculature to the sweat gland, molecular mass, pKa, protein binding, lipophilicity, where the patch is applied, patch adherence to the skin, and impact of potential adulterants. Development of more successful technical and scientific guidelines is needed for these alternate specimens before they can be used as a substitute for a urine specimen.

Urine Drug Testing

Comprehensive urine drug testing is a two-step process ( Table 46.1 ). The first step is an enzyme-mediated immunoassay screen (IAS), which is strictly a qualitative test used to screen for the presence or absence of drug classes. IASs included in the federal workplace test for five classes mandated by the Substance Abuse and Mental Health Services Administration (SAMHSA): amphetamine, cocaine, marijuana, PCP, and opiates (limited to codeine, morphine, and 6-monoacetyl-morphine to test for heroin use). Most IASs performed in the clinical setting test for the same “SAMHSA-5,” but maintaining such a limited panel is not recommended. Other drugs or classes, such as benzodiazepines, barbiturates, methamphetamine, semisynthetic opioids, methadone, and buprenorphine should also be included. Since it is neither cost efficient nor practical to test for all drugs and illicit substances, clinicians may need to customize their IAS and UDT panels to identify the most commonly used drugs and illicit substances. Furthermore, because it is impossible to identify all drugs present in a specimen, let alone all drugs within the same class, astute clinicians must recognize that an IAS is not definitive. Therefore, an IAS is only helpful for making preliminary treatment decisions.

IASs typically work by measuring an antigen-antibody reaction. Antigens—the free drug and/or free drug metabolite and the same labeled drug and/or labeled drug metabolite—compete for antibodies to elicit an enzymatic reaction. When the free drug and metabolite are absent, the labeled drug and metabolite bind the antibody to prevent enzymatic activity. However, when the free drug or metabolite is present, it displaces the labeled drug or metabolite to create an enzymatic reaction that is measurable and proportional to the concentration of the free drug or metabolite. Regarding an IAS’s antigen-antibody specificity, this can account for why an immunoassay can be specific for particular drugs (e.g., it principally detects the cocaine metabolite, benzoylecgonine, which has a longer half-life than cocaine itself and, if used as a legitimate topical anesthetic, does not cross-react with any other local anesthetic); it can be so specific for a particular drug that it excludes similar drugs (e.g., it detects morphine and codeine, but not methadone); or it can be so nonspecific that it has difficulty differentiating drugs in the same class (e.g., it cannot distinguish morphine from codeine, and it has low sensitivity for detecting semisynthetic opioids); or it cross-reacts with unrelated drugs which are structurally similar enough to trigger a false positive for a particular drug class ( Table 46.2 ).

In addition to identifying illicit drugs, advantages of an IAS are that it is cheap, yields results within minutes, and is convenient (either performed with an in-office POC test or sent to a laboratory for testing). Originally developed to monitor workers for illicit substance use, a POC IAS offers the advantage of a faster turnaround time (minutes to hours) while the patient could still be in the clinic than a laboratory-based IAS. However, performance of a POC IAS depends on having clinic personnel who are trained in precisely following the manufacturer’s specific instructions (e.g., amount of sample to use, sample application, and timing of reaction) and understanding how to interpret the result given the test’s inherent limitations. Since a POC IAS is a noninstrumented test, in most cases, the person handling the “device” (dipstick, cup, card, or cassette) must visually interpret its appearance and manually enter the data into the electronic medical record. Because interpretation of some devices depends on a color change after application of a specimen, any delay in when the change is interpreted, even as little as 10 minutes, can result in an inaccurate analysis since the color can continue to change over time. Some POC IASs, however, can be read by a meter, which then transfers the result electronically to the electronic health record. A POC IAS should also include a “control” to be certain that the device is working as expected.

Because manufacturers of POC IASs may differ in terms of threshold of detectability, specificity for identifying the target drugs of interest, reproducibility, and complexity of performing the test, the IAS results can differ between brand manufacturers. But not only can there be variation between brand manufacturers, there can also be variations between manufactured lots/batches that can lead to differing outcomes. Studies have also demonstrated inconsistencies in product performance versus the manufacturer’s claims and deviations in threshold reporting (identifying drugs or metabolites below the threshold or not identifying drugs or metabolites above the threshold). Crouch et al. compared the utility and accuracy of five POC IAS brand manufacturers (800 specimens) and found that each brand had a false-negative rate of less than 1% for all drug classes and false-positive rates of less than 0.25% (marijuana, cocaine, and opiates), less than 1.5% (PCP), and less than 1.75% (amphetamine). While studies comparing the accuracy of POC IASs and laboratory-based IASs suggest both provide similar results, limitations of the studies were due to the fact that laboratory-trained personnel performed the POC IASs, and challenges in interpreting the results were greatest when at the lower end of threshold of detectability.

For clinicians who opt to use a POC IAS, it must be certified by the Clinical Laboratory Improvement Amendments of 1988 (CLIA) depending on the Food and Drug Administration’s (FDA) categorization of test complexity (e.g., waived, moderate, or high). Medicare reimbursement also requires this certification. A CLIA Certificate of Waiver can be obtained for those POC IASs that the FDA approves for use in nonlaboratory settings (e.g., home and office) provided the POC IAS is easy to use and interpret and the clinic follows the manufacturer’s explicit testing instructions. To minimize testing errors and maximize quality assurance, the Centers for Disease Control and Prevention’s Division of Laboratory Systems created “Good Laboratory Practices for Waived Testing Sites.” In addition, the manufacturers of POC IASs include specific instructions on specimen collection, handling, storage and testing, reference values, and recording of test results. It is up to the clinician to review the device manufacturer’s instructions on whether confirmatory testing is or is not needed. Violating the manufacturer’s instructions may otherwise invalidate the device’s CLIA-waived status. It is up to the clinician to determine which POC IAS is covered by any given insurance company and to compare the cost and expediency of performing a POC versus laboratory-based IAS. If one requires an immediate result to assist with making a clinical decision while the patient is still in the clinic, a POC IAS would be most prudent. If an immediate result is not needed, then the clinician may consider sending the specimen to the laboratory. From an insurance standpoint, Medicare will not reimburse for both a POC IAS and laboratory-based IAS at the same clinical encounter.

In a laboratory setting, the IAS is performed by licensed personnel using automated analyzers. The advantage of using an automated analyzer is that results can be automatically exported to the patient’s electronic health record. Similar to a POC IAS, a laboratory IAS is also subject to variability among testing products. Because of its complex regulatory status (ensuring both quality control of the test product and analyzer and proficiency of the personnel doing the testing) and overhead (equipment and trained personnel), the cost and reimbursement is higher than with a POC IAS.

The second step in comprehensive urine drug testing is a confirmatory UDT, which requires laboratory-based testing using gas chromatography-mass spectrometry (GC/MS) or liquid chromatography-mass spectrometry (LC/MS). A UDT is a quantitative test that adds a much higher level of sensitivity and specificity than an IAS and identifies, where applicable, the specific drug within a class as well as drug metabolite and drug concentration. Unlike an IAS, most UDTs can identify codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, and oxymorphone. This is especially important for those chronic pain patients who are on more than one type of opioid. With some opioids, metabolism of the parent opioid can lead to a metabolite of an alternate opioid (e.g., codeine is metabolized to morphine and oxycodone is metabolized to oxymorphone). If both a prescribed drug and its metabolite or only the metabolite is identified on an IAS, it is unclear if the patient is compliant versus abusing nonprescribed opioids and highlights why one might see conflicting results with an IAS versus UDT. Because an IAS is only a qualitative screening test, quantitative confirmatory testing with a UDT should also be performed as part of the adherence-monitoring program.

From a simple technical standpoint, chromatography is a separation method that involves both a stationary phase (contained with the analytical column) and a mobile phase (gas or liquid). A drug that does not interact with the stationary phase exits at the same flow rate as the mobile phase, whereas a drug that interacts with the stationary phase gets retained in a column and exits at a slower rate. There are two different types of chromatography: gas chromatography (GC) and liquid chromatography (LC). And there are two different types of LC: ultra-performance liquid chromatography (UPLC) and high-performance liquid chromatography (HPLC). While GC is the most popular method, UPLC is increasingly a method of choice because of its many advantages over GC: greater sensitivity, requirement for a smaller sample size, faster analysis time, and less laborious sample preparation time.

While chromatography separates the analytes in a specimen, mass spectroscopy (MS) can be combined with both GC and LC to identify the specific molecular structure of individual drugs and/or metabolites based on their mass-to-charge ratio along with their concentrations. Because GC/MS and LC/MS allow for a qualitative and quantitative analysis of the specimen, ambiguous immunoassay results can be resolved by analyzing the concentration of both the parent compound and its metabolite. This improvement in sensitivity and specificity allows for a reduction in false positives and false negatives. The secondary benefit to testing for drug metabolites is greater assurance that the drug has been consumed and processed by the body, whereas the presence of only the parent drug does not rule out the possibility that the urine specimen was adulterated by directly adding the parent drug.

Threshold Of Detectability

The accuracy of both an IAS and UDT in identifying a drug or illicit substance depends on a number of factors: the IAS’s antigen-antibody specificity, the drug concentration in the sample, and the threshold of detectability. Where a laboratory chooses to set its threshold of detectability may depend on whether it is being run for nonclinical (e.g., workplace or forensic) purposes versus clinical purposes. Unlike nonclinical testing standards, the threshold concentrations in a pain management setting are not standardized.

The threshold of detectability intentionally may be set higher in nonclinical testing to yield the fewest false negatives and false positives. For example, morphine’s threshold of detection is set at 2000 ng/mL for a workplace IAS compared with 300 ng/mL for a clinical IAS or 50 ng/mL for a clinical UDT. When the drug is absent or the concentration falls below the threshold of detectability, the result is reported as negative, and where the concentration rises above the threshold of detectability, it is reported as positive. For clinical purposes, one should ask the lab to set the lowest threshold of detectability to yield the most true positives and fewest false negatives. However, the by-product of setting a low threshold is that higher sensitivity may also detect impurities or contaminants associated with manufacturing process; for example, two different opioids manufactured on the same equipment may result in low levels of a nonprescribed opioid being detected on an IAS despite the patient using only one prescribed opioid. While a laboratory could conceivably eliminate its threshold, there is a certain concentration below which a laboratory cannot reliably report the result with a high level of confidence, thereby yielding inaccurate results.

Why Perform An Immunoassay Screen and Urine Drug Test

Even though a diabetic patient may self-report good glycemic control, clinicians still periodically obtain laboratory tests to objectively confirm the retrospective level of diabetes control without accusing the patient of lying. This thought process should be no different with respect to performing an IAS and UDT in the patient on COT. This includes not only monitoring for the prescribed opioid(s), but also for nonprescribed opioid(s) or illicit substances that identify a treatable substance use disorder. For some patients, knowing they are being monitored may reinforce healthy lifestyle changes; and for those who engage in or relapse into problematic drug use, an unexpected test result may provide a safe harbor for the patient and/or clinician to explore treatment options for a substance use disorder. A testing policy also signals to patients, law enforcement authorities, and regulatory authorities that one’s vigilance demonstrates a commitment to patient and community safety. Used in this manner, testing is one tool that can be used in supporting the clinician’s decision to continue versus discontinue COT.

Caution should be exercised when interpreting test results because of limitations related to thresholds of detection, variables that affect drug concentration (pharmacokinetics, pharmacodynamics, and pharmacogenetics), and variables related to the specimen itself (collection, handling, and analysis). These limitations and variables also, in part, explain why there is no scientifically validated relationship between the urine drug concentration and the amount of drug taken, the timing of when the drug was last taken, or the source of the drug.

Who Should Get an Immunoassay Screen and Urine Drug Test

While every patient is entitled to pain management, COT may not be the safest option for every patient. When a risk-benefit analysis suggests benefits outweigh risks, testing should be performed in patients in whom a trial of COT is being considered, patients already on COT who are transferring care, patients in whom an opioid rotation is being considered, patients being referred to a pain specialist, as part of a random process to monitor for adherence, or when behavioral signs suggest concern (lost or stolen medications, requests for early refills, unannounced clinic visits, doctor shopping, frequent Emergency Department visits, request for certain opioid(s), or allergies to multiple opioids). Those who are candidates for COT and consent to their use must also accept responsibility for using the medication as prescribed and under the conditions stipulated by the opioid agreement the patient signs with the clinician. One of the conditions of prescribing COT should include the patient consenting to random testing. While the patient is within his/her rights to object to random testing, the clinician is not obligated to initiate or continue the COT since opioid analgesics are not a required therapy. For the patient who states he/she cannot submit a specimen (e.g., because he/she already urinated, is late for work, or has another appointment to attend), options include holding the prescription until the patient can urinate later that day vs. giving a limited supply (e.g., one-day supply) and making further refills contingent upon submitting a specimen within a specified period of time (e.g., 24 hours). A uniform practice policy is helpful in avoiding bias in determining who gets tested and reducing the stigma associated with submitting an IAS and UDT.

When To Get an Immunoassay Screen and Urine Drug Test

Katz et al. showed that urine drug testing only those who have a history of addiction or exhibit aberrant behavior missed a significant number of patients who had unexpected test results. To confirm the veracity of a patient’s responses to questions about his/her controlled substance use or illicit substance use, the clinician should consider obtaining an IAS and UDT prior to the initiation of COT, upon inheriting a patient who is already on COT that was initiated by another provider, prior to dose escalation or opioid rotation, in those instances when a patient exhibits behaviors or makes statements that may arouse suspicion, and randomly during maintenance therapy as part of an ongoing monitoring program. Combining urine drug testing with other monitoring techniques makes the most sense. Using this formulaic approach helps the clinician avoid profiling and stigmatizing patients based on race, ethnicity, socioeconomic status, or gender.

How Often To Get an Immunoassay Screen and Urine Drug Test

Because there is no evidence-based guideline that pinpoints which patients with chronic pain should be tested, definitive criteria for frequency of testing similarly do not exist. The frequency of testing beyond baseline urine drug testing is left to the clinician’s discretion based on individual patient needs and documented medical necessity. Table 46.3 shows one suggestion on monitoring frequency. However, some state guidelines may suggest or require certain frequencies.

TABLE 46.3

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

Determination of Disability Epidural Opioids for Postoperative Pain Myofascial Pain Syndrome Anatomy, Imaging, and Common Pain-Generating Degenerative Pathologies of the Spine Chronic Pain Management in Children and Adolescents Legal and Regulatory Issues in Pain Management

Stay updated, free articles. Join our Telegram channel

Join