Urine drug testing for patients with chronic pain

INTRODUCTION — Urine drug testing is commonly performed prior to and during chronic opioid therapy (COT) for patients with chronic pain. Scheduled or random urine drug testing is often part of the opioid agreement or patient-provider agreement (PPA) [1]. Urine drug testing is not always straightforward, due to differences between almost every laboratory test and practice, risks of error in interpretation, false positives and false negatives, all of which have significant implications for patient care.

This topic discusses the use of drug testing and interpretation of test results for patients on COT. Testing for patients on pharmacotherapy for opioid use disorder, and testing for other indications are discussed separately. (See "Opioid use disorder: Pharmacotherapy with methadone and buprenorphine during pregnancy", section on 'Role of urine drug testing' and "Testing for drugs of abuse (DOAs)".)

This review will focus on urine drug testing, as urine is the most commonly used biologic specimen for drug testing.

RATIONALE FOR TESTING — The goal for drug testing prior to and during opioid therapy is to support patient care and improve patient safety. Drug testing is part of risk stratification prior to starting opioid therapy and provides an objective measure of compliance with treatment thereafter. Drug testing can enhance patient care as follows:

●Reinforce the need for therapeutic compliance with the patient

●Identify drugs that may increase adverse events and/or drug-drug interactions

●Suggest misuse or abuse, diversion, or addiction, thereby encouraging behavioral changes and/or referral to an addiction specialist

However, the potential benefits of urine drug testing must be balanced with a mindful consideration of its potential harms [2]:

●Stigma associated with being tested

●Bias in who gets tested based on assumptions about the patient

●Dismissal of patient for inconsistent or unexpected test results

●Delay in providing an opioid prescription while awaiting test results

●Financial burden borne by the patient if the co-pay for the required test is unaffordable or the insurance company does not cover the cost

Multiple studies have reported that chronic pain patients tend to underreport current and prior illicit drug use or deny noncompliance with therapy [3,4]. Noncompliance with therapy is common; retrospective studies have reported noncompliance in 30 to 45 percent of patients prescribed chronic opioid therapy (COT) [5,6]. An industry report from Quest Diagnostics (a drug testing company) including almost four million monitoring tests performed in 2017 across the United States found results inconsistent with prescribed medications in 52 percent of samples [7]. In this report, 45 percent of samples were positive for non-prescribed or illicit drugs in addition to the patients' prescribed drugs, 34 percent did not show the drugs that had been prescribed or any other tested drug, and 22 percent did not show the prescribed drug but showed other illicit or non-prescribed drugs. These percentages were approximately the same as the equivalent tests reported the prior three years but represent a decline in inconsistent results of approximately 10 percent from 2011.

The accuracy of urine drug testing for identifying diversion or opioid misuse has not been determined, and there is inadequate data to tell whether or not drug screening is effective for risk mitigation or improves clinical outcomes [2,8]. However, urine drug testing may provide evidence of opioid and other substance use disorders [9] and may facilitate appropriate treatment.

DRUG TESTING IN CONTEXT — Predicting which patients are at low versus high risk for having problems with opioids is difficult. Drug testing is only one component of what should be a comprehensive program for assessing compliance with opioid therapy, possibility of misuse, and the risks and benefits of opioid therapy. Drug testing cannot diagnose addiction, dependence, or diversion of controlled substance. The results of drug testing should always be interpreted in conjunction with other clinical information when deciding to continue or modify treatment with opioids. Comprehensive risk stratification and monitoring can include a focused history and physical examination, review of past medical records, ongoing assessment of the patient's risks (can include the use of standardized risk assessment tools such as Screener and Opioid Assessment for Patients with Pain [SOAPP], Opioid Risk Tool [ORT], Opioid Risk Tool-Opioid Use Disorder [ORT-OUD], Drug Abuse Screening Test [DAST]), review of the state prescription drug monitoring program (PDMP) database, monitoring for behavioral signs of drug misuse, and ongoing assessment of efficacy and side effects of opioid therapy. (See "Use of opioids in the management of chronic non-cancer pain", section on 'Risk assessment'.)

WHO SHOULD BE TESTED — We suggest a uniform drug testing policy, whereby all patients are tested prior to initiation of chronic opioid therapy (COT), and on a random basis during COT. We recognize that while a uniform testing policy prevents bias with respect to determining who is tested, it does not necessarily reduce the stigma associated with testing itself. We attempt to minimize the stigma by explaining that in addition to opioids, there are non-opioid medications (eg, antibiotics) where testing is done to ensure efficacy and safety. Patients should consent to urine drug testing as part of the patient-provider agreement (PPA) that should be a condition for prescription of COT. The protocol for monitoring should be clearly explained to the patient, including the way in which the results will be used and the fact that insurance may not cover the cost of required testing.

Drug testing for all patients who chronically use opioids is suggested by the United States Centers for Disease Control and Prevention when the potential harms of testing can be moderated [2], and is mandated by some state regulatory agencies [10].

HOW OFTEN SHOULD TESTING BE PERFORMED — There is uniform agreement among guidelines that baseline drug testing should be performed prior to initiation of chronic opioid therapy (COT). Most guidelines recommend testing at least annually thereafter, with periodic more frequent testing based on assessment of risk of opioid misuse or abuse [2,11-13]. Such recommendations are primarily based on expert opinion, since the literature on the optimal frequency of testing during COT remains inconclusive. Some state agencies recommend testing at specific intervals for patients who receive COT.

Many clinical programs assess the level of risk in an individual patient with a standardized screen such as of opioid therapy with the Opioid Risk Tool (form 1) prior to initiation of COT, and base the frequency of testing during COT on the results, as follows:

●Low risk – Every 12 months

●Intermediate risk – Every 6 months

●High risk or opioid dose >120 morphine milligram equivalents per day – Every 3 months

In addition to routine testing, urine drug testing may be used to confirm compliance with COT for patients who are transferring care to a new clinician, prior to referring a patient to a pain specialist, when opioid rotation is considered for lack of efficacy, and for patients with behavioral signs suggestive of opioid misuse (eg, requests for early refills, doctor shopping, lost or stolen prescriptions, frequent emergency room visits). (See "Use of opioids in the management of chronic non-cancer pain", section on 'Ongoing risk assessment and management'.)

RANDOM VERSUS SCHEDULED TESTING — Random urine drug screens may be more informative than scheduled or routine testing, as patients may avoid use of non-prescribed drugs and use prescribed drugs when they expect to be tested. However, truly random testing involves calling the patient in for testing at a time other than the scheduled visit, which may be impractical. An alternative approach is to randomly select scheduled visits for testing. Some even collect a specimen at each visit but then randomly select when to send a specimen. There are no studies comparing these approaches or studies comparing random versus scheduled testing.

WHICH TESTS SHOULD BE PERFORMED

Biologic sample — Urine is the most commonly used bodily specimen for drug testing and is usually easily and noninvasively obtained. Most analytes are present in urine for days after drug ingestion. Though oral fluid (saliva mixed with other oral constituents), serum, hair, and sweat can be analyzed as well, urine has been studied most extensively for compliance monitoring. The most significant disadvantage of urine testing is that it is more easily adulterated or substituted than testing with other biologic substances. (See "Testing for drugs of abuse (DOAs)", section on 'Biologic samples'.)

Oral fluid testing is another method of drug testing that is noninvasive, offers the ability to easily witness specimen collection, and is less susceptible to adulteration than urine testing. Both presumptive and confirmatory testing can be performed on oral fluid, and point-of-care oral fluid testing is now available [14]. However, drug interference, cross-reactivity, and potential adulterants are not as well studied for oral fluid testing. A 2020 systematic review concluded that oral fluid could not replace urine in most instances [15]. While both bodily substances can detect illicit substances, urine has a wider window of detection for certain substances (eg, cocaine and methamphetamine) and retains a greater concentration of drug metabolites for detection.

Presumptive versus confirmatory testing — Two classes of tests are used for urine drug testing: presumptive test (immunoassay screen [IAS]) and confirmatory tests (gas chromatography/mass spectrometry [GC/MS], liquid chromatography/mass spectrometry [LC-MS], or liquid chromatography/tandem mass spectrometry [LC-MS-MS]). In our practice, we follow guideline recommendations that both presumptive and confirmatory testing should be used both for assessing baseline opioid use prior to initiating chronic opioid therapy (COT) for patients with chronic pain and for monitoring during COT [12,16]. (See 'Interpreting baseline testing' below.)

An IAS can be performed in a laboratory or point-of-care setting and is relatively inexpensive, with results provided within minutes to days, depending on the test site. However, there is a high incidence of false positives and false negatives, and IAS does not distinguish between parent drugs and their metabolites. Thus, an IAS should only be used for preliminary treatment decisions. Confirmatory testing should always be performed unless an IAS shows the presence of an illicit substance that has no reasonable alternative explanation. (See 'Interpreting results' below.)

Compared with an IAS, confirmatory tests provide quantitative concentrations of individual drugs and their metabolites, must be performed in a laboratory, are more expensive, and provide results in hours to days, depending on the test site. There are fewer false positives and false negatives with confirmatory testing.

●Presumptive testing – The IAS is referred to as a preliminary, screening, or presumptive test. An IAS is a qualitative test that strictly reports the presence or absence of a drug or drug class, based on a predetermined cutoff point. It does not report the concentration of the substance(s) identified. IAS can be performed in the laboratory or at the point-of-care. (See "Testing for drugs of abuse (DOAs)".)

The basic IAS that is used for workplace testing in the US includes: (See "Testing for drugs of abuse (DOAs)", section on 'What is included in a basic DOA screen?'.)

•Cocaine

•Amphetamine

•Opioids (codeine, morphine, and 6-monoacetyl-morphine to test for heroin),

•Marijuana and

•Phencyclidine.

For clinical testing for chronic pain patients, an expanded panel should usually be used and may include:

•Benzodiazepines,

•Barbiturates,

•Methamphetamine,

•Semisynthetic opioids (hydrocodone, hydromorphone, oxycodone, and oxymorphone), and

•Some synthetic opioids (methadone and buprenorphine).

IAS often includes creatinine and pH for validation, to reduce the risk of undetected adulterated or substituted samples. There are no IAS tests for fentanyl or other synthetic opioids.

●Confirmatory (definitive) testing – These testing methods include GC-MS, LC-MS, or LC-MS-MS. These tests can report quantitative results for individual opioids and their metabolites, including the synthetic opioids (eg, fentanyl).

Technical aspects of both types of drug tests are discussed separately. (See "Testing for drugs of abuse (DOAs)", section on 'Performance of DOA tests'.)

Drugs or drug classes to test for — Each laboratory or testing organization may have different testing protocols and standards that may require interpretation based on specialized information about the individual tests. Clinicians who order urine drug testing must be familiar with the tests that will be performed on routine samples, options for requesting specific tests, and decisions that have been made regarding cutoff points, particularly for IAS. As examples, the clinician may want to know whether the IAS is capable of detecting oxycodone and whether it is likely that an IAS that is positive for opioids is the result of ingestion of poppy seeds. (See "Testing for drugs of abuse (DOAs)", section on 'Opioids' and 'False positive results' below.)

Similarly, clinicians should be aware of the standard testing panel and options for additional tests for confirmatory testing. At some institutions, confirmatory testing routinely includes synthetic and semisynthetic opioids, but this is not always the case. The IAS we use assesses for amphetamine, barbiturates, benzodiazepines, cocaine, opioids, and phencyclidine. The confirmatory test we use assesses for codeine, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone, and some of their metabolites. Confirmatory testing for synthetic opioids is done on a case-by-case basis, and samples are sent to an outside laboratory. For example, a test for a specific synthetic opioid (eg, fentanyl) may be sent for a patient who is prescribed the drug or if there is reason to suspect non-prescribed use of the drug.

Alcohol — The author rarely tests for urine alcohol in chronic pain patients, as false positive results are common, and results are therefore difficult to interpret. Urine alcohol testing may be positive after ingestion of over-the-counter cough syrup, food cooked with alcohol, communion wine, alcohol-free wine or beer, Kombucha beverages, and after use of hand sanitizer or mouthwash.

Marijuana and cannabis products — Whether to test for marijuana and other cannabis products is controversial, and existing guidelines lack recommendations on this issue.

The decision to test is complicated by the existing conflict between federal law in the United States (whereby cannabis products are considered illegal) and the increasing legalization of cannabis products at the state level. Thus, some clinicians may or may not consider cannabis products illicit substances, and this decision can influence prescribing opioids to patients who use or test positive for cannabis.

The risks of prescribing opioids to patients who use cannabis products, particularly on an occasional basis, are unclear. However, like other substance use disorders, cannabis use disorder is a risk factor for opioid use disorder, and patients who use or test positive should be screened for possible use disorder. (See "Cannabis use disorder: Clinical features, screening, diagnosis, and treatment", section on 'Screening and assessment' and "Cannabis use and disorder: Epidemiology, pharmacology, comorbidities, and adverse effects".)

IAS testing does not detect some of the newer forms of synthetic cannabinoid products because they do not cross-react with the tetrahydrocannabinol metabolite, delta-9 tetrahydrocannabinol, the chemical that the IAS is designed to detect. Confirmatory testing is available for some of these synthetic cannabinoid products, but chemical structures are constantly changing. (See "Testing for drugs of abuse (DOAs)", section on 'Marijuana/cannabinoids' and "Synthetic cannabinoids: Acute intoxication", section on 'Testing for synthetic cannabinoids'.)

INTERPRETING RESULTS — Urine drug screen results should be interpreted in the context of individual patient circumstances and within the limitations of the test that is used. Interpretation of test results is not always straightforward. Urine drug tests are susceptible to both false positives and false negatives, and misinterpretation can lead to treatment decisions that can result in patient harm. It is important to understand that urine drug testing cannot be used to verify patient compliance with a prescribed dose or timing of the last dose of a drug. Accuracy of results is limited by the thresholds of detection, patient specific variables that affect drug concentration (eg, pharmacokinetics, pharmacodynamics, pharmacogenetics), and specimen handling and analysis.

Final test results should always be shared with patients. Whenever unexpected results occur and the clinician is uncertain about how to interpret the results, the provider should contact the laboratory for help from their professional experts. In many cases, repeat or confirmatory testing will be indicated. Or if point-of-care testing is used, the manufacturer's technical support should be contacted with questions about results. When unexpected results have been confirmed as accurate, the results should be shared in a nonjudgmental manner and without the threat of dismissal from care. Instead, the focus of the discussion with the patient should center around patient safety [2]. Depending on the unexpected test results, considerations can include one or more of the following:

●Should the opioid dose be reduced versus rotated to another opioid?

●Are opioids even a reasonable therapy to continue, or are there lower risk therapies?

●Does the patient have naloxone, or does it need to be prescribed?

●Does the patient need treatment or a referral for an opioid use disorder?

Interpreting baseline testing — Unexpected results (eg, absence of prescribed opioids, presence of non-prescribed opioids, presence of an illicit substance [ie, heroin, cocaine, or phencyclidine]) with an immunoassay screen (IAS) and/or confirmatory test prior to initiating opioid therapy may indicate a high risk of opioid misuse, abuse, or addiction. In most instances, an IAS should be followed up with confirmatory testing when attempting to identify the presence or absence of a prescribed or non-prescribed opioid.

However, an IAS positive for an illicit substance usually confirms the existence of a substance abuse problem and does not require follow-up with confirmatory testing. Since patients with chronic, nonmalignant pain who have active illicit substance abuse issues are poor candidates for chronic opioid therapy (COT), confirmatory testing results will not change the recommendation to avoid opioids. Instead, these patients should be referred to an addiction specialist or drug treatment program. (See "Use of opioids in the management of chronic non-cancer pain", section on 'Evaluation of risk prior to initiating therapy'.)

Interpreting testing during opioid therapy — The expected results of drug screening during COT depend on the prescribed opioid, its metabolites, and the test that is used, as shown in a table (table 1).

Expected results — In order to determine expected results, including the possibility of interference from drugs, foods, or other substances, the patient should be asked the following questions prior to requesting a urine sample:

●Which opioid are you taking, at what dose, with what frequency, and when did you last take it?

●Which, if any, additional prescribed, nonprescribed, or illicit substances (including marijuana or cannabis products) are you taking, at what dose, with what frequency, and when did you last take it?

●If you drink alcohol, how much do you drink, with what frequency, and when did you last have a drink?

The expected results for patients on COT include the presence of the prescribed drug or drug class (if IAS is used), and absence of non-prescribed opioids and illicit drugs. The expected result with confirmatory testing should include both the parent drug and its metabolites, within the limits of the threshold of detectability (table 2 and table 1). However, the presence of the expected opioid does not necessarily confirm compliance with COT, and interpretation may be complicated. As examples:

●A positive result will occur if the patient takes a dose at the right time to elicit a positive result, while diverting some or all of the remaining prescribed amount.

●If confirmatory testing shows an opioid and its metabolite, the patient may be appropriately taking the parent opioid, or could be taking both the parent drug and the metabolite. For example, hydrocodone is metabolized to hydromorphone. A high urine concentration of hydrocodone and a low concentration of hydromorphone would be consistent with appropriate hydrocodone therapy but does not rule out the possibility that the patient is also taking a small amount of hydromorphone. If confirmatory testing shows a low concentration of hydrocodone and a high concentration of hydromorphone, it is likely that the patient is taking both drugs (ie, the concentration of the metabolite is higher than the concentration of the parent drug).

Unexpected results — Unexpected results include the absence of the prescribed opioid and metabolites if tested, presence of a nonprescribed opioid or illicit substance, or an adulterated specimen. Unexpected results can occur because of noncompliance with COT, opioid misuse, or diversion, but may also represent appropriate but infrequent opioid use (which may explain absence of the drug), false positive results, or false negative results.

Urine drug test results by themselves should not be the basis for decisions to initiate, continue, or discontinue opioid therapy (see 'Drug testing in context' above). When we encounter unexpected results and are uncertain about the interpretation, we contact the laboratory technician to review plausible explanations for the findings, especially if the patient is taking other prescribed and/or over-the-counter medications. Once we know if there are plausible explanations, we discuss the test results with the patient before drawing conclusions or making changes in therapy. We discontinue or taper opioid therapy only if there is no plausible explanation for unexpected results. If opioids are discontinued, we provide supportive treatment to mitigate withdrawal symptoms, and if addiction treatment is needed, we refer to either inpatient or outpatient addiction services. (See "Opioid tapering for patients with chronic pain".)

The likely or possible explanations for unexpected results and suggested actions are discussed here. These recommendations apply to confirmatory testing results.

Drug test negative for prescribed opioid — Possible causes include taking the drug infrequently such that its identification falls below the threshold of detection, noncompliance with therapy, diversion of opioids, or rarely, false negative results.

●If a patient uses opioids infrequently such that detection is not possible due to limitations of the urine drug test, we ensure that the opioid quantity prescribed per month is consistent with the patient’s reported use, to minimize risk of stockpiling opioids. In this setting, diversion is difficult to prove.

●If the laboratory determines that opioid should be detectable with the patient’s daily dose and lab error is excluded, we review this with the patient for an explanation. If the patient’s explanation is not plausible, when diversion or theft is highly suspected, there may be an impulse to notify local law enforcement. This may be appropriate in some situations, but it may also violate Health Insurance Portability and Accountability Act (HIPAA) [17].

If the patient reports that their opioids were stolen, we require that they file and produce a copy of a police report of the theft before prescribing further opioids, though we may prescribe a one to three day supply to allow time to file the report. Patients who repeatedly report theft are poor candidates for ongoing opioid prescription.

Drug test positive for nonprescribed opioid — Unless the detected drug is a metabolite of the prescribed opioid, we discuss the presence of opioid misuse, discontinue prescribing opioids, and refer for treatment opioid use disorder. (See "Opioid use disorder: Treatment overview".)

A false positive result is possible (eg, after ingestion of poppy seeds). (See 'False positive results' below.)

Drug test positive for illicit substances — The patient may be an occasional user or addicted. We discontinue prescribing opioids and place a referral for treatment of substance use disorder.

Drug test positive for parent drug without metabolite — This may occur if the patient took the drug just prior to testing without time for metabolism, in patients with genetic deficiency in metabolic enzymes, or if the patient attempts to subvert the test by adding the opioid to urine. The results and clinical circumstances should be discussed with the testing laboratory. If we suspect the patient is adulterating the specimen by directly adding opioid to the urine, we perform random witnessed urine drug tests.

False results — False results can be the result of laboratory error (eg, mishandling or mislabeling the specimen, equipment malfunction). If the sample is still available in the laboratory, we first ask the laboratory to re-run the specimen and to verify patient identifiers on the specimen. However, there are multiple other possible causes of false results, most of which apply primarily to IAS testing.

False positive results — False positive IAS results can be due to cross reactivity with a number of common drugs, as shown in a table (table 1) [18]. Ingestion of poppy seeds deserves particular mention, as moderate consumption (eg, one teaspoon of commercially available poppy seed filling or one poppy seed bagel) can produce positive IAS results for opioids (depending on the threshold cutoff) and positive definitive testing for morphine and codeine for at least eight hours, and up to 24 hours, after ingestion [19-22]. (See "Testing for drugs of abuse (DOAs)", section on 'Opioids'.)

False negative results — False negatives with IAS can be the result of adulteration of the specimen, administration of negative interferent medications, or limitations of the particular test (eg, a urine drug concentration below the cutoff limit of the test). As an example, for patients who take short-acting opioids, the concentration may fall below the level of detection by the time the urine sample is provided. In patients who are genetically rapid metabolizers of opioids, the concentration of the prescribed opioid can fall below the level of detection, such that only metabolites may be present at the time of sampling (IAS does not test for metabolites).

Adulteration of urine samples is discussed separately. (See "Testing for drugs of abuse (DOAs)", section on 'How can DOA screens be subverted?'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic pain management".)

SUMMARY AND RECOMMENDATIONS

●Purpose of drug testing – Drug testing is part of risk stratification prior to starting opioid therapy and provides an objective measure of compliance with treatment. Drug testing can identify the use of drugs that may increase adverse events with opioid therapy, and may suggest misuse, diversion, or addiction. (See 'Rationale for testing' above.)

●Who and when to test

•We suggest urine drug testing for all patients prior to initiation of chronic opioid therapy (COT), and on a random basis during COT (Grade 2C). (See 'Who should be tested' above.)

•For patients on COT, we base the frequency of urine drug testing on the predicted level of risk of opioid misuse, and test low risk patients every 12 months, intermediate risk patients every six months, and high risk patients or those who take >120 morphine milligram equivalents per day of opioids every three months. (See 'How often should testing be performed' above.)

•In addition to routine testing, urine drug testing may be used to confirm compliance with COT for patients who are transferring care to a new clinician, prior to referring a patient to a pain specialist, when opioid rotation is considered for lack of efficacy, and for patients with behavioral signs suggestive of opioid misuse (eg, requests for early refills, doctor shopping, lost or stolen prescriptions, frequent emergency room visits). (See 'How often should testing be performed' above.)

●Test procedure

•Urine is the most commonly used biologic specimen for drug testing. (See 'Biologic sample' above.)

•Two classes of tests are used for urine drug testing: presumptive test (immunoassay screen [IAS]) and confirmatory tests (gas chromatography/mass spectrometry [GC/MS], liquid chromatography/mass spectrometry [LC-MS], or liquid chromatography/tandem mass spectrometry [LC-MS-MS]). Both presumptive and confirmatory testing should be used both for assessing baseline opioid use prior to initiating COT for patients with chronic pain and for monitoring during COT. (See 'Which tests should be performed' above.)

•The IAS is a qualitative test that reports the presence or absence of a drug or drug class. It is inexpensive and performed rapidly, but is subject to a high incidence of false positives and negatives. Mass spectrometry-based tests are quantitative tests that are more expensive and provide results in hours to days, but are subject to fewer false results and provide results for a wide range of drugs and their metabolites. (See 'Presumptive versus confirmatory testing' above.)

●Interpreting results

•The expected results of drug screening during COT depend on the prescribed opioid, its metabolites, the test that is used, and in some cases, other medications the patient takes. Within the limits of threshold of detectability, confirmatory testing should confirm the presence of the prescribed opioid and its metabolites (table 1). (See 'Expected results' above.)

•Unexpected results (eg, absence of the prescribed opioid and metabolites, presence of non-prescribed opioid or illicit substance) should be interpreted in conjunction with other clinical information prior to making changes in therapy. Unexpected results from baseline presumptive or confirmatory testing prior to initiating COT are conversation starters. Logical and benign explanations may be plausible (eg, interference from drugs, foods, or other substances; infrequent opioid use that falls below the threshold of detectability). However, patients who are suspected of opioid or substance misuse or addiction should be referred for evaluation and treatment. (See 'Unexpected results' above.)

●False results

•False positive results, which apply primarily to IAS testing, can be due to cross reactivity with drugs or foods (table 1). (See 'False positive results' above.)

•False negatives can be the result of adulteration of the specimen, interferent medications, or the limitations of the test. (See 'False negative results' above.)