Latest Review Date: November 2023

Category: Laboratory

POLICY:

In pain management programs for individuals with chronic non-cancer pain, qualitative (i.e., screening, presumptive) urine drug testing may be considered medically necessary up to 4 (four) times per year for:

• Baseline screening before initiating treatment or at the time treatment is initiated using a controlled substance when ALL of the following conditions are met:
  • An adequate clinical assessment of patient history and risk of substance abuse is performed;
  • Clinicians have knowledge of test interpretation;
  • There is a plan in place regarding how to use test findings clinically
• Subsequent monitoring of treatment using a controlled substance

In substance use disorder treatment programs, qualitative (i.e., screening, presumptive) urine drug testing may be considered medically necessary under the following conditions:

• Baseline screening before initiating treatment or at the time treatment is initiated, 1 (one) time per program entry, when ALL of the following conditions are met:
  • An adequate clinical assessment of patient history and risk of substance abuse is performed;
  • Clinicians have knowledge of test interpretation;
  • There is a plan in place regarding how to use test findings clinically
• Stabilization phase – targeted weekly qualitative screening for a maximum of 4 weeks
• Maintenance phase – targeted qualitative screening once every 1 to 3 months

Quantitative (i.e., confirmatory, definitive) urine drug testing, in pain management or substance use disorder treatment, may be considered medically necessary for coverage for up to three (3) confirmatory tests per qualitative urine drug screen when specifically requested by the treating physician and the test results are necessary for treatment planning under the following conditions:

• The result of the qualitative drug screen is positive
• The result of the qualitative drug screen is negative and the negative finding is unexpected or inconsistent with the patient’s current medication program *see documentation requirements

Urine drug testing in pain management or substance use disorder treatment is considered not medically necessary for coverage and is non-covered when the above criteria are not met, including but not limited to:

• routine qualitative urine drug testing (e.g., testing at every visit, without consideration for specific patient risk factors, current clinical presentation, current medication program or how the test findings will impact treatment options)
• quantitative (i.e., confirmatory, definitive) urine drug testing without qualitative (i.e., screening) urine drug testing
• the use of comprehensive confirmatory panels (not to be confused with a comprehensive screening panel)

In pain management and substance use disorder treatment, hair drug testing and oral fluid drug testing is considered investigational.

Testing for the same drug with blood and urine simultaneously is considered not medically necessary for coverage.

Drugs or drug classes which are being tested should reflect only those that are likely to be present based on the medical history, current clinical presentation and current medication program.

POLICY GUIDELINES:

Limits on testing are specific for the patient, not based on the provider.

A comprehensive screening panel should only be considered for initial testing when appropriate or when the patient’s behavior suggests the use of drugs not commonly identified on a basic screening panel. Medical documentation must support the justification for conducting a comprehensive screening panel. Subsequent testing should only be conducted for those substances identified on the patient’s initial profile.

Testing performed for quality control or to determine sample integrity is not a billable service.

Testing on other biologic specimens, e.g., blood, oral fluids, hair or sweat, to circumvent the criteria or intent of this policy is not covered.

Pain Management

The risk-level for an individual patient should include a global assessment of risk factors, and monitoring for the presence of aberrant behavior. Standardized risk assessment tools are available, such as the five-item opioid risk tool (ORT). Another screening instrument is the Screener and Opioid Assessment for Patients in Pain (SOAPP-R), a 24-item tool.

Aberrant behavior is defined by one or more of the following:

• multiple lost prescriptions,
• multiple requests for early refill,
• obtained controlled substances from multiple providers,
• unauthorized dose escalation,
• apparent intoxication during previous visits.

Opinions vary on the optimal frequency of urine drug screening to monitor patients on controlled substance therapy for chronic pain. Frequency of screening using a risk-based approach, as recommended by the Washington State Inter-Agency Guideline is as follows:

• Low risk by Opioid Risk Tool (ORT)*: Up to 1 (one) per year
• Moderate risk by ORT: Up to 2 (two) per year
• High risk or opioid dose >120 morphine milligram equivalents/day: Up to 3 (three) to 4 (four) per year
• Recent history of aberrant behavior: Each visit

*NOTE: The ORT is a copyrighted instrument.

*The Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain does not include specific screening frequencies but states that an individual patient’s risk for controlled substance misuse and addiction should be considered when deciding when to order a urine drug screen.

Substance Use Disorder

The 2017 consensus statement from the American Society of Addiction Medicine provides guidance on appropriate use of drug testing in substance use disorder.

Medical records should support the need for testing for the specific substance(s) of interest by documentation regarding the diagnosis, history and physical examination, and/or behavior of the individual patient. Medical records should also justify the test that is being used and describe how results of testing will guide medical decision-making

Stabilization phase: Most patients are expected to be on a stable dose of opioid medication within 4 (four) weeks of initiating treatment. In some complicated patients, the stabilization phase may last longer than 4 (four) weeks.

Maintenance phase: For most patients, targeted qualitative screening once every 1 (one) to 3 (three) months is sufficient during the maintenance phase of treatment. More frequent testing may be appropriate for some complicated patients.

DOCUMENTATION REQUIREMENTS:

• All documentation must be maintained in the member's medical records and available upon request.
• Every page of the record must be legible and include appropriate member identification information (e.g., complete name, dates of service). The record must include the identity of the physician or non-physician practitioner responsible for and providing the care of the member.
• The submitted medical record should clearly describe the service(s) performed.
• Medical record documentation (e.g., history and physical, progress notes) maintained by the ordering physician/treating physician must indicate the medical necessity for performing a qualitative drug test. All tests must be ordered in writing by the treating provider and all drugs/drug classes to be tested must be indicated in the order. In addition, the names of drugs prescribed, dosages and frequency and dates prescribed should also be clearly documented. Documentation must exist for how the results will drive the treatment options (e.g., an anticipated treatment plan based on confirmation of inconsistencies in the initial urine drug testing, to include implementation and follow-up procedures).
• When a confirmatory (laboratory-based specific identification) test is performed, the record must show that an inconsistent positive finding was noted on the qualitative testing *or that there was no available, commercially or otherwise, qualitative test to evaluate the presence of a semi-synthetic or synthetic controlled substance in a member who met the medical necessity criteria in this policy.
• If the provider of the service is other than the ordering/referring physician, that provider must maintain hard copy documentation of the lab results, along with copies of the ordering/referring physician's order for the qualitative drug test. The physician must include the clinical indication/medical necessity in the order for the qualitative drug test.
• Drugs or drug classes for which testing are performed should reflect only those likely to be present, based on the patient's medical history, current clinical presentation and current medication program. Drugs for which specimens are being tested must be indicated by the ordering health care provider in a written order.
• It is not considered reasonable or necessary to test for the same drug with both a blood and urine specimen simultaneously.

DESCRIPTION OF PROCEDURE OR SERVICE:

Patients in pain management programs and substance abuse treatment may misuse prescribed controlled substances and/or may use non-prescribed drugs. Thus, patients in these settings are often assessed before treatment and monitored while they are receiving treatment. Urine drug testing (UDT) is one monitoring strategy; it is most often used as part of a multifaceted intervention that includes other components such as patient contracts.

Pain Management

According to a 2012 evidence assessment by the American Society of Interventional Pain Physicians, approximately one-third of chronic pain individuals do not use opioids as prescribed or may abuse them. In 2016, the International Narcotics Control Board (INCB) reported that between 1999 and 2010, the number of deaths related to the use of prescription opioid painkillers increased five-fold among United States women and increased by a factor of 3.6 among United States men. As far as age groups, the INCB reported the rates of drug overdose deaths increased over the period from 1999 to 2017 for all age groups, however in 2017, rates were significantly higher for those 25 to 64 years of age (31.4 per 100,000) than for those age 65 and over (6.9 per 100,000). In the United States, drug overdose deaths increased approximately 15% from 2020 to 2021. Additionally, studies have found that a substantial proportion of chronic pain individuals inaccurately report nonadherence to prescribed medications and the use of illicit drugs.

A discussion of the controversies related to opioid therapy for the treatment of chronic non-cancer pain is beyond the scope of this review.

Substance Use Disorder

Substance use, abuse, and addiction involving numerous prescription and illicit drugs is also a serious social and medical problem. Addiction is a primary, chronic disease of brain reward, motivation, memory, and related circuitry and is manifested by the individual pathologic pursuit of reward and/or relief by substance use and other behaviors.

Monitoring Strategies

Various strategies are available to monitor pain management and substance use disorder treatment individuals, and multicomponent interventions are often used. Many settings require individuals to sign a contract before they are given a prescription for opioids. The contracts generally involve obtaining individuals’ agreement on behaviors they will engage in during the treatment period (e.g., taking medication as prescribed) and not engage in (e.g., selling prescribed medication and/or obtaining additional prescriptions from other physicians).

Confirming whether individuals follow these behavioral guidelines can be a challenge. Risk-assessment screening instruments, such as the Screener and Opioid Assessment for Patients with Pain, and the Opioid Risk Tool, can aid in the assessment of individuals’ risk for inappropriate drug use. In addition, the presence of “aberrant behaviors” can be used as a marker for individuals who are at high risk for deviating from treatment protocols. Aberrant behaviors include multiple lost prescriptions, obtaining prescriptions from other practitioners, and displaying evidence of acute intoxication during office visits.

Testing Matrices

Another strategy for monitoring patients is testing of biologic specimens for the presence or absence of drugs. Currently, urine is the most commonly used biologic substance. Advantages of urine drug testing (UDT) are that it is readily available and standardized techniques for detecting drugs in urine exist. Other biologic specimens (e.g., blood, oral fluids, hair, sweat) can also be tested. All matrices have advantages and disadvantages with respect to sensitivity and specificity over different time windows, time to obtain results, different susceptibility to sample tampering, and ease of collection.

Urine Drug Testing

There are 2 primary categories of UDT: presumptive testing (immunoassay) and confirmatory testing (specific drug identification).

Presumptive (Immunoassay) Testing

Immunoassay testing (also called presumptive testing or qualitative testing or screening) can be performed in a laboratory or at point-of-service. Immunoassay tests are based on the principle of competitive binding and use antibodies to detect a particular drug or drug metabolite in a urine sample. With competitive binding, a fixed amount of a labeled drug is added to the urine sample, and the drug or metabolite in the sample competes with the labeled drug for binding sites on the antibody. The amount of labeled antigen that binds with the antibody is inversely proportional to the amount of the drug or metabolite in the sample.

Immunoassay tests vary in the type of compounds they can detect. Some detect specific drugs and may fail to recognize similarly structured drugs within the same class. Other immunoassays identify only classes of drugs and thus results cannot be used to determine which drug a patient is taking. For example, a positive result of an opiate immunoassay can be due to morphine or hydromorphone. The degree of cross reactivity (i.e. an antibody's reactivity with a compound other than the target of the test) varies widely among immunoassays.

Immunoassay findings are generally reported qualitatively as either positive (drug level above a prespecified threshold) or negative (drug level below a prespecified threshold). Raising or lowering the threshold thus changes the proportion of positive tests. A negative test is interpreted as a level below the threshold and does not necessarily mean that the drug or metabolite is absent.

Immunoassays generally have a rapid turnaround time, to within minutes for on-site tests, and one to four hours for laboratory-based tests.

Confirmatory (Specific Drug Identification)

Confirmatory tests are always performed in a laboratory. Gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) are considered to be the criterion standard for confirmatory testing. These techniques involve using GC or LC to separate the analytes in a specimen and for MS to identify the specific molecular structures of the drug and its metabolites. The tests are able to quantify the amount of drug or metabolite present in the urine sample. Definitive quantitative 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 immunoassays. Results are reported as the specific levels of substances detected in the urine. GC/MS and LC/MS generally require the specification of the drug or drugs to be identified. Alternatively, "broad-spectrum screens" can be conducted. There is a several-day turnaround time for GC/MS and LC/MS testing.

An issue with both types of UDT is the possibility of sample tampering to mask the presence of illegal drugs. A variety of products and techniques are available to patients and can be as simple as drinking a large amount of water to dilute the sample. There are also commercial dilution and cleaning products, additives, and urine substitutes. Some of these techniques can be detected by visual inspection of the sample (e.g., color) or by on-site testing of sample characteristics including urine temperature, creatinine concentration, and specific gravity.

The correct interpretation of UDT results is very important. Knowledge of drug metabolites is essential for accurate interpretation. Accurate interpretation of test results also requires knowledge of the drug manufacturing process. For example, due to manufacturing impurities, a small amount of hydrocodone may be present in urine samples from patients prescribed oxycodone. Thus, it would be acceptable to detect a small amount of hydrocodone if high amounts of oxycodone were also present.

There are various approaches to incorporating UDT into pain management and substance use disorder treatment settings. Most commonly, patients undergo urine drug screening before beginning treatment to verify current drug use. Some clinicians believe that UDT should be routinely used to establish baseline information about substance use, but the optimal frequency and interval of testing remains uncertain. A universal approach to screening may uncover more inappropriate use and may reduce patients' sense that testing is being performed due to a lack of trust. However, routine universal screening may place an unnecessary burden on the health care system and on the doctor-patient relationship. An alternative approach is selective testing of patients who are judged to be at increased risk for drug misuse.

Existing protocols vary for the use of presumptive versus definitive tests. Some involve conducting routine confirmation of positive presumptive tests with definitive quantitative testing. Others use selective confirmation of positive presumptive tests, such as when an unexpected immunoassay result is not adequately explained by the patient. There is also a mixed approach, with routine confirmation of presumptive tests only for drugs with poor-performing immunoassays.

Full informed consent is a requirement before UDT. Patients should be informed of the specific drug testing protocol before treatment and should provide written agreement with the plan for monitoring. As stated in a joint U.S. Veterans Affairs/Department of Defense guideline, patients' refusal to consent to urine testing should be considered a factor in the overall assessment of patients' ability to adhere to treatment.

Oral Fluid Drug Testing

Oral fluid (liquid samples obtained from the oral cavity) can potentially be used to test for drug use. Oral fluid contains secretions from several different sources, including secretions from the three pairs of major salivary glands (parotid, sublingual, and submandibular), secretions from the minor salivary glands, oro-nasopharyngeal secretions, and cellular debris. The mixture of fluids obtained varies depending on the collection method used (e.g., spitting, suctioning, draining, or collection on some type of absorbent material). Drug concentrations can be affected by the collection method and by the use of saliva stimulation methods. Several collection devices are commercially available in the U.S., and they generally involve collection on an absorbent material, such as foam pads; pads are then placed in a container with a stabilizing buffer solution. Drug concentrations may also depend on how the oral fluid is recovered from the collection device (e.g., by centrifugation or by applying pressure). Drug concentrations may not reflect blood levels because of residual amounts of a drug (specifically those ingested or smoked) remaining in the oral cavity after recent use.

Analysis techniques must be able to detect drugs present in low concentration and in a small volume of fluid (often <1 mL). Immunoassay techniques are available to detect drugs in oral fluid; they require a small sample volume (»25 μL). Immunoassays tend to be relatively sensitive techniques, but they have low specificity. Confirmation analysis is generally performed using MS-based methods. In recent years, advancements have been made in MS analysis techniques, including the development of multianalyte LC/MS methods.

A practical advantage of oral fluid collection compared with urine collection is that samples can be obtained under the direct supervision and without loss of privacy. It has been used in situations where urine sampling is impractical, such as testing drivers during traffic stops. Oral fluid sampling also has the potential to be useful in pain management or substance use disorder treatment settings, particularly when substitution or tampering with urine drug samples is suspected.

Hair Testing

Hair is composed of protein that traps chemicals in the blood at the time the hair develops in the follicle. Hair on the human head grows at approximately 0.5 inches per month. Thus, a 1.5-inch hair sample could be used to detect drug use during the previous 90 days. Potential advantages of hair as a drug testing source include noninvasive collection; ease of collection, storage, and shipping; availability of samples for testing and retesting; and difficulty in tampering. Potential disadvantages include: recent drug use (i.e., within the past seven days) cannot be detected; difficulty in detecting very light drug use (e.g., a single episode); and drug levels can be affected by environmental exposure. In addition, variation in hair texture as well as cosmetic hair treatments can affect drug incorporation into hair and the accuracy of drug tests on hair samples. As with other types of samples, hair can be initially tested using immunoassay techniques, with confirmation by MS-based methods. Hair testing has been used in a variety of situations where detection of drug use during the previous several months is desired (e.g., pre-employment screening, post-drug-treatment verification of relapse).

DEFINITIONS:

Aberrant Behavior: Behaviors that are outside the boundaries of the agreed-upon treatment plan and may constitute aberrant substance use behavior including, but is not limited to, lost prescriptions, repeated requests for early refills, prescriptions from multiple providers, unauthorized dose escalation, and apparent intoxication.

Compliance (laboratory-based specific drug identification) Testing: Assessment of a patient’s adherence to a treatment plan, typically looking for the presence of prescribed medications.

Enzyme-Linked Immune Assay (EIA): A laboratory technology using drug-class specific antibodies to screen for presence of drugs: this technology is used for screening.

Gas Chromatography/Mass Spectrometry (GC/MS): A laboratory technology used to identify the presence of specific drugs or their metabolites when EIA test screening is positive for unexpected illicit or non-prescribed licit drugs and/or negative for expected drugs.

High-Performance Liquid chromatography (HPLC): A laboratory technology used to identify the presence of specific drugs or their metabolites when EIA test screening is positive for unexpected illicit or non-prescribed licit drugs and/or negative for expected drugs.

Liquid Chromatography/Mass Spectrometry (LC/MS): Liquid chromatography is used to separate the different components in a specimen, and mass spectrometry is used to specifically identify the components of the specimen.

NOTE: This policy does not address the use of UDT in the following circumstances:

• Emergency department testing, including for the detection of potential overdose or poisoning;
• Federally regulated testing;
• Non-forensic testing for commercial drivers licensing or any other job-related testing;
• State/legally mandated drug testing.

KEY POINTS:

The most recent evidence literature review was performed through November 10, 2023.

Summary of Evidence

Guidelines with evidence reviews of published peer-reviewed scientific literature suggests that the evidence of benefit on health outcomes for drug testing for both patients in chronic pain using opioids and patients with substance use disorder is limited and usually confounded with drug testing as part of a multifaceted intervention of risk mitigation or contingency management. Little research exists on the optimal frequency of testing. There are gaps in the literature regarding testing limits. There is also no clear evidence in the literature regarding the most effective frequency of testing.

For individuals who have chronic pain treated with opioids who receive drug testing, as well as for individuals who have a drug addiction and are involved in substance use disorder treatment and receive drug testing, there is limited peer-reviewed scientific literature to guide drug testing strategies. No RCTs evaluating clinical utility were identified. Several nonrandomized comparative studies have provided inconclusive evidence. There exists a paucity of scientific evidence available about diagnostic accuracy. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have a drug addiction and are in substance abuse treatment who receive UDT, the evidence includes two RCTs. No studies were identified that evaluated the accuracy of UDT compared with a valid reference standard in individuals undergoing substance abuse treatment. One RCT focused on the specific situation of testing to determine eligibility for take-home methadone. The second RCT found that UDT identified drug use in a substantial number of patients who denied using; the impact on treatment success was not addressed. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have chronic pain treated with opioids or with a drug addiction in substance abuse treatment who receive oral fluid drug testing, the evidence includes diagnostic accuracy studies using UDT as the reference standard. The limited number of studies on diagnostic accuracy of oral fluid testing compared with urine testing had variable findings. No studies were identified on the impact of oral fluid testing on health outcomes compared with UDT or no drug testing. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have chronic pain treated with opioids or with a drug addiction in substance abuse treatment who receive hair/follicle drug testing, the evidence includes one diagnostic accuracy study in the setting of psychiatric treatment. Hair/follicle testing cannot detect recent drug use (i.e., in the past few days) and thus has limited applicability to pain management or substance abuse treatment settings except, perhaps, for initial intake. There are no studies comparing the diagnostic accuracy of hair testing to urine testing in either of these settings. One relatively small study tested the hair and urine of known drug users recruited from a psychiatric clinic. The study looked for drug use over the past several months rather than the shorter timeframe generally needed in pain management or drug treatment settings. No studies were identified on the clinical utility of hair testing in pain management or substance abuse treatment. The evidence is insufficient to determine the effects of the technology on health outcomes.

Practice Guidelines and Position Statements

Pain Management

American Academy of Pain Medicine

In 2018, the American Academy of Pain Medicine published consensus recommendations on urine drug monitoring in patients receiving opioid for chronic pain. The Society recommended definitive testing at baseline for patients prescribed opioids for chronic pain unless presumptive testing is required by institutional or payer policy. The Society also recommended that the choice of substances to be analyzed should be based on considerations that are specific to each patient and related to illicit drug availability. Baseline risk assessment for aberrant medication-taking behavior, misuse, and opioid use disorder should be conducted using patient history, validated risk assessment tools, prescription drug monitoring program data, previous urine drug monitoring results, and evaluation of behaviors indicative of risk. The recommended frequency of urine drug monitoring was based on risk assessment: At least annually for patients at low risk, two or more times per year for those at moderate risk, and three or more times per year for those at high risk.

American Society of Interventional Pain Physicians

In 2017, the American Society of Interventional Pain Physicians issued guidelines for responsible, safe, and effective opioid prescribing for chronic non-cancer pain. The guidelines included the following recommendations on UDT (see Table 1).

Table 1. Recommendations on Urine Drug Testing for Chronic Non-Cancer Pain

Recommendation	LOE	SOE
"Comprehensive assessment and documentation is recommended before initiating opioid therapy, with documentation of comprehensive history, general medical condition, psychosocial history, psychiatric status, and substance use history."	I	Strong
"Screening for opioid abuse is recommended, as it will potentially identify opioid abusers and reduce opioid abuse."	II-III	Moderate
"Presumptive UDT is implemented at initiation of opioid therapy, along with subsequent use as adherence monitoring, using in-office point of service testing, followed by confirmation with chromatography/mass spectrometry for accuracy in select cases, to identify patients who are not compliant or abusing prescription drugs or illicit drugs. UDT may decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy."	III	Moderate

LOE: level of evidence; SOE: strength of evidence; UDT: urine drug testing.

Centers for Disease Control and Prevention

The CDC Clinical Practice Guidelines for Prescribing Opioids for Pain – United States, 2016 published the following recommendations:

When prescribing opioids for chronic pain, clinicians should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs (recommendation category: B, evidence type: 4).

While experts agreed that clinicians should use urine drug testing before initiating opioid therapy for chronic pain, they disagreed on how frequently urine drug testing should be conducted during long-term opioid therapy. Most experts agreed that urine drug testing at least annually for all patients was reasonable.

In 2022, the guidelines were addressed to update the following four areas: 1) determining whether or not to initiate opioids for pain, 2) selecting opioids and determining opioid dosages, 3) deciding duration of initial opioid prescription and conducting follow-up, and 4) assessing risk and addressing potential harms of opioid use. No changes were made to urine drug testing frequency recommendations.

Department of Veterans Affairs and Department of Defense

In 2022, the Department of Veterans Affairs and Department of Defense updated clinical practice guidelines for managing opioid therapy for the treatment of chronic pain. The recommendations on risk mitigation to prescribed opioids include obtaining a UDT (with individual consent) before initiating opioid therapy, and then randomly at a follow-up to confirm appropriate use. Other strategies recommended include clinical assessment, such as random pill counts and use of prescription drug monitoring programs.

The guidelines included the following specific recommendations on UDT as part of risk mitigation:

"We recommend implementing risk mitigation strategies upon initiation of long-term opioid therapy, starting with an informed consent conversation covering the risks and benefits of opioid therapy as well as alternative therapies. The strategies and their frequency should be commensurate with risk factors and include:

• Ongoing, random urine drug testing (including appropriate confirmatory testing)
• Checking state prescription drug monitoring programs
• Monitoring for overdose potential and suicidality
• Providing overdose education
• Prescribing of naloxone rescue and accompanying education"

The guideline states that gaining consent is required prior to a UDT; if a patient declines consent, “providers should factor that declination into their consideration about whether it is safe to continue opioids. Urine drug testing is required if long-term opioids are to be initiated or continued.”

Washington State Agency Medical Directors' Group

In 2015, the Washington State Agency Medical Directors’ Group updated its interagency guidelines on opioid dosing for chronic non-cancer pain. The guidelines included recommendations on UDT. Recommendations on testing frequency differed depending on the patient risk of opioid addiction and opioid dosage, as listed below:

• Low risk: Once per year
• Moderate risk: Twice per year
• High risk or opioid dose over 120 mg MED/d: 3 (three)-4 (four) times per year
• Aberrant behavior: Each visit.

No pain management guidelines were identified that had recommendations on oral fluid or hair testing.

Substance Use Disorder Treatment

American Society of Addiction Medicine

The American Society of Addiction Medicine (ASAM) has published several documents on drug testing: a public policy statement (2010), a white paper (2013), which provided background on the science and current practices of drug testing, and guidelines (2017) on the effective use of drug testing.

The ASAM’s public policy statement asserts that: “Urine drug testing is a key diagnostic and therapeutic tool that is useful for individual care and in monitoring of the ongoing status of a person who has been treated for addiction. As such, it is a part of medical care, and should not face undue restrictions.” The ASAM recommended drug testing where medically appropriate in clinical diagnostic settings and clinical treatment settings. The term “drug testing” in this document was a broad term that included urine or other body fluids or tissues.

The ASAM White Paper concluded that “The most important challenge in drug testing today is not the identification of every drug that we are technologically capable of detecting, but to do medically necessary and accurate testing for those drugs that are most likely to impact clinical outcomes.” The paper acknowledged that more specific guidance on drug testing was needed, which led to the development of the 2017 guidelines, described below.

The 2017 ASAM guidance on appropriate drug testing in clinical addiction medicine advises health care providers that before choosing the type of drug test, they should first identify the questions they are seeking to answer and be aware of the benefits and limitations of the various drug tests. The following table summarizes the characteristics of urine, oral fluid, and hair drug tests that may inform the decision of what type of drug test to use.

The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update States that given the relative paucity of research directly examining drug testing in SUD populations and settings, the review was not limited to randomized controlled trials or similarly rigorous methodologies; it included cohort studies and case studies. The ASAM acknowledges that there is very limited empirical evidence about whether the use of drug testing in addiction treatment settings leads to improved clinical outcomes. The ASAM makes the point that providers should understand that increasing the frequency of testing increases the likelihood of detection of substance use, but there is insufficient evidence that increasing the frequency of drug testing has an effect on substance use itself.

Table 2. Summary of Drug Testing Characteristics

Characteristics	Urine	Oral Fluid	Hair
General detection period	Hours to days	Minutes to hours	Weeks to months
Point-of-care testing	Yes	Yes	No
Primarily detects	Drug metabolite	Parent drug compound	Parent drug compound
Best use in treatment setting	Intermediate-term detection in ongoing treatment	Short-term detection in ongoing treatment	Long-term monitoring, 3-month history
Ease of collection	Requires restroom	Easily collected	Easily collected
Resistance to tampering	Low	High, with some uncertainty	High when chemically untreated
Retesting same sample	Possible	Difficult	Easy

Adapted from Jarvis et al (2017).

U.S. Preventive Services Task Force Recommendations

Not applicable

KEY WORDS:

Urine drug testing, UDT, chronic pain, substance abuse

APPROVED BY GOVERNING BODIES:

The Food and Drug Administration (FDA) regulates drugs of abuse tests that are sold to consumers or health care professionals in the United States. The FDA reviews many of these tests before they are sold for use. In its review, the FDA evaluates the design and performance of tests and sample collection systems to help ensure that they produce accurate results. The FDA does not review drugs of abuse tests intended for employment and insurance testing provided they include a statement in their labeling that the device is intended solely for use in employment and insurance testing. The FDA review does not include test systems intended for federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration, the Department of Transportation, and the U.S. military.)

The FDA has cleared assays for urine testing of drugs of abuse as well as oral fluid specimen collection devices and assays for analysis of oral fluid for drugs of abuse through the 510(k) regulatory pathways. Several collection devices are commercially available in the United States, and they generally involve collection on an absorbent material, such as foam pads; pads are then placed in a container with a stabilizing buffer solution. Immunoassays of urine specimens have previously been cleared by the FDA and are used as the predicates for the oral fluid immunoassays.

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Testing with GC/MS and some immunoassays are performed in laboratory settings. Laboratories that offer laboratory-developed tests must be licensed by CLIA for high-complexity testing.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP: Special benefit consideration may apply. Refer to member’s benefit plan. 

CURRENT CODING:

CPT Codes:

80305	Drug test(s), presumptive, any number of drug classes, any number of devices or procedures capable of being read by direct optical observation only (e.g., utilizing immunoassay [e.g. dipsticks, cups, cards, cartridges]) includes sample validation when performed, per date of service.
80306	Drug test(s), presumptive, any number of drug classes, any number of devices or procedures read by instrument assisted direct optical observation (e.g., utilizing immunoassay [e.g. dipsticks, cups, cards, cartridges]), includes sample validation when performed, per date of service.
80307	Drug test(s), presumptive, any number of drug classes, any number of devices or procedures, by instrument chemistry analyzers (e.g., utilizing immunoassay [e.g., EIA, ELISA, EMIT, FPIA, IA, KIMS, RIA]), chromatography (e.g., GC, HPLC), and mass spectrometry either with or without chromatography, (e.g., DART, DESI, GC-MS, GC-MS/MS, LC-MS, LC-MS/MS, LDTD, MALDI, TOF) includes sample validation when performed, per date of service.
80320-80377	Definitive drug testing code range Use of these codes are not reimbursed separately and the appropriate corresponding G code should be billed for quantitative/confirmatory (definitive) testing.

HCPCS Codes:

G0480	Drug test(s), definitive, utilizing drug identification methods able to identify individual drugs and distinguish between structural isomers (but not necessarily stereoisomers), including, but not limited to GC/MS (any type, single or tandem) and LC/MS (any type, single or tandem and excluding immunoassays (e.g., IA, EIA, ELISA, EMIT, FPIA) and enzymatic methods (e.g., alcohol dehydrogenase)), stable isotope or other universally recognized internal standards in all samples (e.g., to control for matrix effects, interferences and variations in signal strength), and method or drug-specific calibration and matrix-matched quality control material (e.g., to control for instrument variations and mass spectral drift); qualitative or quantitative, all sources, includes specimen validity testing, per day; 1-7 drug class(es), including metabolite(s) if performed.
G0481	Drug test(s), definitive, utilizing drug identification methods able to identify individual drugs and distinguish between structural isomers (but not necessarily stereoisomers), including, but not limited to GC/MS (any type, single or tandem) and LC/MS (any type, single or tandem and excluding immunoassays (e.g., IA, EIA, ELISA, EMIT, FPIA) and enzymatic methods (e.g., alcohol dehydrogenase)), stable isotope or other universally recognized internal standards in all samples (e.g., to control for matrix effects, interferences and variations in signal strength), and method or drug-specific calibration and matrix-matched quality control material (e.g., to control for instrument variations and mass spectral drift); qualitative or quantitative, all sources, includes specimen validity testing, per day; 8-14 drug class(es), including metabolite(s) if performed.
G0482	Drug test(s), definitive, utilizing drug identification methods able to identify individual drugs and distinguish between structural isomers (but not necessarily stereoisomers), including, but not limited to GC/MS (any type, single or tandem) and LC/MS (any type, single or tandem and excluding immunoassays (e.g., IA, EIA, ELISA, EMIT, FPIA) and enzymatic methods (e.g., alcohol dehydrogenase)), stable isotope or other universally recognized internal standards in all samples (e.g., to control for matrix effects, interferences and variations in signal strength), and method or drug-specific calibration and matrix-matched quality control material (e.g., to control for instrument variations and mass spectral drift); qualitative or quantitative, all sources, includes specimen validity testing, per day; 15-21 drug class(es), including metabolite(s) if performed.
G0483	Drug test(s), definitive, utilizing drug identification methods able to identify individual drugs and distinguish between structural isomers (but not necessarily stereoisomers), including, but not limited to GC/MS (any type, single or tandem) and LC/MS (any type, single or tandem and excluding immunoassays (e.g., IA, EIA, ELISA, EMIT, FPIA) and enzymatic methods (e.g., alcohol dehydrogenase)), stable isotope or other universally recognized internal standards in all samples (e.g., to control for matrix effects, interferences and variations in signal strength), and method or drug-specific calibration and matrix-matched quality control material (e.g., to control for instrument variations and mass spectral drift); qualitative or quantitative, all sources, includes specimen validity testing, per day; 22 or more drug class(es), including metabolite(s) if performed.
G0659	Drug test(s), definitive, utilizing drug identification methods able to identify individual drugs and distinguish between structural isomers (but not necessarily stereoisomers), including but not limited to GC/MS (any type, single or tandem) and LC/MS (any type, single or tandem), excluding immunoassays (e.g., IA, EIA, ELISA, EMIT, FPIA) and enzymatic methods (e.g., alcohol dehydrogenase), performed without method or drug-specific calibration, without matrix-matched quality control material, or without use of stable isotope or other universally recognized internal standard(s) for each drug, drug metabolite or drug class per specimen; qualitative or quantitative, all sources, includes specimen validity testing, per day, any number of drug classes

REFERENCES:

1. American Society of Addiction Medicine (ASAM). Consensus Statement: Appropriate Use of Drug Testing in Clinical Addiction Medicine. 2017;https://journals.lww.com/journaladdictionmedicine/Fulltext/2017/06000/Appropriate_Use_of_Drug_Testing_in_Clinical.1.aspx.
2. American Society of Addiction Medicine (ASAM). Drug Testing: A White Paper of the American Society of Addiction Medicine (ASAM). 2013; https://www.cmm.com.au/files/uploads/resources/20170817102442drug-testing-a-white-paper-by-asam.pdf.
3. American Society of Addiction Medicine (ASAM). Public Policy Statement On Drug Testing as a Component of Addiction Treatment and Monitoring Programs and in other Clinical Settings. 2010; https://www.asam.org/docs/default-source/public-policy-statements/1drug-testing---clinical-10-10.pdf.
4. American Society of Addiction Medicine. The ASAM national practice guideline for the treatment of opioid use disorder: 2020 focused update. J Addict Med 2020; 14(Suppl 1):1–91.
5. Argoff CE, Alford DP, Fudin J, et al. Rational Urine Drug Monitoring in Patients Receiving Opioids for Chronic Pain: Consensus Recommendations. Pain Med. Jan 01 2018; 19(1): 97-117.
6. Bertholf RL, Sharma R, Reisfield GM. Predictive value of positive drug screening results in an urban outpatient population. J Anal Toxicol. Nov 2016; 40 (9):726-731.
7. Brennan PL, Del Re AC, Henderson PT, et al. Healthcare system-wide implementation of opioid-safety guideline recommendations: the case of urine drug screening and opioid-patient suicide- and overdose-related events in the Veterans Health Administration. Transl Behav Med. Dec 2016; 6(4):605-612.
8. Chou R, Fanciullo GJ, Fine PG et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain 2009; 10(2):113-30.
9. Christo PJ, Manchikanti L, Ruan X, et al. Urine Drug Testing In Chronic Pain: Comprehensive Review. Pain Physician 2011; 14:123-143 ISSN 1533-3159.
10. Chronic Opioid Therapy (COT) Safety Guideline For Patients With Chronic Non-Cancer Pain, Copyright 2010–2012 Group Health Cooperative.
11. Conermann T, Gosalia AR, Kabazie AJ, et al. Utility of oral fluid in compliance monitoring of opioid medications. Pain Physician. Jan-Feb 2014; 17(1):63-70.
12. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep 2016; 65(No. RR-1):1–49.
13. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022. MMWR Recomm Rep 2022; 71(No. RR-3):1–95. 
14. Dupouy J, Memier V, Catala H, et al. Does urine drug abuse screening help for managing patients? A systematic review. Drug Alcohol Depend. Mar 1 2014; 136:11-20.
15. Esub-Mg Study Group. Study protocol of the ESUB-MG cluster randomized trial: a pragmatic trial assessing the implementation of urine drug screening in general practice for buprenorphine maintained patients. BMC Fam Pract. Mar 01 2016; 17:24.
16. Hegmann KT, Weiss MS, Bowden K, et al. ACOEM practice guidelines: opioids for treatment of acute, subacute, chronic, and postoperative pain. J Occup Environ Med. Dec 2014; 56 (12):e143-159.
17. Heltsley R, Depriest A, Black DL, et al. Oral fluid drug testing of chronic pain patients. II. Comparison of paired oral fluid and urine specimens. J Anal Toxicol. Mar 2012; 36(2):75-80.
18. International Narcotics Control Board (INCB). Report of the International Narcotics Control Board for 2016. 2016; https://www.incb.org/documents/Publications/AnnualReports/AR2016/English/AR2016_E_ebook.pdf.
19. International Narcotics Control Board (INCB). Report of the International Narcotics Control Board for 2020. 2020; https://www.incb.org/documents/Publications/AnnualReports/AR2020/Annual_Report/E_INCB_2020_1_eng.pdf.
20. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
21. Jarvis M, Williams J, Hurford M, et al. Appropriate use of drug testing in clinical addiction medicine. J Addict Med. May/Jun 2017; 11(3):163-173.
22. Johnson-Davis KL, Sadler AJ, Genzen JR. A retrospective analysis of urine drugs of abuse immunoassay true positive rates at a national reference laboratory. J Anal Toxicol. Mar 2016; 40 (2):97-107.
23. Krishnamurthy P, Ranganathan G, Williams C, et al. Impact of urine drug screening on no shows and dropouts among chronic pain patients: a propensity-matched cohort study. Pain Physician. Feb 2016; 19(2):89-100.
24. Manchikanti L, Abdi S, Atluri S et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part I--evidence assessment. Pain Physician 2012; 15(3 Suppl):S1-65.
25. Manchikanti L, Abdi S, Atluri S et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance. Pain Physician 2012; 15(3 Suppl):S67-116.
26. Manchikanti L, Atluri S, Trescot AM et al. Monitoring opioid adherence in chronic pain patients: tools, techniques, and utility. Pain Physician 2008; 11(2 Suppl):S155-80.
27. Manchikanti L, Kaye AM, Knezevic NN, et al. Responsible, safe, and effective prescription of opioids for chronic non-cancer pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines. Pain Physician. Feb 2017; 20 (2S):S3-S92.
28. Manchikanti L, Malla Y, Wargo BW et al. Comparative evaluation of the accuracy of immunoassay with liquid chromatography tandem mass spectrometry (LC/MS/MS) of urine drug testing (UDT) opioids and illicit drugs in chronic pain patients. Pain Physician 2011; 14(2):175-87.
29. Manchikanti L, Manchukonda R, Damron KS et al. Does adherence monitoring reduce controlled substance abuse in chronic pain patients? Pain Physician 2006; 9(1):57-60.
30. McDonell MG, Graves MC, West, II, et al. Utility of point-of-care urine drug tests in the treatment of primary care patients with drug use disorders. J Addict Med. May-Jun 2016; 10(3):196-201.
31. Moeller KE, Lee KC, Kissack JC. Urine Drug Screening: A Practical Guide for Clinicians. Mayo Clinic Proceedings, 2008 83(1): pp 66–76.
32. Musshoff F, Driever F, Lachenmeier K, et al. Results of hair analyses for drugs of abuse and comparison with self-reports and urine tests. Forensic Sci Int. Jan 27 2006; 156(2-3):118-123.
33. Nuckols TK, Anderson L, Popescu I, et al. Opioid prescribing: a systematic review and critical appraisal of guidelines for chronic pain. Ann Intern Med. Jan 7 2014; 160(1):38-47.
34. Pesce A, Rosenthal M, West R, et al. An Evaluation of the Diagnostic Accuracy of Liquid Chromatography-Tandem Mass Spectrometry Versus Immunoassay Drug Testing in Pain Patients. Pain Physician 2010; 13:273-281.
35. Protocol for Accuracy of Point of Care (POC) or In-Office Urine Drug Testing (Immunoassay) in Chronic Pain Patients: A Prospective Analysis of Immunoassay and Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS). Pain Physician 2010; 13:E1-E22.
36. Snyder ML, Fantz CR, Melanson S. Immunoassay-based drug tests are inadequately sensitive for medication compliance monitoring in patients treated for chronic pain. Pain Physician. Feb 2017; 20 (2S):SE1-SE9.
37. Stammet MM, Spradley SS. Evaluation of treatment changes following electronic consultation to a pharmacist-run urine drug testing service in a veterans healthcare system. J Opioid Manag. Nov/Dec 2016; 12(6):389-395.
38. Standridge JB, Adams SM, Zotos AP. Urine Drug Screening: A valuable Office Procedure. American Family Physician 2010; 81(5):635-640.
39. Starrels JL, Becker WC, Alford DP et al. Systematic review: treatment agreements and urine drug testing to reduce opioid misuse in patients with chronic pain. Ann Intern Med 2010; 152(11):712-20.
40. Tenore PL. Advanced Urine Toxicology Testing. Journal of Addictive Diseases 2010; 29:436-448.
41. Veteran's Affairs (VA) and Department of Defense (DoD) Opioid Therapy for Chronic Pain Work Group. Clinical practice guideline for the use of opioids in the management of chronic pain. 2022; https://www.healthquality.va.gov/guidelines/Pain/cot/VADoDOpioidsCPG.pdf.
42. Vindenes V, Yttredal B, Oiestad EL, et al. Oral fluid is a viable alternative for monitoring drug abuse: detection of drugs in oral fluid by liquid chromatography-tandem mass spectrometry and comparison to the results from urine samples from patients treated with Methadone or Buprenorphine. J Anal Toxicol. Jan 2011; 35(1):32-39.
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POLICY HISTORY:

Medical Policy Group, February 2015(1): New policy

Medical Policy Administration Committee, February 2015

Available for comment January 28 through March 15, 2015

Medical Policy Group, February 2015 (1): Added coverage criteria for qualitative confirmatory urine drug testing along with corresponding HCPCS code G6058 during draft period; policy remains available for comment through March 15, 2015

Medical Policy Group, March 2015 (1): Added coverage criteria for quantitative confirmatory testing along with corresponding applicable HCPCS codes G6030-G6058

Medical Policy Group, December 2015 (1): 2016 Annual Coding Update. Added HCPCS codes G0477-G0483 to current coding section. Moved HCPCS codes G0431, G0434 and G6030-G6058 from current coding section to previous coding section.

Medical Policy Group, February 2016 (1): Added coverage criteria for substance abuse treatment patients, added investigational statement around hair and oral fluid drug testing, changed title to read Drug Testing; updated Key Points, Key Words, Governing Bodies and References.

Medical Policy Administration Committee, February 2016

Available for comment February 19 through April 3, 2016

Medical Policy Group, December 2016 (1): 2016 Updates to Key Points & References; no change in intent of policy statement; 2017 Annual Coding Update, added CPT codes 80305, 80306 and 80307 and HCPCS code G0659 to current coding section. Moved HCPCS codes G0477, G0478 and G0479 from current coding section to previous coding section.

Medical Policy Group, December 2017. Annual Coding Update 2018. Updated verbiage for revised codes 80305 and 80306.

Medical Policy Group, October 2019 (9): Updates to Description, Key Points, References. Removed policy section effective for dates of service March 27, 2015 through April 3, 2016. Removed “effective for dates of service on or after April 4, 2016” verbiage from policy section. Removed previous coding section. No changes to intent of policy statement.

Medical Policy Group, November 2019 (9): Updates to Description, Key Points, References. No changes to policy statement.

Medical Policy Group, November 2020 (9): 2020 Updates to Description, Key Points, References. No changes to policy statement.

Medical Policy Group, December 2021 (9): 2021 Updates to Description, Key Points, References. Policy statement updated to remove “not medically necessary,” no change to policy intent. Removed the following sentence from the current coding section: “Effective for dates of service on or after January 1, 2017: The Plan has adopted the revised coding position articulated by CMS. Use of CPT codes 80320-80377 are not reimbursed separately and the appropriate corresponding G code (G0480-G0483, G0659) should be billed for quantitative/confirmatory (definitive) testing.” Placed codes 80320-80377 into current coding table. No changes to intent of coding.

Medical Policy Group, December 2022 (9): 2022 Updates to Description, Key Points, References. Minor editorial changes made to policy statement: changed word “patient” to “individual”; changed word "substance abuse" to substance use disorder"; added descriptor “presumptive” to qualitative; added descriptor “definitive” to quantitative; no changes to policy intent of coverage.

Medical Policy Group, November 2023 (5): Reviewed by consensus. Updates to Description, Key Points; Practice Guidelines and Position Statements, Benefit Application, and References. There is no new published peer-reviewed literature available that would alter the coverage statement in the policy.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.