Documentation Requirements: Drugs or drug classes for which screening is performed should only reflect those likely to be present based on the patient’s medical history or current clinical presentation, and without duplication. Each drug or drug class being tested for, must be indicated by the referring clinician in a written order and so reflected in the patient’s medical record. Additionally, the clinician’s documentation must be patient specific and accurately reflect the need for each test.

Qualitative urine drug testing (UDT) (i.e., immunoassay to evaluate, indicates the drug is present) that is utilized for pain management or substance abuse monitoring, may be considered medically necessary for:

• Baseline screening/induction phase before initiating treatment or at the time treatment is initiated, when the following conditions are met:

o An adequate clinical assessment of patient history and risk of substance abuse is performed;

o Clinicians have knowledge of test interpretation;

o There is a plan in place regarding how to use test findings clinically.

• Stabilization phase of treatment with targeted weekly qualitative screening for a maximum of 4 weeks. (This type of monitoring is done to identify those patients who are expected to be on a stable dose of opioid medication within a 4-week timeframe.)

• Maintenance phase of treatment with targeted qualitative screening once every 1 to 3 months.

• Subsequent monitoring phase of treatment at a frequency appropriate for the risk-level of the individual patient. (This type of monitoring is done to identify those patients who are non-compliant or abusing prescription drugs or illicit drugs.)

NOTE 1: In general, qualitative urine drug testing should not require more than 15 tests within a 12-month period. Additional testing would require clinical justification of medical necessity.

Quantitative UDT (i.e., gas chromatography-mass spectrometry [GC-MS] as confirmatory, indicates the amount of drug is present) that is utilized for pain management or substance abuse monitoring, may be considered medically necessary under the following circumstances:

• When immunoassays for the relevant drug(s) are not commercially available.

• In specific situations when quantitative drug levels are required for clinical-decision making the following qualitative urine drug screen results must be present and documented:

o Positive for a prescription drug that is not prescribed to the patient; or

o Negative for a prescription drug that is prescribed to the patient; or

o Positive for an illicit drug.

NOTE 2: In general, quantitative urine drug testing should not require more than 12 tests within a 12-month period. Additional testing would require clinical justification of medical necessity.

NOTE 3: Quantitative testing is not appropriate for every specimen and should not be done routinely. This type of test should be performed in a setting of unexpected results and not on all specimens. The rationale for each quantitative test must be supported by the ordering clinician’s documentation. The record must show that an inconsistent positive finding was noted on the qualitative testing or that there was not an available qualitative test to evaluate the presence of semi-synthetic or synthetic opioid in a patient.

NOTE 4: Simultaneous blood and urine drug screening or testing is not appropriate and should not be done.

NOTE 5: Risk stratification is discussed in the Description section of this medical policy.

UDT for pain management or substance abuse monitoring, is considered not medically necessary when the above criteria are not met, including but not limited to routine qualitative or quantitative UDT (see the NOTEs above and the coverage statements below for routine screenings, standing orders, and validity testing).

Routine screenings, including quantitative panels, performed as part of a clinician’s protocol for treatment, without documented individual patient assessment, are considered not medically necessary.

Standing orders are those routine orders given to a population of patients and may result in testing that is not individualized, not used in the management of the patient’s specific medical condition and are considered not medically necessary.

Validity testing includes pH, specific gravity, nitrates, chromates, and creatinine which are performed on the same specimen that is being drug tested. Validity testing is an internal process to affirm that the reported results are accurate and valid, and is considered not medically necessary as a separate evaluation.

In outpatient pain management and substance abuse treatment, hair drug testing and oral fluid drug testing are considered experimental, investigational and/or unproven.

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

Background

According to an evidence assessment by the American Society of Interventional Pain Physicians (ASIPP), approximately one-third of chronic pain patients do not use opioids as prescribed or may abuse them. (1) Moreover, studies have found that a substantial proportion of chronic pain patients inaccurately report nonadherence to prescribed medications and use of illicit drugs. (2)

The U.S. Drug Enforcement Administration (DEA) classifies drugs, substances, and chemicals into 5 distinct categories or schedules depending on the drug’s acceptable medical use and the drug’s abuse or dependency potential. (27) The following schedule listing defines those substances or drugs included in each level:

• Schedule I – Drugs with no currently accepted medical use and a high potential for abuse. Examples include: heroin, lysergic acid diethylamide (LSD), marijuana (cannabis), 3,4-methylenedioxymethamphetamine (ecstasy), methaqualone, and peyote.

• Schedule II – Drugs with higher potential for abuse, with use potentially leading to severe psychological or physical dependence and are considered dangerous. Examples include: combination products with less than 15 mg per of hydrocodone per dosage unit (Vicodin), cocaine, methamphetamine, methadone, hydromorphone (Dilaudid) meperidine (Demerol), oxycodone (OxyContin), fentanyl, Dexedrine, Adderall, and Ritalin.

• Schedule III – Drugs with a moderate to low potential for physical and psychological dependence; abuse potential is less than Schedule I and Schedule II drugs but more than Schedule IV. Examples include: Products containing less than 90 mg of codeine per dosage unit (Tylenol with codeine), ketamine, anabolic steroids, testosterone.

• Schedule IV – Drugs with a low potential for abuse and low risk of dependence. Examples include: Xanax, Soma, Darvon, Darvocet, Valium, Ativan, Talwin, Ambien, Tramadol.

• Schedule V – Drugs with lower potential for abuse than Schedule IV and consist of preparations containing limited quantities of certain narcotics; used for antidiarrheal, antitussive, and analgesic purposes. Examples include: Cough preparations with less than 200 mg of codeine or per 100 mL (Robitussin AC), Lomotil, Motofen, Lyrica, Parapectolin.

Risk stratification assists the clinician (healthcare provider) to determine the individualized treatment strategy for the individual patient. To access the addiction liability, the clinician triages or screens the patient into 1 of the 3 different categories (low-, medium-, and high-risk): (28)

• Low-risk patients with chronic non-cancer pain have no history of substance abuse and lack any major psychiatric co-morbidity. There are no indications of aberrant behaviors in such patients, or any warning signs that they may abuse medications.

• Medium-risk patients may have a prior history of substance abuse, or may have psychiatric co-morbidity.

• High-risk patients are those with active addictive disorders. These individuals are at an increased risk for aberrant behaviors.

Various strategies are available to monitor pain management and substance abuse treatment patients, and multicomponent interventions are often used. Many settings require patients to sign a contract before they are given a prescription for opioids. The contracts generally involve obtaining patients’ 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 patients follow these behavioral guidelines can be a challenge. Risk-assessment screening instruments, such as the 24-item tool Screener and Opioid Assessment for Patients with Pain (SOAPP) (24), and the 5-item Opioid Risk Tool (ORT) (25), can aid in the assessment of patients’ risk for inappropriate drug use or addiction liability. In addition, the presence of “aberrant behaviors” can be used as a marker for patients who are at high-risk for deviating from treatment protocols.

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

• Multiple lost prescriptions,

• Multiple requests for early refill,

• Obtained opioids from multiple providers,

• Unauthorized dose escalation,

• Apparent display of intoxication during office visits.

Another strategy for monitoring patients is testing of biological specimens for the presence or absence of drugs. Currently, urine is the most commonly used biological substance. Advantages of urine drug testing (UDT) are that it is readily available and standardized techniques for detecting drugs in urine exist. Other biological specimens (e.g., blood, oral fluids, hair, and sweat) can also be tested and may gain in popularity over time as techniques for collecting and analyzing these specimens become more standardized. Note that in addition to urine testing, this medical policy will address testing for oral fluids and hair.

The following Table 1 displays the interpretation of the unexpected results of urine drug tests (UDTs) was adapted from one developed by the Canadian National Opioid Use Guideline Group that was cited by ASIPP in their guideline on prescribing opioids for chronic non-cancer pain (1, 4):

Table 1: Interpretation of and Possible Action for Unexpected Results of UDTs (1, 4)

Unexpected Result	Possible Explanations	Possible Actions for the Provider
Test is negative for prescribe opioid.	• False-negative. • Non-compliance. • Diversion.	• Conduct confirmatory testing, specifying the drug of interest (e.g., oxycodone often missed by immunoassay). • Take a detailed history of the patient’s medication used for the preceding 7 days (e.g., could learn that patient ran out several days prior to test). • Ask patient if they’ve given drug to others. • Monitor compliance with pill counts.
Test is positive for non-prescribe opioid or benzodiazepines.	• False-positive. • Patient acquired opioids from other sources (double-doctoring, “street”).	• Repeat UDT regularly. • Ask patients if they accessed opioids from other sources. • Assess for opioid misuse or addiction. • Review or revise treatment agreement.
Urine drug screen (UDS) positive for illicit drugs (e.g., cocaine, cannabis).	• False-positive. • Patient is occasional user or addicted to the illicit drug. • Cannabis is positive for patients taking certain medications (e.g., dronabinol).	• Repeat UDT regularly. • Assess for abuse or addiction and refer for addiction treatment as appropriate.

Additionally, for those patients in a substance abuse treatment plan, monitoring the phases of drug use is considered:

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

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

Urine Drug Testing (UDT)

There are 2 primary categories of UDT: Immunoassay Testing and Specific Drug Identification. Each will be discussed below.

Immunoassay Testing

Immunoassay testing, also called qualitative testing or screening, can be performed either 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 to 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 onsite tests, and 1 to 4 hours for laboratory-based tests. (3)

Specific Drug Identification

Confirmatory tests are always performed in a laboratory. Gas chromatography/mass spectrometry (GC/MS) is considered to be the criterion standard for confirmatory testing. This technique involves using GC 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. 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 generally requires 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 testing. (4)

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 onsite testing of sample characteristics including urine temperature, creatinine concentration, and specific gravity.

In addition, 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 have this degree of hydrocodone if high amounts of oxycodone were also present.

There are various approaches to incorporating UDT into pain management and substance abuse treatment settings. Most commonly, patients undergo UDS 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 use of qualitative versus quantitative tests. Some of these involve conducting routine confirmation of positive qualitative tests with quantitative testing. Others use selective confirmation of positive qualitative 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 qualitative 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 (VA)/Department of Defense (DOD) guideline, patients’ refusal to consent to urine testing should be considered as 1 factor in the overall assessment of patients’ ability to adhere to treatment. (5)

Guidance on Quantitative Testing

Situations for quantitative drug testing may include, but are not limited to the following:

• Unexpected positive test inadequately explained by the patient;

• Unexpected negative test (suspected medication diversion);

• Need for quantitative levels to compare with established benchmarks for clinical decision making.

There may not be commercially available tests for certain synthetic or semisynthetic opioids. The following information on immunoassay availability and diagnostic capacity is included in the Washington State Interagency Guideline (Washington State Agency Medical Directors’ Group [2015]) (22):

• Natural opioids (e.g., codeine, morphine): “Immunoassays for ‘opiates’ are responsive for morphine and codeine but do not distinguish which is present. Confirmatory testing is required to reliably identify drug(s) present. Since codeine is metabolized to morphine and small quantities to hydrocodone, these drugs may be found in the urine. Also, morphine may metabolize to produce a small amount (<10%) of hydromorphone.”

• Semisynthetic Opioids (e.g., hydrocodone, hydromorphone, oxycodone, oxymorphone): “‘Opiates’ immunoassays may also detect semisynthetic opioids depending on their cross-reactivity pattern. However, a negative result does not exclude use of semisynthetic opioids. Confirmatory testing (GC/MS [gas chromatography/mass spectrometry] or LC/MS/MS [liquid chromatography tandem mass spectrometry]) is required to verify compliance with the prescribed semisynthetic opioid(s).” Since hydrocodone is metabolized in small amounts to hydromorphone, both may be found in the urine. Likewise, oxycodone is metabolized to oxymorphone, so these may both be present in the urine of oxycodone users. However, the reverse is not true. In other words, hydromorphone and oxymorphone use does not result in positive screens for hydrocodone and oxycodone, respectively.”

• Synthetic Opioids (e.g., fentanyl, meperidine, methadone, propoxyphene): “Current ‘opiates’ immunoassays do not detect synthetic opioids. Thus confirmatory testing (GC/MS or LC/MS/MS) is needed to identify these drugs. If the purpose is to document compliance with treatment, the laboratory can be instructed to remove the cutoff concentration so that the presence of lower concentrations can be identified.”

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 3 pairs of major salivary glands (parotid, sublingual, and submandibular), secretions from the minor salivary glands, oronaso-pharyngeal 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). In addition, drug concentrations can be affected by the collection method, as well as by whether or not saliva stimulation methods were used. Several collection devices are commercially available in the United States and these generally involve collection on absorbent material (e.g., foam pad). Pads are then placed in a container with a stabilizing buffer solution. Drug concentrations may also vary depending on how the oral fluid is recovered from the collection device (e.g., by centrifugation or by applying pressure). Another issue is that drug concentrations may not reflect blood levels because of residual amounts of 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; these require a small sample volume (»25 μL). Immunoassays tend to be relatively sensitive techniques but they tend to 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 liquid chromatography-mass spectrometry (LC-MS) methods.

A practical advantage of oral fluid collection compared with urine is that samples can be obtained under 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 the pain management or substance abuse treatment settings, particularly when substitution or tampering with urine drug samples is suspected.

Hair Testing

Hair is made up of protein that traps chemicals in the blood at the time the hair was made in the hair follicle. Hair on the human head grows at the rate of approximately 0.5 inch per month. Thus, a 1.5-inch hair sample could be used to reveal drug use during the previous 90 days. Potential advantages of hair as a drug testing source include that its collection is noninvasive; it is easy to collect, store, and ship; sufficient samples are generally available for testing and retesting; and it is difficult to substitute or adulterate. Potential disadvantages are that hair analysis cannot detect recent drug use (i.e., within past 7 days), it is difficult to detect very light drug use (e.g., a single episode), and the fact that drug levels can be due to environmental exposure as well as drug use. 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 sought (e.g., pre-employment screening, post-drug treatment verification of relapse).

Regulatory Status

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Gas chromatography/mass spectrometry (GC/MS) tests and some immunoassays are performed in laboratory settings. Laboratories that offer LDTs must be licensed by CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration (FDA) has chosen not to require any regulatory review of this test.

A CLIA waiver is available for use of certain point-of-care immunoassays. Tests eligible for a CLIA waiver are those considered to be simple, with low risk of error and low potential for harm. FDA is tasked with approving manufacturers’ applications for test system waivers. There are commercially available CLIA-waived urine tests for drugs such as cocaine, methadone, morphine/opiates, and oxycodone. There are also commercially available hair analysis tests such as Quest Diagnostics ELISA tests for amphetamines, opiates, cocaine, marijuana metabolites, and phencyclidine. In addition, Omega Laboratories offers hair drug screening for cocaine and cocaine metabolites.

Several oral fluid drug test collection devices have been cleared for marketing by FDA through the 510(k) process. They include:

• Intercept™ Oral Fluid Drug Testing System (OraSure Technologies, Bethlehem, PA),

• Oral-Eze Saliva Collection System (Quest Diagnostics, Madison NJ),

• Quantisal® Oral Fluid Collection Device (Alere, Waltham, MA).

In addition to the oral fluid collection devices, the FDA has cleared a number of assays for analysis of oral samples. For example, there are FDA-cleared assays for 9 drugs collected with the Intercept device. These are amphetamines, methamphetamine, cocaine/metabolite, opiates, marijuana/THC, phencyclidine, barbiturates, benzodiazepines, and methadone.

The policy was created in December 2014 with a search of the MedLine database and updated with a literature review through March 2016. The policy addresses urine drug testing (UDT) as a component of pain management and substance abuse treatment. For each of these programs or treatments, the literature search focused on the accuracy of testing and on the clinical utility of testing (i.e., the impact of test results on patient management and/or on health outcomes). When published studies were not identified, relevant national and regional clinical practice guidelines were sought. This March 2016 review includes testing oral fluids and hair in addition to UDT.

Urine Drug Testing (UDT)

Accuracy of UDT for Detecting Prescribed Opioids and/or Illicit Drugs

Few studies have evaluated the accuracy of UDT outside of the research setting. One example of a study of this type was published in 2011 by Manchikanti et al. (6) The investigators evaluated in-office immunoassay testing and used gas chromatography/mass spectrometry (GC/MS) as the criterion standard comparison. The study was prospective and included consecutive patients recruited from a single pain management practice. Urine samples were tested for opioids and for illicit drugs. A total of 1000 patients had both the immunoassay and confirmatory tests; both tests were performed on the same urine sample. Personnel analyzing the tests were blinded to the results of the other test and to patient demographics. The study’s primary findings for the diagnostic accuracy of in-office immunoassays for detecting opioids compared with the reference standard are shown in Table 2.

Table 2: Diagnostic Accuracy Findings in Manchikanti et al. (2011) (6)

Group	Sensitivity (95% CI)	Specificity (95% CI)
Patients prescribed morphine, hydrocodone, codeine or hydromorphone (n=748)	92.5% (90%-94%)	89.6% (82-95%)
Patients prescribed oxycodone (n=134)	80.0% (71%-87%)	84.2% (60%-96%)
Patients prescribed methadone (n=46)	97.8% (88%-99%)	100% (2%-100%)

Table Key:

CI: confidence interval.

The most commonly identified illicit drugs were marijuana and amphetamines. The sensitivity and specificity of the immunoassay for detecting marijuana were 90.9% and 98.0%, respectively. Similar statistics for amphetamines were 47.0% and 99.1%, respectively. There were too few data to reliably report diagnostic accuracy of other illicit drugs.

Clinical Utility (i.e., Impact on Patient Management Decisions and/or Health Outcomes)

The preferred study design is a randomized controlled trial (RCT) comparing treatment decisions and/or health outcomes in patients managed with and without use of UDT. When multifaceted interventions are used, it may be difficult to isolate the impact of drug testing from that of other components of the intervention. In that case, the preferred study design would include 1 arm with the full intervention and another arm with the same intervention but without UDT missing. In the absence of RCTs, the next most preferred study design is a nonrandomized controlled trial that adjusts findings for potential confounding factors.

Clinical Utility: Pain Management

Managing Patients with UDT versus without UDT

No RCTs or nonrandomized controlled studies adjusting for potential confounders were identified. A systematic review of the available literature on UDT in the chronic pain management setting, alone or as part of a treatment agreement, was published in 2010 by Starrels et al. (7) Studies were considered eligible for inclusion in the review if they included patients with chronic non-cancer pain who were treated in an outpatient setting and measured opioid misuse outcomes after intervention implementation. Eleven studies met eligibility criteria; none were RCTs. Eight studies addressed UDT, 7 of the 8 interventions also involved treatment agreements. Studies used different protocols for UDT; e.g., some used random screening and others screened on a regular basis. Three studies stated that drug screening was done at a minimum frequency (i.e., at enrollment and/or annually), with additional testing if deemed necessary by the physician. Five studies described the type of testing used; 4 of them included confirmatory GC/MS testing.

The review authors reported that 4 of 11 studies included a control or comparison group. (8-11)
On closer inspection, 2 of the 4 studies labeled as controlled used historic comparison groups and 1 was a prospective single-arm study. Starrels et al. did not pool findings of the 4 studies. In the individual studies, opioid misuse was reduced after intervention initiation from 7% to 23%, compared with pre-intervention or historic controls. (7)

Only 1 of the studies included in the systematic review used a concurrent comparison group. The study, by Goldberg et al., retrospectively reviewed data from a medical center database on 91 patients with a documented pain management contract. (8) By signing the contract, the patient agreed to 8 provisions, 1 of which was “lab tests may be used to check opioid use.” Among the other 7 provisions was an agreement not to use illegal drugs and not to share or sell any medication and an agreement that the patient would receive opioid medication only from a single primary care or pain clinic physician. The comparison group consisted of 224 similar patients without pain management contracts. Consumption of opioids was significantly higher in the intervention group than the comparison group. For example, the intervention group consumed an average of 91 units of opioids quarterly and the comparison group consumed an average of 81 units (p<0.05; an opioid unit was defined as equivalent to 1 systematic administration of 10-mg morphine sulfate). Some of the data presented in the article were contradictory. For example, a table showed significantly greater number of emergency department visits among patients in the pain contract group than the comparison group, but the text stated that there were not more emergency department visits among patients in the pain contract group.

In the uncontrolled studies included in the systematic review, the proportion of patients with opioid misuse after intervention initiation ranged from 3% to 43%. There were 8 studies that included UDT as a component of the intervention. The protocol and frequency of UDT varied in these studies. In 3 studies, there was a minimum baseline frequency, at the time of enrollment, annually, or both, with additional testing performed according to the judgment of the treating clinician. One study performed testing at baseline and on a monthly basis. In the remaining 4 studies, the frequency was not specified explicitly, but was described as “regular” or “random.”

In 2014, Dupouy et al. published a systematic review of literature on the impact of UDT on patient management. (12) All study designs and clinical settings were eligible for inclusion. Other article inclusion criteria were that the urine drug screens (UDS) were conducted using the enzyme immunoassay technique and, for controlled studies, the comparison arm was patient management in the absence of urine testing. In addition, some type of medical management outcome needed to be reported (e.g., reassessment of treatment, referral for specialist visits, hospitalization). Eight studies met the review’s inclusion criteria. Five were rated as poor quality and 3 as fair quality. The studies consisted of 1 RCT, 2 quasi-randomized studies, 1 observational cohort study, and 4 cross-sectional studies. The RCT was a study of routine drug screening in a psychiatric emergency center, a setting that is not addressed in this policy. Most of the other studies were also conducted in settings that fall outside of the scope of the policy. However, 2 studies evaluated relevant populations: 1 was an uncontrolled evaluation of UDT of opioid-addicted patients and the other was a quasi-randomized study conducted in U.S. pain centers. The latter study, by Manchikanti et al., (10) was included in the Starrels et al. 2010 meta-analysis, (7) previously described. The authors of the 2014 systematic review (Dupouy et al. [7]) did not pool study findings.

Managing Patients with Routine UDT versus Selective UDT

No studies were identified.

Managing Patients with Routine Confirmation of Positive Qualitative Tests versus Selective

Confirmation of Positive Qualitative Tests

No studies were identified.

Clinical Utility: Substance Abuse Treatment

Managing Patients with UDT versus without UDT

One RCT was identified that suggests UDT increases treatment compliance when receiving take-home methadone compared with no UDT. In 2001, Chutuape et al. published findings of a study that included patients in a methadone treatment program who had submitted fewer than 80% positive opiate and/or cocaine-positive urine samples during a 5-week baseline period. (13) These patients then participated in a methadone take-home program and were randomized to 1 of 3 groups: 1) continued permission to take-home methadone was contingent on 1 negative urine sample, randomly selected each week; 2) continued permission to take-home methadone was contingent on 1 negative urine sample, randomly selected each month; or 3) permission to take-home methadone was not based on results of urine testing (control group). After participating in the intervention, the rate of sustained (8 or more weeks) opiate and cocaine abstinence was significantly higher in the groups receiving UDT. The percentage of patients with sustained (8 or more weeks) opiate and cocaine abstinence was 56.6%, 38.9%, and 10.5% in the weekly, monthly, and control groups, respectively (p<0.002).

Managing Patients with Routine UDT versus Selective UDT

No studies were identified.

Managing Patients with Routine Confirmation of Positive Qualitative Tests versus Selective

Confirmation of Positive Qualitative Tests

No studies were identified.

Oral Fluid Drug Testing

Accuracy of Oral Fluid Testing for Detecting Prescribed Opioids and/or Illicit Drugs Compared

With UDT

Several studies were identified that compared oral fluid and UDT using paired samples collected concurrently. In 2011, Vindenes et al. in Norway published a study comparing drug detection in oral fluid and urine samples in the drug treatment setting. (14) A total of 164 pairs of urine and oral fluid samples, collected at the same time, were collected from 45 opioid-dependent patients participating in a drug treatment program. Oral fluid samples were collected using the Intercept device and analyzed using a liquid chromatography tandem mass spectrometry (LC/MS/MS) method developed in Norway. Urine samples were screened using immunoassays and confirmed using LC/MS/MS. All patients were being treated with buprenorphine or methadone, so it was expected that 1 of these drugs would be detected in each sample. Other than these 2 drugs, those most commonly detected were 7-aminoflunitrazepam (metabolite of flunitrazepam), amphetamine, and tetrahydrocannabinol (THC). The sensitivity and specificity of the oral fluid samples compared with urine results were calculated. Key findings are shown in Table 3.

Table 3: Sensitivity and Specificity of Oral Fluid Samples in Vindenes et al. (2011) (14), Using Urinalysis as the Reference Standard

Drug	Sensitivity	Specificity
Methadone	100%	100%
Buprenorphine	75%	Not applicable (analytic problems)
7-aminoflunitrazepam	76%	97%
Amphetamine	100%	95%
Tetrahydrocannabinol	82%	98%
6-Monoacetylmorphine (heroin)	95%	80%

A 2012 study by Heltsley et al. included 133 patients undergoing pain management treatment who consented to provide oral fluid and urine samples. (15) Oral samples were collected with the Quantisal device and specimens were analyzed by LC/MS/MS. Urine specimens were screened by immunoassay procedures and non-negative samples were confirmed by MS. Samples were tested for 34 drugs or drug metabolites, although in some instances different analyses were performed on urine and oral fluid specimens. A total of 1544 paired tests were performed. Of these, 329 (21.3%) were positive and 984 (63.7%) were negative in both matrices, for an overall agreement of 85%. Eighty-three (5.4%) findings were positive in oral fluid only and 148 (9.6%) were positive in urine only. The authors conducted several analyses of the sensitivity and specificity of oral fluid samples using urinalysis as the reference standard (see Table 4).

Table 3: Sensitivity and Specificity of Oral Fluid Samples in Heltsley et al. (2012) (15), Using Urinalysis as the Reference Standard

Drug	Sensitivity (95% CI)	Specificity (95% CI)
All drugs	69.0% (64.6% to 73.1%)	92.2% (90.4% to 93.7%)
Four drug categoriesa	76.1% (60.9% to 86.9%)	95.9% (92.0% to 98.0%)
Six drug categoriesb	82.3% (75.0% to 87.9%)	92.2% (88.7% to 94.7%)

Table Key:

CI: confidence interval

^a: Categories include amphetamines, cannabis, cocaine, and opiates;

^b: Includes the above categories plus hydrocodone and oxycodone.

In 2014, Conermann et al. compared findings of oral fluid and urinalysis in 153 paired samples from patients attending a pain management clinic. (16) This study focused on confirmation that a treatment drug was being taken and did not report the sensitivity and specificity of oral fluid samples compared with urine samples. Oral fluid samples were collected with the Quantisal device. All specimens were screened with immunoassays and presumptive positive findings were confirmed using LC/MS. A total of 136 of the 153 paired samples (89%) tested positive for 1 or more treatment drugs (i.e., opioids or benzodiazepines) in 1 or both matrices. After excluding 4 paired samples due to missing data, 101 of 132 positive specimen pairs had exact drug class matches (76.5%). In another 21 paired samples, there was at least 1 drug class match (15.9%). Thus, there was an overall agreement between samples of 92.4%. Two analyses were positive in oral fluid only and 8 were positive in urine only.

Clinical Utility (i.e., Impact on Patient Management Decisions and/or Health Outcomes)

No studies were identified that compared patient management decisions or health outcomes in patients managed using oral fluid drug testing versus UDT or versus no drug testing.

Hair Testing

Accuracy of Hair Testing for Detecting Prescribed Opioids and/or Illicit Drugs Compared With UDT

No studies were identified that compared the accuracy of hair and urine testing using paired samples collected concurrently in the pain management setting or drug abuse treatment setting. One study using paired samples of urine and hair was identified. It was published by Musshoff et al. in 2006 and was conducted in Germany. (17) Patients underwent drug testing as part of the intake process for psychiatric treatment. Urine and hair samples (both head hair and pubic hair) from known drug users were analyzed. Fifty-one patients were included; all provided urine samples, 47 provided head hair samples (1-3 segments), and 36 provided pubic hair samples. Hair samples were washed, dried, and cut into pieces about 1 mm long. Drug analysis was done using GC-MS methods. The hair test was considered positive if any segment had a positive finding. Urine samples were analyzed using standard immunoassays; positive findings were not confirmed. Prevalence rates of drugs identified in hair and urine samples, as well as self-report of drug use, are shown in Table 5.

Table 5: Prevalence Rates of Drug Use in Musshoff et al. (2006) (17) (N=47)

	Opiates	Cocaine	Methadone	Cannabinoids	Amphetamines
Self-Report	42 (89%)	18 (38%)	15 (32%)	26 (55%)	1 (2%)
Urine Test	33 (70%)	13 (28%)	14 (30%)	21 (45%)	0 (0%)
Hair Test	38 (81%)	26 (55%)	23 (49%)	15 (32%)	1 (2%)

Note that values are n (%).

Hair tests revealed a higher prevalence of drug use than UDT for most drugs, with the exception of cannabinoids. The prevalence of amphetamines was too low to make meaningful comparisons. Cannabinoids are known to be excreted slowly in urine and to have a low incorporation rate into hair. It is important to note that the hair analysis was used to detect drug use anytime during the past several months and the urine analysis to detect drug use in the past several days.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 6.

Table 6. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT02345655	Impact of On-site Evaluation of Substances Consumption on Opiate Maintenance in the Context of Family Practice	400	Jan 2018

Table Key:

NCT: national clinical trial.

Practice Guidelines and Position Statements

Pain management

In 2014, Nuckols et al. published a systematic review of guidelines that addressed management of opioid use for chronic pain. (18) The authors included guidelines from national organizations and specialty societies, as well as guidelines from state agencies and specific health systems. The authors identified 9 guidelines with recommendations on UDT. The recommendations varied widely; 2 guidelines recommended mandatory testing for all patients, 1 recommended testing only patients at increased risk of medication abuse, and 2 stated that testing patients at low risk of abuse is not cost-effective. If UDT is used, the recommended frequency of follow-up testing was at least quarterly in 1 guideline, at least yearly in 1 guideline, and randomly in 2 guidelines.

American Society of Interventional Pain Physicians (ASIPP)

In 2012, the ASIPP issued guidelines on responsible opioid prescribing for chronic noncancer pain. (19) The guidelines include the following recommendations on urine drug testing:

• “Comprehensive assessment and documentation is recommended before initiating opioid therapy...” (Evidence: good)

• “Despite limited evidence for reliability and accuracy, screening for opioid use is recommended, as it will identify opioid abusers and reduce opioid abuse.” (Evidence: limited)

• ‘Urine drug testing must be implemented from initiation along with subsequent adherence monitoring, in an in-office,…with immunoassay and confirmation for accuracy with chromatography in select cases, to identify patients who are non-compliant or abusing prescription drugs or illicit drugs, and urine drug testing may decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy.” (Evidence: good)

The evidence behind the above recommendations was not clearly described in either the guidance document or the accompanying evidence assessment document. (1)

American Pain Society (APS) and American Academy of Pain Medicine (AAPM) Opioids Guidelines Panel

In 2009, the APS/AAPM jointly published clinical guidelines on use of opioid therapy in chronic noncancer pain. (20) The guidelines do not address urine drug testing or other forms of monitoring adherence.

American College of Occupational and Environmental Medicine (ACOEM)

In 2011, the ACOEM issued guidelines on the chronic use of opioids which contained the following recommendations on urine drug testing (21): “Routine use of urine drug screening for patients on chronic opioids is recommended as there is evidence that urine drug screens can identify aberrant opioid use and other substance use that otherwise is not apparent to the treating physician.” Evidence (C): “The intervention is recommended for appropriate patients. There is limited evidence that the intervention may improve important health and functional benefits.”

Screening is recommended for all patients at baseline and then randomly at least twice and up to 4 times a year and at termination. Screening should also be performed if the provider suspects abuse of prescribed medication.

Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain Guidelines were issued in 2010 and they include the following recommendation on urine drug screening (4): “When using urine drug screening (UDS) to establish a baseline measure of risk or to monitor compliance, be aware of benefits and limitations, appropriate test ordering and interpretation, and have a plan to use results. (Grade C).”

The guideline also states: “There is no compelling evidence to guide physicians on identifying CNCP (chronic non-cancer pain) patients who should have UDS or how often.” The document states that the following factors should be considered when deciding whether to order a urine drug screen:

• Patient’s risk for opioid misuse and addiction,

• Aberrant drug-related behaviors,

• Testing availability (NOTE: this may be a Canadian-specific issue).

The Canadian Guidelines does not include specific screening frequencies but states that an individual patient’s risk for opioid misuse and addiction should be considered when deciding when to order a urine drug screen. (4)

Veterans Affairs (VA) and Department of Defense (DoD) Management of Opioid Therapy for Chronic Pain Working Group

In 2010, these federal agencies issued clinical practice guidelines for managing opioid therapy for chronic pain treatment. (5) The recommendations on assessing adherence to prescribed opioids includes, with patient consent, obtaining a urine drug test before initiating opioid therapy and randomly at follow-up to confirm appropriate use. Other strategies recommended include clinical assessment and screening aids such as random pill counts, adherence checklists and standardized instruments such as the Screener and Opioid Assessment for Patients with Pain (SOAPP).

The guideline included the following specific recommendations regarding urine drug testing:

1. Inform patients that drug testing is a routine procedure for all patients starting or on opioid therapy, and is an important tool for monitoring the safety of their treatment.

2. With patient consent, obtain a UDT in all patients prior to initiation of OT.

3. With patient consent monitor all patients on OT with periodic random UDTs to confirm adherence to the treatment plan. Increase the frequency of UDTs based on risk level for aberrant drug-related behaviors and following each dose increase.

4. Take into consideration a patient’s refusal to take a UDT as part of the ongoing assessment of the patient’s ability to adhere to the treatment plan and the level of risk for adverse outcomes.

5. When interpreting UDT results take into account other clinical information (e.g., past SUD, other risk factors, aberrant drug-related behaviors, and other conditions indicating risk.)

6. Understanding of lab methods for drug testing and reporting are necessary to interpret UDT results (i.e., screen versus confirmatory test, substances tested, cut-off levels for tests). Maintain a close working relationship with the clinical laboratory to answer any questions about the UDT or for confirming the results.

Washington State Agency Medical Directors' Group

In 2010, this group issued interagency guidelines on opioid dosing for chronic noncancer pain. (22) The guideline included recommendations on urine drug testing. Recommendations on testing frequency differed depending on patient risk of opioid addiction and opioid dosage, and are summarized next and discussed earlier in this policy in Description:

• Low risk: Periodic screening (up to once per year).

• Moderate risk: Regular screening (up to twice per year).

• High risk or opioid dose over 120 mg MED/d.

• Aberrant behavior: Each visit.

Centers for Disease Control and Prevention (CDC)

In 2016, the CDC released a guideline for providers, “CDC Guideline for Prescribing Opioids for Chronic Pain.” (26) Recommendation 10 states the following:

“When prescribing opioids for chronic pain, providers 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).”

The guideline authors admit there is variability in the existing guidelines utilized by providers. However, they agree that the existing guidelines share some common elements, including dosing thresholds, cautious titration, and risk mitigation strategies such as using risk assessment tools, treatment agreements, and UDT.

Since the release of the 2016 CDC guideline, the American Medical Association has suggested the change from testing “annually” to “periodically”, based on the individuality of patient care strategies. As of March 23, 2016, the CDC guideline has not been revised.

Substance abuse treatment

American Society of Addiction Medicine (ASAM)

In 2010, the ASAM issued a statement on drug testing in the substance abuse treatment. (19) As stated in this document, the policy of ASAM is: “Urine drug testing is a key diagnostic and therapeutic tool that is useful for patient care and in monitoring 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.”

Summary

The evidence for UDT in individuals who have chronic pain treated with opioids or who have a drug addiction and are in substance abuse treatment includes 1 well-conducted diagnostic accuracy study and 1 study on eligibility for take-home methadone. Relevant outcomes are test accuracy and validity, health status measures, and resource utilization. Few studies have evaluated the accuracy of UDT outside of the research setting. One study identified evaluated diagnostic accuracy of urine testing compared with a valid reference standard with individuals in a pain management setting; no studies assessed individuals undergoing substance abuse treatment. In terms of clinical utility, for pain management patients, there are no RCTs that isolate the potential effect of UDT on patient management or health outcomes. One RCT was identified on UDT of patients in substance abuse treatment; that trial focused on the specific situation of testing to determine eligibility for take-home methadone. The current published evidence does not permit conclusions on the impact of UDT on clinical outcomes.

The evidence for oral fluid and hair drug testing in individuals who have chronic pain treated with opioids or who have a drug addiction and are in substance abuse treatment includes several diagnostic accuracy studies. Relevant outcomes include test and validity, health status measures, and resource utilization. Two studies of pain management patients and 1 of substance abuse treatment patients have evaluated diagnostic accuracy of oral fluid testing compared with urine testing. The studies reported sensitivities in the range of 75% to 100%, with variability in the sensitivity by type of drug. The reported specificities are higher, generally greater than 90% across different drugs. No studies were identified on the clinical utility of oral fluid testing in pain management or substance abuse treatment. Hair 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 compared to urine testing in either of these settings. However, 1 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 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 current published evidence does not permit conclusions on the impact of hair or oral fluid drug testing on clinical outcomes.

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Drug class testing may be done on any type of specimen, such as urine, blood, oral fluid, meconium, hair. The purpose of the testing can be qualitative, semi-quantitative, or quantitative. More than one test and/or more than one specimen may be tested. Not all procedure codes listed on this medical policy specify in the procedure code the type of specimen. This medical policy addresses only urine drug testing.

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

80156, 80188, 80299, 80303, 80305, 80306, 80307, 80320, 80321, 80322, 80323, 80324, 80325, 80326, 80327, 80328, 80329, 80330, 80331, 80332, 80333, 80334, 80335, 80336, 80337, 80338, 80339, 80340, 80341, 80342, 80343, 80344, 80345, 80346, 80347, 80348, 80349, 80350, 80351, 80352, 80353, 80354, 80355, 80356, 80357, 80358, 80359, 80360, 80361, 80362, 80363, 80364, 80365, 80366, 80367, 80368, 80369, 80370, 80371, 80372, 80373, 80374, 80375, 80376, 80377, 82542, 82570, 83992, 84311, 84999, [Deleted 1/2016: 82491, 82492, 82541], [Deleted 1/2017: 80300, 80301, 80302, 80303, 80304]

HCPCS Codes

G0430, G0477, G0478, G0479, G0480, G0481, G0482, G0483, G0659, G6030, G6031, G6032, G6034, G6035, G6036, G6037, G6038, G6039, G6040, G6041, G6042, G6043, G6044, G6045, G6046, G6047, G6048, G6049, G6050, G6051, G6052, G6053, G6054, G6055, G6056, G6057, G6058, [Deleted 1/2016: G0431, G0434]

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

1. 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. Jul 2012; 15(3 Suppl):S1-65. PMID 22786448

2. Fishbain DA, Cutler RB, Rosomoff HL, et al. Validity of self-reported drug use in chronic pain patients. Clin J Pain. Sep 1999; 15(3):184-91. PMID 10524471

3. Manchikanti L, Atluri S, Trescot AM, et al. Monitoring opioid adherence in chronic pain patients: tools, techniques, and utility. Pain Physician. Mar 2008; 11(2 Suppl):S155-80. PMID 18443638

4. National Opioid Use Guideline Group (NOUGG): Canada. Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain. 2010. Available at: <http://nationalpaincentre.mcmaster.ca> (accessed November 2015).

5. Veteran's Affairs (VA) and Department of Defense (DoD) Management of Opioid Therapy for Chronic Pain Working Group. VA/DoD clinical practice guideline for management of opioid therapy for chronic pain. Available at: <http://www.guideline.gov> (accessed November 2015).

6. 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. Mar-Apr 2011; 14(2):175-87. PMID 21412372

7. 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. Jun 2010; 152(11):712-20. PMID 20513829

8. Goldberg KC, Simel DL, Oddone EZ. Effect of an opioid management system on opioid prescribing and unscheduled visits in a large primary care clinic. J Clinical Outcomes Management. Dec 2005; 12:621-28. PMID not issued by the National Institutes of Health

9. Manchikanti L, Manchukonda R, Damron KS, et al. Does adherence monitoring reduce controlled substance abuse in chronic pain patients? Pain Physician. Jan 2006; 9(1):57-60. PMID 16700282

10. Manchikanti L, Manchukonda R, Pampati V, et al. Does random urine drug testing reduce illicit drug use in chronic pain patients receiving opioids? Pain Physician. Apr 20.06; 9(2):123-9. PMID 17883742

11. Wiedemer NL, Harden PS, Arndt IO, et al. The opioid renewal clinic: a primary care, managed approach to opioid therapy in chronic pain patients at risk for substance abuse. Pain Med. Oct-Nov 2007; 8(7):573-84. PMID 17883742

12. Dupouy J, Memier V, Catala H, et al. Does urine drug abuse screening help for managing patients? A systematic review. Drug Alcohol Depend. Mar 2014; 136:11-20. PMID 24417964

13. Chutuape MA, Silverman K, Stitzer ML. Effects of urine testing frequency on outcome in a methadone take-home contingency program. Drug Alcohol Depend. Mar 2001; 62(1):69-76. PMID11173169

14. 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):32-9. PMID 21219701

15. 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. PMID 22337775

16. 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. PMID 24452646

17. 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):118-23. PMID 16410161

18. 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 2013; 160(1):38-47. PMID 24217469

19. 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. Jul 2012; 15(3 Suppl):S67-116. PMID 22786449

20. Chou R, Fanciullo GJ, Fine PG, et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain Feb 2009; 10(2):113-30. PMID 19187889

21. American College of Occupational and Environmental Medicine (ACOEM). ACOEM Guidelines for Chronic Use of Opioids. Available at: <http://www.acoem.org> (accessed November 2015).

22. Washington State Agency Medical Directors' Group. Interagency guideline on opioid dosing for chronic non-cancer pain: an educational aid to improve care and safety with opioid treatment. Available at: <http://www.guideline.gov> (accessed November 2015).

23. 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. Available at: <http://www.asam.org> (accessed November 2015).

24. Akbik H, Butler SF, Budman SH, et al. Validation and clinical application of the screener and opioid assessment for patients with pain (SOAPP). J Pain Symptom Manage. Sep 2006; 32(3): 297-93. PMID 16939853

25. Opioid Risk Tool (ORT). Available at: <http://www.opioidrisk.com> (accessed November 2015).

26. Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain – United States (2016). Available at <http://www.cdc.gov> (accessed March 2016).

27. Drug Enforcement Agency. Drug Schedules (2016). Available at: <http://www.dea.gov> (accessed September 22, 2016).

28. Manubay JM, Muchow C, Sullivan MA. Prescription drug abuse: epidemiology, regulatory issues, chronic pain management with narcotic analgesics. Primary Care. Mar 2011; 38(1):71-90. PMID 21566422

29. Urine Drug Testing in Pain Management and Substance Abuse Treatment. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2016 January) Pathology/Laboratory 2.04.98.

Title:	Effective Date:	End Date:
Drug Testing in Pain Management and Substance Use Disorder Monitoring	04-01-2021	10-31-2022
Drug Testing in Pain Management and Substance Use Disorder Monitoring	08-01-2020	03-31-2021
Drug Testing In Pain Management and Substance Use Disorder Monitoring	04-15-2018	07-31-2020
Urine Drug Testing Including Pain Management and Substance Abuse Monitoring	04-15-2017	04-14-2018
Urine Drug Testing Including Pain Management and Substance Abuse Monitoring	12-15-2016	04-14-2017
Urine Drug Testing Including Pain Management and Substance Abuse Monitoring	11-01-2015	12-14-2016
Urine Drug Testing Including Pain Management and Substance Abuse Monitoring	12-15-2014	10-31-2015