Proposed LCD - Urine Drug Testing (DL36668)

CMS National Coverage PolicyTitle XVIII of the Social Security Act, 1862(a)(1)(A). Allows coverage and payment for only those services that are considered to be reasonable and necessary.42 CFR 410.32(a). Order diagnostic tests.42 CFR 411.15(k)(1). Particular Services excluded from coverage.CMS On-Line Manual, Publication 100-02, Medicare Benefit Policy Manual, Chapter 15, 80.0, 80.1.1, 80.1.2. Clinical Laboratory services.CMS Internet Only Manuals, Pub 100-02 Medicare Beneficiary Policy Manual chapter 15, 80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests, 80.1.1 Certification Changes.Coverage Indications, Limitations, and/or Medical NecessityPurposeUrine drug testing (UDT) provides timely, objective, and actionable information to clinicians by identifying the presence or absence of drugs of potential abuse in the body to assist the clinician in making treatment decisions.1This policy details:The appropriate indications and allowed number of UDTs billed over time for safe medication management of prescribed substances in risk stratified pain management patients and/or in identifying and treating substance use disorders (SUDs);Designates documentation, by the clinician caring for the beneficiary in the beneficiarys medical record, of medical necessity for, and testing ordered on an individual patient basis;Provides an overview of presumptive UDT and definitive UDT testing by various methodologies.This policy addresses UDT for Medical patients only.DefinitionsAs used in this document, the following terminology relates to the basic forms of UDT:Presumptive/Qualitative Drug Testing(hereafter called "presumptive" UDT) - Covered when medically necessary to immediately determine the presence or absence of drugs or drug classes in a urine sample; results expressed as negative or positive or as a numerical result; includes competitive immunoassays (IA) and thin layer chromatography.2Definitive/Quantitative/Confirmation(hereafter called definitive UDT) - Covered when clinically indicated and medically reasonable and necessary based on this LCD to identify specific medications, illicit substances, and metabolites; reports the results of analytes absent or present typically in concentrations such as ng/mL; definitive methods include but are not limited to GC-MS and LC-MS/MS testing methods only.2Specimen Validity Testing- Urine specimen testing to ensure that it is consistent with normal human urine and has not been adulterated or substituted, may include, but is not limited to pH, specific gravity, oxidants and creatinine. This however is quality assurance, not a Medicare benefit, and thus not separately payable by Medicare.Immunoassay (IA)- Ordered by clinicians primarily to identify the presence or absence of drug classes and some specific drugs; biochemical tests that measure the presence above a cutoff level of a substance (drug) with the use of an antibody; read by photometric technology.2Point of Care Testing (POCT)- Covered when medically necessary by clinicians caring for the beneficiary for immediate test results for the immediate management of the beneficiary; available when the beneficiary and physician are in the same location; IA test method that primarily identifies drug classes and a few specific drugs; platform consists of cups, dipsticks, cassettes, or strips; read by the human eye, or read by instrument assisted direct optical observation.3Standing Orders- Test request for a specific patient representing repetitive testing to monitor a condition or disease for a limited number of sequential visits; individualized orders for certain patients for pre-determined tests based on historical use, risk and community trend patient profiles; clinician can alter the standing order.Note: A profile is developed based on specific characteristics of a specific patient, while a panel is a general non-specific group of tests that may have unnecessary tests for the specific patient being treated.Blanket Orders- Test request that is not for a specific patient; rather, it is an identical order for all patients in a clinicians practice without individualized decision making at every visit.Reflex Testing- Laboratory testing that is performed "reflexively" after initial test results to identify further diagnostic information essential to patient care. This testing is not necessarily based on a specific physician's order.Drug Test MethodsThe Clinical Laboratory Improvement Amendments (CLIA) regulates laboratory testing and requires clinical labs to be certified by their State as well as the Centers for Medicare & Medicaid (CMS) before they can accept human samples for diagnostic testing.3Multiple types of CLIA certificates may be obtained based on the complexity of testing a lab conducts. CLIA levels of complexity (CLIA-waived, moderate complexity, and high complexity) are addressed only as they correspond to the Healthcare Common Procedure Coding System (HCPCS) code description in the related billing and coding article.A. Presumptive Testing Methods:Presumptive UDT:A presumptive UDT consist of various platforms including cards, dipsticks, cassettes and cups based on qualitative competitive immunoassay methodology with one or more analytes in the test. A presumptive IA test detects the presence of the amount of drug/substance present in urine above a predetermined cut-off value and may be read by direct optical observation or by instrument assisted direct optical observation.A positive test result is reported when the concentration of drug is above the cutoff; a negative is reported when the concentration of drug is below the cut-off. Positive test results are presumptive but not necessarily definitive due to sensitivity and cross-reactivity limitations.4Negative test results do not necessarily indicate the absence of a drug or substance in the urine specimen.3The accuracy of the results of a presumptive UDT will depend on the testing environment, type of test, the drug being tested for, and training of the individual conducting the test. This type of test should only be used when results are needed immediately.Presumptive UDT by Instrumented Chemistry Analyzers: 80307Chemistry analyzers with IA UDT technology can be used in an office or clinical laboratory setting. This test provides less immediate test results. At no time is IA technology by chemistry analyzer analysis considered confirmatory (definitive) testing.A presumptive positive IA test detects the presence of a drug/substance in urine at or above the cut-off value. If the concentration of the drug is below the cut-off, the result will be negative. Presumptive positive tests are not always true positives due to sensitivity, specificity, and cross-reactivity limitations. Negative test results do not necessarily indicate the absence of a drug or substance in the urine specimen.3Food and Drug Administration (FDA) approved/cleared test platforms are available in the marketplace as well as laboratory developed tests (LDTs) such as modified FDA approved/cleared and non-FDA approved/cleared platforms and/or reagents. LDTs generally have been modified to test at a lower cutoff in order to detect substances that would have been missed at a higher cutoff. For example, a FDA labeled cutoff may be 300 ng/mL and the LDT cutoff for the same drug may be a 100 ng/mL.3Presumptive UDT can be carried out at any validated cut-off concentration. Lowering of the cut-off concentration provides more stringent cutoffs for illicit drugs. LDTs may include non-FDA cleared tests not available in CLIA-waived or moderate complexity tests (e.g. tramadol, tapentadol, carisoprodol, fentanyl, zolpidem). Lowering the cutoff increases the possibility of detecting a drug when the test has been modified from the recipe of the manufacturer.Limitations of Presumptive UDT:Presumptive UDT testing is limited due to:Primarily screens for drug classes rather than specific drugs, and therefore, the practitioner may not be able to determine if a different drug within the same class is causing the positive result;Produces erroneous results due to cross-reactivity with other compounds or does not detect all drugs within a drug class5;Given that not all prescription medications or synthetic/analog drugs are detectable and/or have assays available, it is unclear as to whether other drugs are present when some tests are reported as positive;Cut-off may be too high to detect presence of a drug.5These limitations may mean that presumptive testing is insufficient for certain clinical needs.An IA involves an antibody that reacts best with the stimulating drug and reacts to a lesser extent (cross-reactive) or not at all with other drugs in the drug class. While presumptive tests vary in their ability to detect illicit drugs such as tetrahydrocannabinol (THC), cocaine, 3,4-methylenedioxy-N-methylamphetamine (MDMA; ecstasy), and phencyclidine (PCP), they may not be optimal tests for many prescription drugs, such as: opiates, barbiturates, benzodiazepines and opioids.For example, opiate reagents are formulated from morphine. Consequently, the cross-reactivity for other opioids and opiates varies based on the manufacturer and lot number. The semisynthetic opioids, hydromorphone and hydrocodone, may contribute to a positive presumptive result, while the semisynthetic opioids, oxycodone and oxymorphone, will not typically be detected even at 300 ng/mL cutoff. Synthetic opioids, such as fentanyl, meperidine and methadone, will not be detected by current opiate IA testing. Consequently, a positive opiate result by IA normally necessitates more specific identification of the substance(s) that account for the positive result, and a negative result does not rule out the presence of opiates or opioids.6Presumptive UDT reagents for benzodiazepine are typically formulated for oxazepam, a metabolite of diazepam (Valium) and chlordiazepoxide (Librium), the main benzodiazepines prescribed twenty years ago. However, many of the more than 10 benzodiazepines that are currently available do not cross-react with IA benzodiazepine reagents. In particular, clonazepam and lorazepam give false negative results with presumptive IA tests and may necessitate more specific identification to account for the negative result. Similarly, a positive screening test result may require definitive UDT to identify the specific drug(s).Synthetic/analog or designer drugs manufactured to elude law enforcement require definitive testing for detection. Most commercially available IA reagents fail to detect designer drugs, such as psychedelic phenethylamines even at very high concentrations.In summary, presumptive IA UDT is often unable to identify specific drugs within many drug classes, particularly within the amphetamine, barbiturate, benzodiazepine, tricyclic antidepressants, and opiate/opioid drug classes. Drugs such as buprenorphine, amphetamines, benzodiazepines, and cocaine/heroin yield false negative IA results due to low cross-reactivity or non-reactivity, and drugs such as fentanyl, carisoprodol, tramadol, tapentadol and synthetic designer drugs cannot be detected by presumptive IA. Therefore, it may be medically necessary for clinicians to utilize definitive UDT when the presumptive tests for these drugs are negative.1,5B.Definitive UDT:Gas Chromatography coupled with Mass Spectrometry (GC-MS) and Liquid Chromatography coupled with Mass Spectrometry (LC-MS/MS) are complex technologies that use the separation capabilities of gaseous or liquid chromatography with the analytical capabilities of mass spectrometry. These methodologies require the competency of on-site highly trained experts in this technology and interpretation of results. While these tests require different sample preparation and analytical runs, they identify specific drugs, metabolites, and most illicit substances and report the results as absent or present typically in concentrations of ng/mL.2Quantification should not be used to determine adherence with a specific dosage or time of dose of a pain medication or illicit drug for clinical purposes. Rather, the use of quantitative drug data may be important for many reasons such as in a differential patient assessment.1For example, when several opioids are present in the urine of a patient prescribed a single opioid, quantification may help the clinician decide whether the presence of the other opioids is consistent with metabolism of the prescribed opioid, opioid contamination during manufacturing, or if more than 1 drug within a class is being used.Quantification may also provide information in the setting of illicit drug use. Serial creatinine-corrected quantitative values may assist in the differential assessment of ongoing drug use or cessation of drug use with continued drug excretion.1GC-MSGC-MS can only be performed on molecules that are volatile. If the test drug is not volatile in its own right, it must be modified or derivatized to a volatile form. To derivatize, the test drug must be extracted from the urine, eluted from the extraction device, concentrated, and then reacted with a chemical reagent to make a volatile product. Each drug class may require a different derivatizing agent. For patients on multiple classes of medications, laboratories using GC procedures must make different volatile derivatives in order to perform comprehensive testing. Since a GC column may not be able to separate more than one class of compounds, multiple chromatographic runs on different column types may be required to monitor multiple drug classes.1Newer GC-MS instruments often use tandem systems. GC-MS methodology allows for the testing of multiple substances but differs in ease of run.LC-MS/MSLC-MS/MS is roughly 100 times more sensitive and selective, involves fewer human steps, provides quicker turn-around time, uses less specimen volume, and can test for a larger number of substances simultaneously when compared to GC-MS.1After sample preparation, it is injected into the LC-MS/MS. The sample has to undergo hydrolysis to break the glucuronide bond that frees the drug and drug metabolites. Hydrolysis is followed by multiple additional steps including protein precipitation, centrifugation and purification. Deuterium-labeled isotopic internal standards are added to quantify the drugs and drug metabolites.