Summary Of Evidence

Providers should consider the prescribed medications, risk assessment, and clinical presentation when selecting which tests to order.

Analysis of Evidence

There are multiple validated surveys the provider can use as part of routine assessment of the individual’s risk potential for abuse and diversion. These surveys typically ask the same questions that are part of the routine clinical assessment. WPS removed the validated survey requirement as this should already be part of the required clinical assessment.

Risk assessment is a widely accepted standard by expert treating entities to be used in clinical treatments and follow-up. The provider shall clearly define risk assessment as part of the reasonable and necessary criteria for UDT.

• 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 beneficiary’s 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.

1. 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.²
2. Definitive/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.²
3. Specimen 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.
4. 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.²
5. Point 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.³
6. Standing 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.
7. Blanket Orders - Test request that is not for a specific patient; rather, it is an identical order for all patients in a clinician’s practice without individualized decision making at every visit.
8. 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.

1. Presumptive UDT:
    
   A presumptive UDT that consists 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.⁴ Negative test results do not necessarily indicate the absence of a drug or substance in the urine specimen.³ The 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.
2. Presumptive UDT by Instrumented Chemistry Analyzers:
    
   Chemistry 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.³
    
   Food 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, an FDA labeled cutoff may be 300 ng/mL and the LDT cutoff for the same drug may be 100 ng/mL.³
    
   Presumptive 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.
3. 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 class;⁵
   • 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.⁵

   These 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 a 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.⁶
    
   Presumptive UDT reagents for benzodiazepine are typically formulated for oxazepam, a metabolite of diazepam (Valium®) and chlordiazepoxide (Librium®), the main benzodiazepines prescribed 20 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.

1. GC-MS
   GC-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 classes¹. Newer GC-MS instruments often use tandem systems. GC-MS methodology allows for the testing of multiple substances but differs in ease of run.
2. LC-MS/MS
   LC-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.¹ After 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.
   

   The sample is injected when the mobile phase is flowing through the chromatographic column. Each drug and drug metabolite interacts with the mobile phase and stationary phase differently and moves at different speeds depending on their chemical properties. In other words, each analyte elutes at different times. Specific drugs and metabolites are identified by their retention time and quantified against isotopic internal standards for each drug and metabolite. Each drug peak has a minimum of 2 mass transmissions to be compared to drug standards (calibrators) to ensure identification.

• Identify a specific substance or metabolite that is inadequately detected by a presumptive UDT screen;
• Definitively identify specific drugs in a large family of drugs;
• Identify a specific substance or metabolite that is not detected by presumptive UDT such as fentanyl, meperidine, synthetic cannabinoids, and other synthetic/analog drugs;
• Identify drugs when a definitive concentration of a drug is needed to guide management (e.g., discontinuation of THC use according to a treatment plan);
• Identify a negative, or confirm a positive, presumptive UDT result that is inconsistent with a patient’s self-report, presentation, medical history, or current prescribed pain medication plan;
• Rule out an error as the cause of a presumptive UDT result;
• Identify non-prescribed medication or illicit use for ongoing safe prescribing of controlled substances; and
• Use in a differential assessment of medication efficacy, side effects, or drug-drug interactions.

1. Presumptive UDT Panels
   Presumptive UDT typically involves testing for multiple analytes based on the specific beneficiary's clinical history and risk assessment and must be documented in the medical record. May be ordered as a panel and billed a "Per Patient encounter" regardless of the number of analytes tested.
2. Definitive UDT Panels
   Physician-directed definitive profile testing is reasonable and necessary when ordered for a particular patient based upon historical use, clinical findings, and community trends. However, the same physician-defined profile is not reasonable and necessary for every patient in a physician’s practice. Definitive UDT orders should be individualized based on clinical history and risk assessment and must be documented in the medical record.

• Coma;
• Altered mental status in the absence of a clinically defined toxic syndrome or toxidrome;
• Severe or unexplained cardiovascular instability (cardiotoxicity);
• Unexplained metabolic or respiratory acidosis in the absence of a clinically defined toxic syndrome or toxidrome;
• Seizures with an undetermined history;
• To provide antagonist to specific drug.

• Patient history, physical examination, and previous laboratory findings;
• Stage of treatment or recovery;
• Suspected abused substance;
• Substances that may present high risk for additive or synergistic interactions with prescribed medication (e.g., benzodiazepines, alcohol).

1. For patients with 0 to 30 consecutive days of abstinence, presumptive UDT is not to exceed 3 presumptive UDTs in a rolling 7 days. More than 3 presumptive UDTs in a rolling 7 days is not reasonable and necessary and is not covered by Medicare.
2. For patients with 31 to 90 consecutive days of abstinence, presumptive UDT is not to exceed 3 presumptive UDTs in a rolling 7 days. More than 3 presumptive UDTs in a rolling 7 days is not reasonable and necessary and is not covered by Medicare.
3. For patients with > 90 consecutive days of abstinence, presumptive UDT is not to exceed 3 presumptive UDTs in a rolling 30 days. More than 3 presumptive UDTs in a rolling 30 days is not reasonable and necessary and is not covered by Medicare.

1. For patients with 0 to 30 consecutive days of abstinence, definitive UDT is not to exceed 1 definitive UDT in a rolling 7 days. More than 1 definitive UDT in a rolling 7 days is not reasonable and necessary and is not covered by Medicare.
2. For patients with 31 to 90 consecutive days of abstinence, definitive UDT is not to exceed 3 definitive UDTs in a rolling 30 days. More than 3 definitive UDTs in a rolling 30 days is not reasonable and necessary and is not covered by Medicare.
3. For patients with > 90 days of consecutive abstinence, definitive UDT is not to exceed 3 definitive UDTs in a rolling 90 days. More than 3 definitive UDTs in a rolling 90 days is not reasonable and necessary and is not covered by Medicare.

1. Identifies absence of prescribed medication and potential for abuse, misuse, and diversion;
2. Identifies undisclosed substances, unsanctioned prescription medication, or illicit substances;
3. Identifies substances that contribute to adverse events or drug-drug interactions;
4. Provides objectivity to the treatment plan;⁹
5. Reinforces therapeutic compliance with the patient;
6. Provides additional documentation demonstrating compliance with patient evaluation and monitoring;¹¹
7. Provides diagnostic information to help assess individual patient response to medications (e.g., metabolism, side effects, drug-drug interaction, etc.) over time for ongoing management of prescribed medications.

1. Patient history, physical examination, and previous laboratory findings;
2. Current treatment plan;
3. Prescribed medication(s);
4. Risk assessment plan.

1. Ongoing testing may be medically reasonable and necessary based on the patient history, clinical assessment, including medication side effects or inefficacy, suspicious behaviors, self-escalation of dose, doctor-shopping, indications/symptoms of illegal drug use, evidence of diversion, or other clinician documented change in affect or behavioral pattern.¹⁴ As part of the clinical evaluation of the patient, the provider should inquire about prescription compliance and potential issues of abuse or diversion such as lost prescriptions, early refill requests, or requests for escalating dose of medication.¹⁴ The number of UDTs billed over time must be based on the individual’s risk potential.¹ Appropriate number of UDTs billed over time based on risk is listed in the table below.¹⁴
2. The clinician should perform random UDT at random intervals to properly monitor a patient.¹⁵ UDT testing does not have to be associated with an office visit.
3. Patients with specific symptoms of medication aberrant behavior or misuse may be tested in accordance with this document’s guidance for monitoring patient adherence and compliance during active treatment (<90 days) for substance use or dependence.

• Patient response to prescribed medication suddenly changes;
• Patient side effect profile changes;
• To assess for possible drug-drug interactions;
• Change in patient’s medical condition;
• Patient admits to use of illicit or non-prescribed controlled substance.

1. Reflex Testing by Reference Laboratories – since reference laboratories do not have access to patient-specific data, reflex testing under the following circumstances is reasonable and necessary:
   1. To verify a presumptive positive UDT using definitive methods that include but are not limited to GC-MS or LC-MS/MS before reporting the presumptive finding to the ordering clinician and without an additional order from the clinician; or
   2. To confirm the absence of prescribed medications when a negative result is obtained by presumptive UDT in the laboratory for a prescribed medication listed by the ordering clinician.
2. When medical record documentation that is individualized for a particular patient satisfies medical necessity requirements found elsewhere in this LCD (e.g., risk assessment, frequency), direct to definitive UDT without a presumptive UDT may be reasonable and necessary.
3. Definitive testing to confirm a negative presumptive UDT result, upon the order of the clinician, is reasonable and necessary in the following circumstances:
   1. The result is inconsistent with a patient’s self-report, presentation, medical history, or current prescribed medication plan (should be present in the sample);
   2. Following a review of clinical findings, the clinician suspects use of a substance that is inadequately detected or not detected by a presumptive UDT; or
   3. When there is an unexpected negative presumptive UDT result, and it is clinically imperative to know if it is truly positive or negative; the medical record should state such.
4. Definitive testing to confirm a presumptive UDT positive result, upon the order of the clinician, is reasonable and necessary when the result is inconsistent with the expected result, a patient’s self-report, presentation, medical history, or current prescribed medication plan.

1. Blanket Orders-same orders for all patients in a health care provider’s practice.
2. Reflex definitive UDT is not reasonable and necessary when presumptive testing is performed at point of care because the clinician may have sufficient information to manage the patient. If the clinician is not satisfied, he/she must determine the clinical appropriateness of and order specific subsequent definitive testing (e.g., the patient admits to using a particular drug, or the IA cut-off is set at such a point that is sufficiently low that the physician is satisfied with the presumptive test result).
3. Routine standing orders for all patients in a physician’s practice are not reasonable and necessary.
4. It is not reasonable and necessary for a physician to perform presumptive POCT and order presumptive IA testing from a reference laboratory. In other words, Medicare will only pay for one presumptive test result per patient per date of service regardless of the number of billing providers.
5. It is not reasonable and necessary for a physician to perform presumptive IA testing and order presumptive IA testing from a reference laboratory. Medicare will only pay for one presumptive test result per patient per date of service regardless of the number of billing providers.
6. It is not reasonable and necessary for a reference laboratory to perform and bill IA presumptive UDT prior to definitive testing without a specific physician’s order for the presumptive testing.
7. IA testing, regardless of whether it is qualitative or semi-quantitative (numerical), may not be used to “confirm” or definitively identify a presumptive test result obtained by cups, dipsticks, cards, cassettes, or other IA testing methods. Definitive UDT provides specific identification and/or quantification typically by GC-MS or LC-MS/MS. Semi-Quantitative is defined as a numerical estimation of the approximate concentrations.
8. Drug testing of 2 different specimen types from the same patient on the same date of service for the same drugs/metabolites/analytes.
9. UDT for medico-legal and/or employment purposes or to protect a physician from drug diversion charges.
10. Specimen validity testing including, but not limited to, pH, specific gravity, oxidants, creatinine.