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LCD Title

MolDX: Molecular Syndromic Panels for Infectious Disease Pathogen Identification Testing

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Issue

Issue Description

This LCD outlines limited coverage for this service with specific details under Coverage Indications, Limitations and/or Medical Necessity.

Issue - Explanation of Change Between Proposed LCD and Final LCD

Title of policy changed and other minor changes were made for clarification.

CMS National Coverage Policy

Title 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) Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

CMS Internet-Only Manual, Pub. 100-02, Medicare Policy Manual, Chapter 15, §80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests, §80.1.1 Certification Changes

Coverage Guidance

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Coverage Indications, Limitations, and/or Medical Necessity

This policy provides limited coverage for outpatient testing with molecular syndromic panels for infectious disease pathogen identification testing. This policy does NOT address coverage for the inpatient setting.

This policy defines a panel as a test that detects > 1 pathogen. This policy also differentiates (where appropriate) between small, targeted panels (up to 5 pathogens) and larger, expanded panels (≥6 pathogens). This distinction is primarily applied
to the Respiratory and Gastrointestinal Panels. A 'syndromic panel' is further defined as one that simultaneously detects multiple different pathogens associated with similar and overlapping clinical symptomatology.

This is NOT a coverage policy for metagenomic next-generation sequencing, mass spectrometry, or fluorescence in situ hybridization (FISH).

General Criteria For Coverage For A Molecular Syndromic Infectious Disease Pathogen Identification Panel Test

This Medicare Contractor will cover molecular syndromic infectious disease pathogen identification panel tests when ALL of the following criteria are met:

• The patient has a clinical indication for infectious disease testing:

• For immunocompetent patients, the clinical indication includes a presumption of active infection OR infection-associated complications (which may include exacerbation of underlying disease) that require the identification of a
causative organism for appropriate management. Atypical clinical presentations of disease are considered appropriate indications for special populations who may not present with classic symptoms of infection (i.e., the elderly).
• For immunocompromised patients (i.e., those with weakened immune systems including those with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), patients who are taking
immunosuppressive medications (i.e., chemotherapy, biologics, transplant-related immunosuppressive drugs, high-dose systemic corticosteroids) and those with inherited diseases that affect the immune system (i.e., congenital
immunoglobulin deficiencies), atypical clinical presentations of disease are considered appropriate indications for testing. In this patient population, testing may be performed ONCE as part of a pre-transplant evaluation,
regardless of the presence of symptoms.
• Note: For certain panels, such as the Urogenital/Anogenital Panel, epidemiologic indication or potential exposure to pathogens as a result of a high-risk experience is considered a covered clinical indication, even in the absence of
clinical symptoms. These are specifically noted below in LIMITED COVERAGE FOR EXPANDED (>5 Pathogens) PANEL TESTING.
• The results of testing will impact clinical management in a manner already demonstrated in the peer-reviewed published literature to improve patient outcomes.
• Testing is performed according to the intended use of the test in the intended patient population for which the test was developed and validated.
• This includes performing the test using the intended sample types along with parallel testing that must accompany the test (i.e., the meningoencephalitis and bloodstream pathogen tests include requirements for parallel testing
using conventional Gram stain and culture-based detection for correlation of results).
• This also includes the provision - by the laboratory to ordering providers - of the major limitations of a given panel test.
• An evaluation for more than 1 pathogen by molecular testing is necessary for patient management (testing for a single pathogen is NOT reasonable and necessary for the specific infection, patient, or indication). The panel performed
includes at least the minimum pathogens required for clinical decision making for its intended use that can be reasonably detected by the test.
• If additional organisms are not included in a panel, testing for those organisms separately for the same indication may be reasonable and necessary in limited circumstances.
• More than 1 panel may not be performed on the same date of service for the same clinical indication, except for bloodstream and meningoencephalitis panels; in such circumstances, a second panel may be performed for
non-duplicative content.
• Expanded panel testing is only indicated when targeted panel testing is not appropriate (i.e., will not provide sufficient information for the appropriate clinical management of the patient). See LIMITED COVERAGE
FOR EXPANDED (>5 Pathogens) PANEL TESTING below.
• Services that do not have Food and Drug Administration (FDA)-cleared/approved indicated uses, as well as FDA-approved tests performed in ways not consistent with their intended-use labeling directions, will require registration with
Molecular Diagnostic Services Program (MolDX®) and a Technical Assessment (TA) to demonstrate compliance of the service with this policy. Similarly, tests (and CPT codes) for which there are no accompanying ICD-10 codes in the
associated Billing and Coding Article will require registration with MolDX® and a TA to demonstrate compliance of the service with this policy.
• Registered tests must demonstrate equivalent or superior test performance characteristics - analytical validity (AV) and clinical validity (CV) - to established standard-of-care (SOC) methods (i.e., culture, pathogen-specific
polymerase chain reaction [PCR]) for the majority of targets included on the panel.
• CV of any new organisms and analytes that are not already established as SOC or that do not have a predicate test that is covered by this contractor, must be established through a study published in the peer-reviewed literature for
the intended use of the test in the intended population.
• Documentation of the following is clearly stated in the medical record:
• Specific clinical indications for testing (i.e., clinical suspicion of a pathogen as the cause of the patient’s condition)
• Specific reasons for performing panel testing
• Provider type/specialty and Place of Service
• Testing must be performed according to Clinical Laboratory Improvement Amendments (CLIA) and/or FDA regulations. For example, CLIA-non-waived tests may only be performed in certified laboratories and according to CLIA
regulations. CLIA-waived tests may be performed in healthcare settings that operate under a CLIA Certificate of Waiver or Certificate of Compliance/Certificate of Accreditation. Panels intended for home use (including those that have
been FDA approved or cleared) do NOT meet the coverage criteria of this policy.

Non-Coverage Criteria

Molecular Syndromic Panel Tests will NOT be covered in the following circumstances:

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 • If the test is performed as a test of cure.
• If the patient has been previously tested by molecular diagnostic methods for the same pathogens within 14 days for the same clinical indication.
• If a previous panel test was performed with a similar/duplicative intended use, a subsequent test is only reasonable and necessary if the non-duplicative content of the second test is reasonable and necessary.
• Exception: Repeat panel testing for the same clinical indication will only be covered if first panel yielded a negative result AND there is a high index of suspicion for a pathogen as the cause of symptoms AND the patient’s
clinical condition is not improving or is deteriorating after a clinically appropriate length of time. In such cases, 1 additional panel test may be covered between 1 and 14 days after the initial panel test, so long as the test fulfills
the criteria for coverage as set forth in this policy.

LIMITED COVERAGE FOR EXPANDED (>5 Pathogens) PANEL TESTING

FOR THE SPECIFIC PANEL TYPES LISTED BELOW, ALL OF THE FOLLOWING ADDITIONAL CRITERIA MUST BE MET:

♦ Respiratory (RP) and Pneumonia (PNP) Panels will only be covered when targeted testing is not appropriate AND according to the following additional criteria:
♦ For immune-competent patients, at least 1 of the following must apply:
♦ Testing is ordered by a clinician specialist in Infectious Diseases or Pulmonology for a patient with severe and established underlying respiratory pathology (i.e., severe asthma, chronic obstructive pulmonary disease
(COPD), cystic fibrosis, pulmonary fibrosis, radiation therapy to the lung) AND treatment with antibiotics may be indicated according to established guidelines.1,2 Specific examples that do NOT meet coverage criteria
according to established guidelines include the following:
♦ Asthma exacerbations without the additional presence of either fever and purulent sputum or radiographic evidence of pneumonia2
♦ Uncomplicated community acquired pneumonia (CAP)1
♦ The patient is seriously or critically ill or at imminent risk of becoming seriously or critically ill (as defined by the American Hospital Association’s “General Guide for the Release of Information on the Condition of
Patients”)3 as a result of a presumed respiratory infection AND the patient is being treated in an appropriate critical care facility.
♦ For immune-suppressed patients: Testing is ordered by a clinician specialist in 1 of the following: Infectious Diseases, Pulmonology, Oncology, Transplant OR the patient is being managed in an appropriate critical care facility.
♦ For ALL patients: Only 1 of the following panels - RP OR PNP- will be covered for a given patient for the same clinical indication. The PNP should be prioritized in the evaluation of pneumonia from lower respiratory tract
specimens (i.e., bronchoalveolar lavage samples [BALs]). For the purposes of repeat panel testing for the same clinical indication, RP and PNP will be considered as equivalent tests, such that if criteria for repeat testing are met
(as defined above), a clinician may choose to perform the repeat test using the PNP, even if the original test was performed using the RP.
♦ For ALL patients, exceptions to the limitation on medical specialists who can order expanded panel tests are provided in the accompanying Billing and Coding Article, such that patient geography and access to care do not
preclude the receipt of appropriate diagnostic testing when indicated.
♦ Gastrointestinal (GI) Panels will only be covered when targeted testing is not appropriate AND according to the following additional criteria:
♦ For immune-competent patients, at least 1 of the following must apply:
♦ Testing is ordered by a clinician specialist in Infectious Diseases or Gastroenterology for a patient with severe and established underlying GI pathology (i.e., inflammatory bowel disease (IBD), paralytic ileus, radiation
therapy to the intestine) AND identification of an infectious cause is necessary to determine next steps in patient management.
♦ The patient is seriously or critically ill or at imminent risk of becoming seriously or critically ill (as defined by the American Hospital Association’s “General Guide for the Release of Information on the Condition of
Patients”)3 as a result of a presumed GI infection AND the patient is being treated in an appropriate critical care facility.
♦ The patient’s clinical indication for GI panel testing is diarrhea, and ALL of the following apply:
♦ The diarrheal illness MUST be acute or persistent with signs or risk factors for severe disease (i.e., fever, bloody diarrhea, dysentery, dehydration, severe abdominal pain) that may warrant hospitalization
AND/OR
♦ The diarrheal illness is not resolving after 7 days AND the patient has NOT taken laxatives within 24 hours of the test.
♦ For immune-suppressed patients:
♦ Testing is ordered by a clinician specialist in 1 of the following: Infectious Diseases, Gastroenterology, Oncology, Transplant OR the patient is being managed in an appropriate critical care facility.
♦ For ALL patients, exceptions to the limitation on medical specialists who can order expanded panel tests are provided in the accompanying Billing and Coding Article, such that patient geography and access to care do not
preclude the receipt of appropriate diagnostic testing when indicated.
♦ Urogenital/Anogenital (UG/AG) Panels
♦ For the UG/AG panels, epidemiologic indication or potential exposure to sexually transmitted pathogens (i.e., in the case of clinical concern for multiple sexually transmitted infections (STIs) due to a high-risk experience) is
considered a covered clinical indication, even in the absence of clinical symptoms. Documentation of the high-risk reason for panel testing is clearly stated in the medical record.
♦ In the absence of a high-risk experience, if the primary clinical concern is for a few specific pathogens due to specific signs and symptoms (i.e., lesions suggestive of herpes simplex virus [HSV]), then it is expected that only a
small targeted panel (i.e., including HSV-1 and HSV-2) will be performed. In such cases, expanded panels are NOT considered reasonable and necessary and will NOT be covered.
♦ For the diagnosis of infectious vaginosis/vaginitis, it is reasonable to perform a (targeted or expanded) panel that includes a combination of at least 2 of the following: Gardnerella vaginalis, other BV-associated bacteria (BVAB)
(such as Atopobium vaginae and/or Megasphaera types), Trichomonas vaginalis, and Candida species.
♦ Meningoencephalitis (ME) Panels will be covered according to the following additional criteria:
♦ For immune-competent patients: the patient has at least 2 of the following indicators of central nervous system (CNS) infection: cerebrospinal fluid (CSF) markers, radiology, clinical signs and symptoms consistent with
meningitis or encephalitis, epidemiologic indication or exposure. For immune-compromised patients, at least 1 of these indicators is required.
♦ For all patients: Testing is from a sample collected via lumbar puncture, and NOT an indwelling medical device (i.e., CSF shunts).
♦ Bloodstream Infection (BSI) Panels will be covered according to the following additional criteria:
♦ There is clinical concern for bacteremia or sepsis AND microbe(s) were seen on a Gram stain from the patient’s blood AND the patient is being managed in an appropriate critical care facility (this includes the Emergency
Room), AND

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 ♦ Personnel (i.e., an antimicrobial stewardship team [ASP]) are equipped for rapid (within 24 hours) tailoring of antimicrobial therapy as a result of rapid testing.
♦ Urinary Tract Infection (UTI) Panels will be covered according to the following additional criteria:
♦ The patient is symptomatic AND at higher risk for UTI complications (i.e., the elderly, patients with recurrent symptomatic UTIs and/or complicated urinary tract anatomy) AND/OR is seen in urogynecology or urology specialty
care settings.

Additional information related to specific panels may be found in the related Billing and Coding article.

Tests that demonstrate similar indicated uses and equivalent or superior performance to SOC or other covered tests, as demonstrated in a TA, may similarly be covered under this policy.

Additional syndromic panel types and indications may also be covered according to the established criteria outlined in this policy.

Summary of Evidence

Molecular panel tests for infectious diseases have changed the landscape of clinical microbiology. They play an important role in diagnostic testing, as they simultaneously detect several different pathogens associated with similar and
overlapping clinical symptomatology. For this reason, they are also known as 'syndromic panel' tests. These panels belong to a category of testing known as culture-independent diagnostic tests (CIDTs), which are tests that detect pathogens
without the need to grow and isolate them in culture. These tests have shorter turnaround times, often have good test performance characteristics, and require limited technical expertise, making them appealing for use by clinicians as well as
clinical laboratories.

Historically, physicians were required to select the specific pathogens most likely thought to be associated with a patient’s disease. They often had to rely on empiric therapy until results from the laboratory could be used in identifying definitive
or targeted antimicrobial therapy, with results taking days and sometimes weeks. In recent years, molecular panel tests, including multiplex PCR, have become increasingly used for the detection of pathogens, and clinicians are no longer required
to name (or separately test for) many of the bacterial, viral, fungal, and parasitic species sought for a given clinical ‘syndrome'. As the use of multiplex molecular tests have decreased the need to perform multiple assays to diagnose a given
infection, results are often available to the physician within minutes to hours. Though culture-based methods of diagnosis are still routinely utilized, and definitive antimicrobial therapy may still lag pending full culture and susceptibility
information, these tests have revolutionized infectious disease diagnostics and have made the road from diagnosis to treatment very rapid, in some cases occurring at the point-of-care (POC).

For some conditions, such as respiratory tract infections, RP panels have become the SOC. These respiratory panels are exceptionally rapid, providing results in minutes to hours.4,5 They are unlike the older conventional respiratory viral testing
methods such as viral culture and immunofluorescence, which could take days to weeks to obtain a result. Moreover, they display test performance characteristics (sensitivity and specificity) which are often superior to other rapid diagnostic tests
for respiratory viruses, such as rapid (antigen-based) influenza detection tests (RIDTs).6-8 For these reasons, many laboratories have stopped offering some of the other diagnostic modalities described for respiratory viral pathogens detection. In
fact, many of those methods have become obsolete in routine clinical care.

Finally, some of these multiplex panels are smaller, or ‘targeted', detecting just a few pathogens whereas others are very large, detecting approximately 20 targets. The larger panels are sometimes referred to as ‘expanded'. These distinctions
most commonly apply to the RP and GI panels, as panels for BSI and ME (and in some circumstances UG/AG) are expected to detect >5 pathogens (though a UG/AG panel is not expected to detect as many as 20 pathogens, due to the
epidemiology of disease in that organ system). Many commercial platforms for multiplex panel testing have been developed for a variety of infection types in different organ systems.4,5 Both smaller and larger panels are being used in clinical
laboratories, though their optimal use and application in various settings, and for various patient populations and indications remains a challenge.

Test Performance

In recent years, molecular syndromic panels have become routinely used for a number of infection types, including respiratory, gastrointestinal, central nervous system, bloodstream, and urogenital/anogenital. These panels provide rapid
turnaround times for results, and are often more sensitive than traditional testing for the various organisms included.4,5,9 However, test performance characteristics do vary depending on the specific panels and pathogens. For example, though
overall sensitivities and specificities have ranged from 84-100% for various RP platforms evaluated, the sensitivities for adenovirus, influenza A H1/2009, and influenza B using the FilmArray® RP have been reported as low as 57%, 73%, and
77%, respectively, while more recent versions of the platform (the FilmArray® RP2) have shown improved detection (94%-100%) of these pathogens.10,11 Additionally, the FilmArray® PNP and RP panels have targets in common, though the
PNP also contains numerous bacterial targets as well as antimicrobial resistance determinants; the PNP is also semiquantitative.12,13 The PNP has shown strong agreement with both SOC methods as well as with the RP in identifying pathogens
from lower respiratory tract specimens.12,13 Because the PNP performs similarly to the RP for viral pathogens, but can additionally detect bacterial pathogens and antimicrobial resistance determinants, it should be prioritized in the evaluation of
pneumonia from lower respiratory tract specimens.14 A study comparing the performance of additional RP assays reported the following sensitivities and specificities: 98.3% and 99.2% for GenMark Dx® eSensor® Respiratory Viral Panel (RVP),
92.7% and 99.8% for Luminex® xTAG® RVPv1, and 84.4% and 99.9% for Luminex® xTAG® RVP Fast.10 In this study, sensitivities also varied by viral target.10 Smaller targeted panels detecting influenza and respiratory syncytial virus (RSV)
have also shown overall high sensitivity and specificity in studies evaluating their performance. A prospective and retrospective evaluation of the Xpert® Flu/RSV XC assay reported sensitivity/specificity of 97.8%/100% and 97.9%/100% for
influenza and RSV, respectively.15 Another study using prospective patient samples reported 96.6%-100% agreement between the ARIES® Flu A/B & RSV and Cepheid® Xpert® Flu/RSV XC assays.16 This is important, as some of the targeted
respiratory panels have been granted CLIA-waived status and are being used in non-laboratory settings.17,18 In a study evaluating the Roche cobas® Liat® Influenza A/B & RSV assay performed by nonlaboratory staff, reported
sensitivities/specificities were 99.6%/97.5%, 99.3%/99.7%, and 96.8%/98.8% for influenza A, B, and RSV, respectively.19 Yet another study comparing rapid POC nucleic acid amplification tests (NAATs) found that the sensitivity of Alere™ i
was only 71.3% (compared to 100% for the Liat®).20 The poor sensitivity of the Alere™ i in that study was attributed to the inclusion of many low-positive samples.20

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The BioFire® FilmArray® and Luminex® xTAG® GI panels demonstrate overall high sensitivity (>90%) for the majority of their targets.21 However, sensitivities have been very low for certain targets, specifically Aeromonas sp. (23.8%) on the
FilmArray® and Yersinia enterocolitica (48.1%) on the xTAG®21; because of its low sensitivity, Aeromonas is not included as a reportable analyte on the cleared version of the FilmArray® test.22 A multicenter study evaluating the FilmArray® GI
panel found the sensitivity to be 100% for 12 of the 22 targets and >94.5% for an additional 7 targets (performance of the remaining targets was not assessed due to their low prevalence); specificity was >97.1% for all panel targets.22 In a study
comparing the Luminex® xTAG® to conventional methods of testing found that the panel had a higher sensitivity than SOC for detecting C. difficile, Campylobacter species, norovirus, and rotavirus.23

The ME panel (the BioFire® FilmArray® ME panel is currently the only commercially available panel) has overall good sensitivity for most targets, but does suffer from a lack of sensitivity for certain targets, such as Cryptococcus species,
relative to conventional testing methods for this pathogen.24-26 In 1 prospective multicenter evaluation, the FilmArray® ME panel showed a percent positive agreement (PPA) with SOC methods of 100% for 9 of 14 analytes, with another 2
analytes showing PPA between 85.7-95.7%; the percent negative agreement (NPA) with SOC methods was >99% for all analytes but S. agalactiae.24 Importantly, the ME panel detected 43 pathogens that were not recovered by conventional
testing; however, additional testing confirmed the ME panel to be correct in only 43% of these cases.24 In this and other studies, false positive results of the ME panel have been reported, primarily for S. pneumoniae, S. agalactiae, and HSV-1,
and false negatives have been reported primarily for HSV-1 and HSV-2, Enterovirus, and Cryptococcus neoformans/gattii.24-26 A systematic review and meta-analysis of 13 studies evaluating the ME panel reported a sensitivity and specificity of
90% and 97%, respectively.26

BSI panel tests also show good overall performance. Studies have found the FilmArray® Blood Culture Identification (BCID) panel and the Verigene® (Gram-positive and Gram-negative blood culture) panels provide correct identification for
87%-99% of monomicrobial samples, compared to conventional methods.27,28 One study comparing the 2 panel tests to SOC found that the FilmArray® and the Verigene® correctly identified 95% and 99% of isolates, respectively, in
monomicrobial cultures.27 False positives and false negatives have been reported in these panels, for both organism and resistance gene identification, particularly in polymicrobial samples; however, the failure to detect organisms in
polymicrobial samples is often the result of organisms not included on the panels.5,29 Nevertheless, because of limitations inherent in the tests (including the fact that not all organisms are represented on the panels and these are high-stakes
infections), both the ME and BSI panel tests must be accompanied by Gram stain and culture.

Molecular panel tests are also increasingly being used for the detection of urogenital and anogenital infections. The BD MAX™ vaginal panel has reported sensitivities and specificities of 89.8%/96.5%, 97.4%/96.8%, and 100%/100% for
bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and trichomoniasis (TV), respectively.30 In another study, the BD Affirm™ VPIII Microbial Identification Test showed a lower specificity of 81.6% for BV and lower sensitivity of 69.4%
for VVC, while it performed equally well as the BD MAX™ for TV.31 These panels, however, have been shown to perform better than clinician assessment of vaginitis, for which many diagnoses remain empirical and for which guideline
non-adherence is broad.32-34 Further, high rates of coinfection with STIs (24.4%-25.7%) have been observed.35-37 Panels detecting sexually transmitted pathogens have also become routine in clinical laboratories, as they provide a rapid result for
organisms like Chlamydia species, that can be difficult to culture. Moreover, it is well-established that N. gonorrhoeae and C. trachomatis not only cause similar clinical syndromes, but also coexist in a significant proportion of patients,
highlighting the need for panel testing.38

For the evaluation of UTI, multiplex PCR panels have shown agreement of ≥90% with SOC urine cultures for the identification of organisms from urine, though there are currently no United States (U.S.) FDA-approved panels for this
indication.39,40 Similarly, there are no currently approved panels for use with sterile body fluids other than blood and CSF, though studies evaluating existing panels (such as the BSI panel) with such fluids have shown pathogen detection in cases
where SOC cultures were negative, possibly due to the effect of prior antimicrobial therapy.41,42 Though testing may require assay optimization for use with ‘other’ sterile fluid specimens, 1 study found 100% detection of organisms from sterile
fluids inoculated into blood culture bottles when tested using BSI panels.43

There are many commercially available multiplex panels for the diagnosis of infectious diseases, and this review of their performance is not inclusive of all of them. As noted in this review, the performance of these panel tests varies, depending
on the platform and specimen types used and the targets included. These panel tests should display performance that is equivalent or superior to SOC or other established tests, with ideal sensitivity and specificity or PPA and NPA of ≥95% for
the majority of targets included on their panels. However, it is important to consider the entire picture. For example, as some of these panels are not intended to be used as stand-alone tests, parallel testing by additional methods can be used to
support their application in clinical settings, particularly in cases where the assay has not achieved the ideal performance metrics for a given target. Finally, the specific performance limitations of the various panel tests (in some cases due to
enhanced sensitivity for targets that may not be pathogenic) must be considered. These issues are further discussed in the Clinical Utility section below.

Clinical Utility - Impact on Patient Management and Interpretation of Results

Rapid diagnostics require rapid intervention to be impactful for patient management. Rapid, user-friendly, multiplexed molecular tests have great potential in this regard, though their impact on patient outcomes is clearer for some types of panels,
infections, and patients than for others, as studies are variable in design and quality.4,5,8,44 A systematic review of the impact of rapid point-of-care testing (POCT) (including molecular assays) for influenza found that, in patients with acute
respiratory infection, a positive POCT result significantly increased use of antivirals for influenza and decreased unnecessary antibiotic use.45 Another study of adult patients found a decreased time to diagnosis (of influenza and non-influenza
viruses) using the FilmArray® RP, compared to conventional methods of testing; moreover, a diagnosis of influenza was associated with lower odds ratio for admission, length of stay (LOS), duration of antimicrobial use, and number of chest
x-rays.46 Better influenza detection, a reduced LOS, and improved antiviral use were also found in a study of routine molecular POCT for respiratory viruses (the ResPOC study), for adults presenting to the hospital with acute respiratory
illness.47 However, studies have shown that other factors, such as the presence of infiltrates on chest x-ray and uncertainty regarding the possibility of a bacterial infection, also play a significant role in the decision to treat with antibiotics,
regardless of the result of the RP test.48 A systematic review of the literature concluded that RPs provide accurate results, and that there is high-quality evidence to support that rapid testing can result in a decreased LOS and can increase
appropriate oseltamivir use.8 Notably, the majority of RP studies have focused on the benefits in influenza-positive patients. For example, in a study evaluating antimicrobial prescriptions following RP testing among adult outpatients, antibiotic
prescription rates were significantly different between patients who tested positive for influenza virus and those who did not; however, antibiotic prescription rates were not different between the patients who tested positive for viruses other than
influenza and those who tested negative.49 Since influenza is 1 of the few respiratory infections that can be treated with antivirals, this suggests that a more targeted testing approach is sufficient for most immune-competent patients with a
presumed acute viral respiratory infection. Moreover, guidelines on CAP by the Infectious Disease Society of America (IDSA) recommend NOT obtaining testing (specifically sputum Gram stain and culture) routinely in adults with CAP
managed in the outpatient setting; rather, they recommend that empiric antibiotic therapy be initiated in adults with clinically suspected and radiographically confirmed CAP, even if these patients test positive for influenza.1 In other words, RP
testing does not impact initial management with antibiotics in such circumstances. However, IDSA guidelines do suggest testing for influenza in adult patients with CAP when influenza is circulating in the community.1 In such cases, a targeted
panel for influenza testing can be performed. Finally, specific diagnosis and definitive antimicrobial therapy is needed for pneumonia that is complicated (i.e., by meningitis, endocarditis, or abscess), and testing using expanded panels is
warranted in these circumstances; however, these patients are expected to be managed in the inpatient setting.

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A more expansive testing approach may be appropriate in patients with underlying pulmonary pathology and in immune-compromised patients, but only in certain circumstances. In a study of adult patients with exacerbation of airway disease,
35% of those testing positive for viruses (using molecular POCT) had early discontinuation of antibiotics compared to 13% of those who tested negative and 6% of controls; moreover, of those positive for viruses, only 20% were positive for
influenza and the discontinuation of antibiotics was not different between the various viruses detected.50 The authors of this study stress that many of the patients in this study should not have been treated with antibiotics, on clinical grounds
alone, “given that antibiotic use in patients with asthma exacerbation is strongly discouraged by national society guidelines.”2,50 The Global Strategy for Asthma Management and Prevention states “evidence does NOT support the role of
antibiotics in asthma exacerbations unless there is strong evidence of lung infection (e.g., fever and purulent sputum or radiographic evidence of pneumonia).”2 Finally, a study evaluating respiratory virus infections prior to hematopoietic cell
transplant (HCT) found that patients with viruses detected pre-HCT had fewer days alive and out of the hospital and lower survival at day 100 than patients with negative results (even when the only virus present was rhinovirus); importantly,
most patients in this study were asymptomatic when surveillance samples were collected.51 This finding suggests that pre-transplant evaluation is 1 limited circumstance in which expanded RP panel testing may be warranted in asymptomatic
patients.

Impact studies of GI panels have been even more mixed, though some have found that implementation of such panels was associated with a decrease in endoscopic procedures, abdominal radiology, and/or antibiotic prescriptions.52,53 A
prospective multi-center study evaluating 1887 fecal specimens from patients with acute diarrhea found that use of a GI panel enhanced organism detection and improved clinical sensitivity, and enabled clinicians to provide more timely and
targeted antimicrobial therapy; moreover, positive Shiga-like toxin producing E. coli (STEC) results led to the appropriate discontinuation of antimicrobials in the majority of cases when empiric therapy had been initiated.9 However, in
outpatients with uncomplicated diarrhea that is likely to be self-limited, testing is often not warranted.5 Guidelines from the American College of Gastroenterology regarding acute diarrheal infections in adults state that diagnostic studies may be
used in cases of “dysentery, moderate-to-severe disease, and symptoms lasting >7 days to clarify the etiology of the patient’s illness and enable specific directed therapy.”54 Regarding the use of the GI panel in special populations, an impact
study in patients with IBD found that GI panel testing led to lower rate of IBD treatment modification.55 In outpatients with relapse of IBD, testing with a GI panel was associated with significantly lower rates of IBD therapy escalation and
endoscopy, compared to patients who underwent conventional testing.56 Finally, in a study evaluating gastrointestinal infections prior to HCT in asymptomatic patients found that 62% of patients colonized with C. difficile pre-transplantation
developed a clinical C. difficile infection post-transplantation, and 80% of patients colonized with enteropathogenic Escherichia coli (EPEC) or enteroaggregative E. coli developed clinical infections due to their colonizing pathogen
post-transplantation.57 As noted above with respiratory infections, these findings suggest that pre-transplant evaluation is 1 limited circumstance in which expanded GI panel testing may be warranted in asymptomatic patients.

Bloodstream and CNS infections are emergency situations that can progress rapidly, even in previously healthy individuals.58 As such, rapid panel testing can prove invaluable in the prompt management of patients with such infections. The
following widely cited statistic is sobering –in sepsis, for each hour of delay in effective (appropriate for a given pathogen) antimicrobial administration, there is an average decrease in patient survival of approximately 8%.59 Because bacterial
culture and full antimicrobial susceptibility results traditionally take 2 or more days, rapid BSI panels have emerged to rapidly (within hours) identify a causative pathogen such that the most appropriate and targeted antibiotics can be
administered. A prospective randomized controlled trial found that use of a BSI panel resulted in a decrease in time between Gram stain to microorganism identification by approximately 21 hours.60 Moreover, the use of broad-spectrum
antibiotics and the treatment of bloodstream contaminants were reduced; further, antimicrobial de-escalation occurred with the additional intervention by the ASP.60 Other studies have similarly shown more rapid organism identification and
antimicrobial de-escalation with the use of BSI panel (plus ASP intervention) over conventional culture methods, even if the latter also included ASP. 61 However, the effect of BSI panels on other outcome measures such as mortality, 30-day
readmission, and LOS has been more variable between studies.5,61 Pre-post intervention studies62 as well as a meta-analysis63 have shown that rapid molecular diagnostic testing is associated with significant decreases in LOS and mortality
risk, particularly when combined with an ASP. For patients with multi-drug resistant bacteria, rapid escalation of antimicrobial therapy is also important. In 1 study, use of a BSI panel decreased the mean time to appropriate antimicrobial therapy
by more than 30 hours in a study of patients with vancomycin-resistant enterococci (VRE) bacteremia.64 In another, more rapid implementation of effective therapy was observed in cases of extended-spectrum beta-lactamase-producing
organisms, but not overall; this same study reported a significantly decreased length of intensive care unit (ICU) stay, 30-day mortality, and mortality associated with multidrug-resistant organisms after the implementation of a BSI panel.62 There
are fewer outcome studies evaluating the clinical utility of ME panels, particularly for patients generalizable to the Medicare population. One study found that use of the FilmArray® ME panel reduced time to diagnosis by approximately 3 days,
allowed an earlier discontinuation of empiric therapy in 32% of patients, and led to an earlier hospital discharge in 18%, saving 82 hospital days.65 Another study found that use of the panel significantly reduced the turnaround time for HSV
detection, days of therapy for antivirals (acyclovir) and antimicrobials, and hospital LOS, in adults undergoing a lumbar puncture for a suspected community-onset CNS infection.66

Results from multiplex molecular panel tests must be interpreted with caution. First, they detect significantly more pathogens than were detected in the past using conventional methods of testing.5,9 For example, studies evaluating multiplex urine
panels (UPs) have detected up to 26% additional organisms that culture methods did not.39 Importantly, multiplex UPs have detected more organisms in polymicrobial infections than urine cultures in symptomatic patients,39,67 and a modeling
study has shown bacterial combinations that increase the probability of antibiotic resistance.68 As with all such panel tests, it is important to determine whether these additional organisms detected are pathogens or colonizers that simply could not
be detected before, using traditional SOC methods. As these tests detect microbial nucleic acid, they do not require live and actively replicating organisms. Therefore, not all positive results indicate current active infection. However, in 1 study of
150 urogynecology patients, standard urine culture missed 50% of uropathogens in patients with severe urinary symptoms; moreover, approximately 40% percent of patients with missed uropathogens reported no symptom resolution after
treatment based on standard urine culture results.69 Importantly, all of the missed uropathogens were detected using the study’s comparator method (an enhanced quantitative culture technique), though additional bacteria of unknown
pathogenicity were also detected.69

Asymptomatic carriage and prolonged shedding (days to weeks) of viral nucleic acid are common, particularly for respiratory and GI pathogens. In BIG-LoVE, a study of 108 adults and children who underwent weekly respiratory panel testing
for a year, approximately half of all viral detection episodes were asymptomatic.70 Further, PCR detection of viruses at ≥3 weeks was a fairly frequent finding, occurring in 16% of episodes; prolonged viral detection was particularly common in
children and in individuals living with children.70 Prolonged shedding is also common in immune-compromised patients.71 On the GI panels, interpretation of a positive C. difficile result in a patient without risk factors for infection with this
organism can be difficult, as 4%-15% of healthy adults, and up to 21% of those admitted to a hospital, are asymptomatically colonized; moreover, detection by PCR does not indicate active infection, particularly in patients without classic clinical
symptoms.72,73 The high rate of mixed infections observed when using expanded RP (in 30%-40% of positive cases)74,75 and GI panels (up to 27% of positive cases)5,21-23 can be difficult to interpret. The significance of previously unidentified
organisms in stool samples (such as Sapovirus and Astrovirus) can also be clinically challenging to interpret, as it is unclear whether detection of these organisms represents colonization or infection. Mixed infections detected by GI panels most
commonly occur with enteropathogenic E. coli, Y. enterocolitica, Norovirus, and C. difficile.9,21,53 Moreover, in some studies with very high rates of observed C. difficile there are also high rates of inappropriate GI panel testing. In 1 study
evaluating more than 440 GI panels at a community hospital, 61% of the panels ordered were deemed inappropriate, for reasons including lack of documented diarrhea, laxative use, and having a duplicate C. difficile PCR test ordered.53 Notably,
in this study, rates of C. difficile were 51%.53

ME and BSI panels also have their own challenges. For example, though co-infections are less commonly observed with multiplex panel testing from sterile body sites (such as from CSF or blood), they do occur and can cause interpretive
challenges.24 Additionally, the ME panel cannot differentiate active from latent infection. It detects certain organisms, such as human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV), that may be latent and not the causative agents of disease,
particularly if the host is immunocompetent. Moreover, there are a number of organisms that can cause meningitis and encephalitis that are not included on the panel, including bacteria (such as non-K1 E. coli serotypes and non-encapsulated

6
strains of Neisseria meningitidis), viruses (including arboviruses), and Mycobacterium tuberculosis. Therefore, there are significant limitations associated with the use of this panel; however, these are mitigated, in part, by a requirement for
additional testing (i.e., bacterial culture, cryptococcal antigen) to occur in parallel, as well as by clinician education and laboratory stewardship. It is important to remember, however, that traditional means of diagnosing CNS infections also come
with diagnostic challenges that can delay a diagnosis. Such challenges include the low sensitivity of CSF culture (particularly in patients with antimicrobial exposure prior to lumbar puncture)76 as well as the historically unrecognized etiology in
most cases of encephalitis.77 The large nature of the panels may cause an ordering clinician to assume that, because so many organisms are being tested, a negative result makes infection a less likely cause of the patient’s symptoms. Therefore, it
is important for clinicians to realize that, even in expanded syndromic panels, not all pathogens will be detected. New strains of viruses may also go undetected, and the panels are limited to only those organisms found on the ‘menu'. Though the
ME panel cannot fully replace current assays, it can provide unparalleled rapid results for a syndrome that can be rapidly fatal. Similarly, BSI panels are limited by the targets available on the panels, both for identification of microbes as well as
identification of genes responsible for resistance mechanisms. In fact, many Gram-negative organisms harbor resistance mechanisms not encoded by any genes on these BSI panels, adding another diagnostic hurdle to overcome. However, they
do tend to detect the most common bloodstream pathogens and can provide rapid results for rapid targeted antimicrobial therapy.4,5,60

Additional Challenges and Appropriate Use of Panel Tests

With few exceptions, the FDA-approved molecular panels for a given platform are ‘fixed’, i.e., they consist of a predetermined test menu of pathogens. The smaller of these tests, sometimes referred to as ‘targeted panels’, typically detect
about 3-5 pathogens. The commonly used commercially available larger, or ‘expanded’, panels detect approximately 20 targets or pathogens, and some include pathogens that typically cause different clinical presentations, such that
simultaneously testing for these pathogens should not be a common event. In other words, they deviate from being ‘syndromic’ in their approach to diagnosis. For example, the classic infection associated with Bordetella pertussis is whooping
cough. The clinical case definition of a probable case of pertussis is a cough illness lasting at least 2 weeks, in the absence of a more likely alternate diagnosis or epidemiologic linkage, and 1 of the following symptoms: paroxysms of coughing,
inspiratory whoop, post-tussive emesis, or apnea.78 Though some individuals (such as those with a history of prior infection or vaccine-induced immunity) may not show classic manifestations or may be altogether asymptomatic,79 diagnosis of
this organism generally should require a high index of suspicion. Although it is a respiratory infection, in most patients, the clinical presentation of whooping cough is unlike that of most other viral respiratory syndromes. Yet, it is included on
many respiratory syndromic panels and a patient who is likely infected with influenza or RSV may still end up being tested for B. pertussis, simply because it is a target on a fixed panel. Finally, the targets and organisms on a panel can vary
between manufacturers, with some panels differentiating among numerous subtypes and strains of species, many of which are not clinically meaningful for the majority of patients.5 For example, differentiating among the different types and
subtypes of parainfluenza virus may be good for epidemiologic tracking, but is not likely to result in any meaningful impact to patient care.

Further, large (fixed) panels do not appropriately regard patient risk factors, or a pre-test probability of a particular pathogen causing infection. The patient’s medical history and exposures are important to assess prior to testing. For example,
infection with Clostridioides difficile (formerly known as Clostridium difficile) is typically associated with specific risk factors including exposure to antimicrobials, healthcare facilities and hospitals, chemotherapy, and GI
procedures.80 Conversely, many of the other pathogens on the panels are typically associated with foodborne transmission.81,82 Variables like season and geography are also pertinent to a specific diagnostic case or patient. In the case of
respiratory panels, a patient can be tested for more than 20 pathogens, when in fact only a couple of viruses may be the predominant ones circulating in the community during a given season. For example, though influenza can circulate
throughout the year, it primarily occurs and peaks during the winter months, whereas certain other viruses are more prevalent during other seasons.83 Fixed panels may also not be applicable across populations, and immune-competent patients
who are not severely ill may not require testing at all, or may require limited testing.84 Viral infections in immune-competent patients are often self-limiting and resolve without complication. Further, with few exceptions, there is often no specific
treatment for viral infections, other than supportive care, and testing may not change patient management. All of this may result in an excess of unnecessary testing in immune-competent individuals. On the other hand, in immune-compromised
patients, common and rare pathogens can cause severe illness, and concurrent infection with multiple respiratory viruses (which occur more commonly than previously thought, thanks to these multi-analyte panels) have been identified as
predictors of in-hospital mortality.85 Moreover, immune-compromised patients often do not present with classic symptoms of infection. Therefore, casting a wider diagnostic net for this population may be both reasonable and necessary.

However, even in immune-competent individuals, expanded panels can provide rapid, highly impactful, and epidemiologically important information.86 They can lead to the diagnosis of some infections that, in the past, may have been missed
altogether. In 1 study, 75% of Mycoplasma pneumoniae infections were unintentionally detected by multiplex PCR; in this study, clinicians had only specifically requested testing for M. pneumoniae in 2 (10%) of 20 patients positive for this
pathogen.87 Importantly, this was an actionable finding, as infection with M. pneumoniae is treatable with antibiotics.87 Expanded panels can also help rapidly diagnose and, in some cases, avert public health outbreaks. For example, during an
outbreak of a ‘mystery’ respiratory illness among children in 2014, hospitals were able to rapidly identify the presumptive cause, which turned out to be enterovirus D68.88 Similarly, use of rapid multiplex GI panels significantly contributed to
the recognition of a large Cyclospora outbreak in 2018.89

For all these reasons, instituting the appropriate use of these panels can be challenging. Notably, these tools do not necessarily replace certain conventional methods of microbial detection, such as bacterial and fungal culture, in the diagnosis of
infection. These many challenges and opportunities have led to the implementation of measures to promote diagnostic stewardship. Some of these include limiting expanded syndromic panels to certain groups of patients, such as the
immune-compromised, hospitalized, critically ill, or patients from specialty clinics (such as pulmonary for respiratory panels). Others include the implementation of test ordering algorithms and ‘controls’, decision support tools, and the
prohibition of repeat testing within a specific timeframe.5,53,90,91

Summary of Contractor Advisory Committee (CAC) Meeting

A multi-jurisdictional CAC Meeting to discuss the clinical literature related to Molecular Diagnostic Testing for Pathogens took place on Monday, January 11, 2021. The general consensus from the CAC panel is that there is accuracy and
reliability in these pathogen panels and that the results from panel testing may improve patient health outcomes. However, the CAC panel also noted that outcome studies from use of these panels is limited, depending on the specific panel (and
use) in question. The panel emphasized the importance of regarding patient population and setting, as indications for testing can vary among beneficiaries with different medical backgrounds and needs, and highlighted differences in testing
requirements between immune-compromised and immune-competent patients. Overall, the panel expressed that a key consideration is whether a result is going to positively impact patient care. Finally, there was consensus from the CAC
participants that the use of this technology in the diagnosis of onychomycosis (fungal infections) of the nail was unnecessary.

Analysis of Evidence (Rationale for Determination)

The goal of diagnostic stewardship is to select the right test for the right patient at the right time, to optimize patient care.92 The evidence shows that molecular syndromic panels for infectious disease testing can result in prompt patient
management, including the rapid initiation of appropriate antimicrobial therapy, the timely de-escalation of therapy, and the decrease in unnecessary therapy. In some cases, these panels have resulted in additional improvements in overall care,

7
including a decrease in the use of unnecessary diagnostic procedures and even a decrease in LOS, morbidity, and mortality. Moreover, infectious disease testing has traditionally relied on testing for multiple organisms when a physician was
unsure of the pathogen causative of a presumed infectious disease. Historically, this investigation was performed using multiple different tests and/or culture (which also detects multiple different organisms using agar plates). In this regard, panel
testing can be thought of as the use of new methodology (i.e., multiplex NAAT) for the detection of many of the same clinically valid pathogens that were historically detected using combinations of SOC methods (culture, antigen testing, etc.).
Importantly, these SOC methods also suffer from significant limitations. For all these reasons, such panel tests are considered reasonable and necessary.

However, the implementation of syndromic panels has also been a challenge, as these panels detect a fixed number of organisms, not all of which are appropriate for a given patient or setting, or during a given season. Some of these pathogens
may, in fact, be extremely rare and not be appropriate for a patient’s medical history and clinical symptoms. Further, infections with some of the organisms included on the panels are self-limited and their detection may not change management.
In such cases, testing is not required.5,18 Finally, despite their many advantages including diagnostic speed, expanded syndromic panels have shown limited clinical utility for routine use in general populations. There is not a common
circumstance in the outpatient setting for which it is reasonable and necessary to perform expanded panel testing. Rather, the clinical utility of expanded panels is most evident for select indications, populations, and settings such as
immune-compromised and hospitalized patients. On the other hand, smaller targeted panels are more applicable to broader populations, and have a broader role in the routine testing of immune-competent beneficiaries.

Additionally, while there is no evidence to suggest that a specific number of pathogens is required for inclusion in limited and expanded panels, the selected cutoff of <6 pathogens for limited panels and ≥6 for expanded panels is based on the
following: 1. CPT® codes for such panel tests are listed according to number of targets, 2. The distinction between limited and expanded panel testing is a conventional distinction used in the field, particularly for the RP and GI panels, 3. In
clinical medicine, a typical differential diagnosis usually includes the top 3-5 diagnoses for most indications for otherwise healthy populations, and is therefore aligned with such a distinction in testing, and 4. A single pathogen in the clinical
sense (i.e., ‘Influenza’) may have multiple types that require testing by the laboratory (i.e., Influenza testing, at a minimum, should include targets for Influenza A and B), rendering this type of test a ‘panel’ if used with even 1 additional
pathogen, such as RSV. While we would prefer to focus solely on relevant pathogens in different patient settings and indications, based on the literature and feedback of the CAC this is currently quite difficult; additionally, the field has settled on
a distinction between smaller targeted panels and larger ‘syndromic’ panels. We will subsequently consider this distinction for the time being in this policy until such time that the distinction is no longer necessary. For these reasons, we believe
in the general Medicare population that, for most indications, only smaller targeted tests are reasonable and necessary outside of immune-compromised patients and other limited special circumstances, as outlined in this policy and in the related
Billing and Coding article. It is important that testing is guided by the evidence in consideration of which patients will truly benefit. At present, acceptable thresholds for coverage have been met for a number of molecular syndromic infectious
disease panels. This contractor will continue to assess the evidence for coverage for additional types and indications, according to the criteria outlined in this policy.

Finally, the landscape of infectious disease diagnostics is rapidly evolving such that currently covered tests may become obsolete as new pathogens and methodologies become important for testing. One example is metagenomic testing for
infectious diseases. Unlike panel tests, which identify fixed organisms on a panel, this technology may further revolutionize the field with its high-throughput capacity, rapid results, and the ability to simultaneously identify all organisms present
in a sample.93-97 This contractor will continue to monitor the evidence, and new developments that may impact this coverage decision.

General Information

Associated Information

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58. Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States, 1998–2007. N Engl J Med. 2011;364(21):2016-2025.
59. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Critl Care Med. 2006;34(6):1589-1596.
60. Banerjee R, Teng CB, Cunningham SA, et al. Randomized trial of rapid multiplex polymerase chain reaction-based blood culture identification and susceptibility testing. Clinical Infect Dis. 2015;61(7):1071-1080.
61. MacVane SH, Nolte FS. Benefits of adding a rapid PCR-based blood culture identification panel to an established antimicrobial stewardship program. J Clin Microbiol. 2016;54(10):2455-2463.
62. Walker T, Dumadag S, Lee CJ, et al. Clinical impact of laboratory implementation of Verigene BC-GN microarray-based assay for detection of gram-negative bacteria in positive blood cultures. J Clin Microbiol. 2016;54(7):1789-1796.
63. Timbrook TT, Morton JB, McConeghy KW, Caffrey AR, Mylonakis E, LaPlante KL. The effect of molecular rapid diagnostic testing on clinical outcomes in bloodstream infections: a systematic review and meta-analysis. Clin Infect
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64. Sango A, McCarter YS, Johnson D, Ferreira J, Guzman N, Jankowski CA. Stewardship approach for optimizing antimicrobial therapy through use of a rapid microarray assay on blood cultures positive for enterococcus species. J Clin
Microbiol. 2013;51(12):4008-4011.
65. Cailleaux M, Pilmis B, Mizrahi A, et al. Impact of a multiplex PCR assay (FilmArray®) on the management of patients with suspected central nervous system infections. Eur J Clin Microbiol Infect Dis. 2020;39(2):293-297.
66. Moffa MA, Bremmer DN, Carr D, et al. Impact of a multiplex polymerase chain reaction assay on the clinical management of adults undergoing a lumbar puncture for suspected community-onset central nervous system
infections. Antibiotics (Basel). 2020;9(6):282.
67. Vollstedt A, Baunoch D, Wojno KJ, et al. Multisite prospective comparison of multiplex polymerase chain reaction testing with urine culture for diagnosis of urinary tract infections in symptomatic patients. J Sur Urol. 2020;1(1). doi:
10.29011/ JSU-102.100002.
68. Vollstedt A, Baunoch D, Wolfe A, et al. Bacterial interactions as detected by pooled antibiotic susceptibility testing (P-AST) in polymicrobial urine specimens. J Sur Urol. 2020;1(1). doi: 10.29011/JSU-101.100001.
69. Price TK, Dune T, Hilt EE, et al. The clinical urine culture: enhanced techniques improve detection of clinically relevant microorganisms. J Clin Microbiol. 2016;54(5):1216-1222.
70. Byington CL, Ampofo K, Stockmann C, et al. Community surveillance of respiratory viruses among families in the Utah better identification of germs-longitudinal viral epidemiology (BIG-LoVE) study. Clin Infect
Dis. 2015;61(8):1217-1224.
71. Richardson L, Brite J, Del Castillo M, et al. Comparison of respiratory virus shedding by conventional and molecular testing methods in patients with haematological malignancy. Clin Microbiol Infect. 2016;22(4):380.e1-380.e7.
72. Crobach MJT, Vernon JJ, Loo VG, et al. Understanding clostridium difficile colonization. Clin Microbiol Rev. 2018;31(2):e00021-17.
73. Loo VG, Bourgault AM, Poirier L, et al. Host and pathogen factors for clostridium difficile infection and colonization. N Engl J Med. 2011;365(18):1693-1703.
74. Gadsby NJ, Russell CD, McHugh MP, et al. Comprehensive molecular testing for respiratory pathogens in community-acquired pneumonia. Clin Infect Dis. 2016;62(7):817-823.
75. Lee SH, Ruan SY, Pan SC, Lee TF, Chien JY, Hsueh PR. Performance of a multiplex PCR pneumonia panel for the identification of respiratory pathogens and the main determinants of resistance from the lower respiratory tract
specimens of adult patients in intensive care units. J Microbiol Immunol Infect. 2019;52(6):920-928.
76. Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic
pretreatment. Pediatrics. 2001;108(5):1169-1174.
77. Glaser CA, Honarmand S, Anderson LJ, et al. Beyond viruses: Clinical profiles and etiologies associated with encephalitis. Clin Infect Dis. 2006;43(12):1565-1577.
78. Centers for Disease Control and Prevention. Pertussis (Whooping Cough)-Surveillance and Reporting. https://www.cdc.gov/pertussis/surv-reporting.html . Accessed January 11, 2022.
79. Craig R, Kunkel E, Crowcroft NS, et al. Asymptomatic infection and transmission of pertussis in households: a systematic review. Clin Infect Dis. 2020;70(1):152-161.
80. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America
(IDSA). Infect Control Hosp Epidemiol. 2010;31(5):431-455.
81. Scallan E, Hoekstra RM, Angulo FJ, et al. Foodborne illness acquired in the United States- major pathogens. Emerg Infect Dis. 2011;17(1):7-15.
82. Marder Mph EP, Griffin PM, Cieslak PR, et al. Preliminary incidence and trends of infections with pathogens transmitted commonly through food - Foodborne Diseases Active Surveillance Network, 10 U.S. sites, 2006-2017. MMWR
Morbidity and Mortality Weekly Report. 2018;67(11):324-328.
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84. Centers for Disease Control and Prevention. Guide for Considering Influenza Testing when Influenza Viruses are Circulating in the Community. https://www.cdc.gov/flu/professionals/diagnosis/consider-influenza-testing.htm . Accessed
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85. Crotty MP, Meyers S, Hampton N, et al. Epidemiology, co-infections, and outcomes of viral pneumonia in adults: an observational cohort study. Medicine. 2015;94(50):e2332.
86. Nickbakhsh S, Thorburn F, Von Wissmann B, McMenamin J, Gunson RN, Murcia PR. Extensive multiplex PCR diagnostics reveal new insights into the epidemiology of viral respiratory infections. Epidemiol
Infect. 2016;144(10):2064-2076.

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 87. Dalpke A, Zimmermann S, Schnitzler P. Underdiagnosing of mycoplasma pneumoniae infections as revealed by use of a respiratory multiplex PCR panel. Diagn Microbiol Infect Dis. 2016;86(1):50-52.
88. Midgley CM, Jackson MA, Selvarangan R, et al. Severe respiratory illness associated with enterovirus D68 - Missouri and Illinois, 2014. MMWR Morbidity and Mortality Weekly Report. 2014;63(36):798-799.
89. Bateman AC, Kim YJ, Guaracao AI, Mason JL, Klos RF, Warshauer DM. Performance and impact of the BioFire FilmArray gastrointestinal panel on a large cyclospora outbreak in Wisconsin, 2018. J Clin
Microbiol. 2020;58(2):e01415-19.
90. Mandelia Y, Procop GW, Richter SS, Worley S, Liu W, Esper F. Optimal timing of repeat multiplex molecular testing for respiratory viruses. J Clin Microbiol. 2020;58(2):e01203-19.
91. Pritt BS. Optimizing test utilization in the clinical microbiology laboratory: tools and opportunities. J Clin Microbiol. 2017;55(12):3321-3323.
92. Messacar K, Parker SK, Todd JK, Dominguez SR. Implementation of rapid molecular infectious disease diagnostics: the role of diagnostic and antimicrobial stewardship. J Clin Microbiol. 2017;55(3):715-723.
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94. Duan H, Li X, Mei A, et al. The diagnostic value of metagenomic next-generation sequencing in infectious diseases. BMC Infect Dis. 2021;21(1):62.
95. Greninger AL, Naccache SN. Metagenomics to assist in the diagnosis of bloodstream infection. J Appl Lab Med. 2019;3(4):643-653.
96. Niles DT, Wijetunge DSS, Palazzi DL, Singh IR, Revell PA. Plasma metagenomic next-generation sequencing assay for identifying pathogens: a retrospective review of test utilization in a large children's hospital. J Clin
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97. Ramachandran PS, Wilson MR. Metagenomics for neurological infections - expanding our imagination. Nature Reviews Neurology. 2020;16(10):547-556.

Revision History Information

Revision History Revision History

Date Number Revision History Explanation Reasons for Change
06/02/2022 R2 Under Bibliography - American Hospital Association. Updated guidelines for releasing information on the condition of patients. 2018. - broken link removed.
• Typographical Error
06/02/2022 R1 NOTE: This is the original entry for this revision:
• Provider Education/Guidance
Revision Explanation: Notice period is being extended until 07/15/2022 as there are 2 policies, L37315 and L37368, that need to go through the retirement
process that overlaps into this foundational policy.

UPDATE: On 5/19/2022, the Notice Period and Revision Effective Date of this LCD were revised. The Notice Period End Date was changed from 7/15/2022 to
6/1/2022. The Revision Effective Date was changed from 7/16/2022 to 6/2/2022. See the note at the top of the LCD for more information.
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A58726 - Billing and Coding: MolDX: Molecular Syndromic Panels for Infectious Disease Pathogen Identification Testing

A59018 - Response to Comments: MolDX: Molecular Syndromic Panels for Infectious Disease Pathogen Identification Testing

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 Updated On Effective Dates Status
12/22/2022 06/02/2022 - N/A Currently in Effect You are here

URL for source document:

https://www.cms.gov/medicare-coverage-database/view/article.aspx?articleId=58726&ver=29

Article Title

Billing and Coding: MolDX: Molecular Syndromic Panels for Infectious Disease Pathogen Identification Testing

Article Type

Billing and Coding

AMA CPT / ADA CDT / AHA NUBC Copyright Statement

CPT codes, descriptions and other data only are copyright 2022 American Medical Association. All Rights Reserved. Applicable FARS/HHSARS apply.

Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or
dispense medical services. The AMA assumes no liability for data contained or not contained herein.

Current Dental Terminology © 2022 American Dental Association. All rights reserved.

Copyright © 2023, the American Hospital Association, Chicago, Illinois. Reproduced with permission. No portion of the American Hospital Association (AHA) copyrighted materials contained within this publication may be copied without the
express written consent of the AHA. AHA copyrighted materials including the UB‐04 codes and descriptions may not be removed, copied, or utilized within any software, product, service, solution or derivative work without the written consent
of the AHA. If an entity wishes to utilize any AHA materials, please contact the AHA at 312‐893‐6816.

Making copies or utilizing the content of the UB‐04 Manual, including the codes and/or descriptions, for internal purposes, resale and/or to be used in any product or publication; creating any modified or derivative work of the UB‐04 Manual
and/or codes and descriptions; and/or making any commercial use of UB‐04 Manual or any portion thereof, including the codes and/or descriptions, is only authorized with an express license from the American Hospital Association. The
American Hospital Association (the "AHA") has not reviewed, and is not responsible for, the completeness or accuracy of any information contained in this material, nor was the AHA or any of its affiliates, involved in the preparation of this
material, or the analysis of information provided in the material. The views and/or positions presented in the material do not necessarily represent the views of the AHA. CMS and its products and services are not endorsed by the AHA or any of
its affiliates.

CMS National Coverage Policy

Title XVIII of the Social Security Act, §1833(e) prohibits Medicare payment for any claim which lacks the necessary information to process the claim.

CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, §80.1.2 A/B MAC (B) Contacts With Independent Clinical Laboratories.

Article Guidance

Article Text

12
The information in this article contains billing, coding or other guidelines that complement the Local Coverage Determination (LCD) for MolDX: Molecular Syndromic Panels for Infectious Disease Testing Panels for Infectious Disease Testing
L39003.

To report a service for Molecular Syndromic Panels for Infectious Disease Pathogen Identification Testing, please submit the following claim information:

• Select the appropriate CPT® or PLA code

• If the panel being used does not have its own proprietary CPT® or PLA code, select the appropriate CPT® code and follow the additional instructions for the given 'panel' in the relevant Group paragraphs below. If no specific
CPT® code exists for the test submitted, bill with CPT® code 87999.
®
• CPT codes that are not billed with the appropriate accompanying ICD-10 codes listed in this Billing and Coding Article will be denied. Tests with other indicated uses may therefore submit for a Z-code and undergo a Technical
Assessment (TA) by MolDX. Tests using CPT® code 87999 will also require a Z-Code and a TA.
• Tests that are FDA-approved/cleared and performed in ways consistent with their intended use labeling directions do not require a Z-code when billed with an appropriate accompanying ICD-10 code. However, the performance of
multiple (>1) FDA-approved/cleared molecular Infectious Disease pathogen identification tests on the same date of service (DOS) for the same intended use on the same patient sample is considered as one distinct service. As such, it
would require the use of CPT® code 87999. Tests using CPT® code 87999 will require a Z-Code and a TA.
• Add modifier 59 for different species or strains reported by the same code, as allowed by the policy.
• Enter 1 unit of service (UOS)
• If applicable, enter the appropriate DEX Z-Code™ identifier adjacent to the CPT® code in the comment/narrative field for the following Part B claim field/types:
• Loop 2400 or SV101-7 for the 5010A1 837P
• Item 19 for paper claim
• If applicable, enter the appropriate DEX Z-Code™ identifier adjacent to the CPT® code in the comment/narrative field for the following Part A claim field/types:
• Line SV202-7 for 837I electronic claim
• Block 80 for the UB04 claim form
• Select the appropriate ICD-10-CM code(s)

ICD-10-CM diagnosis codes supporting medical necessity must be submitted with each claim. Claims submitted without such evidence will be denied as not medically necessary.

Any diagnosis submitted must have documentation in the patient’s record to support coverage and medical necessity.

The submitted medical record must support the use of the selected ICD-10-CM code(s). The submitted CPT/HCPCS code must describe the service performed.

Additional information:

• Panels intended for home use (including those that have been FDA approved or cleared) do NOT meet the coverage criteria of the policy.
• This contractor expects that critically ill patients will be tested and managed in the appropriate critical care facility.
• The test panel is a single test with multiple components and is characterized by a single unit of service (UOS =1). A panel cannot be unbundled and billed as individual components regardless of the fact that the test reports multiple
individual pathogens and/or targets. If additional organisms are not included in a panel, testing for those organisms separately may be reasonable and necessary when ordered in addition to the panel and supported by documentation in the
medical record.
• As outlined in the policy, for a given date of service for the same clinical indication, the performance of an additional panel for content that is non-duplicative can only be billed for the non-duplicative content if supported by
documentation in the medical record and all other criteria outlined in the associated policy.
• When 2 or more codes within a given Group OR from 2 related Groups (i.e., Groups 1 and 6 which pertain to Respiratory panels, or Groups 2 and 7 which pertain to Gastrointestinal panels) are submitted for the same
beneficiary on the same date of service for the same (or highly similar) intended use, the claims processing system will reject every code submitted after the first service. As outlined in the policy, exceptions may be allowed in
limited circumstances for bloodstream and meningoencephalitis panels testing for non-duplicative content. For such cases, if a lab runs more than 1 distinct procedural service from this list on a single date of service, then the lab
must use the 59 modifier with each additional service billed as an attestation that it is a distinct procedural service.
• Repeat panel tests for the same clinical indication will NOT be reimbursed, except according to the criteria outlined in the related LCD (i.e., 1 additional panel test may be performed between 1 and 14 days after the initial panel test, so
long as the test fulfills the criteria for coverage as set forth in the policy).
• Laboratories that are billing for multiple individual pathogens using the 59 modifier rather than panels may be subject to medical review as outliers. Similarly, laboratories billing for multiple related panels may be subject to medical
review as outliers.

It is understood that in certain instances in which only targeted testing is appropriate, institutions may not have access to small panels and may have to perform larger panels for technical reasons. In such cases, Noridian will pay only for
components of a service that are reasonable and necessary.

• For Expanded (>5 pathogens) RP, PNP, and GI Panels the following additional conditions apply:
1. Testing is billed according to 1 of the following:

(a) Places of service 19, 21, 22, 23, OR

13
(b) The test is ordered as follows (for healthcare POS other than the POS listed in (a)):

(1) For immune-competent beneficiaries, the test must be ordered by an Infectious Disease Specialist or 1 of the following: Pulmonologist (for the RP and PNP panels) or Gastroenterologist (for the GI panels) who is diagnosing and treating the
beneficiary.

(2) For immune-compromised beneficiaries, the test must be ordered by a clinician specialist in 1 of the following: Infectious Diseases, Oncology, Transplant (for any panel), Pulmonologist (for the RP and PNP panels), or Gastroenterologist
(for the GI panels) who is diagnosing and treating the beneficiary.

(3) Regarding (1) and (2), An exception may be made in geographic locations where the specialist(s) cannot be reasonably reached by the beneficiary, and the ordering provider is located closer to the beneficiary’s place of residence than the
nearest specialist. We would generally expect that beneficiaries for whom the test is ordered under this exception to be living in rural locations, islands, or some other location where access to care is limited.

(4) An ICD-10 diagnosis code from Group 6 or Group 7 must be on the claim, in addition to the sign or symptom (from Groups 1 or 2) for which there is suspicion of respiratory or gastrointestinal illness in order to bill for the RP/PNP or GI
panels, respectively. See the specific instructions in Groups 6 and 7 below. The exception to this is testing that is performed as part of a pre-transplant evaluation of an immune-compromised beneficiary, regardless of the presence of symptoms.
In such cases, clear documentation of the pre-transplant evaluation must accompany the claim.

The expanded/targeted panel distinction is not applicable to all panels, except as otherwise indicated in the related policy.

Coding Information

CPT/HCPCS Codes

Group 1

(6 Codes)

Group 1 Paragraph

Targeted Respiratory Panels:

These codes are covered under limited circumstances.

Group 1 Codes

Code Description
87631 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); RESPIRATORY VIRUS (EG, ADENOVIRUS, INFLUENZA VIRUS, CORONAVIRUS, METAPNEUMOVIRUS, PARAINFLUENZA VIRUS,
RESPIRATORY SYNCYTIAL VIRUS, RHINOVIRUS), INCLUDES MULTIPLEX REVERSE TRANSCRIPTION, WHEN PERFORMED, AND MULTIPLEX AMPLIFIED PROBE TECHNIQUE, MULTIPLE TYPES OR
SUBTYPES, 3-5 TARGETS
87636 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) (CORONAVIRUS DISEASE [COVID-19]) AND INFLUENZA
VIRUS TYPES A AND B, MULTIPLEX AMPLIFIED PROBE TECHNIQUE
87637 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) (CORONAVIRUS DISEASE [COVID-19]), INFLUENZA VIRUS
TYPES A AND B, AND RESPIRATORY SYNCYTIAL VIRUS, MULTIPLEX AMPLIFIED PROBE TECHNIQUE
87801 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA), MULTIPLE ORGANISMS; AMPLIFIED PROBE(S) TECHNIQUE
0240U INFECTIOUS DISEASE (VIRAL RESPIRATORY TRACT INFECTION), PATHOGEN-SPECIFIC RNA, 3 TARGETS (SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 [SARS-COV-2], INFLUENZA A,
INFLUENZA B), UPPER RESPIRATORY SPECIMEN, EACH PATHOGEN REPORTED AS DETECTED OR NOT DETECTED
0241U INFECTIOUS DISEASE (VIRAL RESPIRATORY TRACT INFECTION), PATHOGEN-SPECIFIC RNA, 4 TARGETS (SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 [SARS-COV-2], INFLUENZA A,
INFLUENZA B, RESPIRATORY SYNCYTIAL VIRUS [RSV]), UPPER RESPIRATORY SPECIMEN, EACH PATHOGEN REPORTED AS DETECTED OR NOT DETECTED
Group 2

(1 Code)

Group 2 Paragraph

Targeted Gastrointestinal Panels:

14
This code is covered under limited circumstances.

Group 2 Codes

Code Description
87505 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); GASTROINTESTINAL PATHOGEN (EG, CLOSTRIDIUM DIFFICILE, E. COLI, SALMONELLA, SHIGELLA, NOROVIRUS, GIARDIA),
INCLUDES MULTIPLEX REVERSE TRANSCRIPTION, WHEN PERFORMED, AND MULTIPLEX AMPLIFIED PROBE TECHNIQUE, MULTIPLE TYPES OR SUBTYPES, 3-5 TARGETS
Group 3

(1 Code)

Group 3 Paragraph

Meningoencephalitis Panels:

This code is covered under limited circumstances.

Group 3 Codes

Code Description
87483 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CENTRAL NERVOUS SYSTEM PATHOGEN (EG, NEISSERIA MENINGITIDIS, STREPTOCOCCUS PNEUMONIAE, LISTERIA, HAEMOPHILUS
INFLUENZAE, E. COLI, STREPTOCOCCUS AGALACTIAE, ENTEROVIRUS, HUMAN PARECHOVIRUS, HERPES SIMPLEX VIRUS TYPE 1 AND 2, HUMAN HERPESVIRUS 6, CYTOMEGALOVIRUS, VARICELLA
ZOSTER VIRUS, CRYPTOCOCCUS), INCLUDES MULTIPLEX REVERSE TRANSCRIPTION, WHEN PERFORMED, AND MULTIPLEX AMPLIFIED PROBE TECHNIQUE, MULTIPLE TYPES OR SUBTYPES, 12-25
TARGETS
Group 4

(1 Code)

Group 4 Paragraph

Bloodstream Infection Panels:

This code is covered under limited circumstances.

Group 4 Codes

Code Description
87154 CULTURE, TYPING; IDENTIFICATION OF BLOOD PATHOGEN AND RESISTANCE TYPING, WHEN PERFORMED, BY NUCLEIC ACID (DNA OR RNA) PROBE, MULTIPLEXED AMPLIFIED PROBE TECHNIQUE
INCLUDING MULTIPLEX REVERSE TRANSCRIPTION, WHEN PERFORMED, PER CULTURE OR ISOLATE, 6 OR MORE TARGETS
Group 5

(7 Codes)

Group 5 Paragraph

Urogenital/Anogenital Panels:

These codes are covered under limited circumstances.

Group 5 Codes

15
 Code Description
81513 INFECTIOUS DISEASE, BACTERIAL VAGINOSIS, QUANTITATIVE REAL-TIME AMPLIFICATION OF RNA MARKERS FOR ATOPOBIUM VAGINAE, GARDNERELLA VAGINALIS, AND LACTOBACILLUS
SPECIES, UTILIZING VAGINAL-FLUID SPECIMENS, ALGORITHM REPORTED AS A POSITIVE OR NEGATIVE RESULT FOR BACTERIAL VAGINOSIS
81514 INFECTIOUS DISEASE, BACTERIAL VAGINOSIS AND VAGINITIS, QUANTITATIVE REAL-TIME AMPLIFICATION OF DNA MARKERS FOR GARDNERELLA VAGINALIS, ATOPOBIUM VAGINAE,
MEGASPHAERA TYPE 1, BACTERIAL VAGINOSIS ASSOCIATED BACTERIA-2 (BVAB-2), AND LACTOBACILLUS SPECIES (L. CRISPATUS AND L. JENSENII), UTILIZING VAGINAL-FLUID SPECIMENS,
ALGORITHM REPORTED AS A POSITIVE OR NEGATIVE FOR HIGH LIKELIHOOD OF BACTERIAL VAGINOSIS, INCLUDES SEPARATE DETECTION OF TRICHOMONAS VAGINALIS AND/OR CANDIDA SPECIES
(C. ALBICANS, C. TROPICALIS, C. PARAPSILOSIS, C. DUBLINIENSIS), CANDIDA GLABRATA, CANDIDA KRUSEI, WHEN REPORTED
87800 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA), MULTIPLE ORGANISMS; DIRECT PROBE(S) TECHNIQUE
87801 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA), MULTIPLE ORGANISMS; AMPLIFIED PROBE(S) TECHNIQUE
87999 UNLISTED MICROBIOLOGY PROCEDURE
0352U INFECTIOUS DISEASE (BACTERIAL VAGINOSIS AND VAGINITIS), MULTIPLEX AMPLIFIED PROBE TECHNIQUE, FOR DETECTION OF BACTERIAL VAGINOSIS-ASSOCIATED BACTERIA (BVAB-2,
ATOPOBIUM VAGINAE, AND MEGASPHERA TYPE 1), ALGORITHM REPORTED AS DETECTED OR NOT DETECTED AND SEPARATE DETECTION OF CANDIDA SPECIES (C. ALBICANS, C. TROPICALIS, C.
PARAPSILOSIS, C. DUBLINIENSIS), CANDIDA GLABRATA/CANDIDA KRUSEI, AND TRICHOMONAS VAGINALIS, VAGINAL-FLUID SPECIMEN, EACH RESULT REPORTED AS DETECTED OR NOT DETECTED
0353U INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA), CHLAMYDIA TRACHOMATIS AND NEISSERIA GONORRHOEAE, MULTIPLEX AMPLIFIED PROBE TECHNIQUE, URINE, VAGINAL, PHARYNGEAL,
OR RECTAL, EACH PATHOGEN REPORTED AS DETECTED OR NOT DETECTED
Group 6

(8 Codes)

Group 6 Paragraph

Expanded Respiratory and Pneumonia Panels:

Covered under limited circumstances. Per policy, these codes are covered in beneficiaries with serious or critical illness or at imminent risk of becoming seriously or critically ill, immunodeficiency, and/or severe underlying condition
contributory to testing using an expanded syndromic panel.

Testing is billed according to 1 of the following:

(a) Places of service (POS) 19, 21, 22, 23, OR

(b) The test is ordered as follows (for healthcare POS other than those listed in (a)):

(1) For immune-competent beneficiaries, the test must be ordered by an Infectious Disease Specialist or Pulmonologist who is diagnosing and treating the beneficiary.

(2) For immune-compromised beneficiaries, the test must be ordered by a clinician specialist in 1 of the following: Infectious Diseases, Oncology, Transplant (for any panel), or Pulmonologist who is diagnosing and treating the beneficiary.

(3) Regarding (1) and (2), An exception may be made in geographic locations where the specialist(s) cannot be reasonably reached by the beneficiary, and the ordering provider is located closer to the beneficiary’s place of residence than the
nearest specialist. We would generally expect that beneficiaries for whom the test is ordered under this exception to be living in rural locations, islands, or some other location where access to care is limited.

(4) For testing in POS other than POS 19, 21, 22, or 23, to bill one of the Group 6 CPT codes, TWO ICD-10 codes are required-one from Group 6 and another from Group 1.

Group 6 Codes

Code Description
87632 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); RESPIRATORY VIRUS (EG, ADENOVIRUS, INFLUENZA VIRUS, CORONAVIRUS, METAPNEUMOVIRUS, PARAINFLUENZA VIRUS,
RESPIRATORY SYNCYTIAL VIRUS, RHINOVIRUS), INCLUDES MULTIPLEX REVERSE TRANSCRIPTION, WHEN PERFORMED, AND MULTIPLEX AMPLIFIED PROBE TECHNIQUE, MULTIPLE TYPES OR
SUBTYPES, 6-11 TARGETS
87633 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); RESPIRATORY VIRUS (EG, ADENOVIRUS, INFLUENZA VIRUS, CORONAVIRUS, METAPNEUMOVIRUS, PARAINFLUENZA VIRUS,
RESPIRATORY SYNCYTIAL VIRUS, RHINOVIRUS), INCLUDES MULTIPLEX REVERSE TRANSCRIPTION, WHEN PERFORMED, AND MULTIPLEX AMPLIFIED PROBE TECHNIQUE, MULTIPLE TYPES OR
SUBTYPES, 12-25 TARGETS
87801 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA), MULTIPLE ORGANISMS; AMPLIFIED PROBE(S) TECHNIQUE
87999 UNLISTED MICROBIOLOGY PROCEDURE
0115U RESPIRATORY INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA AND RNA), 18 VIRAL TYPES AND SUBTYPES AND 2 BACTERIAL TARGETS, AMPLIFIED PROBE TECHNIQUE, INCLUDING
MULTIPLEX REVERSE TRANSCRIPTION FOR RNA TARGETS, EACH ANALYTE REPORTED AS DETECTED OR NOT DETECTED

16
0202U INFECTIOUS DISEASE (BACTERIAL OR VIRAL RESPIRATORY TRACT INFECTION), PATHOGEN-SPECIFIC NUCLEIC ACID (DNA OR RNA), 22 TARGETS INCLUDING SEVERE ACUTE RESPIRATORY
SYNDROME CORONAVIRUS 2 (SARS-COV-2), QUALITATIVE RT-PCR, NASOPHARYNGEAL SWAB, EACH PATHOGEN REPORTED AS DETECTED OR NOT DETECTED
0223U INFECTIOUS DISEASE (BACTERIAL OR VIRAL RESPIRATORY TRACT INFECTION), PATHOGEN-SPECIFIC NUCLEIC ACID (DNA OR RNA), 22 TARGETS INCLUDING SEVERE ACUTE RESPIRATORY
SYNDROME CORONAVIRUS 2 (SARS-COV-2), QUALITATIVE RT-PCR, NASOPHARYNGEAL SWAB, EACH PATHOGEN REPORTED AS DETECTED OR NOT DETECTED
0225U INFECTIOUS DISEASE (BACTERIAL OR VIRAL RESPIRATORY TRACT INFECTION) PATHOGEN-SPECIFIC DNA AND RNA, 21 TARGETS, INCLUDING SEVERE ACUTE RESPIRATORY SYNDROME
CORONAVIRUS 2 (SARS-COV-2), AMPLIFIED PROBE TECHNIQUE, INCLUDING MULTIPLEX REVERSE TRANSCRIPTION FOR RNA TARGETS, EACH ANALYTE REPORTED AS DETECTED OR NOT DETECTED
Group 7

(2 Codes)

Group 7 Paragraph

Expanded Gastrointestinal Panels:

Covered under limited circumstances. Per policy, these codes are covered in beneficiaries with serious or critical illness or at imminent risk of becoming seriously or critically ill, immunodeficiency, and/or severe underlying condition
contributory to testing using an expanded syndromic panel.

(a) Places of service (POS) 19, 21, 22, 23, OR

(b) The test is ordered as follows (for healthcare POS other than those listed in (a)):

(1) For immune-competent beneficiaries, the test must be ordered by an Infectious Disease Specialist or Gastroenterologist who is diagnosing and treating the beneficiary.

(2) For immune-compromised beneficiaries, the test must be ordered by a clinician specialist in 1 of the following: Infectious Diseases, Oncology, Transplant (for any panel), or Gastroenterologist who is diagnosing and treating the beneficiary.

(3) Regarding (1) and (2), An exception may be made in geographic locations where the specialist(s) cannot be reasonably reached by the beneficiary, and the ordering provider is located closer to the beneficiary’s place of residence than the
nearest specialist. We would generally expect that beneficiaries for whom the test is ordered under this exception to be living in rural locations, islands, or some other location where access to care is limited.

(4) For testing in POS other than POS 19, 21, 22, or 23, to bill one of the Group 7 CPT codes, TWO ICD-10 codes are required-one from Group 7 and another from Group 2.

Group 7 Codes

Code Description
87506 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); GASTROINTESTINAL PATHOGEN (EG, CLOSTRIDIUM DIFFICILE, E. COLI, SALMONELLA, SHIGELLA, NOROVIRUS, GIARDIA),
INCLUDES MULTIPLEX REVERSE TRANSCRIPTION, WHEN PERFORMED, AND MULTIPLEX AMPLIFIED PROBE TECHNIQUE, MULTIPLE TYPES OR SUBTYPES, 6-11 TARGETS
87507 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); GASTROINTESTINAL PATHOGEN (EG, CLOSTRIDIUM DIFFICILE, E. COLI, SALMONELLA, SHIGELLA, NOROVIRUS, GIARDIA),
INCLUDES MULTIPLEX REVERSE TRANSCRIPTION, WHEN PERFORMED, AND MULTIPLEX AMPLIFIED PROBE TECHNIQUE, MULTIPLE TYPES OR SUBTYPES, 12-25 TARGETS
Group 8

(90 Codes)

Group 8 Paragraph

Conditionally Non-covered CPT codes:

The following CPT codes are NOT covered for a given beneficiary on the same DOS when >1 is billed in combination with another CPT or PLA code from Groups 1-7 for the same intended use.

Additionally, the following CPT codes are NOT covered for a given beneficiary on the same DOS when >2 are billed for the same intended use.

Group 8 Codes

Code Description

17
87149 CULTURE, TYPING; IDENTIFICATION BY NUCLEIC ACID (DNA OR RNA) PROBE, DIRECT PROBE TECHNIQUE, PER CULTURE OR ISOLATE, EACH ORGANISM PROBED
87150 CULTURE, TYPING; IDENTIFICATION BY NUCLEIC ACID (DNA OR RNA) PROBE, AMPLIFIED PROBE TECHNIQUE, PER CULTURE OR ISOLATE, EACH ORGANISM PROBED
87153 CULTURE, TYPING; IDENTIFICATION BY NUCLEIC ACID SEQUENCING METHOD, EACH ISOLATE (EG, SEQUENCING OF THE 16S RRNA GENE)
87468 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); ANAPLASMA PHAGOCYTOPHILUM, AMPLIFIED PROBE TECHNIQUE
87469 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); BABESIA MICROTI, AMPLIFIED PROBE TECHNIQUE
87471 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); BARTONELLA HENSELAE AND BARTONELLA QUINTANA, AMPLIFIED PROBE TECHNIQUE
87472 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); BARTONELLA HENSELAE AND BARTONELLA QUINTANA, QUANTIFICATION
87475 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); BORRELIA BURGDORFERI, DIRECT PROBE TECHNIQUE
87476 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); BORRELIA BURGDORFERI, AMPLIFIED PROBE TECHNIQUE
87478 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); BORRELIA MIYAMOTOI, AMPLIFIED PROBE TECHNIQUE
87480 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CANDIDA SPECIES, DIRECT PROBE TECHNIQUE
87481 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CANDIDA SPECIES, AMPLIFIED PROBE TECHNIQUE
87482 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CANDIDA SPECIES, QUANTIFICATION
87484 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); EHRLICHIA CHAFFEENSIS, AMPLIFIED PROBE TECHNIQUE
87485 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CHLAMYDIA PNEUMONIAE, DIRECT PROBE TECHNIQUE
87486 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CHLAMYDIA PNEUMONIAE, AMPLIFIED PROBE TECHNIQUE
87487 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CHLAMYDIA PNEUMONIAE, QUANTIFICATION
87490 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CHLAMYDIA TRACHOMATIS, DIRECT PROBE TECHNIQUE
87491 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CHLAMYDIA TRACHOMATIS, AMPLIFIED PROBE TECHNIQUE
87492 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CHLAMYDIA TRACHOMATIS, QUANTIFICATION
87493 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CLOSTRIDIUM DIFFICILE, TOXIN GENE(S), AMPLIFIED PROBE TECHNIQUE
87495 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CYTOMEGALOVIRUS, DIRECT PROBE TECHNIQUE
87496 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CYTOMEGALOVIRUS, AMPLIFIED PROBE TECHNIQUE
87497 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); CYTOMEGALOVIRUS, QUANTIFICATION
87498 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); ENTEROVIRUS, AMPLIFIED PROBE TECHNIQUE, INCLUDES REVERSE TRANSCRIPTION WHEN PERFORMED
87501 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); INFLUENZA VIRUS, INCLUDES REVERSE TRANSCRIPTION, WHEN PERFORMED, AND AMPLIFIED PROBE TECHNIQUE, EACH TYPE OR
SUBTYPE
87502 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); INFLUENZA VIRUS, FOR MULTIPLE TYPES OR SUB-TYPES, INCLUDES MULTIPLEX REVERSE TRANSCRIPTION, WHEN PERFORMED,
AND MULTIPLEX AMPLIFIED PROBE TECHNIQUE, FIRST 2 TYPES OR SUB-TYPES
87503 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); INFLUENZA VIRUS, FOR MULTIPLE TYPES OR SUB-TYPES, INCLUDES MULTIPLEX REVERSE TRANSCRIPTION, WHEN PERFORMED,
AND MULTIPLEX AMPLIFIED PROBE TECHNIQUE, EACH ADDITIONAL INFLUENZA VIRUS TYPE OR SUB-TYPE BEYOND 2 (LIST SEPARATELY IN ADDITION TO CODE FOR PRIMARY PROCEDURE)
87510 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); GARDNERELLA VAGINALIS, DIRECT PROBE TECHNIQUE
87511 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); GARDNERELLA VAGINALIS, AMPLIFIED PROBE TECHNIQUE
87512 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); GARDNERELLA VAGINALIS, QUANTIFICATION
87516 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HEPATITIS B VIRUS, AMPLIFIED PROBE TECHNIQUE
87517 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HEPATITIS B VIRUS, QUANTIFICATION
87520 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HEPATITIS C, DIRECT PROBE TECHNIQUE
87521 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HEPATITIS C, AMPLIFIED PROBE TECHNIQUE, INCLUDES REVERSE TRANSCRIPTION WHEN PERFORMED
87522 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HEPATITIS C, QUANTIFICATION, INCLUDES REVERSE TRANSCRIPTION WHEN PERFORMED
87525 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HEPATITIS G, DIRECT PROBE TECHNIQUE
87526 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HEPATITIS G, AMPLIFIED PROBE TECHNIQUE
87527 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HEPATITIS G, QUANTIFICATION
87528 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HERPES SIMPLEX VIRUS, DIRECT PROBE TECHNIQUE
87529 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HERPES SIMPLEX VIRUS, AMPLIFIED PROBE TECHNIQUE
87530 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HERPES SIMPLEX VIRUS, QUANTIFICATION
87531 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HERPES VIRUS-6, DIRECT PROBE TECHNIQUE
87532 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HERPES VIRUS-6, AMPLIFIED PROBE TECHNIQUE
87533 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HERPES VIRUS-6, QUANTIFICATION
87534 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HIV-1, DIRECT PROBE TECHNIQUE
87535 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HIV-1, AMPLIFIED PROBE TECHNIQUE, INCLUDES REVERSE TRANSCRIPTION WHEN PERFORMED
87536 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HIV-1, QUANTIFICATION, INCLUDES REVERSE TRANSCRIPTION WHEN PERFORMED
87537 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HIV-2, DIRECT PROBE TECHNIQUE
87538 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HIV-2, AMPLIFIED PROBE TECHNIQUE, INCLUDES REVERSE TRANSCRIPTION WHEN PERFORMED
87539 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HIV-2, QUANTIFICATION, INCLUDES REVERSE TRANSCRIPTION WHEN PERFORMED

18
87540 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); LEGIONELLA PNEUMOPHILA, DIRECT PROBE TECHNIQUE
87541 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); LEGIONELLA PNEUMOPHILA, AMPLIFIED PROBE TECHNIQUE
87542 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); LEGIONELLA PNEUMOPHILA, QUANTIFICATION
87550 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOBACTERIA SPECIES, DIRECT PROBE TECHNIQUE
87551 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOBACTERIA SPECIES, AMPLIFIED PROBE TECHNIQUE
87552 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOBACTERIA SPECIES, QUANTIFICATION
87555 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOBACTERIA TUBERCULOSIS, DIRECT PROBE TECHNIQUE
87556 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOBACTERIA TUBERCULOSIS, AMPLIFIED PROBE TECHNIQUE
87557 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOBACTERIA TUBERCULOSIS, QUANTIFICATION
87560 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOBACTERIA AVIUM-INTRACELLULARE, DIRECT PROBE TECHNIQUE
87561 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOBACTERIA AVIUM-INTRACELLULARE, AMPLIFIED PROBE TECHNIQUE
87562 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOBACTERIA AVIUM-INTRACELLULARE, QUANTIFICATION
87563 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOPLASMA GENITALIUM, AMPLIFIED PROBE TECHNIQUE
87580 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOPLASMA PNEUMONIAE, DIRECT PROBE TECHNIQUE
87581 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOPLASMA PNEUMONIAE, AMPLIFIED PROBE TECHNIQUE
87582 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); MYCOPLASMA PNEUMONIAE, QUANTIFICATION
87590 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); NEISSERIA GONORRHOEAE, DIRECT PROBE TECHNIQUE
87591 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); NEISSERIA GONORRHOEAE, AMPLIFIED PROBE TECHNIQUE
87592 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); NEISSERIA GONORRHOEAE, QUANTIFICATION
87593 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); ORTHOPOXVIRUS (EG, MONKEYPOX VIRUS, COWPOX VIRUS, VACCINIA VIRUS), AMPLIFIED PROBE TECHNIQUE, EACH
87623 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HUMAN PAPILLOMAVIRUS (HPV), LOW-RISK TYPES (EG, 6, 11, 42, 43, 44)
87624 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HUMAN PAPILLOMAVIRUS (HPV), HIGH-RISK TYPES (EG, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68)
87625 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); HUMAN PAPILLOMAVIRUS (HPV), TYPES 16 AND 18 ONLY, INCLUDES TYPE 45, IF PERFORMED
87634 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); RESPIRATORY SYNCYTIAL VIRUS, AMPLIFIED PROBE TECHNIQUE
87635 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) (CORONAVIRUS DISEASE [COVID-19]), AMPLIFIED PROBE
TECHNIQUE
87640 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); STAPHYLOCOCCUS AUREUS, AMPLIFIED PROBE TECHNIQUE
87641 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); STAPHYLOCOCCUS AUREUS, METHICILLIN RESISTANT, AMPLIFIED PROBE TECHNIQUE
87650 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); STREPTOCOCCUS, GROUP A, DIRECT PROBE TECHNIQUE
87651 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); STREPTOCOCCUS, GROUP A, AMPLIFIED PROBE TECHNIQUE
87652 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); STREPTOCOCCUS, GROUP A, QUANTIFICATION
87653 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); STREPTOCOCCUS, GROUP B, AMPLIFIED PROBE TECHNIQUE
87660 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); TRICHOMONAS VAGINALIS, DIRECT PROBE TECHNIQUE
87661 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); TRICHOMONAS VAGINALIS, AMPLIFIED PROBE TECHNIQUE
87662 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA); ZIKA VIRUS, AMPLIFIED PROBE TECHNIQUE
87797 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA), NOT OTHERWISE SPECIFIED; DIRECT PROBE TECHNIQUE, EACH ORGANISM
87798 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA), NOT OTHERWISE SPECIFIED; AMPLIFIED PROBE TECHNIQUE, EACH ORGANISM
87799 INFECTIOUS AGENT DETECTION BY NUCLEIC ACID (DNA OR RNA), NOT OTHERWISE SPECIFIED; QUANTIFICATION, EACH ORGANISM
U0001 CDC 2019 NOVEL CORONAVIRUS (2019-NCOV) REAL-TIME RT-PCR DIAGNOSTIC PANEL
U0002 2019-NCOV CORONAVIRUS, SARS-COV-2/2019-NCOV (COVID-19), ANY TECHNIQUE, MULTIPLE TYPES OR SUBTYPES (INCLUDES ALL TARGETS), NON-CDC
CPT/HCPCS Modifiers

Group 1

(1 Code)

Group 1 Paragraph

N/A

Group 1 Codes

Code Description
59 DISTINCT PROCEDURAL SERVICE: UNDER CERTAIN CIRCUMSTANCES, THE PHYSICIAN MAY NEED TO INDICATE THAT A PROCEDURE OR SERVICE WAS DISTINCT OR INDEPENDENT FROM OTHER

19
 SERVICES PERFORMED ON THE SAME DAY. MODIFIER -59 IS USED TO IDENTIFY PROCEDURES/SERVICES THAT ARE NOT NORMALLY REPORTED TOGETHER, BUT ARE APPROPRIATE UNDER THE
CIRCUMSTANCES. THIS MAY REPRESENT A DIFFERENT SESSION OR PATIENT ENCOUNTER, DIFFERENT PROCEDURE OR SURGERY, DIFFERNET SITE OR ORGAN SYSTEM, SEPARATE
INCISION/EXCISION, SEPARATE LESION, OR SEPARATE INJURY (OR AREA OF INJURY IN EXTENSIVE INJURIES) NOT ORDINARILY ENCOUNTERED OR PERFORMED ON THE SAME DAY BY THE SAME
PHYSICIAN. HOWEVER, WHAN ANOTHER ALREADY ESTABLISHED MODIFIER IS APPROPRIATE IT SHOULD BE USED RATHER THAN MODIFIER -59. ONLY IF NO MORE DESCRIPTIVE MODIFIER IS
AVAILABLE, AND THE USE OF MODIFIER -59 BEST EXPLAINS THE CIRCUMSTANCES, SHOULD MODIFIER -59 BE USED. MODIFIER CODE 09959 MAY BE USED AS AN ALTERNATE TO MODIFIER -59.
Group 2

(1 Code)

Group 2 Paragraph

N/A

Group 2 Codes

Code Description
59 DISTINCT PROCEDURAL SERVICE: UNDER CERTAIN CIRCUMSTANCES, THE PHYSICIAN MAY NEED TO INDICATE THAT A PROCEDURE OR SERVICE WAS DISTINCT OR INDEPENDENT FROM OTHER
SERVICES PERFORMED ON THE SAME DAY. MODIFIER -59 IS USED TO IDENTIFY PROCEDURES/SERVICES THAT ARE NOT NORMALLY REPORTED TOGETHER, BUT ARE APPROPRIATE UNDER THE
CIRCUMSTANCES. THIS MAY REPRESENT A DIFFERENT SESSION OR PATIENT ENCOUNTER, DIFFERENT PROCEDURE OR SURGERY, DIFFERNET SITE OR ORGAN SYSTEM, SEPARATE
INCISION/EXCISION, SEPARATE LESION, OR SEPARATE INJURY (OR AREA OF INJURY IN EXTENSIVE INJURIES) NOT ORDINARILY ENCOUNTERED OR PERFORMED ON THE SAME DAY BY THE SAME
PHYSICIAN. HOWEVER, WHAN ANOTHER ALREADY ESTABLISHED MODIFIER IS APPROPRIATE IT SHOULD BE USED RATHER THAN MODIFIER -59. ONLY IF NO MORE DESCRIPTIVE MODIFIER IS
AVAILABLE, AND THE USE OF MODIFIER -59 BEST EXPLAINS THE CIRCUMSTANCES, SHOULD MODIFIER -59 BE USED. MODIFIER CODE 09959 MAY BE USED AS AN ALTERNATE TO MODIFIER -59.
Group 3

(1 Code)

Group 3 Paragraph

N/A

Group 3 Codes

Code Description
59 DISTINCT PROCEDURAL SERVICE: UNDER CERTAIN CIRCUMSTANCES, THE PHYSICIAN MAY NEED TO INDICATE THAT A PROCEDURE OR SERVICE WAS DISTINCT OR INDEPENDENT FROM OTHER
SERVICES PERFORMED ON THE SAME DAY. MODIFIER -59 IS USED TO IDENTIFY PROCEDURES/SERVICES THAT ARE NOT NORMALLY REPORTED TOGETHER, BUT ARE APPROPRIATE UNDER THE
CIRCUMSTANCES. THIS MAY REPRESENT A DIFFERENT SESSION OR PATIENT ENCOUNTER, DIFFERENT PROCEDURE OR SURGERY, DIFFERNET SITE OR ORGAN SYSTEM, SEPARATE
INCISION/EXCISION, SEPARATE LESION, OR SEPARATE INJURY (OR AREA OF INJURY IN EXTENSIVE INJURIES) NOT ORDINARILY ENCOUNTERED OR PERFORMED ON THE SAME DAY BY THE SAME
PHYSICIAN. HOWEVER, WHAN ANOTHER ALREADY ESTABLISHED MODIFIER IS APPROPRIATE IT SHOULD BE USED RATHER THAN MODIFIER -59. ONLY IF NO MORE DESCRIPTIVE MODIFIER IS
AVAILABLE, AND THE USE OF MODIFIER -59 BEST EXPLAINS THE CIRCUMSTANCES, SHOULD MODIFIER -59 BE USED. MODIFIER CODE 09959 MAY BE USED AS AN ALTERNATE TO MODIFIER -59.
Group 4

(1 Code)

Group 4 Paragraph

N/A

Group 4 Codes

Code Description
59 DISTINCT PROCEDURAL SERVICE: UNDER CERTAIN CIRCUMSTANCES, THE PHYSICIAN MAY NEED TO INDICATE THAT A PROCEDURE OR SERVICE WAS DISTINCT OR INDEPENDENT FROM OTHER
SERVICES PERFORMED ON THE SAME DAY. MODIFIER -59 IS USED TO IDENTIFY PROCEDURES/SERVICES THAT ARE NOT NORMALLY REPORTED TOGETHER, BUT ARE APPROPRIATE UNDER THE
CIRCUMSTANCES. THIS MAY REPRESENT A DIFFERENT SESSION OR PATIENT ENCOUNTER, DIFFERENT PROCEDURE OR SURGERY, DIFFERNET SITE OR ORGAN SYSTEM, SEPARATE
INCISION/EXCISION, SEPARATE LESION, OR SEPARATE INJURY (OR AREA OF INJURY IN EXTENSIVE INJURIES) NOT ORDINARILY ENCOUNTERED OR PERFORMED ON THE SAME DAY BY THE SAME

20
 PHYSICIAN. HOWEVER, WHAN ANOTHER ALREADY ESTABLISHED MODIFIER IS APPROPRIATE IT SHOULD BE USED RATHER THAN MODIFIER -59. ONLY IF NO MORE DESCRIPTIVE MODIFIER IS
AVAILABLE, AND THE USE OF MODIFIER -59 BEST EXPLAINS THE CIRCUMSTANCES, SHOULD MODIFIER -59 BE USED. MODIFIER CODE 09959 MAY BE USED AS AN ALTERNATE TO MODIFIER -59.
Group 5

(1 Code)

Group 5 Paragraph

N/A

Group 5 Codes

Code Description
59 DISTINCT PROCEDURAL SERVICE: UNDER CERTAIN CIRCUMSTANCES, THE PHYSICIAN MAY NEED TO INDICATE THAT A PROCEDURE OR SERVICE WAS DISTINCT OR INDEPENDENT FROM OTHER
SERVICES PERFORMED ON THE SAME DAY. MODIFIER -59 IS USED TO IDENTIFY PROCEDURES/SERVICES THAT ARE NOT NORMALLY REPORTED TOGETHER, BUT ARE APPROPRIATE UNDER THE
CIRCUMSTANCES. THIS MAY REPRESENT A DIFFERENT SESSION OR PATIENT ENCOUNTER, DIFFERENT PROCEDURE OR SURGERY, DIFFERNET SITE OR ORGAN SYSTEM, SEPARATE
INCISION/EXCISION, SEPARATE LESION, OR SEPARATE INJURY (OR AREA OF INJURY IN EXTENSIVE INJURIES) NOT ORDINARILY ENCOUNTERED OR PERFORMED ON THE SAME DAY BY THE SAME
PHYSICIAN. HOWEVER, WHAN ANOTHER ALREADY ESTABLISHED MODIFIER IS APPROPRIATE IT SHOULD BE USED RATHER THAN MODIFIER -59. ONLY IF NO MORE DESCRIPTIVE MODIFIER IS
AVAILABLE, AND THE USE OF MODIFIER -59 BEST EXPLAINS THE CIRCUMSTANCES, SHOULD MODIFIER -59 BE USED. MODIFIER CODE 09959 MAY BE USED AS AN ALTERNATE TO MODIFIER -59.
Group 6

(1 Code)

Group 6 Paragraph

N/A

Group 6 Codes

Code Description
59 DISTINCT PROCEDURAL SERVICE: UNDER CERTAIN CIRCUMSTANCES, THE PHYSICIAN MAY NEED TO INDICATE THAT A PROCEDURE OR SERVICE WAS DISTINCT OR INDEPENDENT FROM OTHER
SERVICES PERFORMED ON THE SAME DAY. MODIFIER -59 IS USED TO IDENTIFY PROCEDURES/SERVICES THAT ARE NOT NORMALLY REPORTED TOGETHER, BUT ARE APPROPRIATE UNDER THE
CIRCUMSTANCES. THIS MAY REPRESENT A DIFFERENT SESSION OR PATIENT ENCOUNTER, DIFFERENT PROCEDURE OR SURGERY, DIFFERNET SITE OR ORGAN SYSTEM, SEPARATE
INCISION/EXCISION, SEPARATE LESION, OR SEPARATE INJURY (OR AREA OF INJURY IN EXTENSIVE INJURIES) NOT ORDINARILY ENCOUNTERED OR PERFORMED ON THE SAME DAY BY THE SAME
PHYSICIAN. HOWEVER, WHAN ANOTHER ALREADY ESTABLISHED MODIFIER IS APPROPRIATE IT SHOULD BE USED RATHER THAN MODIFIER -59. ONLY IF NO MORE DESCRIPTIVE MODIFIER IS
AVAILABLE, AND THE USE OF MODIFIER -59 BEST EXPLAINS THE CIRCUMSTANCES, SHOULD MODIFIER -59 BE USED. MODIFIER CODE 09959 MAY BE USED AS AN ALTERNATE TO MODIFIER -59.
Group 7

(1 Code)

Group 7 Paragraph

N/A

Group 7 Codes

Code Description
59 DISTINCT PROCEDURAL SERVICE: UNDER CERTAIN CIRCUMSTANCES, THE PHYSICIAN MAY NEED TO INDICATE THAT A PROCEDURE OR SERVICE WAS DISTINCT OR INDEPENDENT FROM OTHER
SERVICES PERFORMED ON THE SAME DAY. MODIFIER -59 IS USED TO IDENTIFY PROCEDURES/SERVICES THAT ARE NOT NORMALLY REPORTED TOGETHER, BUT ARE APPROPRIATE UNDER THE
CIRCUMSTANCES. THIS MAY REPRESENT A DIFFERENT SESSION OR PATIENT ENCOUNTER, DIFFERENT PROCEDURE OR SURGERY, DIFFERNET SITE OR ORGAN SYSTEM, SEPARATE
INCISION/EXCISION, SEPARATE LESION, OR SEPARATE INJURY (OR AREA OF INJURY IN EXTENSIVE INJURIES) NOT ORDINARILY ENCOUNTERED OR PERFORMED ON THE SAME DAY BY THE SAME
PHYSICIAN. HOWEVER, WHAN ANOTHER ALREADY ESTABLISHED MODIFIER IS APPROPRIATE IT SHOULD BE USED RATHER THAN MODIFIER -59. ONLY IF NO MORE DESCRIPTIVE MODIFIER IS
AVAILABLE, AND THE USE OF MODIFIER -59 BEST EXPLAINS THE CIRCUMSTANCES, SHOULD MODIFIER -59 BE USED. MODIFIER CODE 09959 MAY BE USED AS AN ALTERNATE TO MODIFIER -59.
Group 8

21
(1 Code)

Group 8 Paragraph

N/A

Group 8 Codes

Code Description
59 DISTINCT PROCEDURAL SERVICE: UNDER CERTAIN CIRCUMSTANCES, THE PHYSICIAN MAY NEED TO INDICATE THAT A PROCEDURE OR SERVICE WAS DISTINCT OR INDEPENDENT FROM OTHER
SERVICES PERFORMED ON THE SAME DAY. MODIFIER -59 IS USED TO IDENTIFY PROCEDURES/SERVICES THAT ARE NOT NORMALLY REPORTED TOGETHER, BUT ARE APPROPRIATE UNDER THE
CIRCUMSTANCES. THIS MAY REPRESENT A DIFFERENT SESSION OR PATIENT ENCOUNTER, DIFFERENT PROCEDURE OR SURGERY, DIFFERNET SITE OR ORGAN SYSTEM, SEPARATE
INCISION/EXCISION, SEPARATE LESION, OR SEPARATE INJURY (OR AREA OF INJURY IN EXTENSIVE INJURIES) NOT ORDINARILY ENCOUNTERED OR PERFORMED ON THE SAME DAY BY THE SAME
PHYSICIAN. HOWEVER, WHAN ANOTHER ALREADY ESTABLISHED MODIFIER IS APPROPRIATE IT SHOULD BE USED RATHER THAN MODIFIER -59. ONLY IF NO MORE DESCRIPTIVE MODIFIER IS
AVAILABLE, AND THE USE OF MODIFIER -59 BEST EXPLAINS THE CIRCUMSTANCES, SHOULD MODIFIER -59 BE USED. MODIFIER CODE 09959 MAY BE USED AS AN ALTERNATE TO MODIFIER -59.
ICD-10-CM Codes that Support Medical Necessity

Group 1

(112 Codes)

Group 1 Paragraph

One of the following diagnosis codes must be on the claim to bill for:

Targeted Respiratory Panels

Group 1 Codes

Code Description
A37.00 Whooping cough due to Bordetella pertussis without pneumonia
A37.01 Whooping cough due to Bordetella pertussis with pneumonia
A37.10 Whooping cough due to Bordetella parapertussis without pneumonia
A37.11 Whooping cough due to Bordetella parapertussis with pneumonia
A37.80 Whooping cough due to other Bordetella species without pneumonia
A37.81 Whooping cough due to other Bordetella species with pneumonia
A37.90 Whooping cough, unspecified species without pneumonia
A37.91 Whooping cough, unspecified species with pneumonia
A41.81 Sepsis due to Enterococcus
A41.89 Other specified sepsis
A41.9 Sepsis, unspecified organism
A48.1 Legionnaires' disease
A48.2 Nonpneumonic Legionnaires' disease [Pontiac fever]
B25.0 Cytomegaloviral pneumonitis
B33.23 Viral pericarditis
B33.24 Viral cardiomyopathy
B59 Pneumocystosis
B97.21 SARS-associated coronavirus as the cause of diseases classified elsewhere
B97.29 Other coronavirus as the cause of diseases classified elsewhere
J05.0 Acute obstructive laryngitis [croup]
J06.9 Acute upper respiratory infection, unspecified
J09.X1 Influenza due to identified novel influenza A virus with pneumonia
J09.X2 Influenza due to identified novel influenza A virus with other respiratory manifestations
J09.X3 Influenza due to identified novel influenza A virus with gastrointestinal manifestations

22
J09.X9 Influenza due to identified novel influenza A virus with other manifestations
J10.01 Influenza due to other identified influenza virus with the same other identified influenza virus pneumonia
J10.08 Influenza due to other identified influenza virus with other specified pneumonia
J10.1 Influenza due to other identified influenza virus with other respiratory manifestations
J10.2 Influenza due to other identified influenza virus with gastrointestinal manifestations
J10.81 Influenza due to other identified influenza virus with encephalopathy
J10.82 Influenza due to other identified influenza virus with myocarditis
J10.83 Influenza due to other identified influenza virus with otitis media
J10.89 Influenza due to other identified influenza virus with other manifestations
J11.08 Influenza due to unidentified influenza virus with specified pneumonia
J11.1 Influenza due to unidentified influenza virus with other respiratory manifestations
J11.2 Influenza due to unidentified influenza virus with gastrointestinal manifestations
J11.81 Influenza due to unidentified influenza virus with encephalopathy
J11.82 Influenza due to unidentified influenza virus with myocarditis
J11.83 Influenza due to unidentified influenza virus with otitis media
J11.89 Influenza due to unidentified influenza virus with other manifestations
J12.0 Adenoviral pneumonia
J12.1 Respiratory syncytial virus pneumonia
J12.2 Parainfluenza virus pneumonia
J12.3 Human metapneumovirus pneumonia
J12.81 Pneumonia due to SARS-associated coronavirus
J12.82 Pneumonia due to coronavirus disease 2019
J12.89 Other viral pneumonia
J12.9 Viral pneumonia, unspecified
J13 Pneumonia due to Streptococcus pneumoniae
J15.0 Pneumonia due to Klebsiella pneumoniae
J15.1 Pneumonia due to Pseudomonas
J15.20 Pneumonia due to staphylococcus, unspecified
J15.211 Pneumonia due to Methicillin susceptible Staphylococcus aureus
J15.212 Pneumonia due to Methicillin resistant Staphylococcus aureus
J15.29 Pneumonia due to other staphylococcus
J15.3 Pneumonia due to streptococcus, group B
J15.4 Pneumonia due to other streptococci
J15.7 Pneumonia due to Mycoplasma pneumoniae
J15.8 Pneumonia due to other specified bacteria
J15.9 Unspecified bacterial pneumonia
J16.0 Chlamydial pneumonia
J16.8 Pneumonia due to other specified infectious organisms
J18.0 Bronchopneumonia, unspecified organism
J18.1 Lobar pneumonia, unspecified organism
J18.2 Hypostatic pneumonia, unspecified organism
J18.8 Other pneumonia, unspecified organism
J18.9 Pneumonia, unspecified organism
J20.0 Acute bronchitis due to Mycoplasma pneumoniae
J20.1 Acute bronchitis due to Hemophilus influenzae
J20.2 Acute bronchitis due to streptococcus
J20.3 Acute bronchitis due to coxsackievirus
J20.4 Acute bronchitis due to parainfluenza virus
J20.5 Acute bronchitis due to respiratory syncytial virus
J20.6 Acute bronchitis due to rhinovirus
J20.8 Acute bronchitis due to other specified organisms
J20.9 Acute bronchitis, unspecified
J21.9 Acute bronchiolitis, unspecified
J22 Unspecified acute lower respiratory infection

23
J44.0 Chronic obstructive pulmonary disease with (acute) lower respiratory infection
J44.1 Chronic obstructive pulmonary disease with (acute) exacerbation
J45.31 Mild persistent asthma with (acute) exacerbation
J45.32 Mild persistent asthma with status asthmaticus
J45.41 Moderate persistent asthma with (acute) exacerbation
J45.42 Moderate persistent asthma with status asthmaticus
J45.51 Severe persistent asthma with (acute) exacerbation
J45.52 Severe persistent asthma with status asthmaticus
J45.901 Unspecified asthma with (acute) exacerbation
J45.902 Unspecified asthma with status asthmaticus
J84.116 Cryptogenic organizing pneumonia
J84.117 Desquamative interstitial pneumonia
J84.2 Lymphoid interstitial pneumonia
J85.0 Gangrene and necrosis of lung
J85.1 Abscess of lung with pneumonia
J85.2 Abscess of lung without pneumonia
J85.3 Abscess of mediastinum
R05.1 Acute cough
R05.2 Subacute cough
R05.3 Chronic cough
R05.8 Other specified cough
R06.02 Shortness of breath
R06.03 Acute respiratory distress
R06.2 Wheezing
R50.9 Fever, unspecified
R65.20 Severe sepsis without septic shock
R65.21 Severe sepsis with septic shock
R78.81 Bacteremia
T86.33 Heart-lung transplant infection
T86.812 Lung transplant infection
Z03.818 Encounter for observation for suspected exposure to other biological agents ruled out
Z20.822 Contact with and (suspected) exposure to COVID-19
Z20.828 Contact with and (suspected) exposure to other viral communicable diseases
U07.1 COVID-19
Group 2

(104 Codes)

Group 2 Paragraph

One of the following diagnosis codes must be on the claim to bill for:

Targeted Gastrointestinal Panels

Group 2 Codes

Code Description
A00.0 Cholera due to Vibrio cholerae 01, biovar cholerae
A00.1 Cholera due to Vibrio cholerae 01, biovar eltor
A00.9 Cholera, unspecified
A01.00 Typhoid fever, unspecified
A01.09 Typhoid fever with other complications
A01.1 Paratyphoid fever A
A01.2 Paratyphoid fever B

24
A01.3 Paratyphoid fever C
A02.0 Salmonella enteritis
A02.1 Salmonella sepsis
A02.8 Other specified salmonella infections
A03.0 Shigellosis due to Shigella dysenteriae
A03.1 Shigellosis due to Shigella flexneri
A03.2 Shigellosis due to Shigella boydii
A03.3 Shigellosis due to Shigella sonnei
A03.8 Other shigellosis
A04.0 Enteropathogenic Escherichia coli infection
A04.1 Enterotoxigenic Escherichia coli infection
A04.2 Enteroinvasive Escherichia coli infection
A04.3 Enterohemorrhagic Escherichia coli infection
A04.5 Campylobacter enteritis
A04.6 Enteritis due to Yersinia enterocolitica
A04.71 Enterocolitis due to Clostridium difficile, recurrent
A04.72 Enterocolitis due to Clostridium difficile, not specified as recurrent
A04.8 Other specified bacterial intestinal infections
A04.9 Bacterial intestinal infection, unspecified
A05.0 Foodborne staphylococcal intoxication
A05.1 Botulism food poisoning
A05.2 Foodborne Clostridium perfringens [Clostridium welchii] intoxication
A05.3 Foodborne Vibrio parahaemolyticus intoxication
A05.4 Foodborne Bacillus cereus intoxication
A05.5 Foodborne Vibrio vulnificus intoxication
A06.0 Acute amebic dysentery
A06.1 Chronic intestinal amebiasis
A06.2 Amebic nondysenteric colitis
A07.1 Giardiasis [lambliasis]
A07.2 Cryptosporidiosis
A07.4 Cyclosporiasis
A08.0 Rotaviral enteritis
A08.11 Acute gastroenteropathy due to Norwalk agent
A08.19 Acute gastroenteropathy due to other small round viruses
A08.2 Adenoviral enteritis
A08.31 Calicivirus enteritis
A08.32 Astrovirus enteritis
A08.39 Other viral enteritis
A08.8 Other specified intestinal infections
A09 Infectious gastroenteritis and colitis, unspecified
A32.11 Listerial meningitis
A32.12 Listerial meningoencephalitis
A32.7 Listerial sepsis
A41.50 Gram-negative sepsis, unspecified
A41.51 Sepsis due to Escherichia coli [E. coli]
A41.52 Sepsis due to Pseudomonas
A41.53 Sepsis due to Serratia
A41.59 Other Gram-negative sepsis
A41.81 Sepsis due to Enterococcus
A41.89 Other specified sepsis
A41.9 Sepsis, unspecified organism
D59.30 Hemolytic-uremic syndrome, unspecified
D59.31 Infection-associated hemolytic-uremic syndrome
K50.014 Crohn's disease of small intestine with abscess

25
K50.114 Crohn's disease of large intestine with abscess
K50.814 Crohn's disease of both small and large intestine with abscess
K50.914 Crohn's disease, unspecified, with abscess
K51.014 Ulcerative (chronic) pancolitis with abscess
K51.214 Ulcerative (chronic) proctitis with abscess
K51.314 Ulcerative (chronic) rectosigmoiditis with abscess
K51.414 Inflammatory polyps of colon with abscess
K51.514 Left sided colitis with abscess
K51.814 Other ulcerative colitis with abscess
K51.914 Ulcerative colitis, unspecified with abscess
K52.1 Toxic gastroenteritis and colitis
K56.0 Paralytic ileus
K92.1 Melena
M31.19 Other thrombotic microangiopathy
R10.0 Acute abdomen
R10.11 Right upper quadrant pain
R10.12 Left upper quadrant pain
R10.13 Epigastric pain
R10.31 Right lower quadrant pain
R10.32 Left lower quadrant pain
R10.33 Periumbilical pain
R10.811 Right upper quadrant abdominal tenderness
R10.812 Left upper quadrant abdominal tenderness
R10.813 Right lower quadrant abdominal tenderness
R10.814 Left lower quadrant abdominal tenderness
R10.815 Periumbilic abdominal tenderness
R10.817 Generalized abdominal tenderness
R10.821 Right upper quadrant rebound abdominal tenderness
R10.822 Left upper quadrant rebound abdominal tenderness
R10.823 Right lower quadrant rebound abdominal tenderness
R10.824 Left lower quadrant rebound abdominal tenderness
R10.825 Periumbilic rebound abdominal tenderness
R10.826 Epigastric rebound abdominal tenderness
R10.827 Generalized rebound abdominal tenderness
R10.829 Rebound abdominal tenderness, unspecified site
R10.84 Generalized abdominal pain
R19.5 Other fecal abnormalities
R19.7 Diarrhea, unspecified
R50.9 Fever, unspecified
R65.20 Severe sepsis without septic shock
R65.21 Severe sepsis with septic shock
R78.81 Bacteremia
T86.852 Intestine transplant infection
Group 3

(56 Codes)

Group 3 Paragraph

One of the following diagnosis codes must be on the claim to bill for:

Meningoencephalitis Panels

Group 3 Codes

26
 Code Description
A39.0 Meningococcal meningitis
A39.81 Meningococcal encephalitis
A39.9 Meningococcal infection, unspecified
A41.9 Sepsis, unspecified organism
A54.81 Gonococcal meningitis
A80.0 Acute paralytic poliomyelitis, vaccine-associated
A80.1 Acute paralytic poliomyelitis, wild virus, imported
A80.2 Acute paralytic poliomyelitis, wild virus, indigenous
A80.30 Acute paralytic poliomyelitis, unspecified
A80.39 Other acute paralytic poliomyelitis
A80.4 Acute nonparalytic poliomyelitis
A80.9 Acute poliomyelitis, unspecified
A85.0 Enteroviral encephalitis
A85.1 Adenoviral encephalitis
A85.8 Other specified viral encephalitis
A86 Unspecified viral encephalitis
A87.0 Enteroviral meningitis
A87.8 Other viral meningitis
A87.9 Viral meningitis, unspecified
B00.3 Herpesviral meningitis
B00.4 Herpesviral encephalitis
B01.0 Varicella meningitis
B01.11 Varicella encephalitis and encephalomyelitis
B02.1 Zoster meningitis
B10.01 Human herpesvirus 6 encephalitis
B20 Human immunodeficiency virus [HIV] disease
B27.02 Gammaherpesviral mononucleosis with meningitis
B27.12 Cytomegaloviral mononucleosis with meningitis
B27.82 Other infectious mononucleosis with meningitis
B37.5 Candidal meningitis
B45.1 Cerebral cryptococcosis
B60.2 Naegleriasis
G00.0 Hemophilus meningitis
G00.1 Pneumococcal meningitis
G00.2 Streptococcal meningitis
G00.8 Other bacterial meningitis
G00.9 Bacterial meningitis, unspecified
G03.0 Nonpyogenic meningitis
G03.9 Meningitis, unspecified
G04.01 Postinfectious acute disseminated encephalitis and encephalomyelitis (postinfectious ADEM)
G04.02 Postimmunization acute disseminated encephalitis, myelitis and encephalomyelitis
G04.30 Acute necrotizing hemorrhagic encephalopathy, unspecified
G04.31 Postinfectious acute necrotizing hemorrhagic encephalopathy
G04.32 Postimmunization acute necrotizing hemorrhagic encephalopathy
G04.39 Other acute necrotizing hemorrhagic encephalopathy
G04.81 Other encephalitis and encephalomyelitis
G04.82 Acute flaccid myelitis
G04.89 Other myelitis
G04.90 Encephalitis and encephalomyelitis, unspecified
G04.91 Myelitis, unspecified
G05.3 Encephalitis and encephalomyelitis in diseases classified elsewhere
G05.4 Myelitis in diseases classified elsewhere
R41.82 Altered mental status, unspecified

27
R50.9 Fever, unspecified
R65.20 Severe sepsis without septic shock
R65.21 Severe sepsis with septic shock
Group 4

(76 Codes)

Group 4 Paragraph

One of the following diagnosis codes must be on the claim to bill for:

Bloodstream Infection Panels

Group 4 Codes

Code Description
A01.00 Typhoid fever, unspecified
A01.01 Typhoid meningitis
A01.02 Typhoid fever with heart involvement
A01.03 Typhoid pneumonia
A01.04 Typhoid arthritis
A01.05 Typhoid osteomyelitis
A01.09 Typhoid fever with other complications
A01.1 Paratyphoid fever A
A01.2 Paratyphoid fever B
A01.3 Paratyphoid fever C
A32.7 Listerial sepsis
A40.0 Sepsis due to streptococcus, group A
A40.1 Sepsis due to streptococcus, group B
A40.3 Sepsis due to Streptococcus pneumoniae
A40.8 Other streptococcal sepsis
A40.9 Streptococcal sepsis, unspecified
A41.01 Sepsis due to Methicillin susceptible Staphylococcus aureus
A41.02 Sepsis due to Methicillin resistant Staphylococcus aureus
A41.1 Sepsis due to other specified staphylococcus
A41.2 Sepsis due to unspecified staphylococcus
A41.3 Sepsis due to Hemophilus influenzae
A41.4 Sepsis due to anaerobes
A41.50 Gram-negative sepsis, unspecified
A41.51 Sepsis due to Escherichia coli [E. coli]
A41.52 Sepsis due to Pseudomonas
A41.53 Sepsis due to Serratia
A41.59 Other Gram-negative sepsis
A41.9 Sepsis, unspecified organism
A54.86 Gonococcal sepsis
A79.82 Anaplasmosis [A. phagocytophilum]
B37.7 Candidal sepsis
B99.9 Unspecified infectious disease
D59.30 Hemolytic-uremic syndrome, unspecified
D59.31 Infection-associated hemolytic-uremic syndrome
D70.3 Neutropenia due to infection
E08.52 Diabetes mellitus due to underlying condition with diabetic peripheral angiopathy with gangrene
E10.52 Type 1 diabetes mellitus with diabetic peripheral angiopathy with gangrene
E11.52 Type 2 diabetes mellitus with diabetic peripheral angiopathy with gangrene

28
I33.0 Acute and subacute infective endocarditis
M31.19 Other thrombotic microangiopathy
R50.81 Fever presenting with conditions classified elsewhere
R50.9 Fever, unspecified
R65.20 Severe sepsis without septic shock
R65.21 Severe sepsis with septic shock
R78.81 Bacteremia
T80.211A Bloodstream infection due to central venous catheter, initial encounter
T80.211D Bloodstream infection due to central venous catheter, subsequent encounter
T80.211S Bloodstream infection due to central venous catheter, sequela
T80.218A Other infection due to central venous catheter, initial encounter
T80.218D Other infection due to central venous catheter, subsequent encounter
T80.218S Other infection due to central venous catheter, sequela
T80.219A Unspecified infection due to central venous catheter, initial encounter
T80.219D Unspecified infection due to central venous catheter, subsequent encounter
T80.219S Unspecified infection due to central venous catheter, sequela
T80.22XA Acute infection following transfusion, infusion, or injection of blood and blood products, initial encounter
T80.22XD Acute infection following transfusion, infusion, or injection of blood and blood products, subsequent encounter
T80.22XS Acute infection following transfusion, infusion, or injection of blood and blood products, sequela
T80.29XA Infection following other infusion, transfusion and therapeutic injection, initial encounter
T80.29XD Infection following other infusion, transfusion and therapeutic injection, subsequent encounter
T80.29XS Infection following other infusion, transfusion and therapeutic injection, sequela
T82.6XXA Infection and inflammatory reaction due to cardiac valve prosthesis, initial encounter
T82.6XXD Infection and inflammatory reaction due to cardiac valve prosthesis, subsequent encounter
T82.6XXS Infection and inflammatory reaction due to cardiac valve prosthesis, sequela
T82.7XXA Infection and inflammatory reaction due to other cardiac and vascular devices, implants and grafts, initial encounter
T82.7XXD Infection and inflammatory reaction due to other cardiac and vascular devices, implants and grafts, subsequent encounter
T82.7XXS Infection and inflammatory reaction due to other cardiac and vascular devices, implants and grafts, sequela
T85.71XA Infection and inflammatory reaction due to peritoneal dialysis catheter, initial encounter
T85.71XD Infection and inflammatory reaction due to peritoneal dialysis catheter, subsequent encounter
T85.71XS Infection and inflammatory reaction due to peritoneal dialysis catheter, sequela
T85.72XA Infection and inflammatory reaction due to insulin pump, initial encounter
T85.72XD Infection and inflammatory reaction due to insulin pump, subsequent encounter
T85.72XS Infection and inflammatory reaction due to insulin pump, sequela
T86.03 Bone marrow transplant infection
T86.23 Heart transplant infection
T86.33 Heart-lung transplant infection
T86.5 Complications of stem cell transplant
Group 5

(97 Codes)

Group 5 Paragraph

One of the following diagnosis codes must be on the claim to bill for:

Urogenital/Anogenital Panels

NOTE: Claims with diagnosis code Z11.3 would be expected to also include a high-risk diagnosis code.

Group 5 Codes

Code Description
A51.0 Primary genital syphilis

29
A51.1 Primary anal syphilis
A51.31 Condyloma latum
A52.76 Other genitourinary symptomatic late syphilis
A54.00 Gonococcal infection of lower genitourinary tract, unspecified
A54.01 Gonococcal cystitis and urethritis, unspecified
A54.02 Gonococcal vulvovaginitis, unspecified
A54.03 Gonococcal cervicitis, unspecified
A54.09 Other gonococcal infection of lower genitourinary tract
A54.1 Gonococcal infection of lower genitourinary tract with periurethral and accessory gland abscess
A54.21 Gonococcal infection of kidney and ureter
A54.22 Gonococcal prostatitis
A54.23 Gonococcal infection of other male genital organs
A54.24 Gonococcal female pelvic inflammatory disease
A54.29 Other gonococcal genitourinary infections
A54.6 Gonococcal infection of anus and rectum
A56.00 Chlamydial infection of lower genitourinary tract, unspecified
A56.01 Chlamydial cystitis and urethritis
A56.02 Chlamydial vulvovaginitis
A56.09 Other chlamydial infection of lower genitourinary tract
A56.11 Chlamydial female pelvic inflammatory disease
A56.19 Other chlamydial genitourinary infection
A56.2 Chlamydial infection of genitourinary tract, unspecified
A56.3 Chlamydial infection of anus and rectum
A59.00 Urogenital trichomoniasis, unspecified
A59.01 Trichomonal vulvovaginitis
A59.02 Trichomonal prostatitis
A59.03 Trichomonal cystitis and urethritis
A59.09 Other urogenital trichomoniasis
A60.00 Herpesviral infection of urogenital system, unspecified
A60.01 Herpesviral infection of penis
A60.02 Herpesviral infection of other male genital organs
A60.03 Herpesviral cervicitis
A60.04 Herpesviral vulvovaginitis
A60.09 Herpesviral infection of other urogenital tract
A60.1 Herpesviral infection of perianal skin and rectum
A60.9 Anogenital herpesviral infection, unspecified
A63.0 Anogenital (venereal) warts
B20 Human immunodeficiency virus [HIV] disease
B37.31 Acute candidiasis of vulva and vagina
B37.32 Chronic candidiasis of vulva and vagina
B37.41 Candidal cystitis and urethritis
B37.42 Candidal balanitis
B37.49 Other urogenital candidiasis
B37.89 Other sites of candidiasis
B97.35 Human immunodeficiency virus, type 2 [HIV 2] as the cause of diseases classified elsewhere
D26.0 Other benign neoplasm of cervix uteri
L29.2 Pruritus vulvae
L29.3 Anogenital pruritus, unspecified
N34.1 Nonspecific urethritis
N34.2 Other urethritis
N41.0 Acute prostatitis
N41.3 Prostatocystitis
N48.5 Ulcer of penis
N76.0 Acute vaginitis

30
N76.1 Subacute and chronic vaginitis
N76.2 Acute vulvitis
N76.3 Subacute and chronic vulvitis
N76.5 Ulceration of vagina
N76.6 Ulceration of vulva
N76.82 Fournier disease of vagina and vulva
N76.89 Other specified inflammation of vagina and vulva
N77.1 Vaginitis, vulvitis and vulvovaginitis in diseases classified elsewhere
N89.8 Other specified noninflammatory disorders of vagina
N90.89 Other specified noninflammatory disorders of vulva and perineum
N93.0 Postcoital and contact bleeding
N93.8 Other specified abnormal uterine and vaginal bleeding
O98.711 Human immunodeficiency virus [HIV] disease complicating pregnancy, first trimester
O98.712 Human immunodeficiency virus [HIV] disease complicating pregnancy, second trimester
O98.713 Human immunodeficiency virus [HIV] disease complicating pregnancy, third trimester
R10.2 Pelvic and perineal pain
R30.0 Dysuria
T74.21XA Adult sexual abuse, confirmed, initial encounter
T74.21XD Adult sexual abuse, confirmed, subsequent encounter
T74.21XS Adult sexual abuse, confirmed, sequela
T74.51XA Adult forced sexual exploitation, confirmed, initial encounter
T74.51XD Adult forced sexual exploitation, confirmed, subsequent encounter
T74.51XS Adult forced sexual exploitation, confirmed, sequela
T76.21XA Adult sexual abuse, suspected, initial encounter
T76.21XD Adult sexual abuse, suspected, subsequent encounter
T76.21XS Adult sexual abuse, suspected, sequela
T76.51XA Adult forced sexual exploitation, suspected, initial encounter
T76.51XD Adult forced sexual exploitation, suspected, subsequent encounter
T76.51XS Adult forced sexual exploitation, suspected, sequela
Z04.41 Encounter for examination and observation following alleged adult rape
Z04.71 Encounter for examination and observation following alleged adult physical abuse
Z04.81 Encounter for examination and observation of victim following forced sexual exploitation
Z11.3 Encounter for screening for infections with a predominantly sexual mode of transmission
Z20.2 Contact with and (suspected) exposure to infections with a predominantly sexual mode of transmission
Z20.6 Contact with and (suspected) exposure to human immunodeficiency virus [HIV]
Z21 Asymptomatic human immunodeficiency virus [HIV] infection status
Z33.1 Pregnant state, incidental
Z33.3 Pregnant state, gestational carrier
Z72.51 High risk heterosexual behavior
Z72.52 High risk homosexual behavior
Z72.53 High risk bisexual behavior
Z72.89 Other problems related to lifestyle
Group 6

(124 Codes)

Group 6 Paragraph

These are the diagnosis codes corresponding to coverage of CPT/HCPCS Codes Group 6: Codes - Expanded (>5 pathogens) Respiratory and Pneumonia Panels.

For testing in POS other than POS 19, 21, 22 or 23, to bill one of the Group 6 CPT codes, TWO ICD-10 codes are required- one from Group 6 and another from Group 1.

For immunocompromised patients, testing may be performed as part of a pre-transplant evaluation (once per transplant), regardless of the presence of symptoms. In such cases, clear documentation of the pre-transplant evaluation must
accompany the claim.

31
Group 6 Codes

Code Description
B20 Human immunodeficiency virus [HIV] disease
C46.0 Kaposi's sarcoma of skin
C46.1 Kaposi's sarcoma of soft tissue
C46.2 Kaposi's sarcoma of palate
C46.3 Kaposi's sarcoma of lymph nodes
C46.4 Kaposi's sarcoma of gastrointestinal sites
C46.50 Kaposi's sarcoma of unspecified lung
C46.51 Kaposi's sarcoma of right lung
C46.52 Kaposi's sarcoma of left lung
C46.7 Kaposi's sarcoma of other sites
D57.01 Hb-SS disease with acute chest syndrome
D61.09 Other constitutional aplastic anemia
D61.1 Drug-induced aplastic anemia
D61.2 Aplastic anemia due to other external agents
D61.3 Idiopathic aplastic anemia
D61.810 Antineoplastic chemotherapy induced pancytopenia
D61.811 Other drug-induced pancytopenia
D61.818 Other pancytopenia
D61.82 Myelophthisis
D61.89 Other specified aplastic anemias and other bone marrow failure syndromes
D61.9 Aplastic anemia, unspecified
D64.81 Anemia due to antineoplastic chemotherapy
D64.89 Other specified anemias
D70.0 Congenital agranulocytosis
D70.1 Agranulocytosis secondary to cancer chemotherapy
D70.2 Other drug-induced agranulocytosis
D70.3 Neutropenia due to infection
D70.4 Cyclic neutropenia
D70.9 Neutropenia, unspecified
D80.0 Hereditary hypogammaglobulinemia
D80.1 Nonfamilial hypogammaglobulinemia
D80.2 Selective deficiency of immunoglobulin A [IgA]
D80.3 Selective deficiency of immunoglobulin G [IgG] subclasses
D80.4 Selective deficiency of immunoglobulin M [IgM]
D80.5 Immunodeficiency with increased immunoglobulin M [IgM]
D80.6 Antibody deficiency with near-normal immunoglobulins or with hyperimmunoglobulinemia
D80.8 Other immunodeficiencies with predominantly antibody defects
D80.9 Immunodeficiency with predominantly antibody defects, unspecified
D81.0 Severe combined immunodeficiency [SCID] with reticular dysgenesis
D81.1 Severe combined immunodeficiency [SCID] with low T- and B-cell numbers
D81.2 Severe combined immunodeficiency [SCID] with low or normal B-cell numbers
D81.30 Adenosine deaminase deficiency, unspecified
D81.31 Severe combined immunodeficiency due to adenosine deaminase deficiency
D81.32 Adenosine deaminase 2 deficiency
D81.39 Other adenosine deaminase deficiency
D81.4 Nezelof's syndrome
D81.5 Purine nucleoside phosphorylase [PNP] deficiency
D81.6 Major histocompatibility complex class I deficiency
D81.7 Major histocompatibility complex class II deficiency
D81.810 Biotinidase deficiency
D81.818 Other biotin-dependent carboxylase deficiency

32
D81.82 Activated Phosphoinositide 3-kinase Delta Syndrome [APDS]
D81.89 Other combined immunodeficiencies
D81.9 Combined immunodeficiency, unspecified
D82.0 Wiskott-Aldrich syndrome
D82.1 Di George's syndrome
D82.2 Immunodeficiency with short-limbed stature
D82.3 Immunodeficiency following hereditary defective response to Epstein-Barr virus
D82.4 Hyperimmunoglobulin E [IgE] syndrome
D82.8 Immunodeficiency associated with other specified major defects
D83.0 Common variable immunodeficiency with predominant abnormalities of B-cell numbers and function
D83.1 Common variable immunodeficiency with predominant immunoregulatory T-cell disorders
D83.2 Common variable immunodeficiency with autoantibodies to B- or T-cells
D83.8 Other common variable immunodeficiencies
D83.9 Common variable immunodeficiency, unspecified
D84.0 Lymphocyte function antigen-1 [LFA-1] defect
D84.1 Defects in the complement system
D84.821 Immunodeficiency due to drugs
D84.822 Immunodeficiency due to external causes
D84.89 Other immunodeficiencies
D84.9 Immunodeficiency, unspecified
D89.0 Polyclonal hypergammaglobulinemia
D89.1 Cryoglobulinemia
D89.3 Immune reconstitution syndrome
D89.41 Monoclonal mast cell activation syndrome
D89.42 Idiopathic mast cell activation syndrome
D89.43 Secondary mast cell activation
D89.44 Hereditary alpha tryptasemia
D89.49 Other mast cell activation disorder
D89.810 Acute graft-versus-host disease
D89.811 Chronic graft-versus-host disease
D89.812 Acute on chronic graft-versus-host disease
D89.813 Graft-versus-host disease, unspecified
D89.82 Autoimmune lymphoproliferative syndrome [ALPS]
D89.89 Other specified disorders involving the immune mechanism, not elsewhere classified
E08.43 Diabetes mellitus due to underlying condition with diabetic autonomic (poly)neuropathy
E10.43 Type 1 diabetes mellitus with diabetic autonomic (poly)neuropathy
E11.43 Type 2 diabetes mellitus with diabetic autonomic (poly)neuropathy
E13.43 Other specified diabetes mellitus with diabetic autonomic (poly)neuropathy
E84.0 Cystic fibrosis with pulmonary manifestations
J44.9 Chronic obstructive pulmonary disease, unspecified
J45.991 Cough variant asthma
J70.1 Chronic and other pulmonary manifestations due to radiation
J84.01 Alveolar proteinosis
J84.02 Pulmonary alveolar microlithiasis
J84.03 Idiopathic pulmonary hemosiderosis
J84.10 Pulmonary fibrosis, unspecified
J84.112 Idiopathic pulmonary fibrosis
J84.114 Acute interstitial pneumonitis
J84.170 Interstitial lung disease with progressive fibrotic phenotype in diseases classified elsewhere
J84.178 Other interstitial pulmonary diseases with fibrosis in diseases classified elsewhere
J84.81 Lymphangioleiomyomatosis
J84.82 Adult pulmonary Langerhans cell histiocytosis
J84.89 Other specified interstitial pulmonary diseases
O98.711 Human immunodeficiency virus [HIV] disease complicating pregnancy, first trimester

33
O98.712 Human immunodeficiency virus [HIV] disease complicating pregnancy, second trimester
O98.713 Human immunodeficiency virus [HIV] disease complicating pregnancy, third trimester
T80.82XS Complication of immune effector cellular therapy, sequela
Z51.11 Encounter for antineoplastic chemotherapy
Z92.850 Personal history of Chimeric Antigen Receptor T-cell therapy
Z92.858 Personal history of other cellular therapy
Z92.86 Personal history of gene therapy
Z94.0 Kidney transplant status
Z94.1 Heart transplant status
Z94.2 Lung transplant status
Z94.3 Heart and lungs transplant status
Z94.4 Liver transplant status
Z94.5 Skin transplant status
Z94.6 Bone transplant status
Z94.81 Bone marrow transplant status
Z94.82 Intestine transplant status
Z94.83 Pancreas transplant status
Z94.84 Stem cells transplant status
Z94.89 Other transplanted organ and tissue status
Group 7

(161 Codes)

Group 7 Paragraph

These are the diagnosis codes corresponding to coverage of CPT/HCPCS Codes Group 7: Codes - Expanded (>5 pathogens) Gastrointestinal Panels.

For testing in POS other than POS 19, 21, 22 or 23, to bill one of the Group 7 CPT codes, TWO ICD-10 codes are required- one from Group 7 and another from Group 2.

For immunocompromised patients, testing may be performed as part of a pre-transplant evaluation (once per transplant), regardless of the presence of symptoms. In such cases, clear documentation of the pre-transplant evaluation must
accompany the claim.

Group 7 Codes

Code Description
B20 Human immunodeficiency virus [HIV] disease
B25.1 Cytomegaloviral hepatitis
B25.2 Cytomegaloviral pancreatitis
C46.0 Kaposi's sarcoma of skin
C46.1 Kaposi's sarcoma of soft tissue
C46.2 Kaposi's sarcoma of palate
C46.3 Kaposi's sarcoma of lymph nodes
C46.4 Kaposi's sarcoma of gastrointestinal sites
C46.50 Kaposi's sarcoma of unspecified lung
C46.51 Kaposi's sarcoma of right lung
C46.52 Kaposi's sarcoma of left lung
C46.7 Kaposi's sarcoma of other sites
D61.09 Other constitutional aplastic anemia
D61.1 Drug-induced aplastic anemia
D61.2 Aplastic anemia due to other external agents
D61.3 Idiopathic aplastic anemia
D61.810 Antineoplastic chemotherapy induced pancytopenia
D61.811 Other drug-induced pancytopenia
D61.818 Other pancytopenia

34
D61.82 Myelophthisis
D61.89 Other specified aplastic anemias and other bone marrow failure syndromes
D61.9 Aplastic anemia, unspecified
D64.81 Anemia due to antineoplastic chemotherapy
D64.89 Other specified anemias
D70.0 Congenital agranulocytosis
D70.1 Agranulocytosis secondary to cancer chemotherapy
D70.2 Other drug-induced agranulocytosis
D70.3 Neutropenia due to infection
D70.4 Cyclic neutropenia
D70.9 Neutropenia, unspecified
D80.0 Hereditary hypogammaglobulinemia
D80.1 Nonfamilial hypogammaglobulinemia
D80.2 Selective deficiency of immunoglobulin A [IgA]
D80.3 Selective deficiency of immunoglobulin G [IgG] subclasses
D80.4 Selective deficiency of immunoglobulin M [IgM]
D80.5 Immunodeficiency with increased immunoglobulin M [IgM]
D80.6 Antibody deficiency with near-normal immunoglobulins or with hyperimmunoglobulinemia
D80.8 Other immunodeficiencies with predominantly antibody defects
D80.9 Immunodeficiency with predominantly antibody defects, unspecified
D81.0 Severe combined immunodeficiency [SCID] with reticular dysgenesis
D81.1 Severe combined immunodeficiency [SCID] with low T- and B-cell numbers
D81.2 Severe combined immunodeficiency [SCID] with low or normal B-cell numbers
D81.30 Adenosine deaminase deficiency, unspecified
D81.31 Severe combined immunodeficiency due to adenosine deaminase deficiency
D81.32 Adenosine deaminase 2 deficiency
D81.39 Other adenosine deaminase deficiency
D81.4 Nezelof's syndrome
D81.5 Purine nucleoside phosphorylase [PNP] deficiency
D81.6 Major histocompatibility complex class I deficiency
D81.7 Major histocompatibility complex class II deficiency
D81.810 Biotinidase deficiency
D81.818 Other biotin-dependent carboxylase deficiency
D81.82 Activated Phosphoinositide 3-kinase Delta Syndrome [APDS]
D81.89 Other combined immunodeficiencies
D81.9 Combined immunodeficiency, unspecified
D82.0 Wiskott-Aldrich syndrome
D82.1 Di George's syndrome
D82.2 Immunodeficiency with short-limbed stature
D82.3 Immunodeficiency following hereditary defective response to Epstein-Barr virus
D82.4 Hyperimmunoglobulin E [IgE] syndrome
D82.8 Immunodeficiency associated with other specified major defects
D83.0 Common variable immunodeficiency with predominant abnormalities of B-cell numbers and function
D83.1 Common variable immunodeficiency with predominant immunoregulatory T-cell disorders
D83.2 Common variable immunodeficiency with autoantibodies to B- or T-cells
D83.8 Other common variable immunodeficiencies
D83.9 Common variable immunodeficiency, unspecified
D84.0 Lymphocyte function antigen-1 [LFA-1] defect
D84.1 Defects in the complement system
D84.821 Immunodeficiency due to drugs
D84.822 Immunodeficiency due to external causes
D84.89 Other immunodeficiencies
D84.9 Immunodeficiency, unspecified
D89.0 Polyclonal hypergammaglobulinemia

35
D89.1 Cryoglobulinemia
D89.3 Immune reconstitution syndrome
D89.41 Monoclonal mast cell activation syndrome
D89.42 Idiopathic mast cell activation syndrome
D89.43 Secondary mast cell activation
D89.44 Hereditary alpha tryptasemia
D89.49 Other mast cell activation disorder
D89.810 Acute graft-versus-host disease
D89.811 Chronic graft-versus-host disease
D89.812 Acute on chronic graft-versus-host disease
D89.813 Graft-versus-host disease, unspecified
D89.82 Autoimmune lymphoproliferative syndrome [ALPS]
D89.89 Other specified disorders involving the immune mechanism, not elsewhere classified
E08.43 Diabetes mellitus due to underlying condition with diabetic autonomic (poly)neuropathy
E10.43 Type 1 diabetes mellitus with diabetic autonomic (poly)neuropathy
E11.43 Type 2 diabetes mellitus with diabetic autonomic (poly)neuropathy
E13.43 Other specified diabetes mellitus with diabetic autonomic (poly)neuropathy
K50.011 Crohn's disease of small intestine with rectal bleeding
K50.012 Crohn's disease of small intestine with intestinal obstruction
K50.013 Crohn's disease of small intestine with fistula
K50.018 Crohn's disease of small intestine with other complication
K50.111 Crohn's disease of large intestine with rectal bleeding
K50.112 Crohn's disease of large intestine with intestinal obstruction
K50.113 Crohn's disease of large intestine with fistula
K50.118 Crohn's disease of large intestine with other complication
K50.812 Crohn's disease of both small and large intestine with intestinal obstruction
K50.813 Crohn's disease of both small and large intestine with fistula
K50.818 Crohn's disease of both small and large intestine with other complication
K50.911 Crohn's disease, unspecified, with rectal bleeding
K50.912 Crohn's disease, unspecified, with intestinal obstruction
K50.913 Crohn's disease, unspecified, with fistula
K50.918 Crohn's disease, unspecified, with other complication
K51.011 Ulcerative (chronic) pancolitis with rectal bleeding
K51.012 Ulcerative (chronic) pancolitis with intestinal obstruction
K51.013 Ulcerative (chronic) pancolitis with fistula
K51.018 Ulcerative (chronic) pancolitis with other complication
K51.019 Ulcerative (chronic) pancolitis with unspecified complications
K51.211 Ulcerative (chronic) proctitis with rectal bleeding
K51.212 Ulcerative (chronic) proctitis with intestinal obstruction
K51.213 Ulcerative (chronic) proctitis with fistula
K51.218 Ulcerative (chronic) proctitis with other complication
K51.219 Ulcerative (chronic) proctitis with unspecified complications
K51.311 Ulcerative (chronic) rectosigmoiditis with rectal bleeding
K51.312 Ulcerative (chronic) rectosigmoiditis with intestinal obstruction
K51.313 Ulcerative (chronic) rectosigmoiditis with fistula
K51.318 Ulcerative (chronic) rectosigmoiditis with other complication
K51.319 Ulcerative (chronic) rectosigmoiditis with unspecified complications
K51.411 Inflammatory polyps of colon with rectal bleeding
K51.412 Inflammatory polyps of colon with intestinal obstruction
K51.413 Inflammatory polyps of colon with fistula
K51.418 Inflammatory polyps of colon with other complication
K51.419 Inflammatory polyps of colon with unspecified complications
K51.511 Left sided colitis with rectal bleeding
K51.512 Left sided colitis with intestinal obstruction

36
K51.513 Left sided colitis with fistula
K51.518 Left sided colitis with other complication
K51.519 Left sided colitis with unspecified complications
K51.811 Other ulcerative colitis with rectal bleeding
K51.812 Other ulcerative colitis with intestinal obstruction
K51.813 Other ulcerative colitis with fistula
K51.818 Other ulcerative colitis with other complication
K51.911 Ulcerative colitis, unspecified with rectal bleeding
K51.912 Ulcerative colitis, unspecified with intestinal obstruction
K51.913 Ulcerative colitis, unspecified with fistula
K51.918 Ulcerative colitis, unspecified with other complication
K52.0 Gastroenteritis and colitis due to radiation
K56.3 Gallstone ileus
K62.7 Radiation proctitis
O98.711 Human immunodeficiency virus [HIV] disease complicating pregnancy, first trimester
O98.712 Human immunodeficiency virus [HIV] disease complicating pregnancy, second trimester
O98.713 Human immunodeficiency virus [HIV] disease complicating pregnancy, third trimester
T80.82XS Complication of immune effector cellular therapy, sequela
Z51.11 Encounter for antineoplastic chemotherapy
Z92.850 Personal history of Chimeric Antigen Receptor T-cell therapy
Z92.858 Personal history of other cellular therapy
Z92.86 Personal history of gene therapy
Z94.0 Kidney transplant status
Z94.1 Heart transplant status
Z94.2 Lung transplant status
Z94.3 Heart and lungs transplant status
Z94.4 Liver transplant status
Z94.5 Skin transplant status
Z94.6 Bone transplant status
Z94.81 Bone marrow transplant status
Z94.82 Intestine transplant status
Z94.83 Pancreas transplant status
Z94.84 Stem cells transplant status
Z94.89 Other transplanted organ and tissue status
ICD-10-CM Codes that DO NOT Support Medical Necessity

Group 1

Group 1 Paragraph

N/A

Group 1 Codes

N/A

ICD-10-PCS Codes

Group 1

Group 1 Paragraph

N/a

37
Group 1 Codes

N/A

Additional ICD-10 Information

N/A

Bill Type Codes

Contractors may specify Bill Types to help providers identify those Bill Types typically used to report this service. Absence of a Bill Type does not guarantee that the article does not apply to that Bill Type. Complete absence of all Bill Types
indicates that coverage is not influenced by Bill Type and the article should be assumed to apply equally to all claims.

N/A

Revenue Codes

Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report this service. In most instances Revenue Codes are purely advisory. Unless specified in the article, services reported under other
Revenue Codes are equally subject to this coverage determination. Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Code and the article should be assumed to apply equally to all Revenue Codes.

N/A

N/A

Other Coding Information

Group 1

Group 1 Paragraph

N/A

Group 1 Codes

N/A

Revision History Information

Revision History Revision History

Date Number Revision History Explanation
07/01/2023 R10 The previous revision effective date of 7/1/2023 is incorrect. The deletion of U0003, U0004, and U0005 from CPT/HCPCS Group 8: Codes is related to the end of the COVID-19 PHE and is effective
for dates of service on or after 5/12/2023.
07/01/2023 R9 Under CPT/HCPCS Codes Group 6: Codes added 87999. This revision is effective on 3/24/2023.

Under CPT/HCPCS Group 8: Codes deleted U0003, U0004, and U0005. This revision is due to the 2023 Q3 CPT/HCPCS Code Update and is effective on 7/1/2023.
04/20/2023 R8 Under CPT/HCPCS Codes Group 6: Paragraph revised 2nd sentence to add “Per policy, these”. Added last sentence. Under CPT/HCPCS Codes Group 7: Paragraph revised 2nd sentence to add
“Per policy, these”. Added last sentence. Under ICD-10 Codes that Support Medical Necessity Group 5: Codes added B37.89 and R30.0. Deleted N93.9 and N95.0. This revision is retroactive
effective for dates of service on or after 06/02/2022.

Under CPT/HCPCS Codes Group 8: Codes added 87149, 87150, and 87513. This revision is effective on 04/20/2023.
01/01/2023 R7 Under CPT/HCPCS Codes Group 5: Codes the description was revised for 87999. This revision is due to the 2023 Annual/Q1 CPT/HCPCS Code Update and is effective on January 1, 2023.

38
 Under CPT/HCPCS Codes Group 8: Codes added 87468, 87469, 87478, and 87484. This revision is due to the 2023 Annual/Q1 CPT/HCPCS Code Update and is effective on January 1, 2023.

Under ICD-10 Codes that Support Medical Necessity Group 5: Codes added L29.2, L29.3, N90.89, N93.0, N93.8, N93.9, N95.0, R10.2, and Z20.2. This revision is effective for dates of service on or
after 06/02/2022.

Revision History Corrections: The effective date of this article was changed from 04/17/2022 to 06/02/2022, to align with the revision effective date of LCD L39001 MolDX: Molecular Syndromic
Panels for Infectious Disease Pathogen Identification Testing.

Correction to R6 - Under Article Text revised the thirteenth bullet first sentence to add “for the same (or highly similar) intended use”. Under CPT/HCPCS Codes Group 5: Codes added 87999. This
revision is effective for dates of service on or after 06/02/2022.

Correction to R4 - Under ICD-10 Codes that Support Medical Necessity Group 6: Paragraph revised second sentence to add “POS 19, 21, 22 or 23”. Under ICD-10 Codes that Support Medical
Necessity Group 7: Paragraph revised second sentence to add “POS 19, 21, 22 or 23”. This revision is retroactive effective for dates of service on or after 06/02/2022.

Correction to R3 - Under CPT/HCPCS Codes Group 6: Codes deleted 0151U. Under CPT/HCPCS Codes Group 7: Codes deleted 0097U. This revision is due to the Q2 CPT/HCPCS Code Update and
is effective for dates of service on or after 06/02/2022.
10/01/2022 R6 Under Article Text revised the thirteenth bullet first sentence to add “for the same (or highly similar) intended use”. Under CPT/HCPCS Codes Group 5: Codes added 87999. This revision is
retroactive effective for dates of service on or after 4/17/2022.

Under CPT/HCPCS Codes Group 5: Codes added 0352U and 0353U. Under CPT/HCPCS Codes Group 8: Codes added 87593. This revision is due to the Q4 CPT/HCPCS Code Update and is
effective for dates of service on or after 10/1/2022.
10/01/2022 R5 Under ICD-10 Codes that Support Medical Necessity Group 7: Codes deleted D59.30 and D59.31. This addition of codes in Revision 3 was done in error

Under Article Text corrected typographical error and revised from Palmetto to Noridian in following sentence: In such cases, Noridian will pay only for components of a service that are reasonable and
necessary.
10/01/2022 R4 Under ICD-10 Codes that Support Medical Necessity Group 6: Paragraph revised second sentence to add “POS 19, 21, 22 or 23”. Under ICD-10 Codes that Support Medical Necessity Group 7:
Paragraph revised second sentence to add “POS 19, 21, 22 or 23”. This revision is retroactive effective for dates of service on or after 5/17/2022.

Under ICD-10 Codes that Support Medical Necessity Group 5: Paragraph added “NOTE: Claims with diagnosis code Z11.3 would be expected to also include a high-risk diagnosis code”. Under
ICD-10 Codes that Support Medical Necessity Group 5: Codes added Z11.3, Z33.1, Z33.3, Z72.51, Z72.52, Z72.53, Z72.89. This revision is retroactive effective for dates of service on or after
9/6/2022.

Under ICD-10 Codes that Support Medical Necessity Group 2: Codes added D59.30 and D59.31. Under ICD-10 Codes that Support Medical Necessity Group 4: Codes added D59.30 and D59.31.
Under ICD-10 Codes that Support Medical Necessity Group 5: Codes deleted B37.3. Added B37.31, B37.32, and N76.82. Under ICD-10 Codes that Support Medical Necessity Group 6:
Codes added D81.82. Under ICD-10 Codes that Support Medical Necessity Group 7: Codes added D59.30, D59.31, and D81.82. This revision is due to the Annual ICD-10-CM Update and will
become effective on 10/1/2022.
06/02/2022 R3 Under CPT/HCPCS Codes Group 6: Codes deleted 0151U. Under CPT/HCPCS Codes Group 7: Codes deleted 0097U. This revision is due to the Q2 CPT/HCPCS Code Update and is effective for
dates of service on or after 4/1/2022.

Under Article Text revised first and second bullet verbiage to add “or PLA” and deleted third and fourth bullet verbiage. Revised fifth bullet verbiage to add, “and a TA.” Deleted the sixth and seventh
bullet verbiage. Added two new bullet verbiages, “Tests that are FDA-approved/cleared and performed in ways consistent with their intended-use labeling directions do not require a Z-code when
billed with an appropriate accompanying ICD-10 code. However, the performance of multiple (>1) FDA-approved/cleared molecular Infectious Disease pathogen identification tests on the same date of
service (DOS) for the same intended use on the same patient sample is considered as one distinct service. As such, it would require the use of CPT® code 87999. Tests using CPT® code 87999 will
require a Z-code and a TA.” And “Add modifier 59 for different species or strains reported by the same code, as allowed by the policy.” Revised Additional Information nineth bullet verbiage to
“Places of service (POS) 19, 21, 22, 23 OR” and “(for healthcare POS other than the POS listed in 1 (a).” Under CPT/HCPCS Group 1: Paragraph deleted second sentence. Under CPT/HCPCS
Codes Group 1: Codes added 87801. Under CPT/HCPCS Group 2: Paragraph deleted second sentence. Under CPT/HCPCS Group 3: Paragraph deleted second sentence. Under CPT/HCPCS
Group 4: Paragraph deleted second sentence. Under CPT/HCPCS Group 5: Paragraph deleted second sentence. Under CPT/HCPCS Group 5: Codes deleted 87623, 87624, and 87625.
Under CPT/HCPCS Group 6: Paragraph deleted third sentence. Revised fourth sentence to add “POS 19, 21, 22, 23” and “(for healthcare POS other than those listed in (a).” Under CPT/HCPCS
Group 6: Codes added 87801. Under CPT/HCPCS Group 7: Paragraph deleted third sentence. Revised fourth sentence to add “POS 19, 21, 22, 23” and “(for healthcare POS other than those listed
in (a).” Under CPT/HCPCS Group 8: Paragraph added verbiage, “Conditionally Non-covered CPT codes: The following CPT codes are NOT covered for a given beneficiary on the same DOS
when >1 is billed in combination with another CPT or PLA code from Groups 1-7 for the same intended use. Additionally, the following CPT codes are NOT covered for a given beneficiary on the
same DOS when >2 are billed for the same intended use.” Under CPT/HCPCS Group 8: Codes added U0001, U0002, U0003, U0004, U0005, 87471, 87472, 87475, 87476, 87480, 87481, 87482,
87485, 87486, 87487, 87490, 87491, 87492, 87493, 87495, 87496, 87497, 87498, 87501, 87502, 87503, 87510, 87511, 87512, 87516, 87517, 87520, 87521, 87522, 87525, 87526, 87527, 87528,
87529, 87530, 87531, 87532, 87533, 87534, 87535, 87536, 87537, 87538, 87539, 87540, 87541, 87542, 87550, 87551, 87552, 87555, 87556, 87557, 87560, 87561, 87562, 87563, 87580, 87581,

39
 87582, 87590, 87591, 87592, 87623, 87624, 87625, 87634, 87635, 87640, 87641, 87650, 87651, 87652, 87653, 87660, 87661, 87662, 87797, 87798, and 87799. Under CPT/HCPCS Modifiers Group
8: Codes added 59. Under ICD-10 Codes that Support Medical Necessity Group 3: Codes added B60.2. Under ICD-10 Codes that Support Medical Necessity Group 5: Codes added N76.89, N77.1,
and N89.8. This revision is effective 06/02/2022.
06/02/2022 R2 The effective date of this article was changed from 04/17/2022 to 06/02/2022, to align with the revised effective date of LCD L39003 MolDX: Molecular Syndromic Panels for Infectious Disease
Pathogen Identification Testing.
04/17/2022 R1 Under ICD-10 Codes that Support Medical Necessity Group 1: Codes added A37.00, A37.01, A37.10, A37.11, A37.80, A37.81, A37.90, A37.91, A41.81, A41.89, A48.1, A48.2, B25.0, B33.23,
B33.24, B59, J05.0, J12.0, J12.2, J12.3, J13, J15.0, J15.1, J15.20, J15.211, J15.212, J15.29, J15.3, J15.4, J15.7, J15.8, J15.9, J16.0, J20.0, J20.1, J20.2, J20.3, J20.4, J20.6, J22, J84.116, J84.117, J84.2,
J85.0, J85.1, J85.2, J85.3, T86.33, and T86.812. Under ICD-10 Codes that Support Medical Necessity Group 2: Paragraph added the verbiage “Targeted”. Under ICD-10 Codes that Support
Medical Necessity Group 2: Codes added A08.31, A08.32, A32.11, A32.12, A32.7, K51.414, K92.1, R10.11, R10.12, R10.13 and T86.852. Deleted B20, K50.018, K50.111, K50.818, K50.918,
K51.018, K51.218, K51.318, K51.518, and K51.818. Under ICD-10 Codes that Support Medical Necessity Group 3: Codes added R41.82 and R50.9. Deleted B00.1. Under ICD-10 Codes that
Support Medical Necessity Group 4: Codes deleted E10.69, E11.69, and E13.69. Under ICD-10 Codes that Support Medical Necessity Group 5: Codes added O98.711, O98.712, and O98.713.
Under ICD-10 Codes that Support Medical Necessity Group 6: Paragraph added verbiage “For testing in POS other than POS 21 or 23” to beginning of second sentence and “(once per transplant)”
to third sentence. Under ICD-10 Codes that Support Medical Necessity Group 6: Codes added E08.43, E10.43, E11.43, and E13.43. Deleted A37.00, A37.01, A37.10, A37.11, A37.80, A37.81,
A37.90, A37.91, A41.81, A41.89, A41.9, A48.1, A48.2, B25.0, B25.1, B25.2, B25.8, B33.23, B33.24, B59, B97.21, B97.29, D80.7, J05.0, J12.0, J12.2, J12.3, J12.81, J12.82, J12.89, J12.9, J13, J15.0,
J15.1, J15.20, J15.211, J15.212, J15.29, J15.3, J15.4, J15.7, J15.8, J15.9, J16.0, J16.8, J18.1, J20.0, J20.1, J20.2, J20.3, J20.4, J20.5, J20.6, J20.8, J20.9, J21.9, J22, J44.0, J44.1, J45.31, J45.32, J45.41,
J45.42, J45.51, J45.52, J45.901, J45.902, J84.116, J84.117, J84.2, J85.0, J85.1, J85.2, J85.3, R65.20, R65.21, R78.81, T86.33, and T86.812. Under ICD-10 Codes that Support Medical Necessity
Group 7: Paragraph added verbiage “For testing in POS other than POS 21 or 23” to beginning of second sentence and “(once per transplant)” to third sentence. Under ICD-10 Codes that Support
Medical Necessity Group 7: Codes deleted A00.0, A00.1, A00.9, A01.00, A01.09, A01.1, A01.2, A01.3, A02.0, A02.1, A02.8, A03.0, A03.1, A03.2, A03.3, A03.8, A04.0, A04.1, A04.2, A04.3,
A04.5, A04.6, A04.71, A04.72, A04.8, A04.9, A05.0, A05.1, A05.2, A05.3, A05.4, A05.5, A06.0, A06.1, A06.2, A07.1, A07.2, A07.4, A08.0, A08.11, A08.19, A08.2, A08.31, A08.32, A08.39, A08.8,
A09, A32.11, A32.12, A32.7, A41.50, A41.51, A41.52, A41.53, A41.59, A41.81, A41.89, A41.9, B25.0, B25.8, D80.7, K50.014, K50.114, K50.814, K50.914. K51.014, K51.214, K51.314, K51.414,
K51.514, K51.814, K51.914, K52.1, K56.0, K92.1, M31.19, R10.0, R10.11, R10.12, R10.13, R10.31, R10.32, R10.33, R10.811, R10.812, R10.813, R10.814, R10.815, R10.817, R10.821, R10.822,
R10.823, R10.824, R10.825, R10.826, R10.827, R10.829, R10.84, R19.5, R19.7, R50.9, R65.20, R65.21, R78.81, and T86.852.
Associated Documents

Related Local Coverage Documents

LCDs

L39003 - MolDX: Molecular Syndromic Panels for Infectious Disease Pathogen Identification Testing

Related National Coverage Documents

N/A

Statutory Requirements URLs

N/A

Rules and Regulations URLs

N/A

CMS Manual Explanations URLs

N/A

Other URLs

N/A

Public Versions

40
 Updated On Effective Dates Status
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Article Title

Response to Comments: MolDX: Molecular Syndromic Panels for Infectious Disease Pathogen Identification Testing

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Article Guidance

Article Text

The comment period for the MolDX: Molecular Syndromic Panels for Infectious Disease Pathogen Identification Testing DL39003 Local Coverage Determination (LCD) began on 05/20/2021 and ended on 07/03/2021. The notice period for
L39003 begins on 3/3/2022 and will become effective on 4/17/2022.

The title of the LCD was revised from MolDX: Multiplex Nucleic Acid Amplification Test (NAAT) Panels for Infectious Disease Testing to MolDX: Molecular Syndromic Panels for Infectious Disease Pathogen Identification Testing.

The comments below were received from the provider community.

Response To Comments

Number Comment Response

41
1 The following comment was submitted to Palmetto GBA, CGS, WPS, and Noridian and was received from 1. Clarity regarding restrictions pertaining to ordering provider and POS
multiple stakeholders:
A. Comments requesting clarity regarding how the restrictions impact access to care
1. Clarity regarding restrictions pertaining to ordering provider and place of service (POS).
2. Clarity regarding CLIA and FDA Regulations Required for Tests under this Policy. First, this policy (LCD) does not restrict targeted panels on the basis of POS or specialty of ordering clinician. As such, it
3. Why foundational policies do not list covered tests within the policy. does NOT prohibit the use of targeted panels in the community. The clinician specialist requirement is only applicable to
4. Clarity regarding scope of MolDX and scope of the policy - including requirements for registering the expanded respiratory and gastrointestinal panels and does not apply to smaller targeted panels (i.e., for Influenza A/B,
tests with MolDX and for a Technical Assessment (TA). RSV, and SARS-CoV-2).
5. Clarity regarding criteria for orthogonal comparator (‘reference’) tests as the standards of care
evolve with time. Second, the LCD and accompanying billing and coding article (LCA) provide information and instructions regarding
6. Clarity regarding billing. exceptions of the physician specialist requirement for patients in geographic areas that do not have reasonable access to
7. Clarity regarding the inclusion of (new CPT codes for) Infectious Vaginosis/Vaginitis (BV) panels. certain physician specialists.
8. Comments regarding inclusion of Urinary Tract Infection (UTI) panels in the LCA.
9. Comments requesting inclusion of ICD-10 code R19.7 for Gastrointestinal (GI) panels. We have revised the LCA for clarity as follows:

For Expanded (>5 pathogens) RP, PNP, and GI Panels the following additional conditions apply:

1. Testing is billed according to 1 of the following:

(a) Places of service (POS) 21, 23, (Inpatient Hospital or Emergency Room, respectively) OR

(b) The test is ordered as follows (for healthcare POS other than 21 or 23):

(1) For immune-competent beneficiaries, the test must be ordered by an Infectious Disease Specialist or 1 of the
following: Pulmonologist (for the RP and PNP panels) or Gastroenterologist (for the GI panels) who is diagnosing and
treating the beneficiary.

(2) For immune-compromised beneficiaries, the test must be ordered by a clinician specialist in 1 of the following:
Infectious Diseases, Oncology, Transplant (for any panel),Pulmonologist (for the RP and PNP panels) or
Gastroenterologist (for the GI panels) who is diagnosing and treating the beneficiary.

(3) Regarding (1) and (2), An exception may be made in geographic locations where the specialist(s) cannot be reasonably
reached by the beneficiary, and the ordering provider is located closer to the beneficiary’s place of residence than the
nearest specialist. We would generally expect that beneficiaries for whom the test is ordered under this exception to be
living in rural locations, islands, or some other location where access to care is limited.

Therefore, according to the above, beneficiaries under the care of certain clinician specialists are NOT limited to inpatient
or emergency care settings for expanded panel testing. However, in settings OTHER than an inpatient hospital or
Emergency Room, only a clinician specialist in one of the medical disciplines outlined in the policy will be permitted to
order the expanded RP, PNP, and GI panels; in such cases, POS 81 and other healthcare POSs are allowed, when all
criteria of the policy are met. Finally, for testing immune-competent patients with the expanded RP/PNP or GI panels, the
policy states that the patient must be “seriously or critically ill or at imminent risk of becoming seriously or critically ill
(as defined by the American Hospital Association’s “General Guide for the Release of Information on the Condition of
Patients”) as a result of a presumed GI infection AND the patient is being treated in an appropriate critical care facility.”

B. Comments requesting clarity regarding the rationale for inclusion of POS 21 and 23

First, as stated in the LCD, “this policy does NOT address coverage for the inpatient setting.” However, POS 21 and 23
(inpatient hospital and emergency room, respectively) will remain included in the LCA. The LCA does refer to scenarios
in which a patient is seriously or critically ill or is at imminent risk of becoming seriously or critically ill; therefore, we
have also added the following language for clarity: “This contractor expects that critically ill patients will be tested and
managed in the appropriate critical care facility.” Finally, as stated in the LCD, “this policy does NOT address coverage
for the inpatient setting.”

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2. Clarity regarding CLIA and FDA Regulations Required for Tests under this Policy

Testing must be performed according to Clinical Laboratory Improvement Amendments (CLIA) and/or Food and Drug
Administration (FDA) regulations. For example, CLIA-non-waived tests may only be performed in certified laboratories
and according to CLIA regulations. CLIA-waived tests may be performed in healthcare settings that operate under a CLIA
Certificate of Waiver or Certificate of Compliance/Certificate of Accreditation.

Panels intended for home use (including those that have been FDA approved or cleared) do NOT meet the coverage
criteria of this policy. This has been added to the LCD and LCA for clarity.

3. Why foundational policies do not list covered tests within the policy

The Proposed LCD is foundational in nature. As such, the coverage criteria listed are not specific to a particular product
but rather to a service measuring specific analytes/organisms. This is comparable with other Molecular Diagnostics
Services Program (MolDX) foundational LCDs. The LCA further identifies CPT codes and tests that meet the criteria
established in the policy. Moreover, any tests requiring registration with MolDX (according to the criteria outlined in the
policy) will have a coverage determination listed in the DEX registry.

Therefore, coverage decisions meet transparency requirements, as all necessary coverage criteria are outlined in the
policy, as required by the Program Integrity Manual and according to the provisions of the 21st Century Cures Act.

4. Clarity regarding scope of MolDX and scope of the policy - including requirements for registering tests with
MolDX and for a Technical Assessment (TA)

Scope of MolDX: The scope of MolDX involves testing using DNA/RNA. It is not restricted to human DNA/RNA.

Scope of the policy - Broadening the scope of testing (beyond multiplex PCR):

We agree with broadening the scope of the policy to accommodate other (beyond multiplex PCR) molecular panels. As
such, we have revised the title and language of the policy to reflect this broader scope and to accommodate these other
tests (i.e., amplified probe tests). To this end, we have also removed the references to ‘multiplex’ and ‘closed system.’
The scope of the revised policy is therefore Molecular Syndromic Panels for Infectious Disease Pathogen
Identification Testing (with some exceptions that are specifically listed in the policy).

Additionally,

• A ‘panel’ herein is defined as any test (billed on the same beneficiary on the same date of service for the same
intended purpose) that detects >1 pathogen. This definition is in alignment with the MolDX definition of panel
testing for genes, as described in MolDX: Testing of Multiple Genes. A ‘syndromic panel’ is further defined as
one that simultaneously detects multiple different pathogens associated with similar and overlapping clinical
symptomatology.

• Restrictions regarding repeat testing/tests of cure also apply solely to testing using
molecular syndromic panel tests. Single-pathogen tests remain outside the scope of this policy.

Requirement for registration of tests within the scope of this policy:

“Services that do not have FDA-cleared/approved indicated uses as well as FDA-approved tests performed in ways not
consistent with their intended-use labeling directions will require registration with MolDX and a Technical Assessment
(TA) to demonstrate compliance of the service with this policy. Similarly, tests (and CPT codes) for which there are not
accompanying ICD-10 codes in the associated Billing and Coding Article will require registration with MolDX and a TA
to demonstrate compliance of the service with this policy.”

• Example - there are currently no FDA cleared/approved indicated uses for urinary tract infection (UTI) panels

43
 (and there are no covered predicate UTI tests). As such, at present, molecular UTI panel tests must submit for a
Z-code and undergo a TA in order to demonstrate compliance with the coverage criteria of the policy. The
necessary criteria for coverage of such panels are further outlined in the policy.

The following has also been added to the LCA for clarity - “CPT codes that are not billed with the appropriate
accompanying ICD-10 codes listed in this Billing and Coding Article will be denied. Tests with other indicated uses may
therefore submit for a Z-code and undergo a TA by MolDX. Tests using CPT code 87999 will also require a Z-code.”

5. Clarity regarding criteria for orthogonal comparator (‘reference’) tests as the standards of care evolve with
time

The term ‘standard of care’ (SOC) herein refers to a range of potential diagnostic approaches that are considered
medically acceptable for a given patient in a given clinical situation. As the SOC may change over time, this policy does
not limit a comparator test to a specific SOC test, but rather to the medically accepted SOC tests at a given time. As such,
the policy states that a comparator test may include any of a number of methodologies, so long as these are accepted SOC
methods for the diagnosis of a particular pathogen(s).

Specifically, the policy outlines the requirements for new tests registering with MolDX as follows - “Registered tests must
demonstrate equivalent or superior test performance characteristics - analytical validity (AV) and clinical validity (CV) -
to established standard-of-care (SOC) methods (i.e., culture, pathogen-specific PCR) for the majority of targets included
on the panel.”

Finally, we agree with the comments requesting clarity regarding analytes vs pathogens, and we have revised the
following statement regarding comparisons to established SOC tests as follows - “CV of any new organisms and
analytes not already established as SOC or that do not have a covered predicate test by this contractor, must be
established through a study published in the peer-reviewed literature for the intended use of the test in the intended
population.”

• For example, until the multiple other organisms associated with Bacterial Vaginosis (BV) were identified, it was
thought that the primary associated organism was Gardenerella vaginalis. As other bacteria have demonstrated
clinical validity in BV, testing for those is fast becoming the new SOC.

Finally, the policy clearly states that “This contractor will continue to monitor the evidence, and new developments may
impact this coverage decision.” Therefore, covered tests may periodically be required to demonstrate validity against an
evolving SOC and coverage of certain tests may be rescinded if they no longer demonstrate compliance with the criteria of
the policy.

6. Clarity regarding billing

A. Regarding the comments requesting clarity for the circumstance in which only targeted testing is appropriate
but institutions do not have access to smaller panels -

The policy states “Expanded panel testing is only indicated when targeted panel testing is not appropriate (i.e., will not
provide sufficient information for the appropriate clinical management of the patient).”

The LCA has been modified to address the above circumstance as follows-

“It is understood that in certain instances in which only targeted testing is appropriate, institutions may not have access
to small panels and may have to perform larger panels for technical reasons. In such cases, Palmetto will pay only for
components of a service that are reasonable and necessary.”

B. Regarding comments requesting clarity for circumstances where additional testing may be needed for the same
clinical indication –

44
The policy states “The panel performed includes at least the minimum pathogens required for clinical decision making for
its intended use that can be reasonably detected by the test.”

The policy, however, recognizes exceptional circumstances as follows “If additional organisms are not included in a
panel, testing for those non-duplicative pathogens separately for the same indication may be reasonable and necessary in
limited circumstances.”

♦ Regarding the performance of additional panels for the same clinical indication on the same date of service (DOS)

The LCA has been modified to further clarify this circumstance as follows - “When 2 or more codes within a given Group
OR from 2 related Groups (i.e., Groups 1 and 6 which pertain to Respiratory panels, or Groups 2 and 7 which pertain to
Gastrointestinal panels) are submitted for the same beneficiary on the same date of service, the claims processing system
will reject every code submitted after the first service.”

♦ “As outlined in the policy, exceptions may be allowed in limited circumstances for bloodstream and
meningoencephalitis panels.” For example, in the event that a Gram-positive bloodstream pathogen panel is
performed but a Gram-negative bloodstream pathogen panel must also be performed (i.e., in the event that there
was an error in interpreting the original Gram stain), the Gram-negative panel may be performed with the
supporting documentation from the medical record.” Note that if the original panel was inclusive of both
Gram-positive and Gram-negative pathogens, this scenario would not apply. In such cases, if a lab runs more than
1 distinct procedural service from this list on a single date of service, then the lab must use the 59 modifier with
each additional service billed as an attestation that it is a distinct procedural service.
♦ Reimbursement for other (other than bloodstream and meningoencephalitis) panels may be appealed if supported
by documentation in the medical record and all other criteria outlined in this policy. The performance of any other
additional panel on the same DOS is expected to occur with extreme rarity.
♦ Regarding repeat panel tests for the same clinical indication NOT performed on the same DOS – These will NOT
be reimbursed, except according to the criteria outlined in the related LCD (i.e., “1 additional panel test may be
performed between 1 and 14 days after the initial panel test, so long as the test fulfills the criteria for coverage as
set forth in this policy”).

The policy states –

“Molecular syndromic panel tests will NOT be covered in the following circumstances:

• If the test is performed as a test of cure.

• If the patient has been previously tested by molecular diagnostic methods for the same pathogens within 14 days
for the same clinical indication.
• If a previous panel test was performed with a similar/duplicative intended use, a subsequent test is only
reasonable and necessary if the non-duplicative content of the second test is reasonable and necessary.
• Exception: Repeat panel testing for the same clinical indication will only be covered if first panel yielded a
negative result AND there is a high index of suspicion for a pathogen as the cause of symptoms AND the patient’s
clinical condition is not improving or is deteriorating after a clinically appropriate length of time. In such cases, 1
additional panel test may be covered between 1 and 14 days after the initial panel test, so long as the test fulfills
the criteria for coverage as set forth in this policy.”

C. Additional modifications to the LCA for clarity can be seen here -

• The test panel is a single test with multiple components and is characterized by a single unit of service (UOS
=1). A panel cannot be unbundled and billed as individual components regardless of the fact that the test reports
multiple individual pathogens and/or targets.”
• Select the appropriate CPT® code

45
 • If the panel being used does not have its own proprietary CPT® code, select the appropriate CPT® code and
follow the additional instructions for the given ‘panel’ in the relevant Group paragraphs below. If no specific
CPT code exists for the test submitted, bill with CPT code 87999.
• If the test does have a PLA code then submit the appropriate code

• Add modifier 59 for different species or strains reported by same code, as allowed by the policy

• CPT codes that are not billed with the appropriate accompanying ICD-10 codes listed in this Billing and Coding
Article will be denied. Tests with other indicated uses may therefore submit for a Z-code and undergo a Technical
Assessment (TA) by MolDX. Tests using CPT code 87999 will also require a Z-code.

• Laboratories that are billing for multiple individual pathogens using the 59 modifier rather than panels may be
subject to medical review as outliers. Similarly, laboratories billing for multiple related panels may be subject to
medical review as outliers.”

7. Clarity regarding the inclusion of (new CPT codes for) Infectious Vaginosis/Vaginitis (BV) panels

• Because mixed infections are common in BV, and because clinical assessment alone is not sufficient to
differentiate among common causes of BV, we have added the following clarifying language to the policy:

“For the diagnosis of infectious vaginosis/vaginitis, it is reasonable to perform a (targeted or expanded) panel that
includes a combination of at least 2 of the following: Gardnerella vaginalis, other BV-associated bacteria (BVAB) (such
as Atopobium vaginae and/or Megasphaera types), Trichomonas vaginalis, and Candida species.”

• Transcription-mediated amplification (TMA) is a NAAT test and MolDX considers tests such as the Aptima® BV
Assay a ‘panel,’ as it detects multiple organisms, regardless of whether it reports results for the individual
organisms.
• The new CPT codes 81513 and 81514 have been included in the associated LCA, as they meet the criteria of the
policy.

8. Comments regarding inclusion of Urinary Tract Infection (UTI) panels in the LCA

As stated in Response #4, there are currently no FDA cleared/approved indicated uses for UTI panels (and there are no
covered predicate UTI tests). Therefore, at present, UTI panel tests must submit for a Z-code and undergo a TA in order to
demonstrate compliance with the coverage criteria of the policy.

The necessary criteria for coverage of such panels are outlined in the policy. As such, we have modified the language in
the LCD and LCA to more clearly accommodate the inclusion of UTI and other panels when they have demonstrated that
they have met the criteria outlined in the policy.

9. Comments requesting inclusion of ICD-10 code R19.7 for Gastrointestinal (GI) panels

We agree that, in the absence of detection of a specific pathogen, ICD-10 code R19.7, Diarrhea unspecified, is a key
diagnosis code, and has been included in Groups 2 and 7 in the LCA.
2 The following comment was submitted to CGS: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
UnityPoint Health appreciates this opportunity to provide comments on the Proposed Local Coverage
Determination (LCD): MolDX: Multiplex Nucleic Acid Amplification Test (NAAT) Panels for Infectious
Disease Testing. UnityPoint Health is one of the nation’s most integrated health care systems. Through
more than 33,000 employees and our relationships with more than 480 physician clinics, 40 hospitals in
urban and rural communities and 14 home health agencies throughout our 9 regions, UnityPoint Health
provides care throughout Iowa, central Illinois and southern Wisconsin. UnityPoint Health is both a

46
 Medicare Part A and Part B provider. On an annual basis, UnityPoint Health hospitals, clinics and home
health provide a full range of coordinated care to patients and families through more than 8.4 million
patient visits.

UnityPoint Health recognizes the time and effort of CGS Administrators reflected in the Proposed Local
Coverage Determination (LCD): MolDX: Multiplex Nucleic Acid Amplification Test (NAAT) Panels for
Infectious Disease Testing as well as the Draft Local Coverage Article Billing and Coding: MolDX:
Multiplex Nucleic Acid Amplification Test (NAAT) Panels for Infectious Disease Testing. We are
providing comment on this proposed LCD in support of our place of service (POS) 11 providers, which
include both physician clinics and urgent care locations. Our comments are limited to the LCD as it
pertains to NAAT respiratory panels, which LCDs have been similarly adopted by WPS GHA
Medicare1 and Palmetto GBA2. As this is currently the only mechanism open (through August 7, 2021) for
public comments on multiplex NAAT for respiratory panels, we respectfully offer the following input.

Timely Access to NAAT RP – Limited Panels of less than Six Pathogens

Background: Infectious disease physicians within UnityPoint Health have recommended we transition
to molecular testing for influenza in our ambulatory clinics, replacing antigen testing as much as
possible. This recommendation conforms to the clinical practice guidelines set forth by Infectious Diseases
Society of America (IDSA).3 Antigen testing for influenza has been utilized widely for clinic settings but,
in 2017, the U.S Food and Drug Administration (FDA) reclassified these assays due to poor performance
(low sensitivity) and instituted stricter requirements for antigen tests that were to be used for patient testing.
In addition, on July 21, 2021, the Centers for Disease Control and Prevention (CDC) issued a Lab Alert4 to
encourage laboratory adoption of a multiplexed method that can facilitate detection and differentiation of
SARS-CoV-2 and influenza viruses. The Alert stated that “Such assays can facilitate continued testing for
both influenza and SARS-CoV-2 and can save both time and resources as we head into influenza season.”
Based upon this information, the continuing evolution of the COVID pandemic, and subsequent
development of new molecular multiplex assays by several vendors (to include FLU, COVID and RSV),
UnityPoint Health is reviewing LCDs to identify any coverage restrictions for molecular testing in
ambulatory clinic and urgent care locations (POS 11) in anticipation of the 2021-2022 respiratory season.
As NAAT panel tests are the gold standard, we are concerned with billing and coding restrictions that limit
orders to specific clinician specialists, who are often not as prevalent in ambulatory settings, are
disproportionately located in urban practice settings, and are the subject of health care professional
shortages. To promote timely access to care and treatment, we firmly believe that small, targeted
Respiratory Panels (RP) should be reimbursed if ordered by primary care providers in POS
11. Particularly relevant during the current COVID-19 pandemic are multiplex NAAT viral panels,
including 4 in 1 panels (Flu A, Flu B, RSV and COVID) and 3 in 1 panels (Flu A, Flu B and COVID).

Request: In our review it does not appear that there are either restrictions on POS or ordering clinicians for
small, targeted RP tests. UnityPoint Health seeks confirmation that this interpretation is correct. If this
LCD does impose either POS or ordering clinician restrictions for small, targeted panels, UnityPoint
Health requests CGS Administrators reconsider these coverage restrictions. If no such restrictions are
imposed for small, targeted panels, we support this LCD for small, targeted panels and would urge other
Medicare Administrative Contractors (MACs) to follow suit.

We are pleased to provide input on this proposed LCD and its impact on our clinics and health system, our
patients and communities served.

References were provided for review.

3 The following comment was submitted to CGS: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
UnityPoint Health appreciates this opportunity to provide comments on the Proposed Local Coverage
Determination (LCD): MolDX: Multiplex Nucleic Acid Amplification Test (NAAT) Panels for Infectious
Disease Testing. UnityPoint Health is one of the nation’s most integrated health care systems. Through

47
 more than 33,000 employees and our relationships with more than 480 physician clinics, 40 hospitals in
urban and rural communities and 14 home health agencies throughout our 9 regions, UnityPoint Health
provides care throughout Iowa, central Illinois and southern Wisconsin. UnityPoint Health is both a
Medicare Part A and Part B provider. On an annual basis, UnityPoint Health hospitals, clinics and home
health provide a full range of coordinated care to patients and families through more than 8.4 million
patient visits.

UnityPoint Health recognizes the time and effort of CGS Administrators reflected in the Proposed Local
Coverage Determination (LCD): MolDX: Multiplex Nucleic Acid Amplification Test (NAAT) Panels for
Infectious Disease Testing as well as the Draft Local Coverage Article Billing and Coding: MolDX:
Multiplex Nucleic Acid Amplification Test (NAAT) Panels for Infectious Disease Testing. We are
providing comment on this proposed LCD in support of our place of service (POS) 81 independent
laboratories. Our comments are limited specifically to the LCD as it pertains to NAAT respiratory,
pneumonia, and GI panels, which have been similarly adopted by WPS GHA Medicare1and Palmetto
GBA2. As this is currently the only mechanism open (through August 7, 2021) for public comments on
multiplex NAAT panels, we respectfully offer the following input.

Timely Access to NAAT RP, PNP, and GI panels – Expanded Panels Six or More Pathogens

Background: We agree with the general premise that “the clinical utility of expanded panels is most
evident for select indications, populations and settings such as immune-compromised patients and
hospitalized patients.” These tests should be targeted to higher acuity patients under the care of a clinician
specialist. In terms of expanded RP, PNP, and GI panels, the LCD proposes, and the article supports,
coverage restrictions that target specific beneficiaries and require clinician specialists to order the tests for
places of service limited to POS 20, 21, 23, or 81. For POS 81 (independent labs), billing is limited solely
for cases of a pre-transplant evaluation for an immune-compromised beneficiary. The LCD and articles do
not provide rationale for this POS 81 distinction. There are case uses for expanded RP, PNP, and GI panels
to be performed by independent laboratories beyond transplant. For instance, immune-compromised
beneficiaries can be appropriately cared for and remotely monitored in a home setting. It seems contrary to
goal of diagnostic stewardship that immune-compromised beneficiaries under the care of clinician specialist
should be required to seek expanded testing in an urgent care, inpatient, or emergency care setting.
Additionally, both immune-competent and immune-compromised patients often seek care through their
primary care provider, who may deem it medically necessary to perform an expanded panel for patient
management. It is not uncommon for these outreach specimens to be referred to a POS 81 Independent
Laboratory setting for testing.

Request: UnityPoint Health requests that CGS Administrators remove the billing stipulation for
pre-transplant evaluation so that expanded RP, PNP, and GI panels may be ordered and billed in POS
81, just like POS 20, 21, and 23.

We are pleased to provide input on this proposed LCD and its impact on our clinics and health system, our
patients and communities served.

References were provided for review.

4 The following comment was submitted to Palmetto GBA, CGS, WPS, and Noridian: Thank you for your thoughtful comments and support of this policy.

BioFire Diagnostics, LLC would like to take this opportunity to participate in the comment period for the We have addressed your comments in Response 1 listed above. Additionally, regarding your comment about Bloodstream
proposed LCD titled “MolDX: Multiplex Nucleic Acid Amplification Test (NAAT) Panels for Infectious Panels, we agree and have modified the wording for availability of antimicrobial stewardship from same-day to within 24
Disease Testing” and billing article titled “Draft Local Coverage Article: Billing and Coding: MolDX: hours.
Multiplex Nucleic Acid Amplification Test (NAAT) Panels for Infectious Disease Testing.” After careful
review of the proposed LCD, we feel that great progress has been made in making expanded panels
available to the patient populations who will benefit the most from comprehensive testing. To ensure that
the proposed LCD is interpreted and applied correctly, we hope to address a few points that we feel will be
beneficial to providers and the patients that they serve.

48
Please carefully review the attached document which details the need for additional verbiage and
clarification surrounding the following points:

1. Billing and reimbursement procedures for providers utilizing expanded panels in the care of
patients who only meet criteria for targeted panel testing
2. The need of an ICD-10 code that allows gastrointestinal panel reimbursement in the event of a
negative result
3. Clarification regarding the availability of antimicrobial stewardship staff for blood culture panel
testing

We will appreciate your review of the following comments and thank you for your time and consideration

1. Many laboratories and providers exclusively use expanded panels in patient care either out of the
necessity of what is available at their location, or because they prefer the extra diagnostic information

Many facilities have been using expanded panel platforms for all eligible patients for years, and as a result
have not integrated targeted panel platforms into their workflow. In many cases, these facilities are
reluctant to incorporate a new system due to clinical, logistical, and/or financial reasons. In the final LCD,
it is extremely important to address the billing procedure for circumstances when a clinician, for various
reasons, desires to use an expanded panel to diagnose a patient who does not meet the criteria in the LCD
for expanded panel testing. Specifically, language is needed in the final LCD stating that it is appropriate
for a provider to receive reimbursement at the targeted panel rate (using targeted panel CPT codes) after
using an expanded panel in the care of a patient that only meets criteria for targeted panel testing. Having
such language will ensure that providers can confidently continue using the system that they trust in clinical
practice, while also ensuring that the appropriate reimbursement rate is applied in the care of each
individual patient per the LCD guidelines.

An example of such language has been adopted into eviCore policy, and the following example of what
could be included in the final LCD is inspired by the eviCore policy language:

“If the laboratory’s testing platform consists of a multiplexed EXPANDED (>5 Pathogens) PANEL, yet
only a subset of the organisms are considered medically necessary based on the above criteria in this
Article, the lab may run and report the EXPANDED (>5 Pathogens) PANEL while requesting
reimbursement for that subset of organisms using a procedure code that does not represent all organisms
included on the panel.”

Please consider this important issue, as many providers who exclusively use expanded panels for the
reasons below (as quoted from the proposed LCD) will be reluctant to bill in this manner without having
written authorization from the payer:

“However, even in immune-competent individuals, expanded panels can provide rapid, highly impactful,
and epidemiologically important information. They can lead to the diagnosis of some infections that, in the
past, may have been missed altogether. In 1 study, 75% of Mycoplasma pneumoniae infections were
unintentionally detected by multiplex PCR; in this study, clinicians had only specifically requested testing
for M. pneumoniae in 2 (10%) of 20 patients positive for this pathogen. Importantly, this was an actionable
finding, as infection with M. pneumoniae is treatable with antibiotics. Expanded panels can also help
rapidly diagnose and, in some cases, avert public health outbreaks. For example, during an outbreak of a
‘mystery’ respiratory illness among children in 2014, hospitals were able to rapidly identify the
presumptive cause, which turned out to be enterovirus D68. Similarly, use of rapid multiplex GI panels
significantly contributed to the recognition of a large Cyclospora outbreak in 2018.”

2. ICD-10 codes included in groups 2 and 7

The use of provider specialty requirements and place of service requirements both ensure that expanded

49
 panels are ordered by experts in settings where patients are presenting with moderate to severe disease. We
generally agree with the ICD-10 codes listed in Group 2 for targeted gastrointestinal (GI) panels and Group
7 which support utilization of an expanded GI panel.

We propose that ICD-10 code R19.7, Diarrhea unspecified, be added to Group 2 and Group 7 codes. After
reviewing the listed ICD-10 codes and talking with providers, we are concerned that without this code,
providers would not have an appropriate ICD-10 code that applies to their Medicare patients that present
with the most common sign of infectious GI illness. While there are general ICD-10 codes for unspecified
viral and bacterial pathogens in these groups, we believe most providers and coders would agree they don’t
apply in the absence of a viral or bacterial detection. Further, because these ICD-10 codes only represent
positive results, it is unclear how to accurately submit for reimbursement when a panel yields a negative
result. This lack of clarity may result cause confusion in the appropriate clinical use of these panels leading
to underutilization of GI panels and poorer patient outcomes. Diarrhea is one of the most prevalent
symptoms of patients with pathogenic GI illness and currently none of the codes address this important
symptom.

The American College of Gastroenterology Clinical Guidelines on the Diagnosis, Treatment, and
Prevention of Acute Diarrheal Infections in Adults are included in the criteria for expanded panel testing in
the LCD. These guidelines are specific to diarrheal illness and are used by gastroenterologist to determine
when diagnostic testing is needed. The symptom of diarrhea is at the crux of these guidelines. Without
including that symptom as a Group 2 and 7 code, it would make it challenging for gastroenterologist and
other clinicians to follow best practice guidelines recommended by their professional associations when
ordering appropriate testing for their patients who present with acute diarrheal illness.

3. Requirement of same-day antimicrobial stewardship team availability for blood culture panel
testing

The following comments are regarding the following LCD text:

“Personnel (i.e., an antimicrobial stewardship team) are equipped for rapid (same-day) tailoring of
antimicrobial therapy as a result of rapid testing.”

The majority of antimicrobial stewardship teams in the United States operate on a Monday through Friday
schedule, and therefore may not be available for same-day tailoring during the weekend. We suggest adding
a more lenient time window (such as within 24 hours) to account for the additional time it may take to
obtain consult when staff is not on duty. Additionally, as currently worded, it would be impossible to meet
this requirement in cases when the results of panel testing are obtained shortly before 12:00 AM.

4. Thank you

Thank you for your work in revising this important LCD. Many patients and their providers will benefit
from the broader coverage of diagnostic panels that the proposed LCD will provide. As you proceed to
ensure that this LCD is optimally applied, we will greatly appreciate your consideration of the changes
suggested in the above comments. We look forward to your thoughtful responses to these suggestions
5 The following comment was submitted to Palmetto GBA, CGS, WPS, and Noridian: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
On behalf of the Association for Molecular Pathology (AMP), the American Gastroenterological
Association (AGA), and the College of American Pathologists (CAP), we thank you for the opportunity to Additionally -
review and comment on the proposed policy for MolDX: Multiplex Nucleic Acid Amplification Test
(NAAT) Panels for Infectious Disease Testing. Regarding the comment relevant to the General Coverage Criteria, ICD-10 codes consistent with
immune-compromising conditions are provided in the associated LCA. However, as requested, we have also added a few
The AMP is an international medical and professional association representing approximately 2,500 examples of such conditions to the policy.
physicians, doctoral scientists, and medical technologists who perform or are involved with laboratory
testing based on knowledge derived from molecular biology, genetics, and genomics. Membership includes Regarding the comment relevant to the Non-Coverage Criteria, we have determined that the sample type will not be

50
professionals from academic medicine, hospital-based and private clinical laboratories, the government, andincluded. Though we recognize there are circumstances where repeat testing is warranted, this is already allowed
the in vitro diagnostics industry. (regardless of sample type) as per the current language in the policy, in specific circumstances.

The AGA is the trusted voice of the GI community. Founded in 1897, the AGA has grown to more than Regarding comments relevant to the Specific Panel Coverage Criteria -
16,000 members from around the globe who are involved in all aspects of the science, practice, and
advancement of gastroenterology. 1. The proposed language ‘or a healthcare guideline or algorithm with contribution of infectious disease or pulmonary
specialist’ is confusing rather than clarifying and we will not incorporate it into the policy.
The CAP is the world’s largest organization of board-certified pathologists and leading provider of
laboratory accreditation and proficiency testing programs. The CAP serves patients, pathologists, and the 2. PNP and expanded RP tests – this policy covers Medicare beneficiaries and is not applicable to general pediatrics.
public by fostering and advocating excellence in the practice of pathology and laboratory medicine Moreover, for clarity, we have added the following statement to the policy: For the purposes of repeat panel testing for
worldwide. the same clinical indication, RP and PNP will be considered as equivalent tests, such that if criteria for repeat testing are
met (as defined above), a clinician may choose to perform the repeat test using the PNP, even if the original test was
We are submitting joint comments because currently our organizations share the same position regarding performed using the RP.
this draft LCD. Together, we would like to thank you for proposing limited coverage for outpatient testing
with panels using NAATs for infectious disease testing, particularly panels with greater than 5 pathogens. Finally, as already mentioned, if the upper respiratory is negative or non-diagnostic, then a lower respiratory panel may be
We believe thoughtful consideration was given to the published literature and appreciate that you sought covered under this policy IF all other coverage criteria are met.
out input from subject matter experts by convening the Contractor Advisory Committee (CAC) in January;
the resulting proposed LCD will positively impact patient care through early detection and implementation 3. Gastrointestinal (GI) Panels:
of appropriate treatment therapy, early in the illness when it is most effective. After reviewing the proposed
policy’s coverage criteria, we ask that Palmetto GBA consider incorporating the following AMP and CAP Recommendation #1: We believe that these criteria would hinder the ability of physicians to conduct vital public health
recommendations into the final coverage policy. surveillance. We recommend that an exception be made for “diarrhea with signs or symptoms of and epidemiologic
indication of an event of public health significance.”
General Coverage Criteria
Palmetto response: While we recognize the importance of public health surveillance, this policy’s focus is not on public
1. “For immunocompetent patients, the clinical indication includes a presumption of active infection OR health surveillance but rather on testing that is reasonable and necessary (R&N) for the diagnosis or treatment of an
infection-associated complications (which may include exacerbation of underlying disease) that require the illness or injury for an individual beneficiary. Note also that the policy does allow expanded panel testing in patients with
identification of a causative organism for appropriate management. Atypical clinical presentations of acute or persistent diarrhea, even without the listed signs or risk factors for severe disease IF the diarrhea has not resolved
disease are considered appropriate indications for special populations who may not present with classic after 7 days (in a patient who had also not taken laxatives). Therefore, even diarrhea that may be of significance for public
symptoms of infection (i.e., the elderly).” health may be detected while also fulfilling the R&N patient criteria listed in the policy.

Recommendation: The proposed LCD offers no definition of, or specific examples for, an underlying Recommendation #2: We request that the policy specify what constitutes an instance of severe dehydration. Specifically,
condition or immunocompromised patient. We fear that this will create coding issues leading to improper we ask that the difference between mild, moderate, and severe dehydration, and what is enough to qualify as “severe
reimbursement and/or unwarranted denial of coverage. It is also necessary for providers to understand how disease” be specified.
the policy applies to patients. We recommend that the LCD provide examples of immunocompromised
patients such as patients with weakened immune systems including those with HIV/AIDS, patients who are Palmetto response: The following signs of severe disease (fever, bloody diarrhea, dysentery, dehydration, severe
taking immunosuppressive drugs (e.g., corticosteroids); and those with inherited diseases that affect the abdominal pain) that may warrant hospitalization are specifically outlined in the policy. For example, dehydration
immune system (e.g., congenital IgA deficiency). requiring intravenous fluid repletion constitutes severe disease. There is no distinction in the policy between mild and
moderate disease.
Non-Coverage Criteria
Recommendation #3: We believe that the requirement stating that a patient must not have used laxatives within 24 hours
1. “If a previous panel test was performed with a similar/duplicative intended use, a subsequent test is only of the test, is overly restrictive. Patients who utilize laxatives are still capable of contracting an infection, regardless of
reasonable and necessary if the non-duplicative content of the second test is reasonable and necessary. laxative use. Further, there are other medications other than laxatives that may exacerbate normal bowel movements. This
requirement would have negative impact on multiple patient groups; for example, those patients with CDIF. We
Exception: Repeat panel testing for the same clinical indication will only be covered if first panel yielded a recommend striking this language.
negative result AND there is a high index of suspicion for a pathogen as the cause of symptoms AND the
patient’s clinical condition is not improving or is deteriorating after a clinically appropriate length of Palmetto response: While it is true that patients taking laxatives can also contract gastrointestinal infections, laboratories
time. In such cases, 1 additional panel test may be covered between 1 and 14 days after the initial panel often emphasize laxative use as a contraindication to C. difficile testing, as it can confound the diagnosis of C.
test, so long as the test fulfills the criteria for coverage as set forth in this policy.” difficile disease. Therefore, the comment about how this requirement would negatively impact C. difficile testing is
unfounded. However, we have modified this criterion such that the statement about laxative use only applies to a patient
Recommendation: There are circumstances where repeat testing is warranted, such as if you were sampling whose diarrheal illness is not resolving after 7 days. It does not apply to a patient with signs of severe disease (fever,
too early or if sampling another body might be helpful as the disease progresses (e.g., lower respiratory bloody diarrhea, dysentery, dehydration, severe abdominal pain) that may warrant hospitalization regardless of the prior
tract when upper respiratory tract has become negative). It should only be considered a duplicate if it is a use of laxatives.
repeat of the same sample type, not just the same test. Therefore, we request that the following language be
added for repeat testing: “For the same sample type and same clinical indication” if the “same sample had Recommendation #4: We believe that it is unnecessary to wait for seven days to identify a massive outbreak and instead

51
a negative result or a clinically insignificant finding.” the language should state “or not resolving after 7 days” instead of “and/or.”

Specific Panel Coverage Criteria Palmetto response: Please see the response to Recommendation #1 above. Additionally, 'and/or' suggests that 'OR' is a
valid alternative.
1. “Respiratory (RP) & Pneumonia Panels (PNP): Testing is ordered by a clinician specialist in Infectious
Diseases or Pulmonology for a patient with severe and established underlying respiratory pathology (i.e., 4. Urogenital/Anogenital (UG/AG) Panels:
severe asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pulmonary fibrosis,
radiation therapy to the lung) AND treatment with antibiotics may be indicated according to established Recommendation #1: We ask that clarification be made as to what other indications, outside of epidemiologic indication,
guidelines.” would qualify as a covered clinical indication.

Recommendation: We believe that limiting ordering to the two named specialties will be problematic and Palmetto response: Covered clinical indications in the absence of clinical symptoms include an epidemiologic indication
produce substandard patient outcomes. We believe that a worrisome assumption is being made that there or potential exposure to sexually transmitted pathogens (i.e., in the case of clinical concern for multiple sexually
will be subspeciality experts at all points of care. This is not the case, especially in rural areas where critical transmitted infections (STIs) due to a high-risk experience). Otherwise, the presence of clinical symptoms is required for
care or other health specialists are not available. This requirement presents serious problems with access to testing.
care and patient safety.
Recommendation #2: We ask that clarification be made as to what qualifies as a “small, targeted panel.” Specifically, we
In many cases, the patient’s infectious disease physician is not directly involved in the outpatient would like to inquire as to whether this would cover a bacterial vaginosis (BV) panel; given this represents one of the
encounter. Requiring an infectious disease consultation, in the outpatient setting, will only add to the costs highest reasons for number of office visits.
of the visit and delay test results. We ask that the following language be added after “testing is ordered by a
clinician specialist in Infectious Diseases or Pulmonology”: “or a healthcare guideline or algorithm with Palmetto response: a “small, targeted panel” is defined in the policy is a panel with ≤5 pathogens. This is a uniform
contribution of infectious disease or pulmonary specialist.” This language should also be added for the definition applicable to any of the panels outlined in the policy.
section on immunocompromised patients.
Regarding infectious vaginosis/vaginitis panels, see also the Response 1 listed above.
2. “Respiratory (RP) & Pneumonia Panels (PNP): For ALL patients: Only 1 of the following panels - RP
OR PNP- will be covered for a given patient for the same clinical indication. The PNP should be prioritized 5. Meningoencephalitis (ME) Panels:
in the evaluation of pneumonia from lower respiratory tract specimens (i.e., bronchoalveolar lavage
samples (BALs)).” Recommendation: We believe that these indicators will prevent both adult and pediatric patients from getting covered
treatment in an emergency room setting. This is since most immunocompromised and pediatric patients, presenting in the
Recommendation: We believe that this language will negatively affect pediatric patients. In this patient emergency room, will likely not have two of the stated indicators. We recommend that the language be changed from “at
population an upper respiratory panel is performed each time a respiratory disease or pneumonia is least 2” to state “one or more of the following indicators.”
suspected. In addition, an upper viral respiratory tract infection may progress to a lower respiratory tract
disease involving bacteria which may warrant PNP. PNP does not encompass RP completely. As a result, Palmetto response: We are aware that immunocompromised patients may not present with >1 of the findings mentioned;
there should be an exception added for pediatric and adult Medicaid patients. If the upper respiratory is for that reason, the policy states: For immune-compromised patients, at least 1 of these indicators is required. As stated
negative or non-diagnostic, then the lower respiratory should be covered. above, this policy covers Medicare beneficiaries and is not generally applicable to pediatrics.

3. “Gastrointestinal (GI) Panels: Testing is ordered by a clinician specialist in Infectious Diseases or 6. Bloodstream Infection (BSI) Panels
Gastroenterology for a patient with severe and established underlying GI pathology (i.e., inflammatory
bowel disease (IBD), paralytic ileus, radiation therapy to the intestine) AND identification of an infectious Recommendation #1: We believe that the coverage requirement mandating a positive Gram stain does not reflect the
cause is necessary to determine next steps in patient management.” reality of clinical treatment; especially in patient groups such as immunocompromised individuals. The results of a Gram
stain are not always indicative of overall findings as it pertains to a diagnosis. We suggest that this coverage indication be
Recommendation: We believe that limiting ordering to the two named specialties will be problematic and reviewed for the general patient populations and all coverage requirements be waived for immunocompromised patients.
produce substandard patient outcomes. In many cases, the patient’s infectious disease physician and/or
gastroenterologist is not directly involved in the outpatient encounter. A strict requirement for these Palmetto response: A Gram stain remains a standard-of-care method and must be performed in the diagnosis of
consultations, in the outpatient setting, will only add time and cost to the visit and delay test results. We bloodstream infections (BSI); moreover, it is a stat procedure when performed from blood culture bottles which means the
recommend that the following language be added after “Testing is ordered by a clinician specialist in result of the stain is available nearly immediately. Therefore, the expectation that the Gram stain is performed reflects the
Infectious Diseases or Gastroenterology”: “or a healthcare guideline or algorithm with contribution of reality of appropriate laboratory practice. The Gram stain also sets the stage for whatever may be found on a bloodstream
infectious disease or gastrointestinal specialist.” This language should also be added for the section on pathogen panel test. For example, panel tests do not encompass all possible organisms; moreover, polymicrobial
immunocompromised patients. specimens may result reduced accuracy of the results by panel tests. Finally, certain panels must be performed based on
the findings of the Gram stain (i.e., Gram positive vs Gram negative panels). Therefore, we stand by the requirement for a
4. “Gastrointestinal (GI) Panels: The patient is seriously or critically ill (as defined by the American Gram stain to be performed in advance of the panel test. The test can be run as a reflex – i.e., Gram stain with reflex to the
Hospital Association’s “General Guide for the Release of Information on the Condition of Patients”) as a panel, thereby not delaying the additional testing and the administration of empirical antibiotics. As blood culture is also a
result of a presumed GI infection AND the patient is being treated in an appropriate critical care facility. current gold standard in the diagnosis of BSI, the policy also requires that this is also performed in parallel on all patients
The patient’s clinical indication for GI panel testing is diarrhea, and ALL the following apply: The receiving the panel test.
diarrheal illness MUST be acute or persistent with signs or risk factors for severe disease (fever, bloody

52
diarrhea, dysentery, dehydration, severe abdominal pain that may warrant hospitalization) AND/OR not Recommendation #2: We would ask for the removal of the coverage requirement for a patient to be managed in a critical
resolving after 7 days, AND the patient has NOT taken laxatives within 24 hours of the test.” care facility since this LCD is for diagnostic tests being performed in an outpatient setting. We recommend removal of
“AND the patient is being managed in an appropriate clinical care facility” as this language is too restrictive.
Recommendation #1: We believe that these criteria would hinder the ability of physicians to conduct vital Alternatively, this language could be revised to state “or will be called back for re-admission or avoid unnecessary
public health surveillance. We recommend that an exception be made for “diarrhea with signs or symptoms re-admission depending on the results of the panel identification”.
of and epidemiologic indication of an event of public health significance.”
Palmetto response: This contractor expects that critically ill patients will be tested and managed in the appropriate
Recommendation #2: We request that the policy specify what constitutes an instance of severe dehydration. critical care facility. Moreover, for cancer patients, the latest ASCO/IDSA guidelines state the following: “Patients should
Specifically, we ask that the difference between mild, moderate, and severe dehydration, and what is also be evaluated for admission to the hospital if any of the following occur: . blood cultures drawn on presentation
enough to qualify as “severe disease” be specified. become positive, ” In this case, the panel is acting as the surrogate for the blood culture (which is also expected to be
performed but from which results will be delayed relative to the panel). For added clarity, we have added a statement to
Recommendation #3: We believe that the requirement stating that a patient must not have used laxatives the policy indicating that the emergency room is included as an appropriate location for BSI panel testing, as follows
within 24 hours of the test, is overly restrictive. Patients who utilize laxatives are still capable of contracting “There is clinical concern for bacteremia or sepsis AND microbe(s) were seen on a Gram stain from the patient’s blood
an infection, regardless of laxative use. Further, there are other medications other than laxatives that may AND the patient is being managed in an appropriate critical care facility (this includes the Emergency Room).’ We have
exacerbate normal bowel movements. This requirement would have negative impact on multiple patient also modified the following statement, to accommodate the risk of impending serious or critical illness: “The patient is
groups; for example, those patients with CDIF. We recommend striking this language. seriously or critically ill or at imminent risk of becoming seriously or critically ill.”

Recommendation #4: We believe that it is unnecessary to wait for seven days to identify a massive Recommendation #3: We think that the language on personnel is hard to quantify, and we request clarification on how this
outbreak and instead the language should state “or not resolving after 7 days” instead of “and/or.” would be evaluated in a claim.

5. “Urogenital/Anogenital (UG/AG) Panels: For the UG/AG panels, epidemiologic indication or potential Palmetto response: Gram stain and culture are long-standing available tests for the evaluation of BSI. A rapid molecular
exposure to sexually transmitted pathogens (i.e., in the case of clinical concern for multiple sexually test for BSI will only be covered in facilities prepared to manage the patient quickly based on the return of a rapid result;
transmitted infections (STIs) due to a high-risk experience) is considered a covered clinical indication, even otherwise, the rapid molecular test is not considered reasonable and necessary. This has been established in multiple
in the absence of clinical symptoms. Documentation of the high-risk reason for panel testing is clearly studies showing that a rapid result requires rapid intervention in order to be clinically useful. We therefore stand by this
stated in the medical record. requirement. An antimicrobial stewardship team is only one example of such personnel that may be available; further, it is
important to note that the requirement does not state that the availability of such personnel be on-site.
In the absence of a high-risk experience, if the primary clinical concern is for 1 or few specific pathogens
due to specific signs and symptoms (i.e., lesions suggestive of herpes simplex virus (HSV)), then it is 7. Urinary Tract Infection (UTI) Panels
expected that only a small, targeted panel (i.e., including HSV-1 and HSV-2) will be performed. In such
cases, expanded panels are NOT considered reasonable and necessary and will NOT be covered.” Recommendation: We believe that limiting coverage to patients seen in urogynecology or urology specialty care settings
is too restrictive. We request that the following language be added “or a healthcare guideline or algorithm with
Recommendation #1: We ask that clarification be made as to what other indications, outside of contribution of urogynecology or urology specialist.”
epidemiologic indication, would qualify as a covered clinical indication.
Palmetto response: The policy, as written, allows for high-risk symptomatic patients to be tested outside of the
Recommendation #2: We ask that clarification be made as to what qualifies as a “small, targeted panel.” requirement for urology/urogynecology specialty care. As mismanagement of asymptomatic bacteriuria (ASB) is
Specifically, we would like to inquire as to whether this would cover a bacterial vaginosis (BV) panel; common, patients that are not symptomatic should be evaluated by a specialist before determining the need for testing.
given this represents one of the highest reasons for number of office visits.
8. ICD-10 Codes
6. “Meningoencephalitis (ME) Panels: For immune-competent patients: the patient has at least 2 of the
following indicators of central nervous system (CNS) infection: cerebrospinal fluid (CSF) markers, Recommendation: We request that the following additional ICD-10 codes be added to the associated coverage article:
radiology, clinical signs, and symptoms consistent with meningitis or encephalitis, epidemiologic indication
or exposure. For immune-compromised patients, at least 1 of these indicators is required. O98.7- Human immunodeficiency virus [HIV] disease complicating pregnancy, childbirth and the puerperium

For all patients: Testing is from a sample collected via lumbar puncture, and NOT an indwelling medical 098.71- Human immunodeficiency virus [HIV] disease complicating pregnancy
device (i.e., CSF shunts).”
O98.711- Human immunodeficiency virus [HIV] disease complicating pregnancy, first trimester
Recommendation: We believe that these indicators will prevent both adult and pediatric patients from
getting covered treatment in an emergency room setting. This is since most immunocompromised and O98.712- Human immunodeficiency virus [HIV] disease complicating pregnancy, second trimester
pediatric patients, presenting in the emergency room, will likely not have two of the stated indicators. We
recommend that the language be changed from “at least 2” to state “one or more of the following O98.713- Human immunodeficiency virus [HIV] disease complicating pregnancy, third trimester
indicators.”
C46.0 Kaposi's sarcoma of skin
7. “Bloodstream Infection (BSI) Panels will be covered according to the following additional criteria:
There is clinical concern for bacteremia or sepsis AND microbe(s) were seen on a Gram stain from the C46.1 Kaposi's sarcoma of soft tissue

53
patient’s blood AND the patient is being managed in an appropriate critical care facility, AND personnel C46.2 Kaposi's sarcoma of palate
(i.e., an antimicrobial stewardship team) are equipped for rapid (same day) tailoring of antimicrobial
therapy as a result of rapid testing.” C46.3 Kaposi's sarcoma of lymph nodes

Recommendation #1: We believe that the coverage requirement mandating a positive Gram stain does not C46.4 Kaposi's sarcoma of gastrointestinal sites
reflect the reality of clinical treatment; especially in patient groups such as immunocompromised
individuals. The results of a Gram stain are not always indicative of overall findings as it pertains to a C46.5 Kaposi's sarcoma of lung
diagnosis. We suggest that this coverage indication be reviewed for the general patient populations and all
coverage requirements be waived for immunocompromised patients. C46.50 Kaposi's sarcoma of unspecified lung

Recommendation #2: We would ask for the removal of the coverage requirement for a patient to be C46.51 Kaposi's sarcoma of right lung
managed in a critical care facility since this LCD is for diagnostic tests being performed in an outpatient
setting. We recommend removal of “AND the patient is being managed in an appropriate clinical care C46.52 Kaposi's sarcoma of left lung
facility” as this language is too restrictive. Alternatively, this language could be revised to state “or will be
called back for re-admission or avoid unnecessary re-admission depending on the results of the panel C46.7 Kaposi's sarcoma of other sites
identification”.
B25.8 Other cytomegaloviral diseases
Recommendation #3: We think that the language on personnel is hard to quantify, and we request
clarification on how this would be evaluated in a claim. B25.0 Cytomegaloviral pneumonitis

8. “Urinary Tract Infection (UTI) Panels will be covered according to the following additional criteria: B25.1 Cytomegaloviral hepatitis
The patient is symptomatic AND at higher risk for UTI complications (i.e., the elderly, patients with
recurrent symptomatic UTIs and/or complicated urinary tract anatomy) OR is seen in urogynecology or B25.9 Cytomegaloviral disease, unspecified
urology specialty care settings.”
B25.2 Cytomegaloviral pancreatitis
Recommendation: We believe that limiting coverage to patients seen in urogynecology or urology specialty
care settings is too restrictive. We request that the following language be added “or a healthcare guideline Palmetto response: We agree and have added the relevant ICD-10 codes to the LCA.
or algorithm with contribution of urogynecology or urology specialist.”

9. ICD-10 Codes

Recommendation: We request that the following additional ICD-10 codes be added to the associated
coverage article:

O98.7- Human immunodeficiency virus [HIV] disease complicating pregnancy, childbirth and the
puerperium

098.71- Human immunodeficiency virus [HIV] disease complicating pregnancy

O98.711- Human immunodeficiency virus [HIV] disease complicating pregnancy, first trimester

O98.712- Human immunodeficiency virus [HIV] disease complicating pregnancy, second trimester

O98.713- Human immunodeficiency virus [HIV] disease complicating pregnancy, third trimester

C46.0 Kaposi's sarcoma of skin

C46.1 Kaposi's sarcoma of soft tissue

C46.2 Kaposi's sarcoma of palate

C46.3 Kaposi's sarcoma of lymph nodes

C46.4 Kaposi's sarcoma of gastrointestinal sites

54
 C46.5 Kaposi's sarcoma of lung

C46.50 Kaposi's sarcoma of unspecified lung

C46.51 Kaposi's sarcoma of right lung

C46.52 Kaposi's sarcoma of left lung

C46.7 Kaposi's sarcoma of other sites

B25.8 Other cytomegaloviral diseases

B25.0 Cytomegaloviral pneumonitis

B25.1 Cytomegaloviral hepatitis

B25.9 Cytomegaloviral disease, unspecified

B25.2 Cytomegaloviral pancreatitis

Thank you again for the opportunity to review and comment on this proposed policy.

6 The following comment was submitted to Palmetto GBA, CGS, WPS, and Noridian: Thank you for your thoughtful comments and support of this policy.

Luminex appreciates the opportunity to comment on the MolDX proposed LCD, for multiplex nucleic acid We have addressed your comments in Response 1 listed above. Additionally-
amplification test (NAAT) panels for infectious disease testing. As written, the proposed coverage criteria
would unnecessarily restrict Medicare beneficiary access to multiplex NAAT infectious disease panel tests Regarding Gastrointestinal (GI) Panels – First, we agree that physicians may not always order the tests that will yield the
(specifically, targeted and expanded panels) and the clinically actionable results they provide. Luminex identification of the illness-causing pathogen(s). However, as syndromic panel tests are comprised of multiple pathogens,
encourages MolDX to expand coverage for targeted and expanded respiratory and gastrointestinal panels this policy allows for physician judgment to order the panel most suitable for the patient’s illness. This is different than
and remove provider ordering restrictions. ordering multiple different tests for each given pathogen. Second, regarding expanded panel GI testing, the policy states
that for immune-competent patients, at least 1 of the following must apply... one of these criteria being that the diarrheal
Luminex manufactures multiple FDA-cleared solutions for identifying infectious diseases, including both illness is not resolving after 7 days. The policy is therefore aligned with the clinical guidelines (CAP and IDSA) that
targeted and expanded panels. For respiratory testing, Luminex offers IVD solutions such as the recommend GI panels for patients with symptoms lasting longer than seven days.
NxTAG® Respiratory Pathogen Panel (RPP), VERIGENE® Respiratory Panel Flex (RP Flex) Assay and
ARIES® Flu A/B & RSV Assay. For gastrointestinal testing, Luminex offers two IVD solutions, the Regarding Diagnostic Stewardship – CMS requires testing that is Reasonable and Necessary (R&N) for a beneficiary. The
xTAG® Gastrointestinal Pathogen Panel (GPP) and the VERIGENE® Enteric Pathogens Test (EP). fact is, for most patients, expanded panels are not R&N. It is therefore incumbent on diagnostic companies and
laboratories to innovate and provide testing that is R&N. We agree that a flexible testing approach would be one way to
Timely testing and reporting are critical to ensuring the most informed, appropriate, and cost-effective enable laboratories to offer clinically appropriate testing for pathogens, including those that fluctuate seasonally.
patient care. To be impactful for patient management, rapid intervention is required, which can only be
achieved by simultaneously detecting different pathogens.1 Multiplex NAAT panels provide simultaneous
pathogen detection with superior sensitivity and specificity compared to single pathogen testing, which
requires multiple assays to diagnose a given infection. Furthermore, the use of multiplex NAAT panels
reduces the number of complementary procedures (e.g., chest x-rays), thereby reducing the total cost of
care.2

Respiratory Panels

Respiratory infections are challenging to differentiate and diagnose because they often have overlapping
symptoms. To treat patients most effectively, it is critical to ensure a timely and accurate diagnosis. The
literature review in the policy recognizes that influenza testing has greatly decreased unnecessary antibiotic
use. However, the proposed coverage criteria would limit coverage for influenza testing, which requires a
minimum of two pathogens. Multiple peer-reviewed publications support the use of multiplex NAAT
panels leading to de-escalation of antibiotics in outpatient adults.2,3 Moreover, Qian et al. demonstrated that

55
physicians changed treatment decisions based on the results of a multiplex NAAT panel–physicians
removed antibiotic therapy from patients who were positive for viral targets.4 Further, Lee et al. found that
low clinical suspicion resulted in a lack of testing for RSV, leading to high hospitalization rates and
negative clinical outcomes.5 Using a targeted panel for Flu A/B and RSV, physicians can correctly identify
the infectious pathogen and direct appropriate antiviral usage, minimizing the need for hospitalization.

Based on proposed policy language, respiratory panels are limited to ordering by Infectious Disease
Specialists or Pulmonologists, which will unnecessarily restrict access to patients in the community who
could benefit from the results and rapid turnaround times associated with these respiratory tests. Effectively
diagnosing patients at the community level can reduce morbidity, as well as over-testing. As indicated by
Lyu et al., specialty care can lead to both an increase in antibiotics prescribed and specialty
imaging.6 Therefore, Luminex recommends removing this criterion.

Gastrointestinal (GI) Panels

GI symptoms often overlap, hampering the ability for clear diagnosis during the differential work-up. A
study conducted by Beal et al. demonstrated that by using targeted testing, based on the differential
diagnosis, 13% of targets eventually identified as causing illness were not ordered by the physician
following the differential diagnosis; rather, they were found retrospectively using a multiplex NAAT
panel.7 Offering the multiplex NAAT panel in these patients at the outset would have reduced the need for
additional diagnostic tests, ultimately reducing time to appropriate treatment initiation. Axelrad, et al. found
similar results across multiple care settings.8 The benefits of GI panels, reduction in antibiotic use, and
follow-on testing were found in community-based testing as well. Using GI panels results in fewer
additional tests and imaging studies, including endoscopy, regardless of care setting.

The proposed coverage criteria for GI panels is unnecessarily restrictive. The use of expanded GI panels is
supported by clinical guidelines (CAP and IDSA), which recommend GI panels for patients with symptoms
lasting longer than seven days.9 The guideline indicates culture-independent methods should be used for
patients with moderate to severe illness. The language in the proposed guidance prohibits testing of
moderately ill patients and minimizes the potential benefits of further procedures when ordered in the
community. Therefore, Luminex recommends removing the specialty ordering requirement from the
proposed coverage criteria.

Diagnostic Stewardship

Luminex is a strong supporter of diagnostic stewardship and appreciates the concern for over-testing,
resulting in this policy. Choosing the right test for the right patient at the right time is critical to improving
the health and wellbeing of patients.10 Luminex recognizes that expanded panels are not always an
appropriate solution and that, in cases where symptoms indicate a narrow list of potential pathogens,
single-pathogen tests and targeted panels can lead to more appropriate treatment quickly. However, as our
comments illustrate, there is clinical value in targeted panels that can be customized based on the
differential diagnosis of the patient. While relatively new, a flexible testing approach enables laboratories to
offer testing for many pathogens deemed clinically appropriate by the ordering provider. As indicated
above, targeted panels such as Flu A/B and RSV can rapidly identify illness-causing pathogens. However,
based on the seasonal fluctuations of some respiratory and GI pathogens, a targeted panel is not always
effective. Consider respiratory illness outside of the flu season: a targeted Flu A/B and RSV panel has
limited utility. However, using a customizable panel, more seasonally appropriate targets can be selected
for testing. This customization allows physicians to choose the right test at the right time for the most

effective patient treatment. In addition, as indicated by Couturier and Bard, there is a need for flexible
panels to address emerging infectious pathogens.11 As we have learned during the pandemic, testing is
critical. The proposed policy language prohibits the effective use of targeted panels in the community.
Therefore, Luminex recommends removing targeted panels from the specialty ordering requirements for
expanded panels.

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 Luminex appreciates the opportunity to comment on this proposed LCD.

References were provided for review.

7 The following comment was submitted to Palmetto GBA, CGS, WPS, and Noridian: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above. Additionally –
LabCorp appreciates the opportunity to comment on MolDX Draft LCD and companion Draft Article.
1. It is not uncommon that multiple tests utilize the same CPT code. A test that is registered with MolDX also has
1. Comment regarding Bloodstream Infection Panels: The CPT code referenced in the draft article test-specific Z-codes; therefore, this distinction can be made.
(87801) is not specific to BSI panels. This CPT code represents a non-specified amplified probe technique. 2. CPT 87801 has been added to Group 5 in draft article.
Please address the following question: How will the contractor differentiate BSI panels from unrelated tests 3. The addition of new panels to the accompanying article is predicated upon the test fulfilling all criteria outlined in
billed with CPT 87801 when processing claims? the current policy. As this policy has already been available for public comment, additional public comment is not
necessary for the addition of each new test that meets coverage criteria already outlined in the policy.
2. Comment in reference to Urogenital/Anogenital Panels referenced under Group 5. The draft article 4. As a matter of process, we cannot comment on the fate of other policies. However, our intent is not to have
includes a "Note: Only a single probe technique (direct OR amplified) should be used when submitting conflicting policies. We will follow our due process for publishing, revising, and retiring policies.
claims." The list of published Group 5 CPT codes includes a direct probe technique (87800) but does not 5. Many of the ICD-10 codes listed in the table are included in Groups 6 and 7 of draft article. They have not been
include the amplified probe (87801). We request that CPT 87801 be added. added to Groups 1 and 2, as even in immunocompromised patients, there must be a clinical indication for
infectious disease testing, according to the policy. Though we recognize that certain populations may present with
3. The draft policies appear to be inclusive of current and future NAAT PCR panel testing as indicated atypical clinical symptoms, an underlying immune-compromising condition alone - without any other clinical
by, "Finally, the landscape of infectious disease diagnostics is rapidly evolving such that currently covered indication - is not a sufficient indication for testing according to the policy. The exception to this, as outlined in
tests may become obsolete as new pathogens and methodologies become important for testing. One the policy, is when testing may be performed ONCE as part of a pre-transplant evaluation, regardless of the
example is metagenomic testing for infectious diseases. Unlike panel tests, which identify fixed organisms presence of symptoms. Finally, some of the pathogen-specific codes have not been added to Group 1, as they
on a panel, this technology may further revolutionize the field with its high-throughput capacity, rapid would be expected to be present on expanded panels and not on small targeted panels (i.e., human
results, and the ability to simultaneously identify all organisms present in a sample.93-97 This contractor metapneumovirus pneumonia).
will continue to monitor the evidence, and new developments may impact this coverage
decision." And, "Tests that demonstrate similar indicated uses and equivalent or superior performance to
SOC or other covered tests, as demonstrated in a TA, may similarly be covered under this
policy." And, "There are currently NO covered Urinary Tract Infection (UTI) or Sterile Fluid and Tissue
Panel tests".

Please address the following questions:

• What process will be followed for the addition of new panels into this policy (if implemented), and
is it the contractor’s intent to modify the accompanying article with new coverage and coding
criteria as new tests are developed?
• Will the public have the ability to comment when these additions are made?

4. This policy appears to overlap with existing MolDX policies for GI and Respiratory Panels. Is it the
intent of the contractor to replace and retire existing NAAT Panel policies? Existing policy examples:

• Foodborne Gastrointestinal Panels Identified by Multiplex Nucleic Acid Amplification (NAATs)

• MolDX: Multiplex Nucleic Acid Amplified Tests for Respiratory Viral Panels

• Please address whether draft policy and article are intended to replace existing policies
such as those referenced above. If this is the contractor’s intent, we request that the draft
policy indicate all policies being replaced.

5. The existing coverage policies indicate coverage for specific diagnostic conditions excluded from the
draft policy. If multiple policies exist for the same tests, we request that MolDX provide consistency in
coverage across all policies. Please consider expanding the draft Article to include ICD-10 codes (attached)
presented in the existing Articles:

♦ For Group 1 Targeted Respiratory Panel codes, please consider the addition of ICD-10 codes
present in existing policy.
♦ For Group 7 Expanded Gastrointestinal Panel codes, please consider the addition of ICD-10 codes

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 present in existing policy.

6. Conversely, we also request that ICD-10 codes included in the draft article currently be added to these
policies for coverage consistency across all policies.

We appreciate the contractor’s consideration of these additional diagnostic indications.

Thank you for providing the opportunity to analyze and comment on published draft policies.

One table was provided for review.

8 The following comment was submitted to CGS and Noridian: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
Quest Diagnostics appreciates the opportunity to comment on the CGS proposed LCD and Article listed
above. We appreciated the opportunity to listen to presentations on July 13, 2021 regarding CGS’s
Proposed Modifications to LCD related to Multiplex Nucleic Acid Amplification Testing. We respectfully
request that CGS consider Article revisions to explicitly provide coverage for new CPT/HCPCS codes
related to nucleic acid amplification testing (NAAT) for the diagnosis of bacterial vaginosis (BV) and
candidiasis.

In 2021, the CPT Editorial Panel added two new MAAA codes for Bacterial Vaginosis. These codes have
been reviewed and placed on the Clinical Laboratory Fee Schedule by CMS. At the aforementioned
meeting, we heard a presentation requesting inclusion of CPT code 81514 among the procedures covered as
part of the LCD and Article revisions. Recognizing that there are two new codes, we request that revisions
explicitly incorporate both procedure codes into the accompanying Article associated with the LCD.

81513 Infectious disease, bacterial vaginosis, quantitative realtime amplification of RNA markers for
Atopobium vaginae, Gardnerella vaginalis, and Lactobacillus species, utilizing vaginal-fluid specimens,
algorithm reported as a positive or negative result for bacterial vaginosis (Hologic)

81514 Infectious disease, bacterial vaginosis and vaginitis, quantitative real-time amplification of DNA
markers for Gardnerella vaginalis, Atopobium vaginae, Megasphaera type 1, Bacterial Vaginosis
Associated Bacteria-2 (BVAB-2), and Lactobacillus species (L. crispatus and L. jensenii), utilizing
vaginal-fluid specimens, algorithm reported as a positive or negative for high likelihood of bacterial
vaginosis, includes separate detection of Trichomonas vaginalis and/or Candida species (C. albicans, C.
tropicalis, C. parapsilosis, C. dubliniensis), Candida glabrata, Candida krusei, when reported (Becton
Dickinson)

The proposed LCD recognizes the non-specific nature of vaginitis and the high sensitivity and specificity of
multi-organism NAAT testing to detect BV, CVV, and TV. Furthermore, it acknowledges that NAAT
significantly surpasses other diagnostic approaches and has the ability to detect co-infection.2,3 Improved
diagnostic performance is important because of the nonspecific nature of vaginitis symptoms, and
treatments are infection-specific. An incorrect diagnosis may result in continued symptoms and/or sexual
dysfunction, increased risk for STIs, repercussions from inappropriate treatment (e.g., candidiasis from
unnecessary antibiotic use, antibiotic resistance), and unnecessary health system encounters (e.g., return
visits, incorrect medications).2-8

The American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin #215 has relevant
changes in guidance for vaginitis. ACOG does not recommend the single organism Gardnerella DNA probe
method for evaluating BV that is covered by your current policy.21 However, ACOG now supports
FDA-approved commercial tests, such as NAAT, when POC tests are unavailable.21 FDA-approved NAAT
tests (i.e., Hologic Aptima® , BD MAXTM Vaginal Panel) detect and quantify multiple organisms to more
accurately diagnose BV.

The Centers for Disease Control and Prevention (CDC) is revising their 2015 guideline on diseases

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 characterized by vaginal discharge within the sexually transmitted diseases treatment guideline.4,26 The
“CDC 2021 Sexually Transmitted Infection (STI) Treatment Guidelines Update Webinar” presented in
December 2020 is available26 where they discuss data supporting increases in STI and HIV risk associated
with BV, not previously included in their guideline.

We appreciate the opportunity to provide CGS with this input as you consider changes to this important
LCD and Article.

One table and references were provided for review.

9 The following comment was submitted to CGS: Thank you for your thoughtful comment and support of this policy. We have addressed your comments in Response 1
listed above.
After review of the proposed LCD MolDX: Multiplex Nucleic Acid Amplification Test (NAAT) Panels for
Infectious Disease Testing, we have one comment we wish to submit;

“MolDX: Multiplex Nucleic Acid Amplified Tests for Respiratory Viral Panels restricts the use of
respiratory NAATs to the settings ER, urgent care, inpatient hospital, and independent lab if it is not
ordered by an infectious disease specialist; the proposed LCD notes the coverage is only for outpatient
testing but are there provider types (i.e. family medicine, internal medicine, infectious disease) which are
restricted from ordering a 2-5 target panel in the outpatient setting?”
10 The following comment was submitted to Palmetto GBA, WPS, and Noridian: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
I’m writing to comment on the use of expanded molecular panels. Many institutions have adopted these
panels and as a result have decided not to provide a targeted panel. This may be done for a variety of
reasons, including workflow issues in the laboratory and clinical and financial reasons. It is very important
that Noridian address the billing procedure for circumstances when a clinician, for various reasons, desires
to use an expanded panel to diagnose a patient who does not meet the criteria in the LCD for expanded
panel testing. Specifically, language is needed in the final LCD stating that it is appropriate for a provider to
receive reimbursement at the targeted panel rate (using targeted panel CPT codes) after using an expanded
panel in the care of a patient that only meets criteria for targeted panel testing. This would greatly simplify
clinical practice for clinicians that have access to only one platform for testing. Thank you for considering
this request.
11 The following comment was submitted to Palmetto GBA and Noridian: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
On behalf of Pathnostics, I am submitting comments regarding the Proposed LCD MolDX: Multiplex
Nucleic Acid Amplification Test (NAAT) Panels for Infectious Disease Testing. Pathnostics is an
independent clinical laboratory focused on developing tests for infectious pathogens. We concentrate on
conditions where Standard of Care diagnostic testing methods have limited clinical sensitivity, specificity,
and utility.

We commend Noridian, MolDX, and associated MACs on their efforts to develop a new LCD to address
the dynamic field of infectious pathogen testing. We want to provide several comments, specifically on
coverage of tests for urinary tract infections.

1. We agree with the intended use population for molecular tests for urinary tract infections.
2. We ask that Guidance UTI be covered in the LCD as a predicate test.
3. The current Technical Assessment process for UTIs would benefit from greater transparency.
4. We recommend that the LCD apply to all amplified probe panels.
5. We ask you to address issues related to coding.

1. We agree with the intended use population for molecular tests for urinary tract infections.

The proposed LCD covers expanded panel testing for the following indications:

The patient is symptomatic AND at higher risk for UTI complications (i.e., the elderly, patients with

59
recurrent symptomatic UTIs and/or complicated urinary tract anatomy) OR is seen in urogynecology or
urology specialty care settings.

We agree with this critical coverage language for rapid and accurate UTI testing in the elderly and
complicated/recurrent cases, generally seen in urology offices and home/assisted living/nursing home
facilities. The significantly higher risk of complications in this population, including hospitalization and
sepsis, makes the need for UTI panels with faster turnaround time critical. This is especially true when
antibiotic susceptibility is provided to guide therapy decisions and avoid or reduce empiric treatment.

2. We ask that Guidance UTI be covered in the LCD as a predicate test.

The LCD provides clear coverage language for UTIs but does not cover or non-cover any specific analyte
or pathogen. The billing and coding article states, "There are currently NO covered Urinary Tract Infection
(UTI) or Sterile Fluid and Tissue panel tests." Since there was sufficient evidence of benefit in the indicated
population (cited in the LCD) leading to the coverage language for UTI testing, the LCD should include a
predicate test for this category. This provides a benchmark for validating other UTI panels while allowing
testing to continue in the indicated population once the LCD is effective.

Since the evidence cited includes publications on Guidance UTI and a clear need for UTI testing in the
indicated population, we ask that Guidance UTI be included as a predicate test. The evidence submitted in
our coverage request demonstrates the improved performance of Guidance UTI over the current standard of
care (urine culture), especially in polymicrobial infections. In the interest of allowing for continued care for
the elderly and patients with recurrent/complicated UTIs, we ask that Guidance UTI be listed in the LCD as
a "predicate test."

3. The current technical assessment process would benefit from greater transparency.

The LCD does not cover any specific UTI test, analyte, or pathogen. Instead, it relegates the coverage
information regarding specific tests (which represent the billable Medicare services) to the technical
assessment process. We believe that this only makes sense when there are clear criteria in the technical
assessment process listed in the LCD. The current language describing the technical assessment
requirement:

• The test demonstrates equivalent or superior test performance characteristics -analytical validity
(AV) and clinical validity (CV) - to established standard-of-care (SOC) methods (i.e., culture,
pathogen-specific PCR) for the majority of targets included on the panel.

• CV of any new analytes that are not already established as SOC or that do not have a predicate test
that is covered by this contractor must be established through a study published in the
peer-reviewed literature for the intended use of the test in the intended population.

• Tests that perform identification of new analytes or are performed according to new intended uses
not already covered by this contractor will require a Technical Assessment (TA) for compliance of
that service with this policy.

This language is difficult to interpret for UTI tests since there is no listed predicate test, and clarity is
needed on the requirements needed for coverage. Please clarify that a TA is the next step in seeking
coverage under this LCD for UTI panels. Details on AV, CV, and CU requirements would also be helpful.
In addition, if a predicate test is not added to the LCD, please indicate if the current standard of care (urine
culture) is the comparator.

4. Application of the LCD to all amplified probe techniques

The draft LCD is explicitly limited to panels using multiplex PCR, with a clear statement that it does not

60
 apply to microbiology tests using other techniques. If the LCD is going to apply to multiplex PCR, it should
apply to all panels relying on amplified probe techniques. Limiting the scope of the LCD to PCR only,
rather than addressing amplified probe techniques generally, seems to be arbitrary.

Moreover, as a matter of enforcement, the CPT codes that apply to PCR tests apply to tests using amplified
probe techniques. Therefore, to enable claims processing enforcement consistent with the LCD, we
recommend that the LCD scope not be so narrow.

5. Coding concerns

The panel coding instructions are unclear given the inclusion of single pathogen CPT codes in the LCD.
The panel coding instructions are as follows:

A test panel is a single service with a single unit of service (UOS =1). A panel cannot be unbundled and
billed as individual components regardless of the fact that the test reports multiple individual pathogens
and/or targets. The panel is a closed system performed on a single platform, and as such, is a single test
panel with multiple components (UOS=1). If additional organisms are not included in a panel, testing for
those organisms may be reasonable and necessary when ordered in addition to the panel and supported by
documentation in the medical record.

It is unclear what the phrase "closed system performed on a single platform" means. We ask that the
definition of “panel” be clarified to enable stakeholders to determine whether the tests that they provide are
subject to the coverage limitations of this LCD and to understand whether this coding instruction applies to
them.

We also ask that if a specific CPT code to describe a syndrome panel is not listed, then the coding
instructions direct the billing provider to use the CPT codes for individual pathogens to facilitate billing.

Thank you for consideration of these comments.

12 The following comment was submitted to Palmetto GBA and WPS: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
This letter serves to inform you of a coding change for the BD MAX™ Vaginal Panel for use on the BD
MAX™ System that went into effect on January 1, 2021. As of that date, CPT code 81514 is most
applicable to BD MAX™ Vaginal Panel. Please consider this information in your finalization of both the
Proposed Local Coverage Determination (LCD), MolDX: Multiplex Nucleic Acid Amplification Test
(NAAT) Panels for Infectious Disease Testing and Draft Local Coverage Article, Billing and Coding:
MolDX: Multiplex Nucleic Acid Amplification Test (NAAT) Panels for Infectious Disease Testing.

CPT code 81514: Infectious disease, bacterial vaginosis and vaginitis, quantitative realtime amplification
of DNA markers for Gardnerella vaginalis, Atopobium vaginae, Megasphaera type 1, Bacterial Vaginosis
Associated Bacteria-2 (BVAB-2), and Lactobacillus species (L. crispatus and L. jensenii), utilizing ,
vaginal-fluid specimens, algorithm reported as a positive or negative for high likelihood of bacterial
vaginosis, includes separate detection of Trichomonas vaginalis and/or Candida species (C. albicans, C.
tropicalis, C. parapsilosis, C. dubliniensis), Candida glabrata, Candida krusei, when reported

With the positive commentary on multiplex panel NAATs for urogenital and anogenital infections, along
with the specific inclusion of BD MAX™ Vaginal Panel on Page 9 of the LCD, we want to ensure that not
including CPT code 81514 was an oversight. Should this not be the case, we’d appreciate the opportunity
to understand the rationale for it being left out of the DA.
13 The following comment was submitted to WPS: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
We at Beatrice Community Hospital and Health Center would like to take this opportunity to comment on

61
 proposed LCD titled "MOLDX: MULTIPLEX NUCLEIC ACID AMPLIFICATION TEST (NAAT)
PANELS for Infectious Disease Testing," and the associated Article "Local Coverage Article: Billing and
Coding: MolDX: Multiplex Nucleic Acid Amplification Test (NAAT) Panels for Infectious Disease
Testing.

We are rural critical access hospital based in Beatrice, Nebraska. We pride ourselves on providing state−
of-the art health care to our patients. As part of this effort, we have implemented testing on the BioFire
platform. This platform allows us to provide high quality infectious disease molecular diagnostic testing for
providers and patients previously only available at large healthcare facilities. We selected this type of
testing for our facility because of its ease of use, rapid turnaround time, and comprehensive nature allowing
a critical access hospital, like ours, the ability to reduce send-out testing and provide high level diagnostic
tools to providers and patients. Additionally, we don't have a large lab space that allows us to have multiple
testing platforms that can test for multiple panel sizes.

We want to continue using our BioFire tests and have them available for our providers to order as they
deem necessary based off their clinical expertise. We also want to be compliant with the proposed LCD.
We request the following statement be added to the billing articles of the proposed LCD:

"If the laboratory's testing platform consists of a multiplexed EXPANDED (>5 Pathogens) PANEL, yet
only a subset of the organisms are considered medically necessary based on the above criteria in this
Article, the lab may run and report the EXPANDED (>5 Pathogens) PANEL while requesting
reimbursement for that subset of organisms using a procedure code that does not represent all organisms
included on the panel."

We believe this language is consistent with the text of the proposed LCD that highlights the rapid, highly
impactful, and epidemiologically important information this testing offers for all patients. This text also
gives us confidence that we can continue to run this test and code for it in a way that is deemed appropriate
per the LCD and avoid any compliance issues with CMS.

Thank you for considering our comments and request. We look forward to the future effective LCD and are
grateful for your efforts to update the medical policy around NAAT panels for infectious
14 The following comment was submitted to WPS: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above. Additionally -
The University of Kansas Hospital is the region's premier academic medical center, providing a full range
of care. The hospital is a 979-bed general medicine and surgical facility that is nationally ranked in 6 Adult 1. Regarding the administrative burden on the laboratories –
Specialties by U.S. News and has a NCI designated cancer center. We appreciate the opportunity to provide
comments on WPS LCD Draft Policy-MolDX: Multiplex Nucleic Acid Amplification Test (NAAT) Panels Laboratories are expected to be leaders in diagnostic stewardship. As such, expansive panel testing is something about
for Infectious Disease Testing. Our comments are listed below for your consideration. which laboratory leadership is expected to maintain a close watch, even in the absence of a policy such as this.

1) Our first question relates to the policy title beginning with MolDX and are trying to understand how 2. Regarding the availability of alternative FDA-cleared single−pathogen and smaller targeted tests for pathogens on
Medicare categorizes tests as MolDX. When we look in the Molecular Diagnostic Program Manual on the commercially available respiratory panels –
Palmetto website, we see the range of CPT codes are in the 81lXX range. None of the CPT codes listed in
this draft policy are defined as MolDX in the manual. Since WPS is giving this policy a title of MolDX, There must be a clinical indication for testing and, as discussed in this policy, for many respiratory viral pathogens this is
will these infectious disease panels be required to be registered with the Palmetto MolDX program? not the case, as many of these are self-limited infections that will resolve without treatment. Therefore, for most
respiratory viruses (other than influenza, RSV, or SARS-CoV-2), there is often not an additional need for single-pathogen
2) We are concerned about the significant complexity of this coverage policy and the administrative burden testing.
being added to laboratory providers. We are especially concerned with requiring the performing laboratory
to ensure that the provider ordering the test has documented in their medical record: A) Specific reasons for
performing panel testing as opposed to single-pathogen testing and B) In the case of expanded panel
testing, the specific reasons for performing expanded panel testing as opposed to targeted panel testing.
This requirement is vague, adds an enormous administrative burden to labs, and is not proportional to the
reimbursement for the service.

3) While we agree that these panels are not clinically indicated in all patients, access to single-target or

62
 small panel testing for many organisms on multiplex panels is limited. For example, excluding influenza
viruses and RSV, no alternative FDA-cleared single− target or small panel exists for the majority of
pathogens on the commercially available respiratory panels. While the criteria for coverage allows for these
scenarios, we request additional clarity on documentation requirements for coverage, especially in cases
where single-target testing is not available.

We appreciate you considering clarifying and simplifying this complex policy that will add administrative
burden to all parties.
15 The following comment was submitted to Palmetto GBA: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
I have been told that there is some support needed in regards to getting coverage for Guidance (NAAT)
culture testing for my Medicare patients. I'd like to take a few minutes and highlight the multiple areas that
I've found the test to be helpful in treatment of my patients where clearly referral to a specialist was sought
due to shortcomings of our traditional workup/testing.

1. Guidance UTI is extremely helpful in patients referred to me for what appears to be symptomatic
UTI but with polymicrobial cultures that result as "mixed flora" and therefore no sensitivities are
performed and patients told "NO UTI." With the help of guidance culture, I've been able to help
hundreds of patients since I started using it last year.
2. Additionally, the sensitivity testing and resistance gene testing with guidance culture has helped
sort out certain patients who did not find treatment effective with traditional cultures despite being
on what appeared to be culture-directed antibiotics
3. One of my favorite parts about this test lately has been the adaptation of home guidance culture
whereby i or the manufacturer can ship a test kit to patient’s home. This is important as a decent
number of my patients are high-risk and can't come to the office during the pandemic or have
limited mobility and find it hard to make it to the office in a timely manner. This is not only a
convenience issue but also allows me to test expeditiously in a timely manner before they start
getting complications from an untreated infection.

Therefore, I believe it is extremely important that there be coverage for guidance (NAAT) testing for all
Medicare and private insured patients.
16 The following comment was submitted to Palmetto: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
I am writing to you regarding the recent drafts LCD Multiplex Nucleic Acid Amplification Test (NAAT)
Panels for Infectious Disease Testing. My comments will be related to the discussion around
gastrointestinal panels for the diagnosis of infectious diarrhea.

First, just a brief introduction - I specialize in gastroenterology, internal medicine, tropical and travel
medicine. I have had considerable clinical and research experience in the field of travelers' diarrhea over the
past 25+ years. I am one of the primary authors of the American College of Gastroenterology guidelines "
Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults" published in the American
Journal of Gastroenterology in 2016. These guidelines are referenced in your LCD and identified as criteria
for determining if NAAT panels are appropriate for Medicare patients with diarrhea.

I appreciate the efforts of MolDX to convene a contractor advisory committee. I have great respect for the
expertise and experience of my colleagues who were invited to participate. I will note that no experts in
gastroenterology were included on the CAC. I hope my expertise and experience as a board-certified
gastroenterologist and Fellow of the Infectious Disease Society of America (FIDSA) can be considered in
addition to those already offered by my colleagues.

Both the LCD and panel noted the benefits to all patients, including immune-competent individuals,
provided by an expanded panel. Their ability to provide "rapid, high impact, and epidemiologically
important information " is mentioned in the LCD and was supported by the CAC. It is important to
clinicians to have access to expanded panels when determining the cause of their patient' s diarrhea. My

63
own personal experience further supports these benefits to my patients. Before the availability of multiplex
PCR, diagnosis of possible bacterial causes was dependent upon stool cultures, which take 48 to 72 hours,
on average, and detect a possible pathogen only 1.5% to 2.9% of the time (Guerrant, 2001). At our hospital,
New York Presbyterian -Cornell Medical Center, one of the largest teaching hospitals in the country, prior
to this technology, only 5 bacterial pathogens were searched for, leaving the vast majority of pathogens
undiagnosed. Likewise for parasitic causes, requiring ova and parasite (O&P) examination by microscopy,
with or without special stains, is fraught with inaccuracies due to the fact that this procedure is dependent
on technician interpretation, as well as the requirement to provide multiple stool samples because the test
lacks sensitivity. Viral pathogens have been difficult to diagnose because of lack of adequate commercial
testing capability, Traditional stool testing is slow, inaccurate, not comprehensive, and is prone to error in
subjective interpretation forcing many clinicians to make patient management decisions without any
laboratory results available.

Traditional methods have also contributed to an inaccurate understanding of the prevalence of pathogenic
causes of gastroenteritis. Historically, it was believed that bacterial causes, such as Salmonella, Shigella,
Campylobacter, E. coli, and C. Difficile made up the majority of possible gastroenteritis. While those
pathogens are still important and included on most expanded panels, other causes have been observed to be
more prevalent than previously realized. For example, Cyclospora cayetensis, a parasite, was rarely tested
for in the U.S. yet has contributed to several major U.S. outbreaks in 2018 and 2019 and was most likely
detected because of its inclusion on expanded GI panels. (Bateman, 2019). Similarly, viral causes such as
Sapovirus, Astrovirus, Norovirus, Adenovirus, and Rotavirus (all included on the BioFire GI panel, the test
our facility uses) make up, at its peak, close to ~30% of all positive detections on the Biofire GI panel in the
U.S., which may have been missed if not tested for with other methodologies, likely resulting in less than
optimal patient care. Because of comprehensive multiplex PCR tests and their ability to detect a broader
range of targets compared to traditional methods, ideas about pathogen prevalence are shifting and
becoming more finely tuned to the causative agents of gastroenteritis, resulting in accurate diagnoses,
appropriate targeted treatment and in many cases antimicrobial stewardship when antibiotics are not needed
as in cases with viral pathogens.

In light of the LCD comments from the CAC, and my personal experience and expertise, I propose the
following language be added to the billing articles that correspond to the LCD:

"If the laboratory's testing platform consists of a multiplexed EXPANDED (>5 Pathogens) PANEL, yet
only a subset of the organisms are considered medically necessary based on the above criteria in this
Article, the laboratory may run and report the EXPANDED (>5 Pathogens) PANEL while requesting
reimbursement for that subset of organisms using a procedure code that does not represent all organisms
included on the panel."

This will allow clinicians to continue to use GI panels in a way that they feel is best for their patients and
ensure that CMS continues to only pay for what is reasonable and necessary. Additionally, this will ensure
that the "rapid, high impact, and epidemiologically important information" obtained from expanded GI
panel testing are maintained for Medicare beneficiaries.

I also propose that ICD-10 code R19.7, Diarrhea unspecified, be added to Group 2 and Group 7 codes.
After reviewing the listed ICD-10 codes I am concerned that without this code there would not be an
appropriate ICD- 10 code that applies to Medicare patients that present with the most common sign of
infectious GI illness. While there are general ICD-10 codes for unspecified viral and bacterial pathogens in
these groups, most providers and coders would agree they don't apply in the absence of a viral or bacterial
detection. Further, because these ICD- 10 codes only represent positive results, it is unclear how to
accurately submit for reimbursement when a panel yields a negative result. This lack of clarity may cause
confusion in the appropriate clinical use of these panels leading to underutilization of GI panels and poorer
patient outcomes. Diarrhea is one of the most prevalent symptoms of patients with pathogenic GI illness
and currently none of the codes address this important symptom.

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 The American College of Gastroenterology Clinical Guidelines on the Diagnosis, Treatment, and
Prevention of Acute Diarrheal Infections in Adults are included in the criteria for expanded panel testing in
the LCD. These guidelines are specific to diarrheal illness and are used by gastroenterologists and general
internists to determine when diagnostic testing is needed. The symptom of diarrhea is at the crux of these
guidelines.

Without including that symptom as a Group 2 and 7 code, it would make it challenging for
gastroenterologist and other clinicians to follow best practice guidelines recommended by their professional
associations when ordering appropriate testing for their patients who present with acute diarrheal illness.

Thank you for your consideration of my comments and requests.

17 The following comment was submitted to Palmetto GBA: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
On behalf of Hologic, the manufacturer of the Aptima® and Panther® line of amplified probe microbiology
assays, we are pleased to provide comments regarding the above-captioned proposed LCD. Additionally-

We commend the MolDX partner Medicare Administrative Contractors, Palmetto GBA, Noridian, CGS, Regarding the response to the public health events of 2020, Palmetto followed its existing policies. Your comments do not
and WPS (“the MACs”) on their efforts to develop the Proposed LCD to address the dynamic field of seem to apply to this contractor.
infectious pathogen testing using nucleic acid amplified probe (“NAAT” tests). The Proposed LCD sets
forth general, evidence-based coverage criteria regarding the intended use population of NAAT tests for a
number of syndromic conditions. However, the Proposed LCD and accompanying article do not provide
sufficient detail for a provider to confidently determine whether a specific panel will be covered in advance
of submitting a technical assessment. The Proposed LCD sets forth considerations surrounding coverage for
specific panels but leaves actual coverage decisions to a subordinate coverage process that does not align
clearly with the transparency requirements or timelines of the LCD process. By this comment letter, we are
writing to support the coverage outlined in the Proposed LCD, but we also offer several comments
addressing how coverage will be implemented for specific tests under the LCD, when finalized. Our
comments are consistent with the apparent goals of the Proposed LCD as well as the requirements for
coverage set forth in the Program Integrity Manual.

In summary, our detailed comments below address the following:

1. We request that the Proposed LCD clarify that amplified probe testing for bacterial vaginosis
(“BV”) is eligible for coverage either by excluding such testing from the scope of this LCD or by
affirming that such testing is eligible for coverage as a urogenital test.
2. We recommend that the Proposed LCD be designated as outside of the scope of the MolDX
program and its requirements for billing using Z-code identifiers.
3. The Proposed LCD should make coverage clear for specific tests that meet the requirements of the
Proposed LCD without requiring publication of a billing and coding article identifying the specific
tests as covered.
4. We recommend removal of the technical assessment requirement for FDA-cleared or approved
tests as well as the default non-coverage for panels/indications that fall outside the scope of the
Proposed LCD.
5. We recommend that requirements for specialist ordering be removed from the LCD.
6. The Proposed LCD should allow for repeat testing of an identified organism to monitor
improvement or cure where medically necessary given patient signs or symptoms.
7. The Proposed LCD should apply to all nucleic acid amplified probe technique tests rather than
being limited to tests using multiplex PCR methods.
8. The Proposed LCD should make it clear that CLIA waived tests that meet the requirements of the
LCD are eligible for coverage. 9. Technical issues with the Proposed LCD and billing and coding
article implementation.

In response to the above-captioned proposed LCD, we offer the following comments for your
consideration:

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1. We request that the Proposed LCD clarify that amplified probe testing for bacterial vaginosis
(“BV”) is eligible for coverage either by excluding such testing from the scope of this LCD or by
affirming that such testing is eligible for coverage as a urogenital test

The Aptima® BV Assay (“the Assay”) is an FDA-cleared in vitro nucleic acid amplification test (NAAT)
that utilizes real time transcription-mediated amplification (TMA) for detection and quantitation of
ribosomal RNA from bacteria associated with bacterial vaginosis, including Lactobacillus (L. gasseri, L.
crispatus, and L. jensenii), Gardnerella vaginalis, and Atopobium vaginae. The Assay reports a qualitative
result for BV and does not report results for individual organisms. The Assay is intended to aid in the
diagnosis of BV on the automated Panther system using clinician-collected and patient-collected vaginal
swab specimens from females with a clinical presentation consistent with vaginitis and/or vaginosis.1 The
Assay is appropriately reported with CPT code 81513 Infectious disease, bacterial vaginosis, quantitative
real-time amplification of RNA markers for Atopobium vaginae, Gardnerella vaginalis, and Lactobacillus
species, utilizing vaginal-fluid specimens, algorithm reported as a positive or negative result for bacterial
vaginosis.

The proposed LCD applies to “panels using multiplex [NAATs] for infectious disease testing.” The
proposed LCD defines a “panel” as a “NAAT test that detects >1 pathogen.” As noted above, the Assay
detects ribosomal RNA from 5 different bacterial species but does not report quantitative or qualitative
results for the individual organisms. Rather, the Assay takes the quantitative results for each organism and
algorithmically transforms them into a single qualitative result indicating the presence or absence of BV. As
such, the Assay reports results for just one clinical syndrome – BV. In light of this functionality, it is our
understanding that the Assay should fall outside the scope of the proposed LCD and coding article because
it does not represent a multiplex amplified probe panel test.

Alternatively, if the MolDX program decides that the Assay is a “panel” subject to the proposed LCD, we
request confirmation that the Assay is eligible for coverage as a “small, targeted panel” of 5 or fewer
pathogens.

The proposed LCD distinguishes between “targeted” panels (up to 5 pathogens) and “expanded” panels (6
or more pathogens). In general, “expanded” panel testing would only be covered when “targeted” panel
testing is not appropriate (i.e., the “targeted” panel will not provide sufficient information for the
appropriate clinical management of the patient).

As outlined above, it is our understanding that the Assay is not a “panel” and therefore falls outside the
scope of the proposed LCD. However, insofar as MolDX believes that the Assay is a “panel,” we
encourage MolDX to (a) add language to the final LCD and/or comment/response article clarifying that the
Assay would be appropriately characterized as a “targeted” panel (because it detects 5 bacterial species)
and covered consistent with its FDA-cleared indication for use, and (b) add CPT code 81513 to the final
“Group 5” list of covered urogenital/anogenital panel codes in the local coverage article.

2. We recommend that the Proposed LCD be designated as outside the scope of the MolDX program
and its requirements for billing using Z-code identifiers

Palmetto GBA has indicated repeatedly that the scope of the MolDX Program is for tests of human DNA
and RNA only and that microbial testing is not within the scope of the MolDX Program. We do not object
to the collaborative nature of the Proposed LCD across MACs. We recognize that the MolDX collaboration
has specific expertise in clinical laboratory testing, and it is reasonable to apply this expertise to the
development of collaborative policies across MACs. However, the MolDX Program describes a distinct set
of processes including test registration, obtaining a Z-code identifier for each specific test, and submission
and approval of a technical assessment.2 Palmetto GBA has maintained that tests under the MolDX
Program are not covered by Medicare until the MolDX Program has reviewed a technical assessment, and
MolDX agrees to cover the tests.

66
Specialty genetic laboratories offering sole source tests and large reference laboratories that offer esoteric
testing may be able to manage the requirements of the MolDX Program for test registration, Z-code
identifiers, and technology assessment. However, community laboratories and physician office laboratories
that often are at the front line of microbiology testing services are likely unable to accommodate the
administrative burdens of the MolDX program. These care settings are primarily focused on patient facing
clinical care offering point of care testing or local laboratory testing to provide important diagnostic
information to support decisions making by clinicians. Such laboratories would find it technically and
economically prohibitive to register, obtain a Z-code identifier, and submit a technical assessment for each
test they offer. In addition, registration, obtaining Z-code identifiers, and submission of a technical
assessment is unnecessary in these settings given that testing typically involves FDA-cleared or approved
tests run consistent with their labeling directions for use. If the Proposed LCD is finalized as requiring test
registration, Z-code identifiers, and technical assessment by each laboratory for each such test it runs, the
policy will reduce access to care, particularly for Medicare beneficiaries who rely on local health centers
for their care.

We recommend that the MACs rename the LCD to remove reference to “MolDX” and clearly indicate that
this LCD is not subject to MolDX coverage or claims processing requirements.

3. The Proposed LCD should make coverage clear for specific tests that meet the requirements of the
Proposed LCD without requiring publication of a billing and coding article identifying the specific
tests as covered

The Proposed LCD does not provide sufficient clarity to permit stakeholders to determine confidently
whether any specific test is covered. Although the draft billing and coding article identifies some specific
tests, and more can potentially be added in the future, it is our understanding that coverage should be
articulated clearly in an LCD with a billing and coding article simply supplementing the LCD by providing
coding details consistent with the LCD coverage criteria. We note that in 2020, the MolDX Program MACs
withdrew coverage for a number of respiratory panels without an opportunity for notice and comment by
altering a billing and coding article in the midst of a respiratory illness pandemic. Moreover, one MAC
implemented these changes retroactively. We have substantial concerns that the precedent set in 2020
implies that a vaguely worded LCD can be used as a mechanism to give the MACs discretion to add or
remove coverage for specific tests by changing a billing and coding article without opportunity for notice
and comment and without a public explanation of the rationale for the change in coverage.

To maintain the requirements of the LCD process as set forth in the Program Integrity Manual, it is of
paramount importance that the Proposed LCD, when finalized, articulates clear coverage requirements
under which specific tests will or will not be covered without deferring such decision making to publication
of billing and coding articles.

4. We recommend removal of the technical assessment requirement for FDA-cleared or approved

tests as well as the default non-coverage for panels/indications that fall outside the scope of the
Proposed LCD

The Proposed LCD outlines technical assessment requirements as follows:

• The test demonstrates equivalent or superior test performance characteristics- analytical validity
(AV) and clinical validity (CV) - to established standard-of-care (SOC) methods (i.e., culture,
pathogen-specific PCR) for the majority of targets included on the panel.

• CV of any new analytes that are not already established as SOC or that do not have a predicate test
that is covered by this contractor must be established through a study published in the
peer-reviewed literature for the intended use of the test in the intended population.

• Tests that perform identification of new analytes or are performed according to new intended uses

67
 not already covered by this contractor will require a Technical Assessment (TA) for compliance of
that service with this policy.

Our specific concerns with the language are below.

1. It is unclear what is meant by “CV of new analytes.” Clinical validity is generally considered to be
the element of validity that describes how informative the biomarker is about the presence of
absence of disease. Therefore, CV requires the identification of a specific biomarker and a specific
disease. The text as it is currently written could be interpreted to treat pathogens as analytes, and
syndromic conditions as diseases (e.g. rhinovirus and the common cold). Alternatively, analyte
could be interpreted to refer to particular nucleic acid sequences with the disease being an infection
with a specific pathogen (e.g. M1 coding region as an analyte to provide information regarding
influenza infection). If the MACs will require that “new analytes” have CV, it will first be critical
to define what constitutes and an analyte and how disease state will be defined.
2. The requirement to demonstrate CV for new analytes applies to analytes that are not established as
standard of care or covered. However, the LCD stops short of covering any specific analytes; rather
it covers the use of tests for several syndromic conditions. Additionally, “standard of care” is an
immensely ambiguous term that may differ not only between different syndromic conditions, but
even among patients or intended applications for a given syndromic condition. This has been
highlighted by the COVID-19 pandemic in which various other approaches to testing have all been
developed for the same clinical presentation. Moreover, there are few things in medicine for which
a single standard of care exists; rather the term “standard of care” is used to represent a range of
potential diagnostic or treatment approaches that are considered reasonable. Finally, the standard of
care may change over time, and it is not clear whether this would mean that tests could potentially
become non-covered if they did not submit repeat technical assessments demonstrating validity
against an ever-evolving standard of care. We are also concerned that the Proposed LCD text does
not expressly cover any specific panels. Therefore, in the absence of clearly covered analytes in the
LCD, or an objective reference standard of care for each syndrome, the Proposed LCD could
effectively be used to bar coverage for many panels currently in use with well-accepted clinical
utility.
3. The draft LCD introduces technical assessment requirements for intended uses with the following
language: “Tests that perform identification of new analytes or are performed according to new
intended uses not already covered by this contractor.” This statement appears to be a de facto
statement of non-coverage of testing for intended uses that the Proposed LCD does not expressly
cover. This is inconsistent with the requirements of the new LCD process outlined in the Program
Integrity Manual updates in 2019 to implement the coverage provisions of the 21st Century Cures
Act. This requirement introduces particular challenges for manufacturers of FDA-cleared or
approved in vitro diagnostic tests and puts the burden of technical assessment on labs that use these
tests. As noted above, many of these laboratories lack the resources to undergo the technical
assessment process themselves.

To address these concerns, we recommend that Palmetto GBA and the collaborating MACs remove the
technical assessment requirement for FDA-cleared or approved tests with labeled indications for use that
are consistent with the scope of the Proposed LCD. We appreciate the desire to ensure that tests without
clinical value are not billed to Medicare. An alternative approach to requiring submission of technical
assessments for specific tests is to provide specific criteria for coverage in the Proposed LCD, when
finalized. An example of such specific criteria are those set forth by CMS in its recent update to NCD 210.3
for colorectal cancer screening tests.3 In this NCD update, CMS set forth specific coverage requirements
that tests must meet to be eligible for coverage. With such an approach set forth in the Proposed LCD,
when finalized, manufacturers could confirm with Palmetto GBA and the collaborating MACs that a
specific test they offer meets the coverage requirements. In this way, laboratories would not be burdened
with the technical assessment submission process and would have certainty about coverage for specific
tests. This said, since specific performance criteria were not set forth in the Proposed LCD, adopting this
alternative approach would require re-issuance of a Proposed LCD, which we would suggest be left to a

68
later date rather than holding up finalization of the current Proposed LCD. Therefore, we recommend that
the technical assessment requirement be removed from the Proposed LCD, when finalized.

5. Requirements for specialist ordering be removed from the LCD

The Proposed LCD includes requirement for ordering by a specialist for immunocompetent patients for the
expanded respiratory and pneumonia panels (infectious diseases or pulmonology specialist) and the
expanded gastrointestinal panels (infectious diseases or gastroenterology). We recommend that these
requirements be removed from the LCD when finalized.

First, in many regions of the country access to infectious disease, pulmonary, or gastrointestinal diseases
specialists may be limited. In such settings, it may be especially helpful to have access to broader panels for
patients who present with atypical signs or symptoms and where testing results can be available with
relatively rapid turnaround. If an unusual pathogen is identified, this finding may help target appropriate
referrals to guide therapy rather than requiring referral – and where necessary – transportation to obtain
such referrals prior to testing.

Second, operationalizing specialist ordering requirements as outlined in the Proposed LCD may be difficult.
Since the specialist ordering requirement applies only to certain types of panels, the types of specialists
varies by panel, and the requirement does not apply to immune-suppressed patients nor to seriously ill or
critically ill patients, it may be difficult for providers to know exactly under which circumstances testing
will or will not be covered. This may result in a disincentive to testing when such should otherwise be
eligible for coverage under the Proposed LCD.

6. The Proposed LCD should allow for repeat testing of an identified organism to monitor
improvement or cure where medically necessary given patient signs or symptoms

The Proposed LCD limits coverage when performed as a test for cure. It is unclear if this requirement is
intended to apply solely to repeat testing with a multiplex platform for several pathogens after a specific
organism has been identified or if it is intended to limit coverage for any amplified probe test after a
diagnosis is made. We understand that repeated testing with a multiplex panel comprising many target
microorganisms may not be necessary once a specific pathogen has been identified as the likely cause of a
clinical syndrome and treatment has been initiated. That said, in certain clinical conditions—especially ones
where extended courses of treatment may be needed to obtain cure—it may be medically necessary to re-test
over time to confirm that the treatment has eradicated the pathogen. The Centers for Disease Control and
Prevention’s (CDC) guidelines state that it may be appropriate to provide a test of cure if the therapeutic
adherence is in question, symptoms persist, or reinfection is suspected. The CDC also has a special
consideration for pregnant women and suggest that a test of cure be performed 3-4 weeks after completion
of therapy for chlamydia because severe sequelae can occur in mothers and neonates if the infection
persists. Therefore, we recommend that the Proposed LCD remove the limitation on testing for cure
especially insofar as such testing may be an amplified probe test specific for a microorganism previously
identified as the likely pathogen based upon broader panel testing.

7. The Proposed LCD should apply to all nucleic acid amplified probe technique tests rather than
being limited to tests using multiplex PCR methods

There are several nucleic acid amplified probe techniques currently in clinical use, including transcription
mediated amplification [TMA], loop-mediated amplification [LAMP], and polymerase chain reaction
[PCR]). From the standpoint of diagnostic information to support clinical care, the specific method of
amplification is not as relevant as the test analytes and accuracy of the test. Reflecting this point, the
CPT® codes that describe molecular microbiology panels using amplified probe techniques do not specify
PCR but rather describe amplified probe techniques generally. Not only does this mean that the fiscal
impact to Medicare is indifferent to the specific amplified probe technique, this also means that it would be
nearly impossible to implement the Proposed LCD with claims processing logic based on CPT codes if the

69
Proposed LCD applies only to multiplex PCR tests.

For these reasons, we strongly recommend that the Proposed LCD apply to all nucleic acid amplified probe
techniques rather than multiplex PCR alone.

8. The Proposed LCD should make it clear that CLIA waived tests that meet the requirements of the
LCD are eligible for coverage

Many point of care tests have received clearance to be used in settings with CLIA Certificates of Waiver or
Provider Performed Microscopy. This designation applies only to tests that have been cleared through the
FDA with such CLIA complexity categorization.4 W recommend that the Proposed LCD and
accompanying billing and coding article, when finalized, make it clear that CLIA waived tests meeting the
requirements of the Proposed LCD are also covered.

9. Technical Issues and draft article implementation

1. The draft billing and coding article does not appear to comprehend services billed by hospitals or
other institutions that submit claims on an institutional claim form (i.e., CMS-1450). The place of
service codes are used on professional claims (i.e., CMS- 1500) as might be used by physician
office labs or outpatient independent labs. As hospital laboratories submit claims on the CMS-1450
form that does not have a place of service designator, we think it is unlikely that POS of 21 or 23
(inpatient hospital or emergency room) would appear on a claim for a microbiology test. Tests for
patients in these settings, if coded and billed to Medicare, would typically be billed on an
institutional claim form. The ordering physician may indicate such places of service on his or her
bill to Medicare for professional services, but the professional services will not be reflected on the
bill for laboratory services. Therefore, we recommend that the MACs either develop appropriate
billing and coding instructions for institutional claims, or that the MACs limit the Proposed LCD
and the accompanying coding and billing article to the Part B contracts5 to avoid confusion with
claims submitted by Part A providers.
2. The coding instructions for multiplex panels are unclear, especially in light of the inclusion of
single pathogen CPT codes in the LCD. The panel coding instructions are as follows:

A test panel is a single service with a single unit of service (UOS =1). A panel cannot be unbundled and
billed as individual components regardless of the fact that the test reports multiple individual pathogens
and/or targets. The panel is a closed system performed on a single platform, and as such, is a single test
panel with multiple components (UOS=1). If additional organisms are not included in a panel, testing for
those organisms may be reasonable and necessary when ordered in addition to the panel and supported by
documentation in the medical record.

It is unclear what the phrase “closed system performed on a single platform” means, and therefore unclear
what constitutes a “panel” for the purposes of coding. We recommend that for coding, the MACs defer to
existing CPT® codes and CPT® coding guidance. If a CPT® code to describe a panel exists, then labs must
use that code. If there is no specific code to describe a panel, then labs should use the individual
CPT® codes for the analytes that comprise the panel.

3. As discussed during the Contractor Advisory Committee meeting earlier this year, some
laboratories, such as those found in smaller community health centers, or rural hospitals may have
one platform that they use for testing needs and lack the resources to have multiple different tests
for the same syndromic illness. As such, they may only have the option to run an “expanded”
panel for all patients including patients in whom the LCD would cover only a targeted panel. To
ensure that the Proposed LCD does not adversely affect beneficiaries cared for at these institutions,
we urge the MACs to accommodate these laboratory operational constraints. Along these lines, we
recommend that the billing and coding article explicitly allow for billing for a subset of covered
pathogens (or billing for a targeted panel), even if a larger panel that includes non-covered

70
 pathogens (an expanded panel) is run.

Thank you for your consideration of these comments.

References were provided for review.

18 The following comment was submitted to Palmetto GBA: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
As a physician and surgeon in Female Pelvic Medicine & Reconstructive Surgery for the past 20 years at
UC San Diego and as a Tenured professor with extensive experience in clinical research. I have managed
and studied outcomes in women with complicated and recurrent urinary tract infections (UTI). As you are
likely well aware, current standards for diagnosis and treatment of UTIs are archaic, delayed and often
inaccurate. While advances in personalized medicine have been realized across many specialties,
particularly cancer and pharmacotherapy, the field of diagnostics in infectious disease has lagged. It has
taken a global pandemic to bring the diagnostic platforms for infectious diseases (particularly UTIs) to the
21st century.

I am heartened to see that on May 20, Medicare (Palmetto MolDX) issued a draft proposal for coverage of
“Multiples Nucleic Acid Amplification Test (NAAT) Panels for Infectious Disease Testing.” This Local
Coverage Determination (LCD) has positive coverage language for PCR testing in patients who are seen in
a urology or urogynecology specialty care setting for UTI, or symptomatic patients at higher risk for UTI
complications (i.e., the elderly, patients with recurrent symptomatic UTIs and/or complicated urinary tract
anatomy) in other settings.

This decision is important to the treatment of not only my patients, but patients across the country
particularly suffering from recurrent UTI – a condition that nearly 30% of women in my practice suffer
from. Current strategies require that urine analysis be used for screening and cultures take 48-72 hours to
obtain accurate bacterial identification and sensitivity. This strategy results in nearly 50% of women
receiving empiric therapy for several days and need for antibiotic changes, delayed treatment, and
development of collateral damage (c diff, yeast infections and resistance) from inaccurate and incomplete
therapy.

Guidance UTI has the potential to drastically change practice by delivering timely and accurate diagnoses
and appropriate treatment options for patients. Data supports that Guidance UTI detects 97% of
polymicrobial infections, whereas standard urine culture detects only 19% (Volstedt A, et al J. Sur Urol
2020). Equally important is the rapid reporting with precise bacterial pathogens, along with their resistance
gene expression and antibiotic susceptibility within 24 hours of collection. As we have seen with the
COVID 19 crisis, rapid and accurate reporting using PCR technology is critical for the acute management
of infectious diseases. UTI management should be no different given the morbidity and suffering that
patients experience while waiting for standard culture results. Many complicated and recurrent cases that
are seen in urology and urogynecology offices, particularly in higher risk patients such as the elderly and
women with recurrent UTI, will benefit tremendously from a timely and accurate diagnosis and treatment
of their UTI. It is critical to have tests available to use under this policy, Medicare should ensure that tests
such as Guidance UTI, which has strong clinical evidence, are fully covered.
19 The following comment was submitted to Palmetto GBA: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
On behalf of the undersigned manufacturers, we are writing regarding MolDX: Multiplex Nucleic Acid
Amplification Test (NAAT) Panels for Infectious Disease Testing (the “Proposed LCD”). The undersigned
manufacturers share a common goal of seeking to facilitate access to safe, effective, and cost-effective
patient testing by manufacturing in vitro diagnostic tests, including tests that detect the presence of
infectious pathogens. In vitro diagnostic testing in the management of the COVID-19 crisis has been a
significant area of focus for our companies, but our interest and engagement with Palmetto GBA on the
topic of molecular methods for pathogen detection predates the emergence of COVID-19, including our
submission of a request for reconsideration of the current LCDs addressing respiratory viral pathogens and
gastrointestinal pathogens.

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We commend the MolDX partner Medicare Administrative Contractors, Palmetto GBA, Noridian, CGS,
and WPS (“the MACs”) on their efforts to develop the Proposed LCD to address the dynamic field of
infectious pathogen testing using nucleic acid amplified probe (“NAAT” tests). The Proposed LCD sets
forth general, evidence-based coverage criteria regarding the intended use population of NAAT tests for a
number of syndromic conditions. However, the Proposed LCD and accompanying article do not provide
sufficient detail for a provider confidently to determine whether or not a specific panel will be covered in
advance of submitting a technical assessment. The Proposed LCD sets forth considerations surrounding
coverage for specific panels but leaves actual coverage decisions to a subordinate coverage process that
does not align clearly with the transparency requirements or timelines of the LCD process. By this
comment letter, we are writing to support the coverage outlined in the Proposed LCD, but we also offer a
number of comments addressing how coverage will be implemented for specific tests under the LCD, when
finalized. Our comments are consistent with the apparent goals of the Proposed LCD as well as the
requirements for coverage set forth in the Program Integrity Manual.

In summary, our detailed comments below address the following:

1. We recommend that the Proposed LCD be designated as outside of the scope of the MolDX
program and its requirements for billing using Z-code identifiers.
2. The Proposed LCD should make coverage clear for specific tests that meet the requirements of the
Proposed LCD without requiring publication of a billing and coding article identifying the specific
tests as covered.
3. We recommend removal of the technical assessment requirement for FDA-cleared or approved
tests as well as the default non-coverage for panels/indications that fall outside the scope of the
Proposed LCD.
4. We recommend that requirements for specialist ordering be removed from the LCD.
5. The Proposed LCD should allow for repeat testing of an identified organism to monitor
improvement or cure where medically necessary given patient signs or symptoms.
6. The Proposed LCD should apply to all nucleic acid amplified probe technique tests rather than
being limited to tests using multiplex PCR methods.
7. The Proposed LCD should make it clear that CLIA waived tests that meet the requirements of the
LCD are eligible for coverage.
8. Technical issues with the Proposed LCD and billing and coding article implementation.

In addition to offering the detailed comments below, we also offer highlighted copies of the Proposed LCD
and the corresponding billing and coding article on which we have marked recommended changes to these
documents to address the concerns raised in our comments.

1. We recommend that the Proposed LCD be designated as outside the scope of the MolDX program
and its requirements for billing using Z-code identifiers

Palmetto GBA has indicated repeatedly that the scope of the MolDX Program is for tests of human DNA
and RNA only and that microbial testing is not within the scope of the MolDX Program. We do not object
to the collaborative nature of the Proposed LCD across MACs. We recognize that the MolDX collaboration
has specific expertise in clinical laboratory testing, and it is reasonable to apply this expertise to the
development of collaborative policies across MACs. However, the MolDX Program describes a distinct set
of processes including test registration, obtaining a Z-code identifier for each specific test, and submission
and approval of a technical assessment. Palmetto GBA has maintained that tests under the MolDX Program
are not covered by Medicare until the MolDX Program has reviewed a technical assessment, and MolDX
agrees to cover the tests.

Specialty genetic laboratories offering sole source tests and large reference laboratories that offer esoteric
testing may be able to manage the requirements of the MolDX Program for test registration, Z-code
identifiers, and technology assessment. However, community laboratories and physician office laboratories
that often are at the front line of microbiology testing services are likely to be unable to accommodate the

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administrative burdens of the MolDX program. These care settings are primarily focused on patient facing
clinical care offering point of care testing or local laboratory testing to provide important diagnostic
information to support decisions making by clinicians. Such laboratories would find it technically and
economically prohibitive to register, obtain a Z-code identifier, and submit a technical assessment for each
test they offer. In addition, registration, obtaining Z-code identifiers, and submission of a technical
assessment is unnecessary in these settings given that testing typically involves FDA-cleared or approved
tests run consistent with their labeling directions for use. If the Proposed LCD is finalized as requiring test
registration, Z-code identifiers, and technical assessment by each laboratory for each such test it runs, the
policy will reduce access to care, particularly for Medicare beneficiaries who rely on local health centers
for their care.

We recommend that the MACs rename the LCD to remove reference to “MolDX” and clearly indicate that
this LCD is not subject to MolDX coverage or claims processing requirements.

2. The Proposed LCD should make coverage clear for specific tests that meet the requirements of the
Proposed LCD without requiring publication of a billing and coding article identifying the specific
tests as covered

The Proposed LCD does not provide sufficient clarity to permit stakeholders to determine confidently
whether or not any specific test is covered. Although the draft billing and coding article identifies some
specific tests, and more can potentially be added in the future, it is our understanding that coverage should
be articulated clearly in an LCD with a billing and coding article simply supplementing the LCD by
providing coding details consistent with the LCD coverage criteria. We note that in 2020 the MolDX
Program MACs withdrew coverage for a number of respiratory panels without an opportunity for notice
and comment by altering a billing and coding article in the midst of a respiratory illness pandemic.
Moreover, one MAC implemented these changes retroactively. We have substantial concerns that the
precedent set in 2020 implies that a vaguely worded LCD can be used as a mechanism to give the MACs
discretion to add or remove coverage for specific tests by changing a billing and coding article without
opportunity for notice and comment and without a public explanation of the rationale for the change in
coverage.

To maintain the requirements of the LCD process as set forth in the Program Integrity Manual, it is of
paramount importance that the Proposed LCD, when finalized, articulate clear coverage requirements under
which specific tests will or will not be covered without deferring such decision making to publication of
billing and coding articles.

3. We recommend removal of the technical assessment requirement for FDA-cleared or approved

tests as well as the default non-coverage for panels/indications that fall outside the scope of the
Proposed LCD

The Proposed LCD outlines technical assessment requirements as follows:

• The test demonstrates equivalent or superior test performance characteristics - analytical validity
(AV) and clinical validity (CV) - to established standard-of-care (SOC) methods (i.e., culture,
pathogen-specific PCR) for the majority of targets included on the panel.
• CV of any new analytes that are not already established as SOC or that do not have a predicate test
that is covered by this contractor must be established through a study published in the
peer-reviewed literature for the intended use of the test in the intended population.
• Tests that perform identification of new analytes or are performed according to new intended uses
not already covered by this contractor will require a Technical Assessment (TA) for compliance of
that service with this policy.

Our specific concerns with the language are below.

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 1. It is unclear what is meant by “CV of new analytes.” Clinical validity is generally considered to be
the element of validity that describes how informative the biomarker is about the presence of
absence of disease. Therefore, CV requires the identification of a specific biomarker and a specific
disease. The text as it is currently written could be interpreted to treat pathogens as analytes, and
syndromic conditions as diseases. (e.g. rhinovirus and the common cold) Alternatively, analyte
could be interpreted to refer to particular nucleic acid sequences with the disease being an infection
with a specific pathogen. (e.g. M1 coding region as an analyte to provide information regarding
influenza infection). If the MACs will require that “new analytes” have CV, it will first be critical
to define what constitutes and an analyte and how disease state will be defined.
2. The requirement to demonstrate CV for new analytes applies to analytes that are not established as
standard of care or covered. However, the LCD stops short of covering any specific analytes; rather
it covers the use of tests for a number of syndromic conditions. Additionally, “standard of care” is
an immensely ambiguous term that may differ not only between different syndromic conditions, but
even among patients or intended applications for a given syndromic condition. This has been
highlighted by the COVID-19 pandemic in which various different approaches to testing have all
been developed for the same clinical presentation. Moreover, there are few things in medicine for
which a single standard of care exists; rather the term “standard of care” is used to represent a
range of potential diagnostic or treatment approaches that are considered reasonable. Finally, the
standard of care may change over time, and it is not clear whether this would mean that tests could
potentially become non-covered if they did not submit repeat technical assessments demonstrating
validity against an ever-evolving standard of care. We are also concerned that the Proposed LCD
text does not expressly cover any specific panels. Therefore, in the absence of clearly covered
analytes in the LCD, or an objective reference standard of care for each syndrome, the Proposed
LCD could effectively be used to bar coverage for many panels currently in use with well-accepted
clinical utility.
3. The draft LCD introduces technical assessment requirements for intended uses with the following
language: “Tests that perform identification of new analytes or are performed according to new
intended uses not already covered by this contractor.” This statement appears to be a de facto
statement of non-coverage of testing for intended uses that the Proposed LCD does not expressly
cover. This is inconsistent with the requirements of the new LCD process outlined in the Program
Integrity Manual updates in 2019 to implement the coverage provisions of the 21st Century Cures
Act. This requirement introduces particular challenges for manufacturers of FDA-cleared or
approved in vitro diagnostic tests and puts the burden of technical assessment on the labs that use
these tests. As noted above, many of these laboratories lack the resources to undergo the technical
assessment process themselves.

To address these concerns, we recommend that Palmetto GBA and the collaborating MACs remove the
technical assessment requirement for FDA-cleared or approved tests with labeled indications for use that
are consistent with the scope of the Proposed LCD. We appreciate the desire to ensure that tests without
clinical value are not billed to Medicare. An alternative approach to requiring submission of technical
assessments for specific tests is to provide specific criteria for coverage in the Proposed LCD, when
finalized. An example of such specific criteria are those set forth by CMS in its recent update to NCD 210.3
for colorectal cancer screening tests. In this NCD update, CMS sets forth specific coverage requirements
that tests must meet to be eligible for coverage. With such an approach set forth in the Proposed LCD,
when finalized, manufacturers could confirm with Palmetto GBA and the collaborating MACs that a
specific test they offer meets the coverage requirements. In this way, laboratories would not be burdened
with the technical assessment submission process and would have certainty about coverage for specific
tests. This said, since specific performance criteria were not set forth in the Proposed LCD, adopting this
alternative approach would require re-issuance of a Proposed LCD, which we would suggest be left to a
later date rather than holding up finalization of the current Proposed LCD. Therefore, we recommend that
the technical assessment requirement be removed from the Proposed LCD, when finalized.

4. Requirements for specialist ordering be removed from the LCD

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The Proposed LCD includes requirement for ordering by a specialist for immunocompetent patients for the
expanded respiratory and pneumonia panels (infectious diseases or pulmonology specialist) and the
expanded gastrointestinal panels (infectious diseases or gastroenterology). We recommend that these
requirements be removed from the LCD when finalized.

First, in many regions of the country access to infectious disease, pulmonary, or gastrointestinal diseases
specialists may be limited. In such settings, it may be especially helpful to have access to broader panels for
patients who present with atypical signs or symptoms and where testing results can be available with
relatively rapid turnaround. If an unusual pathogen is identified, this finding may help target appropriate
referrals to guide therapy rather than requiring referral – and where necessary – transportation to obtain
such referrals prior to testing.

Second, operationalizing specialist ordering requirements as outlined in the Proposed LCD may be difficult.
Since the specialist ordering requirement applies only to certain types of panels, the types of specialists
varies by panel, and the requirement may not apply to immune-suppressed patients nor to seriously ill or
critically ill patients, it may be difficult for providers to know exactly under which circumstances testing
will or will not be covered. This may result in a disincentive to testing when such otherwise should be
eligible for coverage under the Proposed LCD.

5. The Proposed LCD should allow for repeat testing of an identified organism to monitor
improvement or cure where medically necessary given patient signs or symptoms

The Proposed LCD limits coverage when performed as a test for cure. It is unclear if this requirement is
intended to apply solely to repeat testing with a multiplex platform for a number of pathogens after a
specific organism has been identified or is intended to limit coverage for any amplified probe test after a
diagnosis is made. We understand that repeated testing with a multiplex panel comprising many target
microorganisms may not be necessary once a specific pathogen has been identified as the likely cause of a
clinical syndrome and treatment has been initiated. That said, in certain clinical conditions—especially ones
where extended courses of treatment may be needed to obtain cure—it may be medically necessary to re-test
over time to confirm that the treatment has eradicated the pathogen. The Centers for Disease Control and
Prevention (CDC) guidelines state that it may be appropriate to provide a test of cure if therapeutic
adherence is in question, symptoms persist, or reinfection is suspected. The CDC also has a special
consideration for pregnant women and suggest that a test of cure be performed 3-4 weeks after completion
of therapy for chlamydia because severe sequelae can occur in mothers and neonates if the infection
persists. Therefore, we recommend that the Proposed LCD remove the limitation on testing for cure
especially insofar as such testing may be an amplified probe test specific for a microorganism previously
identified as the likely pathogen based upon broader panel testing.

6. The Proposed LCD should apply to all nucleic acid probe technique tests rather than being limited
to tests using multiplex PCR methods

There are several nucleic acid amplified probe techniques currently in clinical use, including transcription
mediated amplification [TMA], loop-mediated amplification [LAMP], and polymerase chain reaction
[PCR]) in addition to direct probe techniques. From the standpoint of diagnostic information to support
clinical care, the specific method of nucleic acid testing is not as relevant as the test analytes and accuracy
of the test. Reflecting this point, the CPT® codes that describe molecular microbiology panels using
amplified probe techniques do not specify PCR but rather describe amplified probe techniques generally.
Not only does this mean that the fiscal impact to Medicare is indifferent to the specific amplified probe
technique, this also means that it would be nearly impossible to implement the Proposed LCD with claims
processing logic based on CPT codes if the Proposed LCD applies only to multiplex PCR tests.

For these reasons, we strongly recommend that the Proposed LCD apply to all nucleic acid techniques
rather than to multiplex PCR alone.

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We also note that insofar as CPT codes for direct probe tests are included in the draft billing and coding
article, which we agree is appropriate for completeness, we recommend revising the title of the Proposed
LCD to conform the LCD title with the scope of the article.

7. The Proposed LCD should make it clear that CLIA waived tests that meet the requirements of the
LCD are eligible for coverage

Many point of care tests have received clearance to be used in settings with CLIA Certificates of Waiver or
Provider Performed Microscopy. This designation applies only to tests that have been cleared through the
FDA with such CLIA complexity categorization. We recommend that the Proposed LCD and
accompanying billing and coding article, when finalized, make it clear that CLIA waived tests meeting the
requirements of the Proposed LCD are also covered.

8. Technical Issues and draft article implementation

1. The draft billing and coding article does not appear to comprehend services billed by hospitals or
other institutions that submit claims on an institutional claim form (i.e., CMS-1450). The place of
service codes are used on professional claims (i.e., CMS-1500) as might be used by physician
office labs or outpatient independent labs. As hospital laboratories submit claims on the CMS-1450
form that does not have a place of service designator, we think it is unlikely that POS of 21 or 23
(inpatient hospital or emergency room) would appear on a claim for a microbiology test. Tests for
patients in these settings, if coded and billed to Medicare, would typically be billed on an
institutional claim form. The ordering physician may indicate such places of service on his or her
bill to Medicare for professional services, but the professional services will not be reflected on the
bill for laboratory services. Therefore, we recommend that the MACs either develop appropriate
billing and coding instructions for institutional claims, or that the MACs limit the Proposed LCD
and the accompanying coding and billing article to the Part B contracts to avoid confusion with
claims submitted by Part A providers.
2. The coding instructions for multiplex panels are unclear, especially in light of the inclusion of
single pathogen CPT codes in the LCD. The panel coding instructions are as follows:

A test panel is a single service with a single unit of service (UOS =1). A panel cannot be unbundled and
billed as individual components regardless of the fact that the test reports multiple individual pathogens
and/or targets. The panel is a closed system performed on a single platform, and as such, is a single test
panel with multiple components (UOS=1). If additional organisms are not included in a panel, testing for
those organisms may be reasonable and necessary when ordered in addition to the panel and supported by
documentation in the medical record.

It is unclear what the phrase “closed system performed on a single platform” means, and therefore unclear
what constitutes a “panel” for the purposes of coding. We recommend that for coding, the MACs defer to
existing CPT® codes and CPT® coding guidance. If a CPT® code to describe a panel exists, then labs must
use that code. If there is no specific code to describe a panel, then labs should use the individual CPT®
codes for the analytes that comprise the panel.

3. As discussed during the Contractor Advisory Committee meeting earlier this year, some
laboratories, such as those found in smaller community health centers, or rural hospitals may have
one platform that they use for testing needs and lack the resources to have multiple different tests
for the same syndromic illness. As such, they may only have the option to run an “expanded”
panel for all patients including patients in whom the LCD would cover only a targeted panel. To
ensure that the Proposed LCD does not adversely affect beneficiaries cared for at these institutions,
we urge the MACs to accommodate these laboratory operational constraints. Along these lines, we
recommend that the billing and coding article explicitly allow for billing for a subset of covered
pathogens (or billing for a targeted panel), even if a larger panel that includes non-covered
pathogens (an expanded panel) is run.

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 Thank you for consideration of these comments.

Redline drafts of the Policy and Billing and Coding Article were provided for review.
20 The following comment was submitted to Palmetto GBA: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
I am a urologist in a mid-size urology group with a specialty focus on female urology and UTI
management. I have been using Guidance UTI testing for several years now, after being dissatisfied with
equivocal and non-timely results from standard urine cultures.

Antibiotic stewardship is a concern in the medical community and lack of quality evidence from standard
cx to guide (or discourage) antibiotic use is a problem. I see a population of patients who catheterize or
have neurogenic bladder, and polymicrobial samples are common in this population for which pooled
sensitivity testing provided by guidance gives clearer information to often utilize less broad-spectrum
antibiotics.

Turnaround time is also important – when patients are symptomatic – being able to provide results in 48
hours or less, as opposed to 5+ days on standard urine culture (especially when requested to actually run
polymicrobial sensitivity) allows for less time on empiric antibiotics or possibly waiting for results to treat
limiting unnecessary antibiotics exposure.

Utilizing urine testing prior to invasive procedures with reliable and fast turnaround, also reduces risk of
sepsis – due to more accurate and specific results to guide prophylaxis

Having access to higher quality testing, as a specialty practice, allows for better care for these recurrent UTI
or complicated UTI patients.
21 The following comment was submitted to Palmetto GBA: Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1
listed above.
I am writing to say the PCR testing is a very necessary adjunct to treating patients with chronic dysuria. It
has allowed us to provide more directed therapy to patients. In turn, I strongly believe this will help to
prevent drug resistance. Furthermore, many patients come to the office that have been treated empirically
for months without improvement of symptoms, and the PCR test allows us to find the fastidious bacteria
causing their symptoms so the treatment can be more specific to the patient. These Guidance PCR tests are
highly sensitive and specific in picking up the microorganisms and it is imperative that insurance cover
these tests in certain subsets of the population.
Associated Documents

Related Local Coverage Documents

LCDs

L39003 - MolDX: Molecular Syndromic Panels for Infectious Disease Pathogen Identification Testing

Related National Coverage Documents

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Public Versions

Updated On Effective Dates Status

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