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

The following comment was submitted to Palmetto GBA, CGS, WPS, and Noridian and was received from multiple stakeholders:

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.
3. Why foundational policies do not list covered tests within the policy.
4. Clarity regarding scope of MolDX and scope of the policy - including requirements for registering tests with MolDX and for a Technical Assessment (TA).
5. Clarity regarding criteria for orthogonal comparator (‘reference’) tests as the standards of care evolve with time.
6. Clarity regarding billing.
7. Clarity regarding the inclusion of (new CPT codes for) Infectious Vaginosis/Vaginitis (BV) panels.
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.

1. Clarity regarding restrictions pertaining to ordering provider and POS

A. Comments requesting clarity regarding how the restrictions impact access to care

First, this policy (LCD) does not restrict targeted panels on the basis of POS or specialty of ordering clinician. As such, it does NOT prohibit the use of targeted panels in the community. The clinician specialist requirement is only applicable to the expanded respiratory and gastrointestinal panels and does not apply to smaller targeted panels (i.e., for Influenza A/B, RSV, and SARS-CoV-2).

Second, the LCD and accompanying billing and coding article (LCA) provide information and instructions regarding exceptions of the physician specialist requirement for patients in geographic areas that do not have reasonable access to certain physician specialists.

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.”

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 (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 –

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
• 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.

The following comment was submitted to CGS:

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 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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to CGS:

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 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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to Palmetto GBA, CGS, WPS, and Noridian:

BioFire Diagnostics, LLC would like to take this opportunity to participate in the comment period for the proposed LCD titled “MolDX: Multiplex Nucleic Acid Amplification Test (NAAT) Panels for Infectious Disease Testing” and billing article titled “Draft Local Coverage Article: Billing and Coding: MolDX: 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.

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 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

Thank you for your thoughtful comments and support of this policy.

We have addressed your comments in Response 1 listed above. Additionally, regarding your comment about Bloodstream Panels, we agree and have modified the wording for availability of antimicrobial stewardship from same-day to within 24 hours.

The following comment was submitted to Palmetto GBA, CGS, WPS, and Noridian:

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 review and comment on the proposed policy for MolDX: Multiplex Nucleic Acid Amplification Test (NAAT) Panels for Infectious Disease Testing.

The AMP is an international medical and professional association representing approximately 2,500 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 professionals from academic medicine, hospital-based and private clinical laboratories, the government, and the in vitro diagnostics industry.

The AGA is the trusted voice of the GI community. Founded in 1897, the AGA has grown to more than 16,000 members from around the globe who are involved in all aspects of the science, practice, and advancement of gastroenterology.

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 public by fostering and advocating excellence in the practice of pathology and laboratory medicine worldwide.

We are submitting joint comments because currently our organizations share the same position regarding 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. We believe thoughtful consideration was given to the published literature and appreciate that you sought 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 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 recommendations into the final coverage policy.

General Coverage Criteria

1. “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).”

Recommendation: The proposed LCD offers no definition of, or specific examples for, an underlying condition or immunocompromised patient. We fear that this will create coding issues leading to improper reimbursement and/or unwarranted denial of coverage. It is also necessary for providers to understand how 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 taking immunosuppressive drugs (e.g., corticosteroids); and those with inherited diseases that affect the immune system (e.g., congenital IgA deficiency).

Non-Coverage Criteria

1. “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.”

Recommendation: There are circumstances where repeat testing is warranted, such as if you were sampling too early or if sampling another body might be helpful as the disease progresses (e.g., lower respiratory tract when upper respiratory tract has become negative). It should only be considered a duplicate if it is a 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 a negative result or a clinically insignificant finding.”

Specific Panel Coverage Criteria

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., 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.”

Recommendation: We believe that limiting ordering to the two named specialties will be problematic and produce substandard patient outcomes. We believe that a worrisome assumption is being made that there will be subspeciality experts at all points of care. This is not the case, especially in rural areas where critical care or other health specialists are not available. This requirement presents serious problems with access to care and patient safety.

In many cases, the patient’s infectious disease physician is not directly involved in the outpatient encounter. Requiring an infectious disease consultation, in the outpatient setting, will only add to the costs 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 contribution of infectious disease or pulmonary specialist.” This language should also be added for the section on immunocompromised patients.

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 in the evaluation of pneumonia from lower respiratory tract specimens (i.e., bronchoalveolar lavage samples (BALs)).”

Recommendation: We believe that this language will negatively affect pediatric patients. In this patient population an upper respiratory panel is performed each time a respiratory disease or pneumonia is 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, there should be an exception added for pediatric and adult Medicaid patients. If the upper respiratory is negative or non-diagnostic, then the lower respiratory should be covered.

3. “Gastrointestinal (GI) Panels: 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.”

Recommendation: We believe that limiting ordering to the two named specialties will be problematic and 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 consultations, in the outpatient setting, will only add time and cost to the visit and delay test results. We recommend that the following language be added after “Testing is ordered by a clinician specialist in Infectious Diseases or Gastroenterology”: “or a healthcare guideline or algorithm with contribution of infectious disease or gastrointestinal specialist.” This language should also be added for the section on immunocompromised patients.

4.  “Gastrointestinal (GI) Panels: The patient is 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. The patient’s clinical indication for GI panel testing is diarrhea, and ALL the following apply: The diarrheal illness MUST be acute or persistent with signs or risk factors for severe disease (fever, bloody diarrhea, dysentery, dehydration, severe abdominal pain that may warrant hospitalization) AND/OR not resolving after 7 days, AND the patient has NOT taken laxatives within 24 hours of the test.”

Recommendation #1: We believe that these criteria would hinder the ability of physicians to conduct vital public health 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.”

Recommendation #2: We request that the policy specify what constitutes an instance of severe dehydration. Specifically, we ask that the difference between mild, moderate, and severe dehydration, and what is enough to qualify as “severe disease” be specified.

Recommendation #3: We believe that the requirement stating that a patient must not have used laxatives within 24 hours of the test, is overly restrictive. Patients who utilize laxatives are still capable of contracting an infection, regardless of 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 recommend striking this language.

Recommendation #4: We believe that it is unnecessary to wait for seven days to identify a massive outbreak and instead the language should state “or not resolving after 7 days” instead of “and/or.”

5. “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 1 or 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.”

Recommendation #1: We ask that clarification be made as to what other indications, outside of epidemiologic indication, would qualify as a covered clinical indication.

Recommendation #2: We ask that clarification be made as to what qualifies as a “small, targeted panel.” Specifically, we would like to inquire as to whether this would cover a bacterial vaginosis (BV) panel; given this represents one of the highest reasons for number of office visits.

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, 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).”

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 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 indicators.”

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 patient’s blood AND the patient is being managed in an appropriate critical care facility, AND personnel (i.e., an antimicrobial stewardship team) are equipped for rapid (same day) tailoring of antimicrobial therapy as a result of rapid testing.”

Recommendation #1: We believe that the coverage requirement mandating a positive Gram stain does not 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 diagnosis. We suggest that this coverage indication be reviewed for the general patient populations and all coverage requirements be waived for immunocompromised patients.

Recommendation #2: We would ask for the removal of the coverage requirement for a patient to be 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 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 identification”.

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.

8. “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) OR is seen in urogynecology or urology specialty care settings.”

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 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

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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

Additionally -

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 examples of such conditions to the policy.

Regarding the comment relevant to the Non-Coverage Criteria, we have determined that the sample type will not be included. Though we recognize there are circumstances where repeat testing is warranted, this is already allowed (regardless of sample type) as per the current language in the policy, in specific circumstances.

Regarding comments relevant to the Specific Panel Coverage Criteria -

 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.

2. PNP and expanded RP tests – this policy covers Medicare beneficiaries and is not applicable to general pediatrics. Moreover, for clarity, we have added the following statement to the policy: 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.

Finally, as already mentioned, if the upper respiratory is negative or non-diagnostic, then a lower respiratory panel may be covered under this policy IF all other coverage criteria are met.

3. Gastrointestinal (GI) Panels:

Recommendation #1: We believe that these criteria would hinder the ability of physicians to conduct vital public health 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.”

Palmetto response: While we recognize the importance of public health surveillance, this policy’s focus is not on public health surveillance but rather on testing that is reasonable and necessary (R&N) for the diagnosis or treatment of an illness or injury for an individual beneficiary. Note also that the policy does allow expanded panel testing in patients with acute or persistent diarrhea, even without the listed signs or risk factors for severe disease IF the diarrhea has not resolved after 7 days (in a patient who had also not taken laxatives). Therefore, even diarrhea that may be of significance for public health may be detected while also fulfilling the R&N patient criteria listed in the policy.

Recommendation #2: We request that the policy specify what constitutes an instance of severe dehydration. Specifically, we ask that the difference between mild, moderate, and severe dehydration, and what is enough to qualify as “severe disease” be specified.

Palmetto response: The following signs of severe disease (fever, bloody diarrhea, dysentery, dehydration, severe abdominal pain) that may warrant hospitalization are specifically outlined in the policy. For example, dehydration requiring intravenous fluid repletion constitutes severe disease. There is no distinction in the policy between mild and moderate disease.

Recommendation #3: We believe that the requirement stating that a patient must not have used laxatives within 24 hours of the test, is overly restrictive. Patients who utilize laxatives are still capable of contracting an infection, regardless of 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 recommend striking this language.

Palmetto response: While it is true that patients taking laxatives can also contract gastrointestinal infections, laboratories often emphasize laxative use as a contraindication to C. difficile testing, as it can confound the diagnosis of C. 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 whose diarrheal illness is not resolving after 7 days. It does not apply to a patient with signs of severe disease (fever, bloody diarrhea, dysentery, dehydration, severe abdominal pain) that may warrant hospitalization regardless of the prior use of laxatives.

Recommendation #4: We believe that it is unnecessary to wait for seven days to identify a massive outbreak and instead the language should state “or not resolving after 7 days” instead of “and/or.”

Palmetto response: Please see the response to Recommendation #1 above. Additionally, 'and/or' suggests that 'OR' is a valid alternative.

 4. Urogenital/Anogenital (UG/AG) Panels:

Recommendation #1: We ask that clarification be made as to what other indications, outside of epidemiologic indication, would qualify as a covered clinical indication.

Palmetto response: Covered clinical indications in the absence of clinical symptoms include an 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). Otherwise, the presence of clinical symptoms is required for testing.

Recommendation #2: We ask that clarification be made as to what qualifies as a “small, targeted panel.” Specifically, we would like to inquire as to whether this would cover a bacterial vaginosis (BV) panel; given this represents one of the highest reasons for number of office visits.

Palmetto response: a “small, targeted panel” is defined in the policy is a panel with ≤5 pathogens. This is a uniform definition applicable to any of the panels outlined in the policy.

Regarding infectious vaginosis/vaginitis panels, see also the Response 1 listed above.

5. Meningoencephalitis (ME) Panels:

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 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 indicators.”

Palmetto response: We are aware that immunocompromised patients may not present with >1 of the findings mentioned; for that reason, the policy states: For immune-compromised patients, at least 1 of these indicators is required. As stated above, this policy covers Medicare beneficiaries and is not generally applicable to pediatrics.

6. Bloodstream Infection (BSI) Panels

Recommendation #1: We believe that the coverage requirement mandating a positive Gram stain does not 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 diagnosis. We suggest that this coverage indication be reviewed for the general patient populations and all coverage requirements be waived for immunocompromised patients.

Palmetto response: A Gram stain remains a standard-of-care method and must be performed in the diagnosis of bloodstream infections (BSI); moreover, it is a stat procedure when performed from blood culture bottles which means the result of the stain is available nearly immediately. Therefore, the expectation that the Gram stain is performed reflects the reality of appropriate laboratory practice. The Gram stain also sets the stage for whatever may be found on a bloodstream pathogen panel test. For example, panel tests do not encompass all possible organisms; moreover, polymicrobial 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 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 panel, thereby not delaying the additional testing and the administration of empirical antibiotics. As blood culture is also a current gold standard in the diagnosis of BSI, the policy also requires that this is also performed in parallel on all patients receiving the panel test.

Recommendation #2: We would ask for the removal of the coverage requirement for a patient to be 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 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 identification”.

Palmetto response: This contractor expects that critically ill patients will be tested and managed in the appropriate critical care facility. Moreover, for cancer patients, the latest ASCO/IDSA guidelines state the following: “Patients should also be evaluated for admission to the hospital if any of the following occur: …. blood cultures drawn on presentation 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 the policy indicating that the emergency room is included as an appropriate location for BSI panel testing, as follows “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).’ We have also modified the following statement, to accommodate the risk of impending serious or critical illness: “The patient is seriously or critically ill or at imminent risk of becoming seriously or critically ill.”

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.

Palmetto response: Gram stain and culture are long-standing available tests for the evaluation of BSI. A rapid molecular test for BSI will only be covered in facilities prepared to manage the patient quickly based on the return of a rapid result; otherwise, the rapid molecular test is not considered reasonable and necessary. This has been established in multiple studies showing that a rapid result requires rapid intervention in order to be clinically useful. We therefore stand by this 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.

7. Urinary Tract Infection (UTI) Panels

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 contribution of urogynecology or urology specialist.”

Palmetto response: The policy, as written, allows for high-risk symptomatic patients to be tested outside of the requirement for urology/urogynecology specialty care. As mismanagement of asymptomatic bacteriuria (ASB) is common, patients that are not symptomatic should be evaluated by a specialist before determining the need for testing.

8. 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

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

Palmetto response: We agree and have added the relevant ICD-10 codes to the LCA.

The following comment was submitted to Palmetto GBA, CGS, WPS, and Noridian:

Luminex appreciates the opportunity to comment on the MolDX proposed LCD, for multiplex nucleic acid 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 (specifically, targeted and expanded panels) and the clinically actionable results they provide. Luminex encourages MolDX to expand coverage for targeted and expanded respiratory and gastrointestinal panels and remove provider ordering restrictions.

Luminex manufactures multiple FDA-cleared solutions for identifying infectious diseases, including both targeted and expanded panels. For respiratory testing, Luminex offers IVD solutions such as the 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 xTAG^® Gastrointestinal Pathogen Panel (GPP) and the VERIGENE^® Enteric Pathogens Test (EP).

Timely testing and reporting are critical to ensuring the most informed, appropriate, and cost-effective 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 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.

Luminex appreciates the opportunity to comment on this proposed LCD.

References were provided for review.

Thank you for your thoughtful comments and support of this policy.

We have addressed your comments in Response 1 listed above. Additionally-

Regarding Gastrointestinal (GI) Panels – First, we agree that physicians may not always order the tests that will yield the identification of the illness-causing pathogen(s). However, as syndromic panel tests are comprised of multiple pathogens, this policy allows for physician judgment to order the panel most suitable for the patient’s illness. This is different than 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 illness is not resolving after 7 days. The policy is therefore aligned with the clinical guidelines (CAP and IDSA) that recommend GI panels for patients with symptoms lasting longer than seven days.

Regarding Diagnostic Stewardship – CMS requires testing that is Reasonable and Necessary (R&N) for a beneficiary. The 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 enable laboratories to offer clinically appropriate testing for pathogens, including those that fluctuate seasonally.

The following comment was submitted to Palmetto GBA, CGS, WPS, and Noridian:

LabCorp appreciates the opportunity to comment on MolDX Draft LCD and companion Draft Article.

1. Comment regarding Bloodstream Infection Panels: The CPT code referenced in the draft article (87801) is not specific to BSI panels. This CPT code represents a non-specified amplified probe technique. Please address the following question: How will the contractor differentiate BSI panels from unrelated tests billed with CPT 87801 when processing claims?

2. Comment in reference to Urogenital/Anogenital Panels referenced under Group 5. The draft article includes a "Note: Only a single probe technique (direct OR amplified) should be used when submitting claims." The list of published Group 5 CPT codes includes a direct probe technique (87800) but does not include the amplified probe (87801). We request that CPT 87801 be added.

3. The draft policies appear to be inclusive of current and future NAAT PCR panel testing as indicated by, "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 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 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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above. Additionally –

1. It is not uncommon that multiple tests utilize the same CPT code. A test that is registered with MolDX also has test-specific Z-codes; therefore, this distinction can be made.
2. CPT 87801 has been added to Group 5 in draft article.
3. The addition of new panels to the accompanying article is predicated upon the test fulfilling all criteria outlined in 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.
4. As a matter of process, we cannot comment on the fate of other policies. However, our intent is not to have conflicting policies. We will follow our due process for publishing, revising, and retiring policies.
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 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 atypical clinical symptoms, an underlying immune-compromising condition alone - without any other clinical indication - is not a sufficient indication for testing according to the policy. The exception to this, as outlined in the policy, is when testing may be performed ONCE as part of a pre-transplant evaluation, regardless of the presence of symptoms. Finally, some of the pathogen-specific codes have not been added to Group 1, as they would be expected to be present on expanded panels and not on small targeted panels (i.e., human metapneumovirus pneumonia).

The following comment was submitted to CGS and Noridian:

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 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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to CGS:

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?”

Thank you for your thoughtful comment and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to Palmetto GBA, WPS, and Noridian:

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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to Palmetto GBA and Noridian:

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 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 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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to Palmetto GBA and WPS:

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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to WPS:

We at Beatrice Community Hospital and Health Center would like to take this opportunity to comment on 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

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to WPS:

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 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 for Infectious Disease Testing. Our comments are listed below for your consideration.

1) Our first question relates to the policy title beginning with MolDX and are trying to understand how Medicare categorizes tests as MolDX. When we look in the Molecular Diagnostic Program Manual on the 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, will these infectious disease panels be required to be registered with the Palmetto MolDX program?

2) We are concerned about the significant complexity of this coverage policy and the administrative burden 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 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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above. Additionally -

1. Regarding the administrative burden on the laboratories –

Laboratories are expected to be leaders in diagnostic stewardship. As such, expansive panel testing is something about which laboratory leadership is expected to maintain a close watch, even in the absence of a policy such as this.

2. Regarding the availability of alternative FDA-cleared single­pathogen and smaller targeted tests for pathogens on commercially available respiratory panels –

There must be a clinical indication for testing and, as discussed in this policy, for many respiratory viral pathogens this is 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 testing.

The following comment was submitted to Palmetto GBA:

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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to Palmetto:

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 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.

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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to Palmetto GBA:

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.

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 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:

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.

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 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 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 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 pathogens (an expanded panel) is run.

Thank you for your consideration of these comments.

References were provided for review.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

Additionally-

Regarding the response to the public health events of 2020, Palmetto followed its existing policies. Your comments do not seem to apply to this contractor.

The following comment was submitted to Palmetto GBA:

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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to Palmetto GBA:

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.

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 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.

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

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.

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.

  Thank you for consideration of these comments.

Redline drafts of the Policy and Billing and Coding Article were provided for review.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to Palmetto GBA:

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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.

The following comment was submitted to Palmetto GBA:

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.

Thank you for your thoughtful comments and support of this policy. We have addressed your comments in Response 1 listed above.