Response to Comments: Respiratory Pathogen Panel Testing

A comment was received from a stakeholder in a pediatric setting that currently uses the BioFire respiratory panel. The stakeholder indicates that the panel allows for actionable answers in a clinically relevant timeframe and that the panel has reduced antibiotic use while identifying COVID-19 infections earlier. The stakeholder suggests that the panel allows other pathogens to be identified which allow appropriate patient management such as quarantining or not. The stakeholder also suggests that the panel decreases the chance of negative results in a symptomatic patient.

Thank you for your comment. Please note that this LCD pertains only to the Medicare population. Currently data of good quality for the clinical utility of multiplex respiratory pathogen testing is limited. The overall studies suggest that other than testing for influenza and the importance of identifying COVID-19, testing for multiple pathogens has not proven to impact clinical decision making resulting in improved patient outcomes in the outpatient setting. We welcome the submission of new literature as it becomes available using the LCD reconsideration process outlined on our website once the LCD becomes effective.

A comment was submitted from a physician working in fraud and abuse indicating that they were strongly supportive of the LCD, particularly the limit of 5 or fewer pathogens in the outpatient setting. The commenter suggested that the statement addressing viral pathogens in the history and background section could be misunderstood. It was recommended that the term "panel" be defined as all respiratory pathogens tested in the outpatient setting on a single date of service from a single biologic specimen, not ordered as a reflex test. Additionally, the commenter recommended making it clear if U.S. Food and Drug Administration (FDA) approval of a panel is required, but did not suggest that only FDA approved or cleared products be available for use.

Thank you for your comment, we appreciate your support. The related billing and coding article specifies that panel tests must not be unbundled and billed as individual components. We appreciate that currently many labs do not have FDA approval for their products but do fall under pathogen panel tests. https://www.fda.gov/. It is recognized that labs may not have FDA approval of their products, but do meet Clinical Laboratory Improvement Amendments (CLIA) regulations. The intent at this time is not to limit tests to FDA approved/cleared products only. LCDs are based on peer-reviewed published evidence. The language in the final LCD has been revised to provide further clarity.

Comments were submitted on behalf of an industry stakeholder pointing out that while the LCD focuses on Medicare Part B, the contractor information at the start of the LCD includes both Part A and Part B. The commenter requests that the final LCD only include the Part B contractor numbers to ensure clarity and avoid any unintended billing complications. Additionally, the commenter requested that a comment be added to the billing and coding article to indicate that the LCD is not applicable to providers submitting claims on an institutional claim form. The commenters also suggested that creating an upper limit on panel size of 5 pathogens is an arbitrary coverage decision and not supported by evidence citing the Medicare Program Integrity Manual, Chapter 13. The commenters have requested that the upper limit be removed. Clarification in the language to clarify the clinical scenarios for coverage was requested. The commenters agree that testing should provide actionable information to the clinician and they have suggested clarifying the first criterion to focus on management of the patient rather than timeliness. Further, the commenters suggest the language in the second criterion for coverage be changed to reflect that the clinician plans to guide management with the intent to improve outcomes based on the test results. Lastly, the commenters recommended providing some examples of circumstances in which respiratory testing may be considered medically reasonable and necessary.

Thank you for your comment, as noted by the language in the LCD, this LCD is only pertinent to Medicare Part B. Upon finalization of the LCD we will ensure that only the Part B contractor numbers display. Clarification will be added to the billing and coding article to make it clear that this LCD does not apply to Part A. Regarding the upper limit of pathogens, the overall studies suggest that other than testing for influenza and the importance of identifying COVID-19, testing for multiple pathogens has not proven to impact clinical decision making resulting in improved patient outcomes in the outpatient setting. The commenter provided no evidence to the contrary. Based on the studies we believe that testing for more than 5 pathogens in the outpatient setting would be rare and as such these rare situations should be handled through the redetermination process. We appreciate the recommended language clarification for the coverage criterions and have provided clarification consistent with the evidence and the goal of improved health outcomes in the Medicare population. We believe including examples of respiratory testing that would be considered medically reasonable and necessary are more a function of clinical guidelines and provider decision making in that specific circumstance, and if included could be interpreted as confusing or limiting. We believe clinicians are the best ones to judge when respiratory testing is needed in a given patient, based on current guidelines which are consistent with this evidence review.

A comment was submitted on behalf of an industry stakeholder recommending that places of service such as acute, subacute and chronic hospitalizations be included in the final LCD. The commenter also suggests that the target number limitations in the proposed LCD fail to consider differential diagnoses that occur in different medical settings such as the acute, subacute and chronic hospitalizations and fail to accommodate the need for antibiotic resistance gene testing as an important component of antibiotic stewardship programs in nursing homes.

Thank you for your comment. The proposed LCD is only applicable to outpatient settings. The indications and limitations outlined in the LCD are not applicable to inpatient settings or Part A settings. Furthermore, there is no evidence that this LCD conflicts with nursing home regulations.

Comments were submitted by a professional society representing laboratory testing professionals suggesting that the language in the first criterion that must be met for respiratory pathogen panel testing doesn't clearly ensure that the services provided are clinically useful. The commenters also indicated that in addition to improving health outcomes, the diagnostic and treatment values of respiratory pathoghen panel testing are very important. Therefore, the commenters recommend revising the second criterion to state "For patients for whom clinical management can result in an improved health outcome." Additionally, the commenters expressed concern that the proposed LCD's "blanket" approach to limiting the testing to five respiratory pathogens overlooks a vulnerable subset of patients. Specifically, immunocompromised patients and for recognizing co-infection in patients. Several articles were cited, but no full text articles were submitted with the comments. Taking this into consideration the commenters have requested that coverage of panels with more than five pathogens be covered when they are determined to be clinically warranted. Finally, the commenters submitted a list of ICD-10 codes that they would like to have added to the billing and coding article.

Thank you for your comments. The clinical evidence speaks to turn around time with results to the treating provider, not timely management. Therefore, the term timely results has been clarified to timely reporting to the provider. Based on the studies reviewed for this LCD we believe that testing for more than 5 pathogens in the outpatient setting would be rare and as such these rare situations should be handled through the redetermination process. The evidence review did examine all outpatient evidence including immunocomprised patients and the LCD analysis came to this conclusion: "In the immunocompromised, where concerns are great for poor outcomes, the data comes primarily from the inpatient setting. In the inpatient setting, results are inconsistent."^23,24 To further help clinical decision-making, Ramirez 2020 addresses initial treatment of the immunocompromised, as defined in the document, and recommends a low threshold for hospitalization, with the suggestion of a comprehensive individualized microbiological work-up. The document does not address outpatient microbiological studies. We encourage providers with any new literature that may support the use of more than 5 pathogens in the outpatient setting to submit the full-text literature via the reconsideration process outlined on our website once the LCD has become effective. Following review of the requested ICD-10 codes; J12.0, J12.3, Z03.818, and Z20.828 have been added to the billing and coding article. The requested unspecified diagnosis codes have not been added since providers should bill to the highest specificity and it is felt that the billing and coding article includes more specific diagnosis codes for these conditions. The transplant diagnosis codes and neutropenia/chemotherapy related diagnosis codes have not been added to the article because patients should have some other diagnosis represented by one of the included ICD-10 codes in the article to support the need for testing. Please note that J12.82, Z11.52, Z20.822 and Z86.16 are not valid ICD-10 codes for 2021.

A comment by a laboratory association stakeholder expressing concern about the limit of 5 or fewer respiratory pathogens for Part B patients, specifically for residents in skilled nursing facilities (SNFs). The commenter requested that the LCD be revised to allow testing for more than 5 respiratory pathogens in SNF residents. The commenter requests that "timely" be defined as from the time of the laboratory's sample receipt rather than the time of sample collection.

Thank you for your comments. Section 1833g(5)(A)iii of Title XVIII provides that "in case of a clinical diagnostic laboratory test provided under an arrangement (as defined in 1861(w)(l)) made by a hosptial, critical access hospital or skilled nursing facilty, payment shall be made to the hospital or skilled nursing facilty." We note that laboratory tests performed for the SNF's Medicare inpatients covered under Part A are included in the PPS SNF payment. No additional evidence was provided to consider skilled nursing facility patients as being different than either inpatients whereas not addressed by this LCD, or outpatients. The language in the final LCD regarding timely results has been clarified to be most consistent with the clinical evidence.

A comment on behalf of an industry stakeholder was submitted indicating that the proposed LCD does not cover common codes for COVID screening and evaluation. The stakeholder agrees that the panel tests are appropriately covered only when they are being performed for symptomatic patients in order to discriminate the type of infection. It was noted that the CARES Act provides for SARS-CoV-2 testing for the screening and evaluation services that are not included in the draft articles. The stakeholder's concern is that implementing the proposed LCD and draft Article in the current form would result in the need for an Advanced Beneficiary Notice (ABN) or non-coverage for laboratories electing to perform the test. Limited data has shown that most of the orders for CPT code 87636 are for screening indications that are not included in the article. During the public health emergency the stakeholder does not believe it is in the best interest of the public to have patients decline testing or to have laboratories not provide these essential services. Several options were offered for consideration in an effort to allow laboratories to provide and report appropriate services when ordered by providers using panel codes for conditions where only the SARS-CoV-2 component is medically necessary.

Thank you for your comment. As you have pointed out, panel tests are appropriately covered only when they are being performed for symptomatic patients in order to identify the type of infection. Codes for medical necessity of symptomatic patients are included in the related billing and coding article. Screening for COVID-19 is outside the scope of this LCD and this LCD does not limit COVID testing of asymptomatic patients, but does limit screening with panel testing by not including the Z code series as suggested by the industry stakeholder. The focus of the LCD and article is on respiratory pathogen panel testing and when it is considered medically reasonable and necessary. It is important that providers/suppliers order and report services that are medically reasonable and necessary and that services are not "unbundled". It is the responsibility of the provider to report the service that was actually rendered with the most appropriate CPT/HCPCS code. No changes will be made to the LCD or article at this time.

Comments were received from an industry stakeholder explaining the BioFire respiratory panel targets and usefullness and requesting that the panel be covered. The commenter indicated that a comprehensive panel has the potential to increase the likelihood of a definitive diagnosis which can influence appropriate medical management of a patient. It is felt that at least 9 pathogens are necessary to detect for public health and isolation protocols. Early and accurate diagnosis of SARS-CoV-2 is important for proper isolation, contact tracing and other measures to slow the spread of the virus. A negative result for SARS-CoV-2 in conjunction with a positive result for a less serious virus allows patients to avoid isolation and resume their essential activities. The commenter pointed out that the Centers for Medicare & Medicaid Services (CMS) has stated that testing for differential COVID-19 diagnoses should be a covered service. It was noted that the benefits of receiving a positive result for a respiratory pathogen include appropriate prescribing or withholding of antimicrobials, potential avoidance of follow-up tests due to a negative result, appropriate isolation or avoidance of isolation and physician and patient satisfaction that appropriate action was taken. The commenter maintains that statistically speaking the greater the number of targets included on a diagnostic panel the greater the likelihood of receiving a definitive diagnosis to guide therapy. Based on this, several associations have voiced their support for universal coverage of comprehensive respiratory panels and have petitioned this view to CMS. The comment went on to point out that the proposed LCD states “general consensus from the CAC panel is that there is accuracy and reliability in these respiratory pathogen panels and that the results of this testing may improve patient health outcomes” and this statement is at odds with a more limited coverage. A lengthy list of references was noted in the comment, but no full-text articles were submitted for review.

Thank you for the in depth comment. The overall studies suggest that other than testing for influenza and the importance of identifying COVID-19, testing for multiple pathogens has not proven to impact clinical decision making resulting in improved patient outcomes in the outpatient setting. We agree that CMS has advocated for coverage of COVID-19 testing, but we maintain that testing for multiple pathogens in the outpatient setting has not yet demonstrated an impact on clinical decision making. While the proposed LCD states “general consensus from the CAC panel is that there is accuracy and reliability in these respiratory pathogen panels and that the results of this testing may improve patient health outcomes,” it goes on to state "The CAC panel also noted that there is a gap in the literature when it comes to patient health outcomes related to the results and how it affects patient treatment and/or management especially with pathogens of lower prevalence that some of the respiratory pathogen panels include." We appreciate the list of references that was provided, however the majority of the references did not have any links and the full-text articles were not submitted with the comment. Of the references that did include links, it was determined that there was no new evidence in the form of clinical trials, guidelines etc. to support that multiple pathogen testing in the outpatient setting would impact clinical decision making resulting in improved patient outcomes. The reconsideration process as outlined on our website may be used to submit any new full-text articles/evidence once the LCD becomes effective.

A comment was submitted requesting clarification of the definition of "pathogen" as it is used in the proposed LCD. Specifically, the commenter is asking if "pathogen" refers to a single virus (i.e., influenza) or each strain of the virus that the panel tests for (i.e., Influenza A, Influenza A subtype H1 etc.). Several definitions of "pathogen" were provided in the comment, pointing out that all definitions refer to a single organism like a particular strain of a virus and not a group of collective strains. Based on this, the commenter has recommended the following language as a definition: "A pathogen refers to a single organism or strain of a virus or bacterium that can lead to a respiratory infection."

Thank you for your comment. We agree that the definition of pathogen is as you suggest, however we do not feel that it is necessary to provide clarification of pathogen since the Current Procedural Terminology (CPT) code description includes multiple types or subtypes.

A comment was submitted suggesting that a covered indication is needed for immunocompromised patients with less than or equal to 25 respiratory pathogens. The commenter indicated that immunocompromised, elderly and critically ill patients' complications from respiratory tract infections often occur with poor outcomes making it important to rapidly and accurately diagnose respiratory tract infections. It was noted that the symptoms of different viral respiratory tract infections are similar and do not help to distinguish the specific pathogen making it important for these immunocompromised patients to be tested for a battery of pathogens. Rapidly and accurately identifying specific viral pathogens allows for targeted therapy, timely institution of appropriate infection control measures, appropriate monitoring for secondary infections and minimizes empirical treatment for possible concerning alternative conditions. The commenter indicated that while there may only be a few FDA approved tests, there are several additional tests that all test for more than 5 pathogens that will soon be FDA approved which is why the number of pathogens tested should be increased to 25 for the immunocompromised patients. Suggested wording for the additional covered indication was provided. Four articles were submitted with the comment.

Thank you for your comment. The overall studies suggest that other than testing for influenza and the importance of identifying COVID-19, testing for multiple pathogens has not proven to impact clinical decision making resulting in improved patient outcomes in the outpatient setting. A full review of the articles submitted was conducted, with two of the articles previously reviewed. Babady 2018 is an industry funded study examining assay performance, not clinical outcomes of Medicare patients. Hammond is a study in patients with URI symptoms or patient surveillance. The authors note, "testing was performed retrospectively such that the results had no impact on clinical decision making." Murali 2009 notes, "Eventually, these improvements may lead to more effective management strategies and better outcomes." Sanghavi 2012 is a study in pediatric and adult patients, with 258 organ transplant recipient patients that includes routine surveillance, in hospitalized and outpatient settings. This study does not indicate that an actual change in patient management in an outpatient setting occurred. After review of the articles it was determined that the LCD will not be revised as suggested to include panels with less than or equal to 25 for immunocompromised patients. The literature did not support that the larger panels would impact clinical decision making resulting in improved patient outcomes in the outpatient setting. We note this policy does not impact Part A providers. The reconsideration process as outlined on our website may be used to submit any new full-text articles/evidence once the LCD becomes effective.

Comments were submitted in support of syndromic molecular respiratory pathogen panel tests (RPPT). The commenter noted that the impact of RPPTs continues to emerge, but there is ample literature to document the impact of pneumonia to healthcare costs, and improvements observed after rapid antimicrobial optimization. It is felt that the best technology for optimizing antimicrobial therapy of pneumonia, preventing progression of illness and reducing further healthcare costs is the use of RPPTs. The importance of pathogen surveillance is discussed. The commenter provided an in depth summary of several articles supporting the use of RPPTs. Many of the studies related to hospitalized patients and primarily focused on pneumonia. Additionally it was noted that in an outpatient setting, Flu/RSV (small panel) testing was implemented in outpatient clinic-based physician office laboratories throughout Pennsylvania. On-site testing reduced the collect-to-result time by 70% when compared to testing in a centralized core laboratory; over or under-treatment for influenza A and B (measured by antiviral prescription) was reduced by 15%. The commenter strongly endorses the use of RPPTs for hospitalized patients and for high-risk adult out-patients in the Medicare population, as well as all high-risk adult and pediatric populations. There was a comprehensive list of references cited in the comment. However, there were no full-text articles submitted for review.

Thank you for your comment. It should be noted that the proposed LCD is applicable to outpatient settings only. There are no limitations in the LCD specific to inpatients or any providers such as hospitals, critical access hospitals, or skilled nursing facilitites that bill under Part A. Patients with NV-HAP and VAP as discussed in the comment are assumed to be inpatients. Therefore, services to inpatients should be ordered and performed consistent with medically reasonable and necessary guidelines. The overall studies suggest that other than testing for influenza and the importance of identifying COVID-19, testing for multiple pathogens has not proven to impact clinical decision making resulting in improved patient outcomes in the outpatient setting. In the absence of any new evidence to support the use of multipanel testing in the outpatient setting there will not be any change made to the LCD. The reconsideration process as outlined on our website may be used to submit any new full-text articles/evidence once the LCD becomes effective. In addition, Medicare does not directly reimburse providers for pathogen surveillance.