Clinical Policy: Gastrointestinal Pathogen Nucleic Acid Detection Panel Testing

Reference Number: CP.MP.209
Date of Last Revision: 03/24
Coding Implications
Revision Log

See Important Reminder at the end of this policy for important regulatory and legal information.

Description

Multiplex molecular panels are used for the qualitative detection of nucleic acid from multiple viral, parasitic, and bacterial pathogens that cause a variety of illnesses, including infectious gastroenteritis and infectious colitis.¹ The Food and Drug Administration (FDA) have cleared several panels for diagnosis of gastrointestinal infections. This policy addresses the medical necessity criteria for Gastrointestinal Pathogen Nucleic Acid Detection Panel Testing.

Note: For criteria applicable to Medicare plans, please see MC.CP.MP.209 Gastrointestinal Pathogen Nucleic Acid Detection Panel Testing.

Policy/Criteria

I. It is the policy of non-Medicare health plans affiliated with Centene Corporation® that gastrointestinal pathogen panel testing of five or fewer targets is considered medically necessary when meeting all of the following:
A. The member/enrollee has one of the following clinical indications for infectious disease testing:

1. The member/enrollee is immunocompetent, and 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. Note: 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);
2. The member/enrollee is immunocompromised (i.e., those with weakened immune systems including those with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), patients who are taking immunosuppressive medications (i.e., chemotherapy, biologics, transplant-related immunosuppressive drugs, high-dose systemic corticosteroids) and those with inherited diseases that affect the immune system (i.e., congenital immunoglobulin deficiencies). Note: atypical clinical presentations of disease are considered appropriate indications for testing. In this population, testing may be performed once as part of a pre-transplant evaluation, regardless of the presence of symptoms;
   B. The results of testing will impact clinical management in a manner already demonstrated in the peer-reviewed published literature to improve patient outcomes;
   C. Testing is performed according to the intended use of the test in the intended population for which the test was developed and validated;
   D. Targeted testing is not appropriate (i.e., will not provide sufficient information for appropriate clinical management);

CLINICAL POLICY

Gastrointestinal Pathogen Nucleic Acid Detection Panel Testing

E. 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;
F. The registered 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 polymerase chain reaction [PCR]) for the majority of targets included on the panel;
G. Documentation of the following is clearly stated in the medical record:

1. Specific clinical indications for testing (i.e., clinical suspicion of a pathogen as the cause of the patient’s condition);
2. Specific reasons for performing panel testing;
3. Provider type/specialty and Place of Service.

II. It is the policy of non-Medicare health plans affiliated with Centene Corporation that expanded gastrointestinal pathogen panel testing of greater than five targets is considered medically necessary when meeting the following:
A. The criteria in section I are met, and one of the following:

1. The member/enrollee is immunocompromised, as defined in section I.A.2.;
2. The member/enrollee is immunocompetent and any of the following:
   a. Testing is ordered for a patient with severe and established underlying gastrointestinal (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 clinical management;
   b. The member/enrollee is seriously or critically ill or at imminent risk of becoming seriously or critically ill as a result of a presumed GI infection and the patient is being treated in an appropriate critical care facility;
   c. The clinical indication for GI panel testing is diarrhea, and any of the following:
   i. The diarrheal illness is acute or persistent with signs or risk factors for severe disease (i.e., fever, bloody diarrhea, dysentery, dehydration, severe abdominal pain) that may warrant hospitalization;
   ii. The diarrheal illness has not resolved after seven days and the member/enrollee has not taken laxatives within 24 hours of the test.

Background

Infectious gastroenteritis is a significant global health concern characterized by diarrhea, vomiting, and other symptoms, and can lead to life-threatening dehydration in severe cases. Causes include infections with bacteria (e.g., Clostridium difficile, Escherichia coli, Shigella), viruses (e.g., norovirus, rotavirus), or parasites (e.g., Cryptosporidium, Giardia).²

Nucleic acid amplification testing (NAAT) uses a microorganism’s DNA or RNA to directly identify specific bacteria, viruses, and/or protozoa rather than standard microorganism detection techniques (e.g., bacterial culture, individual real-time PCR, immunoassays, and/or microscopy). Multiplex NAAT tests are included in the larger grouping of culture-independent diagnostic tests (CIDT). Multipathogen NAATs can simultaneously detect viral, parasitic, and bacterial agents, including some pathogens that previously could not be easily detected in the clinical setting such as norovirus, and enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), and enteroaggregative E. coli (EAEC), in less time than traditional methods.

Multipathogen NAAT is associated with high clinical validity for the majority of available pathogenic targets relative to conventional testing and has a more rapid turnaround time compared with most types of conventional testing.² Drawbacks of molecular technologies include the need to predefine the particular microbes sought, detection of microbes at non-pathogenic levels, and increased detection of mixed infections; the relative importance of each pathogen identified may be unclear.³

CIDT are touted as providing a more comprehensive assessment of disease etiology by increasing the diagnostic yield compared with conventional diagnostic tests, permitting earlier initiation of appropriate therapeutic agents targeted to the detected pathogen(s), if any, rather than empirical therapy until culture results are available. The short time to results could reduce inappropriate use of antimicrobial agents to treat infections that do not require antimicrobial therapy and could shorten the time to targeted management and isolation measures for certain infections (e.g., STEC O157).⁴

Individuals who are immunocompromised are more likely to experience severe or prolonged illness. Diarrhea in immunocompromised patients may involve a broad spectrum of potential causes, including bacterial, viral, parasitic, and fungal pathogens depending on underlying immune status.⁴

Infectious Diseases Society of America⁴

• Culture-independent, including panel-based multiplex molecular diagnostics from stool and blood specimens, and, when indicated, culture-dependent diagnostic testing should be performed when there is a clinical suspicion of enteric fever or diarrhea with bacteremia.
• A broad differential diagnosis is recommended in immunocompromised people with diarrhea, especially those with moderate and severe primary or secondary immune deficiencies, for evaluation of stool specimens by culture, viral studies, and examination for parasites (strong, moderate). People with acquired immune deficiency syndrome (AIDS) with persistent diarrhea should undergo additional testing for other organisms including, but not limited to, Cryptosporidium, Cyclospora, Cystoisospora, microsporidia, Mycobacterium avium complex, and cytomegalovirus.
• Clinical consideration should be a part of interpreting results of multiple-pathogen nucleic acid amplification tests because these assays are DNA based and detect both viable and nonviable organisms.

American College of Gastroenterology³

• Stool diagnostic studies may be used if available in cases of dysentery, moderate-to-severe disease, and symptoms lasting less than seven days to clarify the etiology of the patient’s illness and enable specific directed therapy.
• Traditional methods of diagnosis (bacterial culture, microscopy with and without special stains and immunofluorescence, and antigen testing) fail to reveal the etiology of the majority of cases of acute diarrheal infection. If available, the use of Food and Drug Administration-approved culture-independent methods of diagnosis can be recommended at least as an adjunct to traditional methods.

Coding Implications

This clinical policy references Current Procedural Terminology (CPT®). CPT® is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2023, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.

Table 1: CPT codes that support medical necessity in any place of service and with any diagnosis

Table 2: CPT codes that support medical necessity when billed with place of service code in Table 3 or a diagnosis code from both Table 4 and Table 5

Table 3: Place of service codes supporting medical necessity for codes in Table 2

Table 4: ICD-10 diagnosis codes that support medical necessity for a CPT code in Table 2 when also billed with an ICD-10 diagnosis code in Table 5

Table 5: ICD-10 diagnosis codes that support medical necessity for a CPT code in Table 2 when also billed with an ICD-10 diagnosis code in Table 4

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CLINICAL POLICY
Gastrointestinal Pathogen Nucleic Acid Detection Panel Testing

Important Reminder
This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures.

This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time.

This clinical policy does not constitute medical advice, medical treatment or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members/enrollees. This clinical policy is not intended to recommend treatment for members/enrollees. Members/enrollees should consult with their treating physician in connection with diagnosis and treatment decisions.

Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over to whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members/enrollees and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members/enrollees and their representatives agree to be bound by such terms and conditions by providing services to members/enrollees and/or submitting claims for payment for such services.

Note: For Medicaid members/enrollees, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.

Note: For Medicare members/enrollees, to ensure consistency with the Medicare National Coverage Determinations (NCD) and Local Coverage Determinations (LCD), all applicable NCDs, LCDs, and Medicare Coverage Articles should be reviewed prior to applying the criteria set forth in this clinical policy. Refer to the CMS website at http://www.cms.gov for additional information.

©2018 Centene Corporation. All rights reserved. All materials are exclusively owned by Centene Corporation and are protected by United States copyright law and international copyright law. No part of this publication may be reproduced, copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise published without the prior written permission of Centene Corporation. You may not alter or remove any trademark, copyright or other notice contained herein. Centene® and Centene Corporation® are registered trademarks exclusively owned by Centene Corporation.

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