Subject:
Molecular Gastrointestinal Pathogen Panel (GIPP) Testing
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Tests performed by nucleic acid amplified probe techniques (NAAT) uses a microorganism's DNA or RNA to directly identify specific bacteria, viruses, and/or protozoa rather than standard microorganism detection techniques such as bacterial culture, microscopy with and without stains, direct fluorescent antibody testing, rapid antigen testing, qualitative and quantitative immunoassay for identification of antigens or toxins from stool and single-plex PCR assays. Multiplex NAAT tests are included in the larger grouping of culture-independent diagnostic tests (CIDT). CIDT includes but is not limited to simplex direct probe and amplified probe techniques.
• This technology offers results in a matter of hours, rather than 2-3 days of time- consuming and labor intensive bacterial cultures and immunoassays for processing stool specimens. 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.
• However, above and beyond microorganism detection, this type of testing does not provide the culture isolates that are needed for antimicrobial susceptibility testing, serotyping, subtyping and whole genome sequencing that are critical for monitoring trends, detecting clusters of illness and investigating outbreaks.1
Test information
• In addition to CLIA-regulated laboratory developed tests (LDTs) by specialty (e.g. academic) laboratories, several commercial GIPP assays are currently available. For example, Binnicker has evaluated three FDA-cleared GIPP assays,2 and all are closed system tests that do not allow random access for physician's to select likely etiologic agents of diarrhea.
• Please note that the NAAT results of GIPP assays can be inconclusive and non-specific, such as the inability to always distinguish pathogenic from non-pathogenic organisms.3
Related Policies
- Identification of Microorganisms Using Nucleic Acid Probes (Policy #074 in the Pathology Section)
Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
1. Molecular gastrointestinal pathogen panel (GIPP) testing is considered medically necessary for any of the following clinical indications:
a. Individuals with acute diarrhea with moderate-to-severe symptoms (such as fever, dysentery, severe dehydration).
b. Individuals with community-acquired diarrhea that persists for more than seven days, or individuals with travel-associated diarrhea of uncertain etiology.
c. Immunocompromised individuals with acute diarrhea.
(NOTE: Immunocompromise may support the use of a relatively large number of testing targets, in concert with other supporting clinical documentation in the medical record.)
2. Molecular GIPP testing is limited to the minimum number of targets needed for therapeutic decision making. When ordering any configuration of infectious disease targets, whether using GIPP or conventional culture, the medical record should clearly indicate the differential diagnosis of possible microorganisms based upon patient history and presenting signs/symptoms.
3. Molecular GIPP testing with any number of targets is not considered medically necessary for all other indications, including but not limited to the following:
a. Immunocompetent individuals with mild diarrhea, particularly of < 7 days' duration.
b. Individuals in whom the clinical presentation of acute diarrhea suggests a specific infectious etiology, unless first-line laboratory testing should fail to detect the suspected organism, and there is still a high clinical suspicion of infectious etiology.
Medicare Coverage:
Effective December 30, 2019, GIP panels utilizing NAATs are covered for the evaluation of individuals with any the following:
1. Acute or persistent diarrhea of at least 7 days duration; or
2. Acute or persistent diarrhea with signs or risk factors for severe disease (fever, bloody diarrhea, dysentery, dehydration, severe abdominal pain, hospitalization or immunocompromised state); or
3. Paralytic ileus with either persistent abdominal pain with fever or nausea and vomiting lasting 24 hours or less.
GIP PANELS UTILIZING MULTIPLEX NAATS ARE NONCOVERED FOR THE FOLLOWING:
1. To test for clearance of pathogen (i.e, “test of cure”).
2. Asymptomatic individuals.
3. Repeat NAAT testing within 7 days during the same episode of diarrhea will be denied (any combination of CPT codes 87505, 87506, 87507 or 0097U) when initial test result is negative.
4. Performance of more than one GIP panel (CPT code 87505, 87506, 87507 or 0097U) on the same date of service by the same or different provider.
For additional information and eligibility, refer to FUTURE Local Coverage Determination (LCD): Gastrointestinal Pathogen (GIP) Panels Utilizing Multiplex Nucleic Acid Amplification Techniques (NAATs) (L38229) and FUTURE Local Coverage Article: Billing and Coding: Gastrointestinal Pathogen (GIP) Panels Utilizing Multiplex Nucleic Acid Amplification Techniques (NAATs) (A56642). Effective 12/30/19. Available at: Available to be accessed at Novitas Solutions, Inc., Medical Policy Search page: https://www.novitas-solutions.com/webcenter/portal/MedicareJL/pagebyid?contentId=00024370.
[INFORMATIONAL NOTE:
Guidelines and evidence
• American College of Gastroenterology 2016 Clinical Guidelines4 include two relevant sections pertaining to GIPP:
o "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. (Strong recommendation, low level of evidence)."
o "The new diagnostics' best applicability is for the clinician in practice, seeing one patient at a time rather than in the public health setting, e.g., in outbreak investigations. One potential drawback of molecular technologies is the need to predefine the particular microbes being sought. In addition the significance of an identified organism may not be clear as these molecular technologies, which involve nucleic acid amplification, are limited to our existing knowledge of a microbes' genome and do not discriminate between viable and non-viable organisms. As a result they can detect microbes at non-pathogenic levels. Given the high rates of asymptomatic carriage of enteropathogens, this can be a considerable problem. To confound matters, further multiplex techniques are more commonly associated with increased detection of mixed infections and the relative importance of each pathogen may be unclear."
• Infectious Diseases Society of America 2017 Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea5 make the following recommendations:
o "A broad differential diagnosis is recommended in immunocompromised people with diarrhea, especially those with moderate and severe primary or secondary immune deficiencies. Some experts have proposed that these assays may be particularly well suited for making an organism-specific diagnosis in immunocompromised patients."
o "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 (strong, moderate)."
o "Multipathogen nucleic acid amplification tests 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. 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 such as STEC O157. With these assays, it is common to detect the presence of >1 pathogen that may differ with regard to clinical management."
o "Even a positive result for 1 pathogen should be interpreted in the context of the patient's clinical presentation, because less is known about the clinical significance of tests that detect nucleic acid as compared with traditional assays that generally detect viable organisms. The importance of detection of multiple pathogens in the same specimen is often unclear; it is unknown if all pathogens detected in the specimen are clinically relevant or if one is more strongly associated with the illness."
• Acute diarrhea, often called gastroenteritis, can be defined as the passage of a greater number of stools of decreased form from the normal lasting < 14 days.
Acute diarrhea is generally associated with clinical features of nausea, vomiting, abdominal pain and cramps, bloating, flatulence, fever, passage of bloody stools, tenesmus and fecal urgency. It is the leading cause of outpatient visits, hospitalizations, and lost quality of life occurring domestically and those traveling abroad.
• Many episodes of acute diarrhea are self-limited and require fluid replacement and supportive care. Oral rehydration is indicated for patients who are mildly to moderately dehydrated. IV fluids may be required for more severe dehydration. Routine use of antidiarrheal agents is not recommended because many of these agents have potentially serious adverse effects, particularly in infants and young children. Antimicrobial therapy is typically warranted for adult and pediatric patients with immune systems which are severely weakened from medications, age and other primary/secondary immunocompromising illnesses/conditions.6-7
• Laboratory testing algorithms for infectious causes of diarrhea generally agree that testing is NOT warranted for community-acquired diarrhea of <7 days duration without signs or symptoms of severe (fever, bloody diarrhea, dysentery, severe abdominal pain, dehydration, hospitalization and immunocompromised state) disease. In general, when community-acquired diarrhea persists for >7 days, or the diarrhea is travel-related, or there are signs/symptoms of severe disease, GIPP testing may be warranted. Additional directed testing may be indicated if the GIPP results are negative and diarrhea persists. No additional testing is indicated for GIPP-positive result unless the clinical pictures changes. Clostridium difficile molecular testing is warranted on health-care associated diarrhea with onset after the 3rd inpatient day or after recent antibiotic use.
• Whereas a majority of microorganisms can be identified with up to 5 targets, typically including Salmonella, Campylobacter, Shigella, Cryptosporidium, and Shiga toxin producing E.coli, additional agents may be in the working differential diagnosis, such as (but not limited to) Clostridium difficile, additional E. coli variants, Yersinia enterocolitica, Vibrio parahaemolyticus, Giardia, Cryptosporidium, and viruses including norovius, rotavirus, and enteric adenoviruses.
• Salient illustrations8-10 of the literature have annotated a diverse set of offending infectious agents (bacterial, parasitic and viral) in patients presenting with acute diarrhea. However, it must be emphasized that such original study recruitment criteria were not designed to stratify probability/incidence distributions of causative organisms, according to more carefully specified patient presentation categories. Furthermore, the molecular predilection for mixed infectious agent identification is a confounding factor when clinicians are trying to pinpoint the precise etiology of acute diarrhea, given the dilemma between pathogenicity and non-pathogenicity, which was briefly cited above.
• As a result, when the patient history, clinical presentation and symptoms, etc. suggest a specific microbial etiology and/or therapy, a broad GIPP consisting of >5 infectious targets is not indicated. However, broader GIPP molecular panels (e.g. 6- 25 targets) might occasionally be indicated when a patient presents with a clinical scenario and overlapping symptoms consistent with multiple possible microbiological etiologies, where both diagnosis and treatment are particularly challenging (e.g., as noted above for immunocompromised patients).]
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Molecular Gastrointestinal Pathogen Panel (GIPP) Testing
Gastrointestinal Pathogen Panel Testing, Molecular
GIPP Testing, Molecular
References:
1. Blaschke AJ, Hersh AL, Beekmann SE, et al. Unmet diagnostic needs in infectious disease. Diagn Microbiol Infect Dis. 2015 Jan;81(1):57-9.
2. Binnicker, MJ. Multiplex molecular panels for diagnosis of gastrointestinal infection: performance, result interpretation, and cost-effectiveness. J Clin Microbiol. 2015 Aug; 53(12):3723-8.
3. Dupont HL. Persistent diarrhea: A clinical review. JAMA. 2016 Jun;315(24):2712- 23.
4. Riddle MS, DuPont HL Connor BA. ACG Clinical Guideline: Diagnosis, treatment and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016 Apr; 111:602-22.
5. Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis. 2017 December;65(12):e45-e80.
6. Montecino-Rodriguez E, Berent-Maoz B, Dorshkind, K. Causes, consequences, and reversal of immune system aging. J Clin Invest. 2013 Mar;123(3):958-65.
7. A garwal S, Mayer L. Diagnosis and Treatment of Gastrointestinal Disorders in Patients With Primary Immunodeficiency. Clin Gastroenterol Hepatol. 2013 Sep;11(9):1050-1063.
8. Svenungsson B, Lagergren A, Ekwall E, et al. Enteropathogens in adult patients with diarrhea and healthy control subjects: A 1-year prospective study in a Swedish clinic for infectious diseases. Clin Infect Dis. 2000 May;30:770-8.
9. Scallan E, Griffin PM, Angulo FJ, et al. Foodborne illness acquired in the United States- unspecified agents. Emerg Infect Dis. 2011 Jan;17(1):16-22.
10. Huang JY, Henao OL, Griffin PM, et al. Infection with pathogens transmitted commonly through food and the effect of increasing use of culture-independent diagnostic tests on surveillance - foodborne diseases active surveillance network, 10 US sites, 2012-2015. MMWR. 2016 Apr;65(14):369-71.
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HCPCS
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
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