Gene Expression Profiling for Noncancer Indications - Medicare Advantage Form

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Type Title ID Number Jurisdiction Medicare Administrative Contractors (MACs) Applicable States/Territories Gene Expression Profiling for Noncancer Indications Page: 2 of 7 LCD MolDX: Envisia™, Veracyte™, Idiopathic Pulmonary Fibrosis Diagnostic Test L37919 LCD Molecular Pathology Procedures L35000 LCD LCD LCD LCD MolDX: Envisia™, Veracyte™, Idiopathic Pulmonary Fibrosis Diagnostic Test MolDX: Envisia™, Veracyte™, Idiopathic Pulmonary Fibrosis Diagnostic Test MolDX: Envisia™, Veracyte™, Idiopathic Pulmonary Fibrosis Diagnostic Test MolDX: Envisia™, Veracyte™, Idiopathic Pulmonary Fibrosis Diagnostic Test L37905 L37887 L37891 L37857 LCD Molecular Pathology Procedures L34519 J5, J8 - Wisconsin Physicians Service Insurance Corporation J6, JK - National Government Services, Inc. J15 - CGS Administrators, LLC (Part A/B MAC) JE - Noridian Healthcare Solutions, LLC JF - Noridian Healthcare Solutions, LLC IA, IN, KS, MI, MO, NE
CT, IL, MA, ME, MN, NH, NY, RI, VT, WI KY, OH CA, HI, NV, American Samoa, Guam, Northern Mariana Islands AK, AZ, ID, MT, ND, OR, SD, UT, WA, WY JJ, JM - Palmetto GBA AL, GA, NC, SC, TN, VA, WV JN - First Coast Service Options, Inc. FL, PR, U.S. VI Description Gene expression profiling (GEP) is a laboratory test that measures the activity, or expression, of ribonucleic acid (RNA) of hundreds to thousands of genes at one time to give an overall picture of gene activity. GEP tests are typically performed on tumor tissue but may also be performed on other specimens such as blood. These tests often use microarray technology though other methodologies, such as next generation sequencing (NGS), whole transcriptome sequencing and reverse transcription polymerase chain reaction (RT-PCR), are also used. GEP tests are currently offered primarily for the management of cancer, most notably breast. However, the scope of testing has broadened to include evaluation of idiopathic pulmonary fibrosis. An example of this type of testing is Envisia Genomic Classifier. GEP tests differ from germline genetic tests. GEP tests analyze RNA which is dynamic, responds to cellular environmental signals, are not usually representative of an individual’s germline DNA and are not inheritable. Germline genetic testing analyzes an individual’s deoxyribonucleic acid (DNA) to detect genetic variants (mutations). Germline mutations are inherited, are constant throughout an individual’s lifetime and are identical in every cell of the body.
Coverage Determination

Gene Expression Profiling for Noncancer Indications Page: 3 of 7 Humana follows the CMS requirements that only allows coverage and payment for services that are reasonable and necessary for the diagnosis and treatment of illness or injury or to improve the functioning of a malformed body member except as specifically allowed by Medicare. Genetic tests must demonstrate clinical utility, analytical and clinical validity and fulfill the CMS “reasonable and necessary” criteria. Analytic validity (test accurately identifies the gene variant), clinical validity (test identifies or predicts the clinically defined disorder) and clinical utility (test measurably improves clinical outcomes) of the genetic test is supported by generally accepted standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, specialty society recommendations, and views of physicians practicing in relevant clinical areas. The test must be ordered by a physician who is treating the beneficiary and the results will be used in the management of a beneficiary’s specific medical problem. For jurisdictions with no Medicare guidance for a particular test, Humana will utilize the MolDX program and Technical Assessments for molecular assays as the standard to evaluate clinical utility, analytical and clinical validity in conjunction with adhering to Medicare’s reasonable and necessary requirement.
In interpreting or supplementing the criteria above and in order to determine medical necessity consistently, Humana may consider the following criteria: Envisia Genomic Classifier (81554) will be considered medically reasonable and necessary when the following requirements are met:1,2,3,4,5 • Individual to be tested has interstitial lung disease (ILD) and is suspected of having idiopathic pulmonary fibrosis (IPF); AND • Absence of a definitive occupational, environmental, medication-related or other cause of the individual’s lung disease; AND • Exclusion of autoimmune disease by clinical evaluation and serologic testing, including an evaluation by a rheumatologist when indicated; AND • High-resolution computed tomography (CT) scan of the chest (defined by high kernel approximately 1mm axial reconstructions, including both inspiratory and expiratory imaging) and shows one of the following: o A probable interstitial pneumonia (UIP) pattern as defined by the Diagnostic Categories of UIP Based on CT Patterns; OR o An indeterminate UIP pattern Diagnostic Categories of UIP Based on CT Patterns; AND • Is healthy enough to undergo a bronchoscopy with transbronchial biopsies The use of the criteria in this Medicare Advantage Medical Coverage Policy provides clinical benefits highly likely to outweigh any clinical harms. Services that do not meet the criteria above are not medically

necessary and thus do not provide a clinical benefit. Medically unnecessary services carry risks of adverse outcomes and may interfere with the pursuit of other treatments which have demonstrated efficacy.
Gene Expression Profiling for Noncancer Indications Page: 4 of 7 Coverage Limitations US Government Publishing Office. Electronic code of federal regulations: part 411 – 42 CFR § 411.15 - Particular services excluded from coverage The following tests may not be considered a benefit (statutory exclusion): • Tests considered screening in the absence of clinical signs and symptoms of disease that are not specifically identified by the law;11 OR • Tests that confirm a diagnosis or known information;11 OR • Tests to determine risk for developing a disease or condition;11 OR • Tests performed to measure the quality of a process;11 OR • Tests without diagnosis specific indications;11 OR • Tests identified as investigational by available literature and/or the literature supplied by the developer and are not a part of a clinical trial11 These treatments and services fall within the Medicare program’s statutory exclusion that prohibits payment for items and services that have not been demonstrated to be reasonable and necessary for the diagnosis and treatment of illness or injury (§1862(a)(1) of the Act). Other services/items fall within the Medicare program’s statutory exclusion at 1862(a)(12), which prohibits payment.
The following items will not be considered medically reasonable and necessary:
• Genetic tests that have not demonstrated clinical utility, analytical and clinical validity via the MolDX Program
A review of the current medical literature shows that the evidence is insufficient to determine that these services are standard medical treatments. There remains an absence of randomized, blinded clinical studies examining benefit and long-term clinical outcomes establishing the value of these services in clinical management.