Pharmacogenomics and Companion Diagnostics - Medicare Advantage Form

Please refer to CMS website for the most current applicable National Coverage Determination (NCD)/ Local Coverage Determination (LCD)/Local Coverage Article (LCA)/CMS Online Manual System/Transmittals.
Pharmacogenomics and Companion Diagnostics Page: 2 of 25 Title ID Number Jurisdiction Medicare Administrative Contractors (MACs) Applicable States/Territories Type NCD LCD
Next Generation Sequencing (NGS) 90.2 MolDX: Pharmacogenomics Testing L38435 LCD Molecular Pathology Procedures L35000 LCD
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MolDX: Pharmacogenomics Testing L38435 MolDX: Pharmacogenomics Testing L38394 MolDX: Pharmacogenomics Testing Billing and Coding: MolDX: Germline testing for use of PARP inhibitors MolDX: Pharmacogenomics Testing Billing and Coding: MolDX: Germline testing for use of PARP inhibitors Pharmacogenomics Testing Biomarkers for Oncology MolDX: Pharmacogenomics Testing L38335 A55294 L38335 A55294 L39063 L35396 L38294 Molecular Pathology Procedures L35000 Pharmacogenomics Testing L39063 Biomarkers for Oncology MolDX: Pharmacogenomics Testing L35396 L38294 J5 - Wisconsin Physicians Service Insurance Corporation J6 - National Government Services, Inc. (Part A/B MAC) J8 - Wisconsin Physicians Service Insurance Corporation J15 - CGS Administrators, LLC (Part A/B MAC) JE - Noridian Healthcare Solutions, LLC JF - Noridian Healthcare Solutions, LLC JH - Novitas Solutions, Inc. (Part A/B MAC) JJ - Palmetto GBA (Part A/B MAC) JK - National Government Services, Inc. (Part A/B MAC JL - Novitas Solutions, Inc. (Part A/B MAC) JM - Palmetto GBA (Part A/B MAC) IA, KS, MO, NE
IL, MN, WI IN, MI KY, OH CA, HI, NV, American Samoa, Guam, Northern Mariana Islands AK, AZ, ID, MT, ND, OR, SD, UT, WA, WY AR, CO, NM, OK, TX, LA, MS AL, GA, TN CT, NY, ME, MA, NH, RI, VT DE, D.C., MD, NJ, PA NC, SC, VA, WV

LCD
Pharmacogenomics Testing L39073 Pharmacogenomics and Companion Diagnostics Page: 3 of 25 JN - First Coast Service Options, Inc. (Part A/B MAC) FL, PR, U.S. VI Description Pharmacogenomics and companion diagnostics tests are laboratory studies that use an individual’s unique genetic makeup to help determine response to a specific medication. Companion diagnostics differ from pharmacogenomics testing because they are co-developed with a specific drug to help evaluate response or nonresponse to the drug. Companion diagnostics are often approved by the US Food & Drug Administration (FDA) corresponding with a specific pharmacotherapy. Both types of tests are used to guide management for several cancers such as non-small cell lung cancer (NSCLC), breast and colorectal cancer (CRC). Techniques can vary from test to test include, but may not be limited to, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and next-generation sequencing (NGS).
Multigene (or expanded) panels analyze a broad set of genes simultaneously (as opposed to single gene testing that searches for variants in one specific gene). Panels often include medically actionable genes but may also include those with unclear medical management. Coverage Determination Humana follows the CMS requirement that only allows coverage and payment for services that are reasonable and necessary for the diagnosis or 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: Somatic (Acquired) Cancer

Pharmacogenomics and Companion Diagnostics Page: 4 of 25 Pharmacogenomics and companion diagnostic testing (including single gene, multi-gene panels, and combinatorial tests) in somatic (acquired) cancer will be considered medically reasonable and necessary when all the following requirements are met: • Testing services are performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, when ordered by a treating physician; AND
• Individual is diagnosed with recurrent, relapsed, refractory, metastatic, or advanced stage III or IV cancer; AND • Individual has not been previously tested with the same test using NGS or other methodology for the same cancer genetic content; AND • Decided to seek further cancer treatment (eg, therapeutic chemotherapy); AND • The diagnostic laboratory test using NGS or other methodology (eg, FISH, IHC) must have: o FDA approval or clearance as a companion in vitro diagnostic; AND o FDA approved or cleared indication for use in that patient’s cancer; AND o Results provided to the treating physician for management of the patient using a report template to specify treatment options Germline (Inherited) Cancer Pharmacogenomics and companion diagnostic testing (including single gene, multi-gene panels, and combinatorial tests) in germline (inherited) cancer (eg, MyChoice CDx [0172U]) when all of the following criteria are met: • Testing services are performed in a CLIA certified laboratory, when ordered by a treating physician; AND • Individual is diagnosed with ovarian (including fallopian tube, primary peritoneal cancer) or breast cancer; AND • Clinical indication for germline testing for hereditary breast or ovarian cancer (per National Comprehensive Cancer Network [NCCN] guidelines); AND • Risk factor for germline breast or ovarian cancer; AND • Individual has not been previously tested with the same germline test using NGS or other methodology for the same germline genetic content

• The diagnostic laboratory test using NGS or other methodology (eg, FISH, IHC) must have all of the Pharmacogenomics and Companion Diagnostics Page: 5 of 25 following: o FDA approval or clearance; AND o Results provided to the treating physician for management of the individual using a report template to specify treatment options 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. Coverage Limitations US Government Publishing Office. Electronic code of federal regulations: part 411 – 42 CFR § 411.15 - Particular services excluded from coverage The following services/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 • Repeat genetic testing utilizing the same tissue sample for the same content A review of the current medical literature shows that the evidence is insufficient to determine that this service is standard medical treatment for these indications. There remains an absence of randomized blinded clinical studies examining benefit and long-term clinical outcomes establishing the value of this service in clinical management for these indications. Screening services such as presymptomatic genetic tests and services used to detect and undiagnosed diseased or disease predisposition are not a Medicare benefit and are not covered. The following test types are examples of testing services that may not be considered a benefit (statutory excluded) and denied as Medicare Excluded tests123:
• Tests considered screening in the absence of clinical signs and symptoms of disease that are not specifically identified by the law; OR • Tests that confirm a diagnosis or known information; OR • Tests to determine risk for developing a disease or condition; OR • Tests performed to measure the quality of a process; OR

Pharmacogenomics and Companion Diagnostics Page: 6 of 25 • Tests without diagnosis specific indications; OR • Tests identified as investigational by available literature and/or the literature supplied by the developer and are not a part of a clinical trial