||Investigational and Experimental Molecular/Genomic Testing
||July 1, 2018
||July 2, 2018
Molecular and genomic (MolGen) tests are routinely released to market that make use of novel technologies or have a novel clinical application. These tests are often available on a clinical basis long before the evidence base required to support clinical validity and utility is established. Because these tests are often proprietary, there may be no independent test evaluation data available in the early stages to support the laboratory's claims regarding test performance and utility.
An experimental or investigational procedure is generally defined as the use of a service, supply, drug or device that is not recognized as standard medical care for the condition, disease, illness or injury being treated as determined by the health plan based on independent review of peer reviewed literature and scientific data. Investigational and experimental (I&E) MolGen tests refer to assays involving chromosomes, DNA, RNA, or gene products that have insufficient data to determine the net health impact, which typically means there is insufficient data to support that a test accurately assesses the outcome of interest (analytical and clinical validity), significantly improves health outcomes (clinical utility), and/or performs better than an existing standard of care medical management option. Such tests are also not generally accepted as standard of care in the evaluation or management of a particular condition. In the case of MolGen testing, FDA clearance is not a reliable standard given the number of laboratory developed tests that currently fall outside of FDA oversight and FDA clearance often does not assess clinical utility.
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
|Policy Position Coverage is subject to the specific terms of the member’s benefit plan.|
Molecular and genomic tests are only eligible for reimbursement when ALL of the following conditions are met:
- Technical and clinical validity: The test must be accurate, sensitive and specific, based on sufficient, quality scientific evidence to support the claims of the test; and
- Clinical utility: Healthcare providers can use the test results to provide significantly better medical care for the individual; and
- Reasonable use: The usefulness of the test is not significantly offset by negative factors, such as expense, clinical risk, or social or ethical challenges.
Novel Oncology Molecular/Genomic Tests
The following tests used in the screening, diagnosis, prognostication, and/or treatment decision-making for various neoplasms do not meet the above criteria and are considered experimental/investigational and therefore non-covered.
Gene Expression Assays:
- BluePrint Molecular Subtyping Profile [Proprietary 80-gene expression signature to classify Basal-type, Luminal-type and ERBB2-type breast cancers by Agendia]
- ColonSentry [Proprietary 7-gene signature to detect colorectal cancer from GeneNews]
- ColoPrint [Proprietary 18-gene signature to assess colon cancer recurrence risk from Agendia]
- DecisionDx- Cutaneous Melanoma assay [Proprietary 31-gene signature to assess melanoma metastatic risk from Castle Biosciences]
- ExosomeDx® Prostate (IntelliScore) [Oncology (prostate) gene expression profile by real-time RT-PCR of 3 genes (ERG, PCA3, and SPDEF), urine, algorithm reported as risk score from Exosome Diagnostics, Inc.]
- myPath Melanoma [Proprietary 23-gene expression assay to assess the risk of malignant melanoma when a result cannot be obtained by clinical assessment and/or histopathology alone from Myriad Genetics]
- OncoTarget/OncoTreat [Oncology, RNA, gene expression by whole transcriptome sequencing, formalin-fixed paraffin embedded tissue or fresh frozen tissue, predictive algorithm reported as potential targets for therapeutic agents from Columbia University Department of Pathology and Cell Biology, Darwin Health]
- Pervenio Lung RS Test [Proprietary 14-gene expression assay for risk stratification of early stage NSCLC from Life Technologies]
|0005U, 0019U, 81455, 81479, 81599, 84999, 0053U, 0057U|
Other Novel Assays:
- ChemoFX [Proprietary test from Helomics to assess chemosensitivity] CPT 81535 and 81536
- DEPArray[Oncology (breast cancer), ERBB2 (HER2) copy number by FISH, tumor cells from formalin fixed paraffin embedded tissue isolated using image-based dielectrophoresis (DEP) sorting, reported as ERBB2 gene amplified or non-amplified from PacificDx] CPT 0009U
- HERmark Breast Cancer Assay [Proprietary test designed to evaluate Her-2 total proteins in formalin-fixed, paraffin-embedded (FFPE) tissue specimens from LabCorp]
- Knowerror [Proprietary test for DNA based specimen provenance confirmation by Strand Diagnostics]
- MatePair Targeted Rearrangements, Oncology, [Oncology (solid organ neoplasia), gene rearrangement detection by whole genome next-generation sequencing, DNA, fresh or frozen tissue or cells, report of specific gene rearrangement(s) from Mayo Clinic] CPT 0013U
- MatePair Targeted Rearrangements, Hematologic, [Hematology (hematolymphoid neoplasia), gene rearrangement detection by whole genome next generation sequencing, DNA, whole blood or bone marrow, report of specific gene rearrangement(s) from Mayo Clinic] CPT 0014U
- miRInform Pancreas Test [Proprietary score based on expression levels of seven microRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis provided by Asuragen]
- NADiA ProsVue [Proprietary nucleic acid detection immunoassay designed to determine the rate of change of serum total prostate specific antigen over time to predict prostate cancer recurrence risk from Iris Personalized Medicine]
- PancraGen [Proprietary topographic genotyping assay to be used when a definitive pathologic diagnosis cannot be made from RedPath Integrated Pathology]
- PAULA [Proprietary panel of six biomarkers designed to detect lung cancer in asymptomatic individuals at high risk from Genesys Biolabs]
- Prostate Core Mitomic Test [Proprietary test using mitochondrial DNA to detect prostate cancer not identified by standard biopsy pathology from Mitomics]
- ProstaVysion [Proprietary panel of two biomarkers designed to predict prostate cancer prognosis from Bostwick Laboratories]
- ROMA Risk of Ovarian Malignancy Algorithm [Proprietary test using the combination of CA125 + HE4 antigens to assess the likelihood of malignancy before surgery; test kit from Fujirebio Diagnostics, Inc. and offered by several reference laboratories] CPT code 81500
- mi-KIDNEYCancer Test [Proprietary microRNA-based assay that differentiates 4 main histological types of primary kidney tumors from Rosetta Genomics]
- mi-LUNG Cancer Test [Proprietary microRNA-based assay that identifies four main subtypes of lung cancer from Rosetta Genomics]
|0009U, 0013U, 0014U, 81500, 81535, 81536, 0056U|
Cardiovascular Molecular/Genomic Tests
The following tests used to predict cardiovascular disease and/or direct therapy do not meet the above criteria and are considered experimental/investigational and therefore non-covered.
- 4q25-AF Risk Genotype Test (rs2200733 allele)
- 9p21 Genotype Test (rs10757278 and rs1333049 alleles)
- Apolipoprotein E Genotype (APOE)
- C-GAAP (Clopidogrel Genetic Absorption Activation Panel) [Proprietary test from Transgenomic Lab, includes ABCB1 and CYP2C19 gene variants]
- KIF6 Genotype Test
- LPA-Aspirin Genotype Test (4399Met allele)
- LPA-Intron 25 Genotype Test
- PAI-1 Testing for Cardiovascular Disease Risk Assessment
- Statin Induced Myopathy Genotype (SLCO1B1)
|81291, 81328, 0055U|
Gene Variant or Marker Risk Assessment Tests
The following tests that make use of inherited genomic information to assess disease risk, prognosis, or subtyping do not meet the above criteria and are considered experimental/investigational and therefore non-covered.
- ARISk Autism Risk Assessment Test [Proprietary test from IntegraGen]
- BREVAGen [Proprietary sporadic breast cancer risk based on genetic markers by Phenogen Sciences]
- Cardiac DNA Insight [Proprietary test from Pathway Genomics that assesses genetic markers for cardiac-related conditions]
- Crohn's prognostic test [NOD2/CARD15 gene variant testing]
- IBD sgi Diagnostic [Proprietary test from Prometheus with genomic components including ATG16L1, STAT3, NKX2-3, and ECM1 gene variants.]
- LactoTYPE [Proprietary test from Prometheus that assesses the hypolactasia C/T genetic variant]
- Macula Risk [Proprietary test from ArcticDx to predict risk of age-related macular degeneration progression]
- Pathway Fit [Proprietary test from Pathway Genomics that focuses on metabolism, diet, and exercise traits]
- RetnaGene AMD [Proprietary test from Sequenom CMM to predict risk of wet AMD progression]
Pharmacogenomic Panels are considered experimental/investigational and therefore non-covered.
- 5-Fluorouracil (5-FU) Toxicity and Chemotherapeutic Response [Proprietary panel of DPYD and TYMS gene variants to assess risk of 5-fluorouracil toxicity from ARUP Laboratory]
- Genecept Assay [Proprietary panel of biomarker tests to predict response to different psychiatric treatments from Genomind]
- GeneSightRx ADHD [Proprietary test from AssureRx assessing three genes]
- GeneSightRx Analgesic [Proprietary test from AssureRx assessing two genes]
- GeneSightRx Psychotropic [Proprietary test from AssureRx assessing six genes]
- Mental Health DNA Insight [Proprietary test from Pathway Genomics]
- OneOme RightMed, [Drug metabolism (adverse drug reactions), DNA, 22 drug metabolism and transporter genes, real-time PCR, blood or buccal swab, genotype and metabolizer status for therapeutic decision support from OneOme, LLC] CPT 0015U
- Pain Medication DNA Insight [Proprietary test from Pathway Genomics]
Non-cancer Gene Expression Assays are considered experimental/investigational and therefore non-covered.
- Renal Transplant Monitoring (FOXP3, Granzyme B, Perforin, IP10) [Gene expression panel that is an indirect indicator of immune response designed to detect or monitor renal transplant rejection from Quest Diagnostics]
- VectraDA [Proprietary panel of 12 biomarkers that yields a rheumatoid arthritis disease activity score from Crescendo Bioscience] CPT 81490
Infectious Disease Assays are considered experimental/investigational and therefore non-covered.
- AmHPR Helicobacter pylori Antibiotic Resistance Next Generation Sequencing Panel, [Helicobacter pylori detection and antibiotic resistance, DNA, 16S and 23S rRNA, gyrA, pbp1, rdxA and rpoB, next generation sequencing, formalin-fixed paraffin embedded or fresh tissue, predictive, reported as positive or negative for resistance to clarithromycin, fluoroquinolones, metronidazole, amoxicillin, tetracycline and rifabutin from American Molecular Laboratories, Inc.] CPT 0008U
- Bacterial Typing by Whole Genome Sequencing, [Infectious disease (bacterial), strain typing by whole genome sequencing, phylogenetic-based report of strain relatedness, per submitted isolate from Mayo Clinic]CPT 0010U
Note: A single CPT/HCPCS code may describe more than one MolGen test. Some tests under a single code may be covered while others are determined to be experimental/investigational.
|Place of Service: Outpatient|
Experimental/Investigational (E/I) services are not covered regardless of place of service.
Experimental/investigational Molecular/Genomic Testing is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.
|The policy position applies to all commercial lines of business|
Services that do not meet the criteria of this policy will be considered experimental/investigational (E/I). A network provider can bill the member for the experimental/investigational service. The provider must give advance written notice informing the member that the service has been deemed E/I. The member must be provided with an estimate of the cost and the member must agree in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.
Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.
Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:
If you need these services, contact the Civil Rights Coordinator.
- Provides free aids and services to people with disabilities to communicate effectively with us, such as:
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If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.
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U.S. Department of Health and Human Services
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Room 509F, HHH Building
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1-800-368-1019, 800-537-7697 (TDD)
Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.
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