evekhm/cms_iom_500 huggingface dataset:
Proposed LCD - Genetic Testing for Oncology (DL39367)
Additionally, testing may be used to check for a single biomarker or multiple biomarkers at the same time via a multigene test or panel.3As a result, the growing compendium of products described as biomarkers requires careful evaluation to determine what testing configurations are medically reasonable and necessary under Medicare.Biomarkers for oncology can be generally classified into four functional types4:Diagnosticbiomarkers detect or confirm the presence of a disease or conditionPrognosticbiomarkers provide information about the likely course of a disease process and potential patient outcomes if left untreatedPredictivebiomarkers forecast a patients response and/or benefit to a specific treatmentTherapeuticbiomarkers identify potential targets for a medical intervention (e.g., targeted drug therapy)In certain circumstances, genetic testing for oncology biomarkers in patients with the corresponding appropriate medical condition could have the potential to assist patient management in the Medicare population. However, given the complexity and rapidly expanding knowledge in this topic area, there is also a potential for testing that does not help the patient or leads to confusion. In order for services to be considered medically reasonable and necessary, they must impact the management of the patient. Specialized clinical expertise in oncology in addition to advanced knowledge in both genetic variation and effect on gene function is required to facilitate optimal outcomes for patients.DefinitionsActionable usedescribes a scenario when the genotype information identified via genetic testing may lead to selection of or avoidance of a specific intervention.Analytical validationis a process intended to determine if a test, tool, or instrument has acceptable technical performance (sensitivity, specificity, accuracy, precision, etc.). Analytical validation is an assessment of the tests technical performance (that it measures what it was intended to measure), not its usefulness or clinical significance.1Clinical validityis defined as the ability of a test to classify a patients specific circumstance into a diagnostic, prognostic, or predictive functional category. It should be noted that clinical validity is not a fixed value.5Clinical utilitycan be defined as the ability of a test to provide information related to the patients care and management, and thus, its ability to inform treatment decisions.5Covered Indications
Proposed LCD - Genetic Testing for Oncology (DL39367)
Clinical utilitycan be defined as the ability of a test to provide information related to the patients care and management, and thus, its ability to inform treatment decisions.5Covered IndicationsThree evidence-based databases and/or knowledge bases have been identified as valid and reliable sources. Note that a specific genetic test may be listed in one database or knowledge base, but not others; therefore, providers may choose to utilize guidelines from any of the three databases/knowledge bases. However,for services to be considered medically reasonable and necessary, #1 below is required regardless of which guidelines are utilized.Genetic testing for oncology will be considered medically reasonable and necessary if:The provider has either established a diagnosis of cancer or found significant evidence to create suspicion for cancer in their patient via a clinical evaluation and abnormal results (cancer or suspicious for cancer) from histologic and/or cytologic examination. If then, as a next step in the clinical management of the patient, genetic testing would directly impact the management of the patients condition, the testing would be indicated.AND ONE OF THE FOLLOWING:The evidence for the gene-disease association is evaluated by the evidence-based, transparent, peer-reviewed process of the National Institutes of Health (NIH) sponsored Clinical Genome Resource (ClinGen)6and is determined to demonstrate actionability in clinical decision making,meeting the criteria for all 5 categories below.At leastoneof the items listed under each of the categories (severity, likelihood of disease, effectiveness, nature of the intervention, and validity) must be satisfied:Disease severity equal to:Sudden death (Level 3), orPossible death or major morbidity (Level 2), orModest morbidity (Level 1)Likelihood of disease equal to:Substantial evidence of a >40% chance (Level 3A), orModerate evidence of a >40% chance (Level 3B)Effectiveness equal to:Substantial evidence of a highly effective intervention (Level 3A), orModerate evidence of a highly effective intervention (Level 3B), orSubstantial evidence of a moderately effective intervention (Level 2A), orModerate evidence of a moderately effective intervention (Level 2B)Nature of the intervention is equal to:Low risk/medically acceptable/low intensity (Level 3), orModerately acceptable/risk/intensive (Level 2)Validity of the gene-disease relationship equal to:Definitive, orStrong, orModerateOR
Proposed LCD - Genetic Testing for Oncology (DL39367)
Low risk/medically acceptable/low intensity (Level 3), orModerately acceptable/risk/intensive (Level 2)Validity of the gene-disease relationship equal to:Definitive, orStrong, orModerateORThe evidence for the intervention is evaluated by the National Comprehensive Cancer Network (NCCN)7and is determined to demonstrate actionability in clinical decision making, meeting the following metric:Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate (Category 1), orBased upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate (Category 2A)ORThe evidence for the intervention is evaluated by the Memorial Sloan Kettering Cancer Center-sponsored Oncology Knowledge Base (OncoKB)8and is determined to demonstrate actionability in clinical decision making, meeting one of the following metrics:For therapeutic use cases:The intervention is an FDA-recognized biomarker predictive of response to an FDA-approved drug in this indication (Level 1)ORThe intervention is a standard care biomarker recommended by the NCCN or other professional guidelines predictive of response to an FDA-approved drug in this indication (Level 2)ORThe intervention is a standard care biomarker predictive of resistance to an FDA-approved drug in this indication (Level R1)For diagnostic use cases:The intervention is an FDA and/or professional guideline-recognized biomarker required for diagnosis in this indication (Level Dx1)ORThe intervention is an FDA and/or professional guideline-recognized biomarker that supports diagnosis in this indication (Level Dx2)For prognostic use cases:The intervention is an FDA and/or professional guideline-recognized biomarker prognostic in this indication based on a well-powered study (or studies) (Level Px1)ORThe intervention is an FDA and/or professional guideline-recognized biomarker prognostic in this indication based on a single study or multiple small studies (Level Px2)LimitationsThe following are considered not medically reasonable and necessary:
Proposed LCD - Genetic Testing for Oncology (DL39367)
ORThe intervention is an FDA and/or professional guideline-recognized biomarker prognostic in this indication based on a single study or multiple small studies (Level Px2)LimitationsThe following are considered not medically reasonable and necessary:A genetic test where either analytical validity, clinical validity, or clinical utility has not been established.Interventions with levels of evidence not identified by either ClinGen, NCCN, or OncoKB as demonstrating actionability in clinical decision making as noted in Covered Indications.Genetic testing in patients who do not have either an established diagnosis of cancer or substantiated suspicion of cancer as determined by a clinical evaluation and abnormal results (cancer or suspicious for cancer) from histologic and/or cytologic examination.Genetic testing of asymptomatic patients for the purposes of screening the patient or their relatives.Repetitions of the same genetic test on the same genetic material.Genetic tests for hereditary cancer syndromes, which are considered germline testing, may only be performed once per beneficiarys lifecycle.Provider QualificationsThe following provider qualification requirements must be met for the service to be considered medically reasonable and necessary.The ordering provider of a genetic test for a patient with an established diagnosis of cancer or substantiated suspicion of cancer:Must be the treating clinician who is responsible for the management of the patients cancer; and,Understands how the test result will impact the patients condition; and,Has presented this information to the patient eliciting patient understanding.Notice:Services performed for any given diagnosis must meet all of the indications and limitations stated in this LCD, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS national coverage determinations, and all Medicare payment rules.General InformationAssociated InformationPlease refer to the related Draft Local Coverage Article: Billing and Coding: Genetic Testing for Oncology (DA59123) for documentation requirements, utilization parameters and all coding information as applicable.Sources of InformationContractor Medical DirectorsPrivate Insurer PoliciesOther Contractor PoliciesBibliographyThis bibliography presents those sources that were obtained during the development of this policy. The Contractor is not responsible for the continuing viability of Website addresses listed below.
Proposed LCD - Genetic Testing for Oncology (DL39367)
Sources of InformationContractor Medical DirectorsPrivate Insurer PoliciesOther Contractor PoliciesBibliographyThis bibliography presents those sources that were obtained during the development of this policy. The Contractor is not responsible for the continuing viability of Website addresses listed below.FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016-. Co-published by National Institutes of Health (US), Bethesda (MD).The Genetics of Cancer. National Cancer Institute website. https://www.cancer.gov/about-cancer/causes-prevention/genetics. Published October 12, 2017. Accessed January 5, 2022 to April 7, 2022.Biomarker Testing for Cancer Treatment. National Cancer Institute website. https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment. Published October 5, 2017. Accessed January 5, 2022 to April 7, 2022.Califf RM. Biomarker definitions and their applications.Exp Biol Med (Maywood).2018;243(3):213-221. doi:10.1177/1535370217750088Joseph L, Cankovic M, Caughron S, et al. The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer: A Report of the Association for Molecular Pathology.J Mol Diagn. 2016;18(5):605-619. doi:10.1016/j.jmoldx.2016.05.007ClinGen. Explore the clinical relevance of genes & variants. https://www.clinicalgenome.org. Published May 2021. Updated January 2, 2022. Accessed January 5, 2022 to April 7, 2022.National Comprehensive Cancer Network (NCCN). Biomarkers Compendium. https://www.nccn.org/compendia-templates/compendia/biomarkers-compendium. Accessed January 5, 2022 to April 7, 2022.
Proposed LCD - Genetic Testing for Oncology (DL39367)
Chakravarty D, Gao J, Phillips SM, et al. OncoKB: A Precision Oncology Knowledge Base.JCO Precision Oncology. 2017;(1):1-16. doi:10.1200/po.17.00011Institute of Medicine (US) Committee to Advise the Public Health Service on Clinical Practice Guidelines, Field MJ, Lohr KN, eds.Clinical Practice Guidelines: Directions for a New Program. Washington (DC): National Academies Press (US); 1990.Development and Update of Guidelines. National Comprehensive Cancer Network website. https://www.nccn.org/guidelines/guidelines-process/development-and-update-of-guidelines. Accessed January 5, 2022 to April 7, 2022.Birkeland ML, McClure JS. Optimizing the Clinical Utility of Biomarkers in Oncology: The NCCN Biomarkers Compendium.Arch Pathol Lab Med. 2015;139(5):608-611. doi:10.5858/arpa.2014-0146-RAPoonacha TK, Go RS. Level of scientific evidence underlying recommendations arising from the National Comprehensive Cancer Network clinical practice guidelines.J Clin Oncol. 2011;29(2):186191. doi:10.1200/JCO.2010.31.6414Genetic Database Recognition Decision Summary for ClinGen Expert Curated Human Variant Data. US Food & Drug Administration. https://www.fda.gov/media/119313/download. Accessed January 5, 2022 to April 7, 2022.Hunter JE, Irving SA, Biesecker LG, et al. A standardized, evidence-based protocol to assess clinical actionability of genetic disorders associated with genomic variation.Genet Med. 2016 Dec;18(12):1258-1268. doi:10.1038/gim.2016.40FDA Recognition of Public Human Genetic Variant Databases. US Food & Drug Administration.FDA. https://www.fda.gov/medical-devices/precision-medicine/fda-recognition-public-human-genetic-variant-databases. Published online October 7, 2021. Accessed January 5, 2022 to April 7, 2022.
Proposed LCD - Genetic Testing for Oncology (DL39367)
Strande NT, Riggs ER, Buchanan AH, et al. Evaluating the Clinical Validity of Gene-Disease Associations: An Evidence-Based Framework Developed by the Clinical Genome Resource.The American Journal of Human Genetics.2017 Jun 1;100(6):895-906. doi:10.1016/j.ajhg. 2017.04.015Berg JS, Foreman AK, O'Daniel JM, et al. A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing.Genet Med. 2016;18(5):467-475. doi:10.1038/gim.2015.104Genetic Database Recognition Decision Summary for OncoKB. US Food & Drug Administration. https://www.fda.gov/media/152847/download. Accessed January 5, 2022 to April 7, 2022.FDA Fact Sheet. US Food & Drug Administration. https://www.oncokb.org/levels#version=FDA_NGS. Updated March 29, 2022. Accessed January 5, 2022 to April 7, 2022.
Proposed LCD - MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer (DL38647)
CMS National Coverage PolicyTitle XVIII of the Social Security Act (SSA), 1862(a)(1)(A), states that no Medicare payment shall be made for items or services that are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.42 Code of Federal Regulations (CFR) 410.32 Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, 80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests, 80.1.1 Certification ChangesCoverage Indications, Limitations, and/or Medical NecessityThis contractor will cover molecular diagnostic tests for use in a beneficiary with bladder cancer when all of the following conditions are met:The beneficiary is being actively managed for bladder cancer.The beneficiary is within the population and has the indication for which the test was developed and is covered. The lab providing the test is responsible for clearly indicating to treating clinicians the population and indication for test use.At least 1 of the 2 criteria are met:The patient is a candidate for multiple potential treatments, which could be considered to have varied or increasing levels of intensity based on a consensus guideline, and the physician and patient must decide among these treatments.ORThe patient is a candidate for multiple therapies, and the test has shown that it predicts response to specific therapy among accepted therapy options based on nationally recognized consensus guidelines.The test demonstrates analytical validity including both analytical and clinical validations. If the test relies on an algorithm (which may range in complexity from a threshold determination of a single numeric value to a complex mathematical or computational function), the algorithm must be validated in a cohort that is not a development cohort for the algorithm.The test has demonstrated clinical validity and utility, establishing a clear and significant biological/molecular basis for stratifying patients and subsequently selecting (either positively or negatively) a clinical management decision (in 4. above) in a clearly defined population.The test successfully completes a Molecular Diagnostic Program (MolDX) technical assessment that ensures the test is reasonable and necessary as described in 4 and 5 above.General InformationAssociated InformationN/ASources of InformationN/ABibliography
Proposed LCD - MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer (DL38647)
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021.CA Cancer J Clin.2021;71(1):7-33.Flaig TW, Spiess PE, Agarwal N, et al. Bladder cancer, version 3.2020, NCCN clinical practice guidelines in oncology.J Natl Compr Canc Netw.2020;18(3): 329-354.Svatek RS, Shariat SF, Novara G, et al. Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort.BJU Int.2011;107(6):898-904.U.S. Food and Drug Administration (FDA).Balversa prescribing information. Accessed April 20, 2022.Helpap B. Morphology and therapeutic strategies for neuroendocrine tumors of the genitourinary tract.Cancer.2002;95(7):1415-1420.Ali SZ, Reuter VE, Zakowski MF. Small cell neuroendocrine carcinoma of the urinary bladder: a clinicopathologic study with emphasis on cytologic features.Cancer.1997;79(2):356-361.National Cancer Institute. Cancer Stat Facts: Bladder Cancer.https://seer.cancer.gov/statfacts/html/urinb.htmlAccessed April 20, 2022.Seiler R, Ashab HAD, Erho N, et al. Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy.Eur Urol.2017;72(4):544-554.Lotan Y, Boorjian SA, Zhang J, et al. Molecular subtyping of clinically localized urothelial carcinoma reveals lower rates of pathological upstaging at radical cystectomy among luminal tumors.Eur Urol.2019;76(2):200-206.
Proposed LCD - MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer (DL38647)
Batista da Costa J, Gibb EA, Bivalacqua TJ, et al. Molecular characterization of neuroendocrine-like bladder cancer.Clin Cancer Res.2019;25(13):3908-3920.Fryback DG, Thornbury JR. The efficacy of diagnostic imaging.Med Decis Making.1991;11(2):88-94.Centers for Disease Control and Prevention. ACCE Model List of 44 Targeted Questions Aimed at a Comprehensive Review of Genetic Testing.https://www.cdc.gov/genomics/gtesting/acce/acce_proj.htm. Accessed April 20, 2022.NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Bladder Cancer, Version 6.2021.https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed April 20, 2022.Ross JS, Wang K, Khaira D, et al. Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations.Cancer. 2016;122(5):702-711.Mori K, Abufaraj M, Mostafaei H, et al. A systemic review and meta-analysis of variant histology in urothelial carcinoma of the bladder treated with radical cystectomy.J Urol.2020;204(6):1129-1140.US Food and Drug Administration (FDA). Prescribing Information. BALVERSA (erdafitinib). 2020.https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212018s001lbl.pdf. Accessed April 20, 2022.Loriot Y, Necchi A, Park SH, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma.N Engl J Med.2019;381(4):338-348.
Proposed LCD - MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer (DL38649)
CMS National Coverage PolicyTitle XVIII of the Social Security Act (SSA), 1862(a)(1)(A), states that no Medicare payment shall be made for items or services that are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.42 Code of Federal Regulations (CFR) 410.32 Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, 80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests, 80.1.1 Certification ChangesCoverage Indications, Limitations, and/or Medical NecessityThis contractor will cover molecular diagnostic tests for use in a beneficiary with bladder cancer when all of the following conditions are met:The beneficiary is being actively managed for bladder cancer.The beneficiary is within the population and has the indication for which the test was developed and is covered. The lab providing the test is responsible for clearly indicating to treating clinicians the population and indication for test use.At least 1 of the 2 criteria are met:The patient is a candidate for multiple potential treatments, which could be considered to have varied or increasing levels of intensity based on a consensus guideline, and the physician and patient must decide among these treatments.ORThe patient is a candidate for multiple therapies, and the test has shown that it predicts response to a specific therapy among accepted therapy options based on nationally recognized consensus guidelines.The test demonstrates analytical validity including both analytical and clinical validations. If the test relies on an algorithm (which may range in complexity from a threshold determination of a single numeric value to a complex mathematical or computational function), the algorithm must be validated in a cohort that is not a development cohort for the algorithm.The test has demonstrated clinical validity and utility, establishing a clear and significant biological/molecular basis for stratifying patients and subsequently selecting (either positively or negatively) a clinical management decision (in 4. above) in a clearly defined population.The test successfully completes a Molecular Diagnostic Program (MolDX) technical assessment that ensures the test is reasonable and necessary as described in 4 and 5 above.General InformationAssociated InformationN/ASources of InformationN/ABibliography
Proposed LCD - MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer (DL38649)
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021.CA Cancer J Clin.2021;71(1):7-33.Flaig TW, Spiess PE, Agarwal N, et al. Bladder cancer, version 3.2020, NCCN clinical practice guidelines in oncology.J Natl Compr Canc Netw.2020;18(3): 329-354.Svatek RS, Shariat SF, Novara G, et al. Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort.BJU Int.2011;107(6):898-904.U.S. Food and Drug Administration (FDA).Balversa prescribing information. Accessed April 20, 2022.Helpap B. Morphology and therapeutic strategies for neuroendocrine tumors of the genitourinary tract.Cancer.2002;95(7):1415-1420.Ali SZ, Reuter VE, Zakowski MF. Small cell neuroendocrine carcinoma of the urinary bladder: a clinicopathologic study with emphasis on cytologic features.Cancer.1997;79(2):356-361.National Cancer Institute. Cancer Stat Facts: Bladder Cancer.https://seer.cancer.gov/statfacts/html/urinb.htmlAccessed April 20, 2022.Seiler R, Ashab HAD, Erho N, et al. Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy.Eur Urol.2017;72(4):544-554.Lotan Y, Boorjian SA, Zhang J, et al. Molecular subtyping of clinically localized urothelial carcinoma reveals lower rates of pathological upstaging at radical cystectomy among luminal tumors.Eur Urol.2019;76(2):200-206.