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Local Coverage Determinations, LCD, Local policies, Implantable Continuous Glucose Monitors (I-CGM), DL38662	Use this page to view details for the Local Coverage Determination for Implantable Continuous Glucose Monitors (I-CGM).	PROPOSED	Proposed LCD - Implantable Continuous Glucose Monitors (I-CGM) (DL38662)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=38787&ver=7	lcd-38787-7-1.txt	1	38787	lcd	7	0	3fdf4f93-0fc4-438b-881e-787283128588	CMS National Coverage PolicyThis LCD supplements but does not replace, modify or supersede existing Medicare applicable National Coverage Determinations (NCDs) or payment policy rules and regulations for Implantable Continuous Glucose Monitors (I-CGM). Federal statute and subsequent Medicare regulations regarding provision and payment for medical services are lengthy. They are not repeated in this LCD. Neither Medicare payment policy rules nor this LCD replace, modify or supersede applicable state statutes regarding medical practice or other health practice professions acts, definitions and/or scopes of practice. All providers who report services for Medicare payment must fully understand and follow all existing laws, regulations and rules for Medicare payment for Implantable Continuous Glucose Monitors (I-CGM) and must properly submit only valid claims for them. Please review and understand them and apply the medical necessity provisions in the policy within the context of the manual rules. Relevant CMS manual instructions and policies may be found in the following Internet-Only Manuals (IOMs) published on the CMS Web site:IOM Citations:CMS IOM 100-08,Medicare Program Integrity Manual,Chapter 13, Section 13.5.4 Reasonable and Necessary Provision in an LCDSocial Security Act (Title XVIII) Standard References:Title XVIII of the Social Security Act, Section 1862(a)(1)(A) states that no Medicare payment shall be made for items or services which are not reasonable and necessary for the diagnosis or treatment of illness or injury.Title XVIII of the Social Security Act, Section 1862(a)(7). This section excludes routine physical examinations.Coverage Indications, Limitations, and/or Medical NecessityCompliance with the provisions in this policy may be monitored and addressed through post payment data analysis and subsequent medical review audits.Covered IndicationsI-CGMs are class III medical devices that require premarket approval by the FDA. In order to be considered reasonable and necessary, the FDA approved indication must include use as a therapeutic CGM.1The FDA recently approved expanding the indications of an implantable CGM product to replace fingerstick blood glucose measurements for diabetes treatment decisions.Therapeutic I-CGMs are considered reasonable and necessary by Medicare when all of the following coverage criteria (1-4) are met:The beneficiary has diabetes mellitus (Refer to the ICD-10 code list in the LCD-related Policy Article for applicable diagnoses); and,The beneficiarys treating practitioner has concluded that the beneficiary (or beneficiarys caregiver) has sufficient training using the I-CGM prescribed as evidenced by providing a prescription; and,The I-CGM is prescribed in accordance with its FDA indications for use; and,The beneficiary for whom a CGM is being prescribed, to improve glycemic control, meets at least one of the criteria below:The beneficiary is insulin-treated; or,The beneficiary has a history of problematic hypoglycemia with documentation of at least one of the following:Recurrent (more than one) level 2 hypoglycemic events (glucose <54mg/dL (3.0mmol/L)) that persist despite multiple (more than one) attempts to adjust medication(s) and/or modify the diabetes treatment plan; or,A history of one level 3 hypoglycemic event (glucose <54mg/dL (3.0mmol/L)) characterized by altered mental and/or physical state requiring third-party assistance for treatment of hypoglycemia.CGM Continued CoverageEvery six (6) months following the initial prescription of the CGM, the treating practitioner conducts an in-person or Medicare-approved telehealth visit with the beneficiary to document adherence to their CGM regimen and diabetes treatment plan.LimitationsI-CGM devices will not be considered reasonable and necessary for short-term (72 hours to 1 week) diagnostic use.Exception:For those beneficiaries who have previously met the coverage criteria for a non-implantable therapeutic continuous glucose monitor through the Medicare DME benefit and subsequently choose to switch to the implantable device, they may do so with a provider order. However, all other coverage criteria above must be fulfilled in order for Medicare payment.General InformationAssociated InformationPlease refer to the related Billing and Coding Article: Implantable Continuous Glucose Monitors (I-CGM) (DA58127) for documentation and utilization requirements as applicable.Sources of InformationN/ABibliography
Local Coverage Determinations, LCD, Local policies, Implantable Continuous Glucose Monitors (I-CGM), DL38662	Use this page to view details for the Local Coverage Determination for Implantable Continuous Glucose Monitors (I-CGM).	PROPOSED	Proposed LCD - Implantable Continuous Glucose Monitors (I-CGM) (DL38662)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=38787&ver=7	lcd-38787-7-1.txt	1	38787	lcd	7	1	ae521d60-63ce-4b1b-88b1-9779ad95d4b9	General InformationAssociated InformationPlease refer to the related Billing and Coding Article: Implantable Continuous Glucose Monitors (I-CGM) (DA58127) for documentation and utilization requirements as applicable.Sources of InformationN/ABibliographyDepartment of Health and Human Services. Centers for Medicare & Medicaid Services. CMS Rulings. CMS-1682-R. Accessed August 16, 2023,https://www.cms.gov/Regulations-and-Guidance/Guidance/Rulings/CMS-Rulings-Items/CMS1682RSapra A, Bhandari P. Diabetes. StatPearls Publishing. Accessed August 9, 2023,https://www.ncbi.nlm.nih.gov/books/NBK551501/Centers for Disease Control and Prevention (CDC). What is Diabetes? Accessed August 10, 2023,https://www.cdc.gov/diabetes/basics/diabetes.htmlCenters for Disease Control and Prevention (CDC). Prevalence of Both Diagnosed and Undiagnosed Diabetes. Accessed August 10, 2023,https://www.cdc.gov/diabetes/data/statistics-report/diagnosed-undiagnosed-diabetes.htmlAmerican Diabetes Association (ADA). Economic Costs of Diabetes in the U.S. in 2017.Diabetes Care. May 2018;41(5):917-928. doi:10.2337/dci18-0007American Diabetes Association (ADA). Standards of Care in Diabetes-2023 Abridged for Primary Care Providers.Clin Diabetes. Winter 2022;41(1):4-31. doi:10.2337/cd23-as01Solano L. Seven facts you need to know about continuous glucose monitors.Jaapa. Sep 1 2022;35(9):41-45. doi:10.1097/01.JAA.0000854536.09072.5eAdolfsson P, Parkin CG, Thomas A, Krinelke LG. Selecting the Appropriate Continuous Glucose Monitoring System - a Practical Approach.Eur Endocrinol. Apr 2018;14(1):24-29. doi:10.17925/ee.2018.14.1.24Cowart K. A Review of the First Long-term Implantable Continuous Glucose Monitoring System Available in the United States.J Diabetes Sci Technol. Jan 2021;15(1):160-166. doi:10.1177/1932296819890865Heinemann L, Schoemaker M, Schmelzeisen-Redecker G, et al. Benefits and Limitations of MARD as a Performance Parameter for Continuous Glucose Monitoring in the Interstitial Space.J Diabetes Sci Technol. Jan 2020;14(1):135-150. doi:10.1177/1932296819855670Freckmann G. Basics and use of continuous glucose monitoring (CGM) in diabetes therapy. 2020;44(2):71-79. Journal of Laboratory Medicine. doi:doi:10.1515/labmed-2019-0189Barnard KD, Kropff J, Choudhary P, et al. Acceptability of Implantable Continuous Glucose Monitoring Sensor.J Diabetes Sci Technol. May 2018;12(3):634-638. doi:10.1177/1932296817735123Boscari F, Vettoretti M, Amato AML, et al. Comparing the accuracy of transcutaneous sensor and 90-day implantable glucose sensor.Nutr Metab Cardiovasc Dis. Feb 8 2021;31(2):650-657. doi:10.1016/j.numecd.2020.09.006Boscari F, Vettoretti M, Cavallin F, et al. Implantable and transcutaneous continuous glucose monitoring system: a randomized cross over trial comparing accuracy, efficacy and acceptance.J Endocrinol Invest. Jan 2022;45(1):115-124. doi:10.1007/s40618-021-01624-2Christiansen MP, Klaff LJ, Bailey TS, Brazg R, Carlson G, Tweden KS. A Prospective Multicenter Evaluation of the Accuracy and Safety of an Implanted Continuous Glucose Sensor: The PRECISION Study.Diabetes Technol Ther. May 2019;21(5):231-237. doi:10.1089/dia.2019.0020Christiansen MP, Klaff LJ, Brazg R, et al. A Prospective Multicenter Evaluation of the Accuracy of a Novel Implanted Continuous Glucose Sensor: PRECISE II.Diabetes Technol Ther. Mar 2018;20(3):197-206. doi:10.1089/dia.2017.0142Dehennis A, Mortellaro MA, Ioacara S. Multisite Study of an Implanted Continuous Glucose Sensor Over 90 Days in Patients With Diabetes Mellitus.J Diabetes Sci Technol. Jul 29 2015;9(5):951-6. doi:10.1177/1932296815596760Fokkert M, van Dijk PR, Edens MA, et al. Performance of the Eversense versus the Free Style Libre Flash glucose monitor during exercise and normal daily activities in subjects with type 1 diabetes mellitus.BMJ Open Diabetes Res Care. Aug 2020;8(1)doi:10.1136/bmjdrc-2020-001193Garg SK, Liljenquist D, Bode B, et al. Evaluation of Accuracy and Safety of the Next-Generation Up to 180-Day Long-Term Implantable Eversense Continuous Glucose Monitoring System: The PROMISE Study.Diabetes Technol Ther. Feb 2022;24(2):84-92. doi:10.1089/dia.2021.0182Jafri RZ, Balliro CA, El-Khatib F, et al. A Three-Way Accuracy Comparison of the Dexcom G5, Abbott Freestyle Libre Pro, and Senseonics Eversense Continuous Glucose Monitoring Devices in a Home-Use Study of Subjects with Type 1 Diabetes.Diabetes Technol Ther. Nov 2020;22(11):846-852. doi:10.1089/dia.2019.0449Kropff J, Choudhary P, Neupane S, et al. Accuracy and Longevity of an Implantable Continuous Glucose Sensor in the PRECISE Study: A 180-Day, Prospective, Multicenter, Pivotal Trial.Diabetes Care. Jan 2017;40(1):63-68. doi:10.2337/dc16-1525Mortellaro M, DeHennis A. Performance characterization of an abiotic and fluorescent-based continuous glucose monitoring system in patients with type 1 diabetes.Biosens Bioelectron. Nov 15 2014;61:227-31. doi:10.1016/j.bios.2014.05.022Sanchez P, Ghosh-Dastidar S, Tweden KS, Kaufman FR. Real-World Data from the First U.S. Commercial Users of an Implantable Continuous Glucose Sensor.Diabetes Technol Ther. Dec 2019;21(12):677-681. doi:10.1089/dia.2019.0234Tweden KS, Deiss D, Rastogi R, Addaguduru S, Kaufman FR. Longitudinal Analysis of Real-World Performance of an Implantable Continuous Glucose Sensor over Multiple Sensor Insertion and Removal Cycles.Diabetes Technol Ther. May 2020;22(5):422-427. doi:10.1089/dia.2019.0342Wang X, Ioacara S, DeHennis A. Long-Term Home Study on Nocturnal Hypoglycemic Alarms Using a New Fully Implantable Continuous Glucose Monitoring System in Type 1 Diabetes.Diabetes Technol Ther. Nov 2015;17(11):780-6. doi:10.1089/dia.2014.0375American Diabetes Association (ADA). Understanding A1C. A1c Does it All. Accessed August 16, 2023,https://diabetes.org/diabetes/a1cIrace C, Cutruzzol A, Nuzzi A, et al. Clinical use of a 180-day implantable glucose sensor improves glycated haemoglobin and time in range in patients with type 1 diabetes.Diabetes Obes Metab. Jul 2020;22(7):1056-1061. doi:10.1111/dom.13993Renard E, Riveline JP, Hanaire H, Guerci B. Reduction of clinically important low glucose excursions with a long-term implantable continuous glucose monitoring system in adults with type 1 diabetes prone to hypoglycaemia: the France Adoption Randomized Clinical Trial.Diabetes Obes Metab. May 2022;24(5):859-867. doi:10.1111/dom.14644American Diabetes Association (ADA). CGM & Time in Range. Accessed June 6, 2023,https://diabetes.org/tools-support/devices-technology/cgm-time-in-range#:~:text=What%20is%20time%20in%20range,mg%2FdL%20for%20most%20people.Deiss D, Irace C, Carlson G, Tweden KS, Kaufman FR. Real-World Safety of an Implantable Continuous Glucose Sensor Over Multiple Cycles of Use: A Post-Market Registry Study.Diabetes Technol Ther. Jan 2020;22(1):48-52. doi:10.1089/dia.2019.0159Fonseca VA, Grunberger G, Anhalt H, et al. CONTINUOUS GLUCOSE MONITORING: A CONSENSUS CONFERENCE OF THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY.Endocr Pract. Aug 2016;22(8):1008-21. doi:10.4158/ep161392.CsNational Institute for Health and Care Excellence (NICE). Type 2 diabetes in adults: management. Accessed August 16, 2023,https://www.nice.org.uk/guidance/ng28Wada E, Onoue T, Kobayashi T, et al. Flash glucose monitoring helps achieve better glycemic control than conventional self-monitoring of blood glucose in non-insulin-treated type 2 diabetes: a randomized controlled trial.BMJ Open Diabetes Res Care. Jun 2020;8(1)doi:10.1136/bmjdrc-2019-001115American Diabetes Association Professional Practice Committee. 7. Diabetes Technology: Standards of Medical Care in Diabetes-2022.Diabetes Care. Jan 1 2022;45(Suppl 1):S97-s112. doi:10.2337/dc22-S007Holt RIG, DeVries JH, Hess-Fischl A, et al. The Management of Type 1 Diabetes in Adults. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetes Care. 2021;44(11):2589-2625. doi:10.2337/dci21-0043Grunberger G, Sherr J, Allende M, et al. American Association of Clinical Endocrinology Clinical Practice Guideline: The Use of Advanced Technology in the Management of Persons With Diabetes Mellitus.Endocr Pract. Jun 2021;27(6):505-537. doi:10.1016/j.eprac.2021.04.008Deiss D, Szadkowska A, Gordon D, et al. Clinical Practice Recommendations on the Routine Use of Eversense, the First Long-Term Implantable Continuous Glucose Monitoring System.Diabetes Technol Ther. May 2019;21(5):254-264. doi:10.1089/dia.2018.0397U.S. Food & Drug Administration (FDA). Approval Order - Eversense Continuous Glucose Monitoring System. Accessed August 16, 2023,https://www.accessdata.fda.gov/cdrh_docs/pdf16/P160048A.pdfGehlaut RR, Dogbey GY, Schwartz FL, Marling CR, Shubrook JH. Hypoglycemia in Type 2 DiabetesMore Common Than You Think: A Continuous Glucose Monitoring Study.J Diabetes Sci Technol. Apr 27 2015;9(5):999-1005. doi:10.1177/193229681558105240. Munshi MN, Segal AR, Suhl E, et al. Frequent hypoglycemia among elderly patients with poor glycemic control.Arch Intern Med. Feb 28 2011;171(4):362-4. doi:10.1001/archinternmed.2010.539
Local Coverage Determinations, LCD, Local policies, Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound, DL39116	Use this page to view details for the Local Coverage Determination for Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound.	PROPOSED	Proposed LCD - Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound (DL39116)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39115&ver=5	lcd-39115-5-1.txt	1	39115	lcd	5	0	dea4c7a5-102e-4b0f-9e01-e64c653c7e01	CMS National Coverage PolicyTitle XVIII of the Social Security Act, 1862(a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.Title XVIII of the Social Security Act, 1862(a)(1)(D) addresses services that are determined to be investigational or experimental.CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 16, 10 General Exclusions from CoverageCMS Internet-Only Manual, Pub. 100-04, Medicare Claims Processing Manual, Chapter 23, 30A Physicians ServicesCMS Internet-Only Manual, Pub. 100-04, Medicare Claims Processing Manual, Chapter 30, 50.3.1 Mandatory ABN UsesCoverage Indications, Limitations, and/or Medical NecessityThis is a NON-coverage policy for allamniotic membrane, amniotic fluid or other placental-derived productinjections and/or applications as a means of managing musculoskeletal injuries, joint conditions, and all other conditions not stated below.This guidance does NOT include discussion on burns, wounds or ophthalmic conditions.NOTE: For information on stem cell transplantation please see CMS National Coverage Determination 110.23 Stem Cell TransplantationIntroductionAmniotic and placental-derived products are reported to possess certain beneficial characteristics. These products have been proposed as a source of stem cells. Stem cells, by definition, have the capability to differentiate into any cell of an organism as well as the capability of self-renewal.1In addition, the extracellular matrix (ECM) of placental and amniotic-based tissues are rich in collagen, glycoproteins, proteoglycans, fibroblasts, as well as many cytokines and growth factors thought to promote healing with a lower risk of low immunologic reaction.Based on these characteristics, amniotic and placental-derived products are currently being studied and marketed as allografts to serve as:scaffolds for tissue engineeringmembrane covering for certain burns, wounds, and ophthalmic corneal injuriesmicronized/particulate products suspended in an aqueous material to be applied topically or injected into joints, tendons, ligamentsapplications or injections performed intra-operatively to promote post-operative healingThese amniotic and placental-derived products are further being investigated for a multitude of indications, including but not limited to musculoskeletal conditions involving joint pain and back pain, chronic pain in general, dental conditions, alopecia, wounds, burns, and a plethora of others. In the quest to find alternative treatments for certain musculoskeletal conditions, the emergence of a class of substances being marketed as orthobiologics has become more prevalent in the pharmaceutical market. Orthobiologics are biological products aimed at treating musculoskeletal conditions purported to heal injury/trauma, slow degenerative processes and affect regeneration of tissues.2The result ideally would be decreased pain and increased function. One such category of orthobiologics involves the incorporation of human amniotic and placental-derived products.The amniotic and placental-derived products are obtained from the placenta of donors, usually, immediately post C-section at full term and screened for transmittable diseases. These products are made up of varying combinations of amniotic membrane, amniotic fluid, chorionic membrane, umbilical cord, umbilical cord blood, and what is known as Whartons jelly.3Definitions:ThePlacentais a multi-layered circulatory temporary organ that supplies food and oxygen to the fetus during pregnancy.The multiple layers of the placenta include the:Amnion- the innermost membrane that surrounds the fetus during gestationChorion- outermost membrane that surrounds the fetus during gestationAmniotic fluidis the fluid surrounding the fetus within the amnion.Umbilical cordis the vascular conduit connecting the fetus to the placenta comprised of the umbilical vein, arteries, allantois and yolk sac embedded in Whartons jelly.Whartons Jellyis a gelatinous soft connective tissue derived from extra-embryonic mesoderm within the umbilical cord.4Theamniotic membraneitself is divided into three histologic layers:A singleepithelial layerA thickbasement membraneAnavascular stromal (mesenchymal) layer5.6,7,8The avascular stromal layer is further divided into three layers:6,7,8TheCompact layerThe middleFibroblast layerTheSpongy layerTheSpongy Layer, loosely connected to the chorionic membrane, is highly concentrated with proteoglycans and glycoproteins including hyaluronic acid, as well as type I, III, and IV collagen.5,6,8,9Themiddle Fibroblast layeris made up of type I, III, V, and VI collagen.6,8,9TheCompact layerthat sits adjacent to the basement membrane is composed of collagen Types I, III, V, and VI, along with fibronectin.5,9Thebasement membraneanchors the epithelial layer (ref 13) and contains collagen Types IV, V and VII, fibronectin, laminin, and hyaluronic acid.6,10Adjacent to the basement membrane and in immediate contact with amniotic fluid is the single layer of epithelial cells.Amniotic epithelial cellsproduce type III and IV collagen, glycoproteins such as laminin and fibronectin, which become the basement membrane.5The amniotic membranes purpose is to house and physically protect the fetus, but additional functions include regulation of the pH of the amniotic fluid, transportation of water and soluble material between the mother and fetus, and the synthesis of numerous growth factors and cytokines. The amniotic membrane also secretes anti-inflammatory proteins. All of this results in these tissues having anti-inflammatory, anti-microbial, anti-fibroblastic, and non-immunogenic properties.Amniotic products have been asserted to be a source of stem cells. Both the amniotic epithelial layer (maternal derived cells) and mesenchymal (avascular stromal) layer derived from the embryonic mesoderm contain their respective stem cells that can differentiate into multiple cell lines, including myocytes, osteocytes, and chondrocytes.8,9Amniotic fluid also is found to contain amniotic mesenchymal stem cells.7The chorionic membrane adjacent to the mothers endometrium during development of the fetus. Umbilical cord, Whartons jelly, and umbilical cord blood have also been found to contain mesenchymal stem cells.7,11Under normal conditions, placental tissues are collected via aseptic technique during cesarean section. Protocols vary as to how the tissues are harvested, prepared, preserved and stored. Testing is also required to ensure these tissues do not carry any communicable diseases transmissible from donor to recipient.Because the spongy layer loosely connects the amniotic membrane to the chorionic membrane, these two layers are easily separated upon blunt dissection at initial harvesting.10Other than ease of separation between amniotic and chorionic membranes, the following steps in processing the tissues into the desired form vary, based on the portions of the placental tissues extracted, sterilization processes (if any) undertaken, and method of preservation utilized. Common methods of preservation include cryopreservation, lyophilization (freeze-drying), glycerol-preservation, (gamma)-sterilization, low heat dehydration, and vitrification.5,8,9,10A process called Decellularization may be used in which the layer of amniotic epithelial cells is removed from the collected amniotic membrane, leaving behind the valuable extracellular matrix components. Removal of all cellular components is thought to lessen the possibility of eliciting an immune response.3,10Different decellularization processes are available. Eventual preparation of sheets, particulate suspensions, liquids, or gels allows the final marketed product.Depending on the methods utilized, the processing of placental and amniotic-based tissues will affect the viability of cellular components, growth factors, and other valuable properties for which these tissues are promoted. To date, there are significant differences that exist in the processing of different placental and amniotic-based tissue products.3,5Lack of consistency and standardization within propriety manufacturing (preparation) processes precludes determination and comparison of the final product form, characteristics, properties, and components.The Food and Drug Administration (FDA), under Sect. 361 of the Public Health Service Act (regulated by the Centers for Biologics Evaluation and Research CBER, an arm of the FDA) oversees the therapeutic use of "Human cells or tissue products" or HCT/Ps. Once these types products are harvested, their process and handling will determine whether the products fall under Section 361 guidance or default to the more regulated section 351 of the Public Health Service Act and/or the Federal Food, Drug, and Cosmetic Act. The regulatory pathway for pre-market FDA approval of new drugs, devices and/or biological products, requires registration as a (NDA) New Drug application, an (IND) Investigational New Drug application, or a (BLA) Biologics License Approval.8,9,12,13If a human cells or tissue product should meet Section 361 FDA requirements, the product will not require FDA pre-market review and approval. To meet Section 361 FDA regulatory requirements, the placental/amniotic-based tissue product must meet the following 4 criteria: The HCT/P is:Minimally ManipulatedIntended for Homologous Use (as reflected by the labeling, advertising, or other indications of the manufacturers objective intent)The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/PEither:The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; orThe HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and:Is for autologous use;Is for allogeneic use in a first-degree or second-degree blood relative; orIs for reproductive use12Due to the ongoing development of new products and clinical trials, the field of FDA regulatory requirements is fluid and evolving. It is the expectation that the respective Medicare Administrative Contractor will continue to follow any guidance and insight as it is brought forward by the FDA.Lack of standard formulation, dose, frequency of administration, and standard of care in treatment with these products further complicates regulation and guidance determinations.Despite this lack of standardization, numerous amniotic and placental-derived products have been released for use in treatment of musculoskeletal conditions. These conditions include, but are not limited to tendon/ligament injuries, musculoskeletal injuries, cartilage damage, osteoarthritis, (or pain related of these conditions) as well as an adjunctive to orthopedic surgical treatments. Due to the lack of component standardization, the remainder of this LCD will use the term amniotic and placental-derived products to mean ANY product derived from ANY combination of amniotic membrane/chorion/placenta/Whartons jelly/umbilical cord/amniotic fluid/umbilical cord blood.Although amniotic and placental-derived products are marketed to treat certain musculoskeletal conditions, there is limited support for safety and efficacy from human clinical trials available.All injectable amniotic and/or placental-derived products fall under FDA section 551 of the Federal Food, Drug, and Cosmetic Act. Promotion relating to novel indication or evidence of new intended use may constitute labeling, adulteration, or misbranding of the drug or device if such dissemination fails to comply with section 551 of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 360aaa) and the requirements of this part. A manufacturers failure to exercise due diligence in submitting the clinical studies necessary for the approval of a new use as subject of information disseminated under this part or in beginning or completing such clinical studies shall be deemed a failure to comply with section 551 of the act and the requirement of this part. Use of any amniotic and/or placental-derived products that have not met the requirements of section 551 of the Federal Food, Drug, and Cosmetic Act will be denied per Medicare Benefit Policy Manual 100-2 Chapter 15 Section 50.4.1 and associated services will also be denied per Medicare Benefit Policy Manual 100-2 Chapter 16 Section 180.General InformationAssociated InformationN/ASources of InformationN/ABibliographyZakrzewski W, Dobrzynski M, Szymonowicz M, and Rybak Z. Stem Cells: Past, Present, and Future. Stem Cell Research & Therapy 2019 10:68.doi:10.1186/s13287-019-1165-5Dhillon MS, Behera P, Patel S, and Shetty V. Orthobiologics and Platelet Rich Plasma. Indian J of Orthop. 2014 Jan-Feb; 48(1):1-9.doi:10.4103/0019-5413.125477
Local Coverage Determinations, LCD, Local policies, Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound, DL39116	Use this page to view details for the Local Coverage Determination for Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound.	PROPOSED	Proposed LCD - Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound (DL39116)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39115&ver=5	lcd-39115-5-1.txt	1	39115	lcd	5	1	0b07354d-16f0-4e33-b5b4-75016e643c0e	General InformationAssociated InformationN/ASources of InformationN/ABibliographyZakrzewski W, Dobrzynski M, Szymonowicz M, and Rybak Z. Stem Cells: Past, Present, and Future. Stem Cell Research & Therapy 2019 10:68.doi:10.1186/s13287-019-1165-5Dhillon MS, Behera P, Patel S, and Shetty V. Orthobiologics and Platelet Rich Plasma. Indian J of Orthop. 2014 Jan-Feb; 48(1):1-9.doi:10.4103/0019-5413.125477Sultan AA, Piuzzi NS, Mont MA. Nonoperative Applications of Placental Tissue Matrix in Orthopaedic Sports Injuries: A Review of Literature. Clin J Sport Med. Jul 2020;30(4):383-389. doi:10.1097/jsm.0000000000000684Gabbe SG, Niebyl JR, Simpson JL, et al. Obstetricsnormal and problem pregnancies. 5th ed. Philadelphia: Churchill Livingstone; 2007.Niknejad H, Peirovi H, Jorjani M, Ahmadiani A, Ghanavi J, Seifalian AM. Properties of the Amniotic Membrane for Potential use in Tissue Engineering. European Cells and Materials. Vol. 15 2008. Pg 88-99.doi:10.22203/ecm.v015a07Huddleston HP, Cohn MR, Haunschild ED, Wong SE, Farr J, Yanke AB. Amniotic Product Treatments: Clinical and Basic Science Evidence. Curr Rev Musculoskelet Med. 2020 Apr;13(2):148-154. PMID: 32076938McIntyre JA, Jones IA, Danilkovich A, Vangsness CT Jr.McIntyre JA, et al. The Placenta: Applications in Orthopaedic Sports Medicine. Am J Sports Med. 2018 Jan;46(1):234-247.
Local Coverage Determinations, LCD, Local policies, Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound, DL39116	Use this page to view details for the Local Coverage Determination for Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound.	PROPOSED	Proposed LCD - Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound (DL39116)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39115&ver=5	lcd-39115-5-1.txt	1	39115	lcd	5	2	7f3290b1-2f7f-4501-b1ba-acc370b82268	Gabbe SG, Niebyl JR, Simpson JL, et al. Obstetricsnormal and problem pregnancies. 5th ed. Philadelphia: Churchill Livingstone; 2007.Niknejad H, Peirovi H, Jorjani M, Ahmadiani A, Ghanavi J, Seifalian AM. Properties of the Amniotic Membrane for Potential use in Tissue Engineering. European Cells and Materials. Vol. 15 2008. Pg 88-99.doi:10.22203/ecm.v015a07Huddleston HP, Cohn MR, Haunschild ED, Wong SE, Farr J, Yanke AB. Amniotic Product Treatments: Clinical and Basic Science Evidence. Curr Rev Musculoskelet Med. 2020 Apr;13(2):148-154. PMID: 32076938McIntyre JA, Jones IA, Danilkovich A, Vangsness CT Jr.McIntyre JA, et al. The Placenta: Applications in Orthopaedic Sports Medicine. Am J Sports Med. 2018 Jan;46(1):234-247.Riboh JC, Saltzman BM, Yanke AB, Cole BJ. Human Amniotic Membrane-Derived Products in Sports Medicine: Basic Science, Early Results, and Potential Clinical Applications. Am J Sports Med. 2016 Sep;44(9):2425-34.Hannon CP, Yanke AB, Farr J. Amniotic Tissue Modulation of Knee Pain-A Focus on Osteoarthritis. J Knee Surg. 2019 Jan;32(1):26-36. doi:10.1055/s-0038-1676370Leal-Marin S, Kern T, Hofmann N, Pogozhykh O, Framme C, Brgel M, Figueiredo C, Glasmacher B, Gryshkov O. Human Amniotic Membrane: A review on tissue engineering, application, and storage. J Biomed Mater Res. 2021;118. doi.org/10.1002/jbm.b.34782Farr J, Gomoll AH, Yanke AB, Strauss EJ, Mowry KC. A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms. J Knee Surg. Nov 2019;32(11):1143-1154. doi:10.1055/s-0039-1696672FDA Guidance for Industry and Food and Drug Administration Staff. Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use. 2020 July.Guidance for Industry Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Small Entity Compliance Guide. U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research. 2007 Aug.Gellhorn A.C., Han A. The use of dehydrated human amnion/chorion membrane allograft injection for the treatment of tendinopathy or arthritis: a case series involving 40 patients.PM&R. 2017;9(12):1236-1243. doi:10.1016/j.pmrj.2017.04.011Buck D. Amniotic umbilical cord particulate for discogenic pain.Am. Osteopath. Assoc.2019;119(12):814-819. doi:10.7556/jaoa.2019.138Ross A, Gambrill V, Main C. Clinical outcomes of amniotic membrane/umbilical cord particulate in spinal disorders: a retrospective study.J Pain Res. 2022;15:3971-3979. doi:10.2147/JPR.S375201, 10.2147/JPR.S375201Ackley JF, Kolosky M, Gurin D, Hampton R, Masin R, Krahe D. Cryopreserved amniotic membrane and umbilical cord particulate matrix for partial rotator cuff tears: A case series. Medicine (Baltimore). Jul 2019;98(30):e16569. doi:10.1097/md.0000000000016569Aufiero, D, Sampson, S, Onishi, K, and Bemden, V. Treatment of medial and lateral elbow tendinosis with an injectable amniotic membrane allografta retrospective case series.J Pain Relief. 2016;5(3):242.Quinet MT, Raghavan M, Morris E, et al. Effectiveness of amniotic fluid injection in the treatment of trigger finger: a pilot study.Journal of Hand Surgery Global Online. 2020;2(5):301-305.Cazzell S., Stewart J., Agnew P.S., et al Randomized controlled trial of micronized dehydrated human amnion/chorion membrane (dHACM) injection compared to placebo for the treatment of plantar fasciitis.Foot Ankle Int. 2018;39(10):1151-1161. doi:10.1177/1071100718788549Zelen C.M., Poka A., Andrews J. Prospective, randomized, blinded, comparative study of injectable micronized dehydrated amniotic/chorionic membrane allograft for plantar fasciitis - A feasibility study.Foot Ankle Int. 2013;34(10):1332-1339. doi:10.1177/1071100713502179Hanselman A.E., Tidwell J.E., Santrock R.D. Cryopreserved human amniotic membrane injection for plantar fasciitis: A randomized, controlled, double-blind pilot study.Foot Ankle Int. 2015;36(2):151-158. doi:10.1177/1071100714552824Matthews M, Betrus CJ, Klein EE, et al. Comparison of Regenerative Injection Therapy and Conventional Therapy for Proximal Plantar Fasciitis.J Foot Ankle Surg. 2022;doi:10.1053/j.jfas.2022.11.010, 10.1053/j.jfas.2022.11.010Nakagawa H, Sung K, Ashkani-Esfahani S, et al. Plantar fasciitis: a comparison of ultrasound-guided fasciotomy with or without amniotic membrane allograft injection.Med. 2022;17(12):931-940. doi:10.2217/rme-2022-0094Werber B: Amniotic tissues for the treatment of chronic plantar fasciosis and Achilles tendinosis.J Sports Med(Hindawi Publ Corp) 2015;2015:219896Lullove E. A flowable placental tissue matrix allograft in lower extremity injuries: a pilot study. 2015;7:e275.Spector JE, Hubbs B, Kot K, et al. Micronized dehydrated human amnion/chorion membrane injection in the treatment of chronic Achilles tendinitis.J Am Podiatr Med Assoc. 2021;111(6)doi:10.7547/19-170, 10.7547/19-170Gomoll A.H., Farr J., Cole B.J., et al. Safety and efficacy of an amniotic suspension allograft injection over 12 months in a single-blinded, randomized controlled trial for symptomatic osteoarthritis of the knee.J. Arthrosc. Relat. Surg.2021;37:22462257. doi: 10.1016/j.arthro.2021.02.044.elik D, oban , Kilioglu . Minimal clinically important difference of commonly used hip-, knee-, foot-, and ankle-specific questionnaires: a systematic review.J Clin Epidemiol. 2019;113:44-57. doi:10.1016/j.jclinepi.2019.04.017McCarthy M Jr, Chang CH, Pickard AS, et al. Visual analog scales for assessing surgical pain.J Am Coll Surg. 2005;201(2):245-252. doi:10.1016/j.jamcollsurg.2005.03.034Landorf KB, Radford JA, Hudson S. Minimal important difference (MID) of two commonly used outcome measures for foot problems.J Foot Ankle Res2010;3(1):7.Gallagher EJ, Liebman M, Bijur PE. Prospective validation of clinically important changes in pain severity measured on a visual analog scale.Ann Emerg Med2001;38(6):633-638.Alden KJ, Harris S, Hubbs B, et al. Micronized dehydrated human amnion chorion membrane injection in the treatment of knee osteoarthritis a large retrospective case series.J Knee Surg. 2021;34(8):841-845. doi:10.1055/s-0039-3400951, 10.1055/s-0039-3400951Castellanos R, Tighe S. Injectable amniotic membrane/umbilical cord particulate for knee osteoarthritis: a prospective, single-center pilot study.Pain Med. 2019;20(11):2283-2291. doi:10.1093/pm/pnz143Mead OG, Mead LP. Intra-articular injection of amniotic membrane and umbilical cord particulate for the management of moderate to severe knee osteoarthritis.Res. Rev.2020;12:161170. doi: 10.2147/ORR.S272980.Natali S, Farinelli L, Screpis D, et al. Human amniotic suspension allograft improves pain and function in knee osteoarthritis: a prospective not randomized clinical pilot study.Clin. Med. 2022;11(12)doi:10.3390/jcm11123295,10.3390/jcm11123295Meadows MC, Elisman K, Nho SJ, et al. A single injection of amniotic suspension allograft is safe and effective for treatment of mild to moderate hip osteoarthritis: a prospective study. 2022;38:325331. doi: 10.1016/j.arthro.2021.04.034.Guimaraes JDS, Arcanjo FL, Leporace G, et al Effects of therapeutic interventions on pain due to plantar fasciitis: A systematic review and meta-analysis.Rehabil. 2022;no pagination. doi:10.1177/02692155221143865Zaffagnini M, Boffa A, Andriolo L, et al. Orthobiologic injections for the treatment of hip osteoarthritis: a systematic review.J Clin Med. 2022;11(22):6663. Published 2022 Nov 10. doi:10.3390/jcm11226663Aratikatla A, Maffulli N, Rodriguez HC, et al. Allogenic perinatal tissue for musculoskeletal regenerative medicine applications: a systematic review protocol. J. Orthop. Surg.2022;17(1):307. doi:10.1186/s13018-022-03197-z,10.1186/s13018-022-03197-zSultan AA, Samuel LT, Roth A, et al. Operative Applications of Placental Tissue Matrix in Orthopaedic Sports Injuries: A Review of the Literature.Surg Technol Int.2019;34:397-402.McIntyre JA, Jones IA, Danilkovich A, Vangsness CT. The placenta: applications in orthopaedic sports medicine.J. Sports Med. 2018;46(1):234-247. doi:10.1177/0363546517697682Tsikopoulos K, Vasiliadis HS, Mavridis D. Injection therapies for plantar fasciopathy ('plantar fasciitis'): A systematic review and network meta-analysis of 22 randomised controlled trials.J. Sports Med. 2016;50(22):1367-1375. doi:10.1136/bjsports-2015-095437Sterne JAC, Savovic J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials.BMJ. 2019;366:l4898. Published 2019 Aug 28. doi:10.1136/bmj.l4898Schnemann H, Brozek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013.The GRADE Working Group, 2013. Available fromguidelinedevelopment.org/handbook.
Local Coverage Determinations, LCD, Local policies, Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound, DL39118	Use this page to view details for the Local Coverage Determination for Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound.	PROPOSED	Proposed LCD - Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound (DL39118)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39117&ver=4	lcd-39117-4-1.txt	1	39117	lcd	4	0	8574a7d6-0452-4199-9bd2-16660aa4fe77	CMS National Coverage PolicyTitle XVIII of the Social Security Act, 1862(a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.Title XVIII of the Social Security Act, 1862(a)(1)(D) addresses services that are determined to be investigational or experimental.CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 16, 10 General Exclusions from CoverageCMS Internet-Only Manual, Pub. 100-04, Medicare Claims Processing Manual, Chapter 23, 30A Physicians ServicesCMS Internet-Only Manual, Pub. 100-04, Medicare Claims Processing Manual, Chapter 30, 50.3.1 Mandatory ABN UsesCoverage Indications, Limitations, and/or Medical NecessityThis is a NON-coverage policy for allamniotic membrane, amniotic fluid or other placental-derived productinjections and/or applications as a means of managing musculoskeletal injuries, joint conditions, and all other conditions not stated below.This guidance does NOT include discussion on burns, wounds or ophthalmic conditions.NOTE: For information on stem cell transplantation please see CMS National Coverage Determination 110.23 Stem Cell TransplantationIntroductionAmniotic and placental-derived products are reported to possess certain beneficial characteristics. These products have been proposed as a source of stem cells. Stem cells, by definition, have the capability to differentiate into any cell of an organism as well as the capability of self-renewal.1In addition, the extracellular matrix (ECM) of placental and amniotic-based tissues are rich in collagen, glycoproteins, proteoglycans, fibroblasts, as well as many cytokines and growth factors thought to promote healing with a lower risk of low immunologic reaction.Based on these characteristics, amniotic and placental-derived products are currently being studied and marketed as allografts that serve as:scaffolds for tissue engineeringmembrane covering certain burns, wounds, and ophthalmic corneal injuriesmicronized/particulate products suspended in an aqueous material to be applied topically or injected into joints, tendons, ligamentsapplications or injections performed intra-operatively to promote post-operative healingThese amniotic and placental-derived products are further being investigated for a multitude of indications, including but not limited to musculoskeletal conditions involving joint pain and back pain, chronic pain in general, dental conditions, alopecia, wounds, burns, and a plethora of others. In the quest to find alternative treatments for certain musculoskeletal conditions, the emergence of a class of substances being marketed as orthobiologics has become more prevalent in the pharmaceutical market. Orthobiologics are biological products aimed at treating musculoskeletal conditions purported to heal injury/trauma, slow degenerative processes and affect regeneration of tissues.2The end result ideally would be decreased pain and increased function. One such category of orthobiologics involves incorporation of human amniotic and placental-derived products.The amniotic and placental-derived products are obtained from the placenta of donors, usually immediately post C-section at full term and screened for transmittable diseases. These products are made up of varying combinations of amniotic membrane, amniotic fluid, chorionic membrane, umbilical cord, umbilical cord blood, and what is known as Whartons jelly.3Definitions:ThePlacentais a multi-layered circulatory temporary organ that supplies food and oxygen to the fetus during pregnancy.The multiple layers of the placenta include the:Amnion- the innermost membrane that surrounds the fetus during gestationChorion- outermost membrane that surrounds the fetus during gestationAmniotic fluidis the fluid surrounding the fetus within the amnion.Umbilical cordis the vascular conduit connecting the fetus to the placenta comprised of the umbilical vein, arteries, allantois and yolk sac embedded in Whartons jelly.Whartons Jellyis a gelatinous soft connective tissue derived from extra-embryonic mesoderm within the umbilical cord.4Theamniotic membraneitself is divided into 3 histologic layers:A singleepithelial layerA thickbasement membraneAnavascular stromal (mesenchymal) layer5.6,7,8The avascular stromal layer is further divided into 3 layers:6,7,8TheCompact layerThe middleFibroblast layerTheSpongy layerTheSpongy Layer, loosely connected to the chorionic membrane, is highly concentrated with proteoglycans and glycoproteins including hyaluronic acid, as well as type I, III, and IV collagen.5,6,8,9Themiddle Fibroblast layeris made up of type I, III, V, and VI collagen.6,8,9TheCompact layerthat sits adjacent to the basement membrane is composed of collagen Types I, III, V, and VI, along with fibronectin.5,9Thebasement membraneanchors the epithelial layer (ref 13) and contains collagen Types IV, V and VII, fibronectin, laminin, and hyaluronic acid.6,10Adjacent to the basement membrane and in immediate contact with amniotic fluid is the single layer of epithelial cells.Amniotic epithelial cellsproduce type III and IV collagen, glycoproteins such as laminin and fibronectin, which become the basement membrane.5The amniotic membranes purpose is to house and physically protect the fetus, but additional functions include regulation of the pH of the amniotic fluid, transportation of water and soluble material between the mother and fetus, and the synthesis of numerous growth factors and cytokines. The amniotic membrane also secretes anti-inflammatory proteins. All of this results in these tissues having anti-inflammatory, anti-microbial, anti-fibroblastic, and non-immunogenic properties.Amniotic products have been asserted to be a source of stem cells. Both the amniotic epithelial layer (maternal derived cells) and mesenchymal (avascular stromal) layer derived from the embryonic mesoderm contain their respective stem cells that can differentiate into multiple cell lines including myocytes, osteocytes, and chondrocytes.8,9Amniotic fluid also is found to contain amniotic mesenchymal stem cells.7The chorionic membrane connected adjacent to the mothers endometrium during development of the fetus. Umbilical cord, Whartons jelly, and umbilical cord blood have also been found to contain mesenchymal stem cells.7,11Under normal conditions, placental tissues are collected via aseptic technique during cesarean section. Protocols vary as to how the tissues are harvested, prepared, preserved and stored. Testing is also required to ensure these tissues do not carry any communicable diseases transmissible from donor to recipient.Because the spongy layer loosely connects the amniotic membrane to the chorionic membrane, these two layers are easily separated upon blunt dissection at initial harvesting.10Other than ease of separation between amniotic and chorionic membranes, the following steps in processing the tissues into the desired form vary, based on the portions of the placental tissues extracted, sterilization processes (if any) undertaken, and method of preservation utilized. Common methods of preservation include cryopreservation, lyophilization (freeze-drying), glycerol-preservation, (gamma)-sterilization, low heat dehydration, and vitrification.5,8,9,10A process called Decellularization may be used in which the layer of amniotic epithelial cells is removed from the collected amniotic membrane, leaving behind the valuable extracellular matrix components. Removal of all cellular components is thought to lessen the possibility of eliciting an immune response.3,10Different decellularization processes are available. Eventual preparation of sheets, particulate suspensions, liquids, or gels allows the final marketed product.Depending on the methods utilized, the processing of placental and amniotic-based tissues will affect the viability of cellular components, growth factors, and other valuable properties for which these tissues are promoted. To date, there are significant differences that exist in the processing of different placental and amniotic-based tissue products.3,5Lack of consistency and standardization within propriety manufacturing (preparation) processes precludes determination and comparison of the final product form, characteristics, properties, and components.The Food and Drug Administration (FDA), under Sect. 361 of the Public Health Service Act (regulated by the Centers for Biologics Evaluation and Research CBER, an arm of the FDA) oversees the therapeutic use of Human cells or tissue products or HCT/Ps. Once these types of products are harvested, their process and handling will determine whether the products fall under Section 361 guidance or default to the more regulated section 351 of the Public Health Service Act and/or the Federal Food, Drug, and Cosmetic Act. The regulatory pathway for pre-market FDA approval of new drugs, devices and/or biological products, requires registration as a (NDA) New Drug application, an (IND) Investigational New Drug application, or a (BLA) Biologics License Approval.8,9,12,13If a human cells or tissue product should meet Section 361 FDA requirements, the product will not require FDA pre-market review and approval. To meet Section 361 FDA regulatory requirements, the placental/amniotic-based tissue product must meet the following 4 criteria: The HCT/P is:Minimally ManipulatedIntended for Homologous Use (as reflected by the labeling, advertising, or other indications of the manufacturers objective intent)The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/PEither:The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; orThe HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and:Is for autologous use;Is for allogeneic use in a first-degree or second-degree blood relative; orIs for reproductive use12Due to the ongoing development of new products and clinical trials, the field of FDA regulatory requirements is fluid and evolving. It is the expectation that the respective Medicare Administrative Contractor will continue to follow any guidance and insight as it is brought forward by the FDA.Lack of standard formulation, dose, frequency of administration, and standard of care in treatment with these products further complicates regulation and guidance determinations.Despite this lack of standardization, numerous amniotic and placental-derived products have been released for use in treatment of musculoskeletal conditions. These conditions include, but are not limited to tendon/ligament injuries, musculoskeletal injuries, cartilage damage, osteoarthritis, (or pain related of these conditions) as well as an adjunctive to orthopedic surgical treatments. Due to the lack of component standardization, the remainder of this LCD will use the term amniotic and placental-derived products to mean ANY product derived from ANY combination of amniotic membrane/chorion/placenta/Whartons jelly/umbilical cord/amniotic fluid/umbilical cord blood.Although amniotic and placental-derived products are marketed to treat certain musculoskeletal conditions, there is limited support for safety and efficacy from human clinical trials available.All injectable amniotic and/or placental-derived products fall under FDA section 551 of the Federal Food, Drug, and Cosmetic Act. Promotion relating to novel indication or evidence of new intended use may constitute labeling, adulteration, or misbranding of the drug or device if such dissemination fails to comply with section 551 of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 360aaa) and the requirements of this part. A manufacturers failure to exercise due diligence in submitting the clinical studies necessary for the approval of a new use as subject of information disseminated under this part or in beginning or completing such clinical studies shall be deemed a failure to comply with section 551 of the act and the requirement of this part. Use of any amniotic and/or placental-derived products that have not met the requirements of section 551 of the Federal Food, Drug, and Cosmetic Act will be denied per Medicare Benefit Policy Manual 100-2 Chapter 15 Section 50.4.1 and associated services will also be denied per Medicare Benefit Policy Manual 100-2 Chapter 16 Section 180.General InformationAssociated InformationN/ASources of InformationN/ABibliographyZakrzewski W, Dobrzynski M, Szymonowicz M, and Rybak Z. Stem Cells: Past, Present, and Future. Stem Cell Research & Therapy 2019 10:68.doi:10.1186/s13287-019-1165-5Dhillon MS, Behera P, Patel S, and Shetty V. Orthobiologics and Platelet Rich Plasma. Indian J of Orthop. 2014 Jan-Feb; 48(1):1-9.doi:10.4103/0019-5413.125477
Local Coverage Determinations, LCD, Local policies, Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound, DL39118	Use this page to view details for the Local Coverage Determination for Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound.	PROPOSED	Proposed LCD - Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound (DL39118)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39117&ver=4	lcd-39117-4-1.txt	1	39117	lcd	4	1	5f9a3773-2622-4f16-9a8e-410520b009c3	General InformationAssociated InformationN/ASources of InformationN/ABibliographyZakrzewski W, Dobrzynski M, Szymonowicz M, and Rybak Z. Stem Cells: Past, Present, and Future. Stem Cell Research & Therapy 2019 10:68.doi:10.1186/s13287-019-1165-5Dhillon MS, Behera P, Patel S, and Shetty V. Orthobiologics and Platelet Rich Plasma. Indian J of Orthop. 2014 Jan-Feb; 48(1):1-9.doi:10.4103/0019-5413.125477Sultan AA, Piuzzi NS, Mont MA. Nonoperative Applications of Placental Tissue Matrix in Orthopaedic Sports Injuries: A Review of Literature. Clin J Sport Med. Jul 2020;30(4):383-389. doi:10.1097/jsm.0000000000000684Gabbe SG, Niebyl JR, Simpson JL, et al. Obstetricsnormal and problem pregnancies. 5th ed. Philadelphia: Churchill Livingstone; 2007.Niknejad H, Peirovi H, Jorjani M, Ahmadiani A, Ghanavi J, Seifalian AM. Properties of the Amniotic Membrane for Potential use in Tissue Engineering. European Cells and Materials. Vol. 15 2008. Pg 88-99.doi:10.22203/ecm.v015a07Huddleston HP, Cohn MR, Haunschild ED, Wong SE, Farr J, Yanke AB. Amniotic Product Treatments: Clinical and Basic Science Evidence. Curr Rev Musculoskelet Med. 2020 Apr;13(2):148-154. PMID: 32076938McIntyre JA, Jones IA, Danilkovich A, Vangsness CT Jr.McIntyre JA, et al. The Placenta: Applications in Orthopaedic Sports Medicine. Am J Sports Med. 2018 Jan;46(1):234-247.
Local Coverage Determinations, LCD, Local policies, Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound, DL39118	Use this page to view details for the Local Coverage Determination for Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound.	PROPOSED	Proposed LCD - Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound (DL39118)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39117&ver=4	lcd-39117-4-1.txt	1	39117	lcd	4	2	5707518f-7a48-46aa-91aa-624425e8971f	Gabbe SG, Niebyl JR, Simpson JL, et al. Obstetricsnormal and problem pregnancies. 5th ed. Philadelphia: Churchill Livingstone; 2007.Niknejad H, Peirovi H, Jorjani M, Ahmadiani A, Ghanavi J, Seifalian AM. Properties of the Amniotic Membrane for Potential use in Tissue Engineering. European Cells and Materials. Vol. 15 2008. Pg 88-99.doi:10.22203/ecm.v015a07Huddleston HP, Cohn MR, Haunschild ED, Wong SE, Farr J, Yanke AB. Amniotic Product Treatments: Clinical and Basic Science Evidence. Curr Rev Musculoskelet Med. 2020 Apr;13(2):148-154. PMID: 32076938McIntyre JA, Jones IA, Danilkovich A, Vangsness CT Jr.McIntyre JA, et al. The Placenta: Applications in Orthopaedic Sports Medicine. Am J Sports Med. 2018 Jan;46(1):234-247.Riboh JC, Saltzman BM, Yanke AB, Cole BJ. Human Amniotic Membrane-Derived Products in Sports Medicine: Basic Science, Early Results, and Potential Clinical Applications. Am J Sports Med. 2016 Sep;44(9):2425-34.Hannon CP, Yanke AB, Farr J. Amniotic Tissue Modulation of Knee Pain-A Focus on Osteoarthritis. J Knee Surg. 2019 Jan;32(1):26-36. doi:10.1055/s-0038-1676370Leal-Marin S, Kern T, Hofmann N, Pogozhykh O, Framme C, Brgel M, Figueiredo C, Glasmacher B, Gryshkov O. Human Amniotic Membrane: A review on tissue engineering, application, and storage. J Biomed Mater Res. 2021;118. doi.org/10.1002/jbm.b.34782Farr J, Gomoll AH, Yanke AB, Strauss EJ, Mowry KC. A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms. J Knee Surg. Nov 2019;32(11):1143-1154. doi:10.1055/s-0039-1696672FDA Guidance for Industry and Food and Drug Administration Staff. Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use. 2020 July.Guidance for Industry Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Small Entity Compliance Guide. U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research. 2007 Aug.Gellhorn A.C., Han A. The use of dehydrated human amnion/chorion membrane allograft injection for the treatment of tendinopathy or arthritis: a case series involving 40 patients.PM&R. 2017;9(12):1236-1243. doi:10.1016/j.pmrj.2017.04.011Buck D. Amniotic umbilical cord particulate for discogenic pain.Am. Osteopath. Assoc.2019;119(12):814-819. doi:10.7556/jaoa.2019.138Ross A, Gambrill V, Main C. Clinical outcomes of amniotic membrane/umbilical cord particulate in spinal disorders: a retrospective study.J Pain Res. 2022;15:3971-3979. doi:10.2147/JPR.S375201, 10.2147/JPR.S375201Ackley JF, Kolosky M, Gurin D, Hampton R, Masin R, Krahe D. Cryopreserved amniotic membrane and umbilical cord particulate matrix for partial rotator cuff tears: A case series. Medicine (Baltimore). Jul 2019;98(30):e16569. doi:10.1097/md.0000000000016569Aufiero, D, Sampson, S, Onishi, K, and Bemden, V. Treatment of medial and lateral elbow tendinosis with an injectable amniotic membrane allografta retrospective case series.J Pain Relief. 2016;5(3):242.Quinet MT, Raghavan M, Morris E, et al. Effectiveness of amniotic fluid injection in the treatment of trigger finger: a pilot study.Journal of Hand Surgery Global Online. 2020;2(5):301-305.Cazzell S., Stewart J., Agnew P.S., et al Randomized controlled trial of micronized dehydrated human amnion/chorion membrane (dHACM) injection compared to placebo for the treatment of plantar fasciitis.Foot Ankle Int. 2018;39(10):1151-1161. doi:10.1177/1071100718788549Zelen C.M., Poka A., Andrews J. Prospective, randomized, blinded, comparative study of injectable micronized dehydrated amniotic/chorionic membrane allograft for plantar fasciitis - A feasibility study.Foot Ankle Int. 2013;34(10):1332-1339. doi:10.1177/1071100713502179Hanselman A.E., Tidwell J.E., Santrock R.D. Cryopreserved human amniotic membrane injection for plantar fasciitis: A randomized, controlled, double-blind pilot study.Foot Ankle Int. 2015;36(2):151-158. doi:10.1177/1071100714552824Matthews M, Betrus CJ, Klein EE, et al. Comparison of Regenerative Injection Therapy and Conventional Therapy for Proximal Plantar Fasciitis.J Foot Ankle Surg. 2022;doi:10.1053/j.jfas.2022.11.010, 10.1053/j.jfas.2022.11.010Nakagawa H, Sung K, Ashkani-Esfahani S, et al. Plantar fasciitis: a comparison of ultrasound-guided fasciotomy with or without amniotic membrane allograft injection.Med. 2022;17(12):931-940. doi:10.2217/rme-2022-0094Werber B: Amniotic tissues for the treatment of chronic plantar fasciosis and Achilles tendinosis.J Sports Med(Hindawi Publ Corp) 2015;2015:219896Lullove E. A flowable placental tissue matrix allograft in lower extremity injuries: a pilot study. 2015;7:e275.Spector JE, Hubbs B, Kot K, et al. Micronized dehydrated human amnion/chorion membrane injection in the treatment of chronic Achilles tendinitis.J Am Podiatr Med Assoc. 2021;111(6)doi:10.7547/19-170, 10.7547/19-170Gomoll A.H., Farr J., Cole B.J., et al. Safety and efficacy of an amniotic suspension allograft injection over 12 months in a single-blinded, randomized controlled trial for symptomatic osteoarthritis of the knee.J. Arthrosc. Relat. Surg.2021;37:22462257. doi: 10.1016/j.arthro.2021.02.044.elik D, oban , Kilioglu . Minimal clinically important difference of commonly used hip-, knee-, foot-, and ankle-specific questionnaires: a systematic review.J Clin Epidemiol. 2019;113:44-57. doi:10.1016/j.jclinepi.2019.04.017McCarthy M Jr, Chang CH, Pickard AS, et al. Visual analog scales for assessing surgical pain.J Am Coll Surg. 2005;201(2):245-252. doi:10.1016/j.jamcollsurg.2005.03.034Landorf KB, Radford JA, Hudson S. Minimal important difference (MID) of two commonly used outcome measures for foot problems.J Foot Ankle Res2010;3(1):7.Gallagher EJ, Liebman M, Bijur PE. Prospective validation of clinically important changes in pain severity measured on a visual analog scale.Ann Emerg Med2001;38(6):633-638.Alden KJ, Harris S, Hubbs B, et al. Micronized dehydrated human amnion chorion membrane injection in the treatment of knee osteoarthritis a large retrospective case series.J Knee Surg. 2021;34(8):841-845. doi:10.1055/s-0039-3400951, 10.1055/s-0039-3400951Castellanos R, Tighe S. Injectable amniotic membrane/umbilical cord particulate for knee osteoarthritis: a prospective, single-center pilot study.Pain Med. 2019;20(11):2283-2291. doi:10.1093/pm/pnz143Mead OG, Mead LP. Intra-articular injection of amniotic membrane and umbilical cord particulate for the management of moderate to severe knee osteoarthritis.Res. Rev.2020;12:161170. doi: 10.2147/ORR.S272980.Natali S, Farinelli L, Screpis D, et al. Human amniotic suspension allograft improves pain and function in knee osteoarthritis: a prospective not randomized clinical pilot study.Clin. Med. 2022;11(12)doi:10.3390/jcm11123295,10.3390/jcm11123295Meadows MC, Elisman K, Nho SJ, et al. A single injection of amniotic suspension allograft is safe and effective for treatment of mild to moderate hip osteoarthritis: a prospective study. 2022;38:325331. doi: 10.1016/j.arthro.2021.04.034.Guimaraes JDS, Arcanjo FL, Leporace G, et al Effects of therapeutic interventions on pain due to plantar fasciitis: A systematic review and meta-analysis.Rehabil. 2022;no pagination. doi:10.1177/02692155221143865Zaffagnini M, Boffa A, Andriolo L, et al. Orthobiologic injections for the treatment of hip osteoarthritis: a systematic review.J Clin Med. 2022;11(22):6663. Published 2022 Nov 10. doi:10.3390/jcm11226663Aratikatla A, Maffulli N, Rodriguez HC, et al. Allogenic perinatal tissue for musculoskeletal regenerative medicine applications: a systematic review protocol. J. Orthop. Surg.2022;17(1):307. doi:10.1186/s13018-022-03197-z,10.1186/s13018-022-03197-zSultan AA, Samuel LT, Roth A, et al. Operative Applications of Placental Tissue Matrix in Orthopaedic Sports Injuries: A Review of the Literature.Surg Technol Int.2019;34:397-402.McIntyre JA, Jones IA, Danilkovich A, Vangsness CT. The placenta: applications in orthopaedic sports medicine.J. Sports Med. 2018;46(1):234-247. doi:10.1177/0363546517697682Tsikopoulos K, Vasiliadis HS, Mavridis D. Injection therapies for plantar fasciopathy ('plantar fasciitis'): A systematic review and network meta-analysis of 22 randomised controlled trials.J. Sports Med. 2016;50(22):1367-1375. doi:10.1136/bjsports-2015-095437Sterne JAC, Savovic J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials.BMJ. 2019;366:l4898. Published 2019 Aug 28. doi:10.1136/bmj.l4898Schnemann H, Brozek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013.The GRADE Working Group, 2013. Available fromguidelinedevelopment.org/handbook.
Local Coverage Determinations, LCD, Local policies, Colon Capsule Endoscopy (CCE), DL38571	Use this page to view details for the Local Coverage Determination for Colon Capsule Endoscopy (CCE).	PROPOSED	Proposed LCD - Colon Capsule Endoscopy (CCE) (DL38571)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39122&ver=3	lcd-39122-3-1.txt	1	39122	lcd	3	0	865fe06e-8fab-4ac7-9bf8-9e2364f248ee	CMS National Coverage PolicyTitle XVIII of the Social Security Act (SSA):Section 1862(a)(1)(A) excludes expenses incurred for items or services which are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.Section 1833(e) prohibits Medicare payment for any claim which lacks the necessary information to process the claim.Code of Federal Regulations:42 CFR 410.32 indicates that diagnostic tests may only be ordered by a treating physician (or other treating practitioner acting within the scope of their license and Medicare requirements) who furnishes a consultation or treats a beneficiary for a specific medical problem and who uses the results in the management of the beneficiary's specific medical problem. Tests not ordered by the physician (or other qualified non-physician provider) who is treating the beneficiary are not reasonable and necessary (see Sec. 411.15(k)(1) of this chapterCMS Publications:CMS Publication 100-04,Medicare Claims Processing Manual, Chapter 23: 10.1 - 10.1.7 ICD-10-CM Coding for Diagnostic Tests.Coverage Indications, Limitations, and/or Medical NecessityDiagnostic and/or surveillance* (performed for signs/symptoms of disease) colon capsule colonoscopy (CCE) is medically necessary for the detection of colon polyps when EITHER of the following criteria are met:Secondary procedure after an incomplete diagnostic optical colonoscopy (OC) with adequate preparation, and a complete evaluation of the colon was not technically possible (1,2) whenEITHERof the following criteria are metDetection or surveillance of colon polyp(s)ORDiagnostic procedure whenANYof the following criteria are met (3):Fecal Occult Blood Test (FOBT) positive (guaiac or immunochemical)ORMultitarget Stool DNA (sDNA) Test positiveORBlood-based biomarker colorectal cancer screening test positiveOROther evidence of lower GI bleed in hemodynamically stable patientsPrimary procedure in patients with major risks for OC or moderate sedation as indicated from an evaluation of the patient by a board certified or board eligible gastroenterologist, a surgeon trained in endoscopy, or a physician with equivalent endoscopic training whenEITHERof the following criteria are met:Surveillance of colon polyp(s) in previously diagnosed patientsORDiagnostic procedure whenANYof the following criteria are met (3):Fecal Occult Blood Test (FOBT) positive (guaiac or immunochemical)ORMultitarget Stool DNA (sDNA) Test positiveORBlood-based biomarker colorectal cancer screening test positiveOROther evidence of lower GI bleed in hemodynamically stable patientsExclusion Criteria (NONE of the below are allowed)Known or suspected gastrointestinal obstruction, stricture, or fistulaCardiac pacemaker or another implanted electro-medical device if the CCE device is contraindicated due to emission of a radiofrequency or other interfering signalSwallowing disorderKnown contraindication or allergy to any medication or preparation agent used before or during the procedureMay not be done in conjunction with CT Colonography (CTC)CCE is not a Medicare Benefit for colorectal cancer screening, regardless of family history or other risk factors for the development of colonic disease* Cancer Diagnostic strategies refer to the measures taken to investigate persons with symptoms suspicious for malignancy or as a result of positive screening tests. Cancer Surveillance refers to the interval utilization of diagnostic strategies in people with previously detected cancerous or pre-cancerous lesions. Cancer Screening strategies refer to those measures taken to diagnose cancerous and pre-cancerous lesions in asymptomatic people with no previous history of such.General InformationAssociated InformationN/ASources of InformationN/ABibliographyFDA approves PillCam COLON as follow-up test.Cancer Discov.2014;4(4):380-381.PillCam COLON 2 Capsule Endoscopy System (K153466). https://www.accessdata.fda.gov/cdrh_docs/pdf15/K153466.pdf. Accessed 2/28/20.National Coverage Determination (NCD) for Colorectal Cancer Screening Tests (210.3).National Coverage Decision. Accessed 6/01/21.Rex DK, Adler SN, Aisenberg J, et al. Accuracy of capsule colonoscopy in detecting colorectal polyps in a screening population.Gastroenterology.2015;148(5):948-957 e942.Rondonotti E, Borghi C, Mandelli G, et al. Accuracy of capsule colonoscopy and computed tomographic colonography in individuals with positive results from the fecal occult blood test.Clin Gastroenterol Hepatol.2014;12(8):1303-1310.Spada C, Hassan C, Barbaro B, et al. Colon capsule versus CT colonography in patients with incomplete colonoscopy: a prospective, comparative trial.Gut. 2015;64(2):272-281.Holleran G, Leen R, OMorain C, McNamara DJE. Colon capsule endoscopy as possible filter test for colonoscopy selection in a screening population with positive fecal immunology.Endoscopy.2014;46(06):473-478.Kobaek-Larsen M, Kroijer R, Dyrvig AK, et al. Back-to-back colon capsule endoscopy and optical colonoscopy in colorectal cancer screening individuals.Colorectal Dis.2018;20(6):479-485.Morikawa T, Kato J, Yamaji Y, et al. Sensitivity of immunochemical fecal occult blood test to small colorectal adenomas.Am J Gastroenterol.2007;102(10):2259.Morgan DR, Malik PR, Romeo DP, Rex DK. Initial US evaluation of second-generation capsule colonoscopy for detecting colon polyps.BMJ Open Gastroenterol.2016;3(1):e000089.Spada C, Hassan C, Munoz-Navas M, et al. Second-generation colon capsule endoscopy compared with colonoscopy.Gastrointest Endosc.2011;74(3):581-589 e581.Eliakim R, Yassin K, Niv Y, et al. Prospective multicenter performance evaluation of the second-generation colon capsule compared with colonoscopy.Endoscopy.2009;41(12):1026-1031.Parodi A, Vanbiervliet G, Hassan C, et al. Colon capsule endoscopy to screen for colorectal neoplasia in those with family histories of colorectal cancer.Gastrointest Endosc.2018;87(3):695-704.Voska M, Zavoral M, Grega T, et al. Accuracy of Colon Capsule Endoscopy for Colorectal Neoplasia Detection in Individuals Referred for a Screening Colonoscopy.Gastroenterol Res Pract.2019;2019:5975438.Ohmiya N, Hotta N, Mitsufuji S, et al. Multicenter feasibility study of bowel preparation with castor oil for colon capsule endoscopy.Dig Endosc.2019;31(2):164-172.Blanes-Vidal V, Nadimi ES, Buijs MM, Baatrup GJIjocd. Capsule endoscopy vs. colonoscopy vs. histopathology in colorectal cancer screening: matched analyses of polyp size, morphology, and location estimates.Int J Colorectal Dis. 2018;33(9):1309-1312.Health Quality O. Colon Capsule Endoscopy for the Detection of Colorectal Polyps: An Evidence-Based Analysis.Ont Health Technol Assess Ser.2015;15(14):1-39.Spada C, Pasha SF, Gross SA, et al. Accuracy of First- and Second-Generation Colon Capsules in Endoscopic Detection of Colorectal Polyps: A Systematic Review and Meta-analysis.Clin Gastroenterol Hepatol.2016;14(11):1533-1543 e1538.Enns RA, Hookey L, Armstrong D, et al. Canadian Clinical Practice Guidelines for the Use of Video Capsule Endoscopy.Gastroenterology.2017;152(3):497-514.Institute E. PillCam Colon 2 Capsule Endoscopy System (Medtronic plc) for Detecting Colon Polyps. .Hayes- Colon Capsule Endoscopy for Colorectal Cancer Screening, Diagnosis and Surveillance. 2019.Rex DK, Boland CR, Dominitz JA, et al. Colorectal cancer screening: Recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer.Gastrointest Endosc.2017;86(1):18-33.Hussey M, Holleran G, Stack R, Moran N, Tersaruolo C, McNamara D. Same-day colon capsule endoscopy is a viable means to assess unexplored colonic segments after incomplete colonoscopy in selected patients.United European Gastroenterol J.2018;6(10):1556-1562.
Local Coverage Determinations, LCD, Local policies, Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound, DL39139	Use this page to view details for the Local Coverage Determination for Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound.	PROPOSED	Proposed LCD - Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound (DL39139)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39138&ver=5	lcd-39138-5-1.txt	1	39138	lcd	5	0	a00c8a26-aeb7-404b-bd16-0e14b8a217db	CMS National Coverage PolicyTitle XVIII of the Social Security Act, 1862(a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.Title XVIII of the Social Security Act, 1862(a)(1)(D) addresses services that are determined to be investigational or experimental.CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 16, 10 General Exclusions from CoverageCMS Internet-Only Manual, Pub. 100-04, Medicare Claims Processing Manual, Chapter 23, 30A Physicians ServicesCMS Internet-Only Manual, Pub. 100-04, Medicare Claims Processing Manual, Chapter 30, 50.3.1 Mandatory ABN UsesCoverage Indications, Limitations, and/or Medical NecessityThis is a NON-coverage policy for allamniotic membrane, amniotic fluid or other placental-derived productinjections and/or applications as a means of managing musculoskeletal injuries, joint conditions, and all other conditions not stated below.This guidance does NOT include discussion on burns, wounds or ophthalmic conditions.NOTE: For information on stem cell transplantation please see CMS National Coverage Determination 110.23 Stem Cell TransplantationIntroductionAmniotic and placental-derived products are reported to possess certain beneficial characteristics. These products have been proposed as a source of stem cells. Stem cells, by definition, have the capability to differentiate into any cell of an organism as well as the capability of self-renewal.1In addition, the extracellular matrix (ECM) of placental and amniotic-based tissues are rich in collagen, glycoproteins, proteoglycans, fibroblasts, as well as many cytokines and growth factors thought to promote healing with a lower risk of low immunologic reaction.Based on these characteristics, amniotic and placental-derived products are currently being studied and marketed as allografts to serve as:scaffolds for tissue engineeringmembrane covering for certain burns, wounds, and ophthalmic corneal injuriesmicronized/particulate products suspended in an aqueous material to be applied topically or injected into joints, tendons, ligamentsapplications or injections performed intra-operatively to promote post-operative healingThese amniotic and placental-derived products are further being investigated for a multitude of indications, including but not limited to musculoskeletal conditions involving joint pain and back pain, chronic pain in general, dental conditions, alopecia, wounds, burns, and a plethora of others. In the quest to find alternative treatments for certain musculoskeletal conditions, the emergence of a class of substances being marketed as orthobiologics has become more prevalent in the pharmaceutical market. Orthobiologics are biological products aimed at treating musculoskeletal conditions purported to heal injury/trauma, slow degenerative processes and affect regeneration of tissues.2The result ideally would be decreased pain and increased function. One such category of orthobiologics involves the incorporation of human amniotic and placental-derived products.The amniotic and placental-derived products are obtained from the placenta of donors, usually, immediately post C-section at full term and screened for transmittable diseases. These products are made up of varying combinations of amniotic membrane, amniotic fluid, chorionic membrane, umbilical cord, umbilical cord blood, and what is known as Whartons jelly.3Definitions:ThePlacentais a multi-layered circulatory temporary organ that supplies food and oxygen to the fetus during pregnancy.The multiple layers of the placenta include the:Amnion- the innermost membrane that surrounds the fetus during gestationChorion- outermost membrane that surrounds the fetus during gestationAmniotic fluidis the fluid surrounding the fetus within the amnion.Umbilical cordis the vascular conduit connecting the fetus to the placenta comprised of the umbilical vein, arteries, allantois and yolk sac embedded in Whartons jelly.Whartons Jellyis a gelatinous soft connective tissue derived from extra-embryonic mesoderm within the umbilical cord.4Theamniotic membraneitself is divided into three histologic layers:A singleepithelial layerA thickbasement membraneAnavascular stromal (mesenchymal) layer5.6,7,8The avascular stromal layer is further divided into three layers:6,7,8TheCompact layerThe middleFibroblast layerTheSpongy layerTheSpongy Layer, loosely connected to the chorionic membrane, is highly concentrated with proteoglycans and glycoproteins including hyaluronic acid, as well as type I, III, and IV collagen.5,6,8,9Themiddle Fibroblast layeris made up of type I, III, V, and VI collagen.6,8,9TheCompact layerthat sits adjacent to the basement membrane is composed of collagen Types I, III, V, and VI, along with fibronectin.5,9Thebasement membraneanchors the epithelial layer (ref 13) and contains collagen Types IV, V and VII, fibronectin, laminin, and hyaluronic acid.6,10Adjacent to the basement membrane and in immediate contact with amniotic fluid is the single layer of epithelial cells.Amniotic epithelial cellsproduce type III and IV collagen, glycoproteins such as laminin and fibronectin, which become the basement membrane.5The amniotic membranes purpose is to house and physically protect the fetus, but additional functions include regulation of the pH of the amniotic fluid, transportation of water and soluble material between the mother and fetus, and the synthesis of numerous growth factors and cytokines. The amniotic membrane also secretes anti-inflammatory proteins. All of this results in these tissues having anti-inflammatory, anti-microbial, anti-fibroblastic, and non-immunogenic properties.Amniotic products have been asserted to be a source of stem cells. Both the amniotic epithelial layer (maternal derived cells) and mesenchymal (avascular stromal) layer derived from the embryonic mesoderm contain their respective stem cells that can differentiate into multiple cell lines, including myocytes, osteocytes, and chondrocytes.8,9Amniotic fluid also is found to contain amniotic mesenchymal stem cells.7The chorionic membrane adjacent to the mothers endometrium during development of the fetus. Umbilical cord, Whartons jelly, and umbilical cord blood have also been found to contain mesenchymal stem cells.7,11Under normal conditions, placental tissues are collected via aseptic technique during cesarean section. Protocols vary as to how the tissues are harvested, prepared, preserved and stored. Testing is also required to ensure these tissues do not carry any communicable diseases transmissible from donor to recipient.Because the spongy layer loosely connects the amniotic membrane to the chorionic membrane, these two layers are easily separated upon blunt dissection at initial harvesting.10Other than ease of separation between amniotic and chorionic membranes, the following steps in processing the tissues into the desired form vary, based on the portions of the placental tissues extracted, sterilization processes (if any) undertaken, and method of preservation utilized. Common methods of preservation include cryopreservation, lyophilization (freeze-drying), glycerol-preservation, (gamma)-sterilization, low heat dehydration, and vitrification.5,8,9,10A process called Decellularization may be used in which the layer of amniotic epithelial cells is removed from the collected amniotic membrane, leaving behind the valuable extracellular matrix components. Removal of all cellular components is thought to lessen the possibility of eliciting an immune response.3,10Different decellularization processes are available. Eventual preparation of sheets, particulate suspensions, liquids, or gels allows the final marketed product.Depending on the methods utilized, the processing of placental and amniotic-based tissues will affect the viability of cellular components, growth factors, and other valuable properties for which these tissues are promoted. To date, there are significant differences that exist in the processing of different placental and amniotic-based tissue products.3,5Lack of consistency and standardization within propriety manufacturing (preparation) processes precludes determination and comparison of the final product form, characteristics, properties, and components.The Food and Drug Administration (FDA), under Sect. 361 of the Public Health Service Act (regulated by the Centers for Biologics Evaluation and Research CBER, an arm of the FDA) oversees the therapeutic use of "Human cells or tissue products" or HCT/Ps. Once these types products are harvested, their process and handling will determine whether the products fall under Section 361 guidance or default to the more regulated section 351 of the Public Health Service Act and/or the Federal Food, Drug, and Cosmetic Act. The regulatory pathway for pre-market FDA approval of new drugs, devices and/or biological products, requires registration as a (NDA) New Drug application, an (IND) Investigational New Drug application, or a (BLA) Biologics License Approval.8,9,12,13If a human cells or tissue product should meet Section 361 FDA requirements, the product will not require FDA pre-market review and approval. To meet Section 361 FDA regulatory requirements, the placental/amniotic-based tissue product must meet the following 4 criteria: The HCT/P is:Minimally ManipulatedIntended for Homologous Use (as reflected by the labeling, advertising, or other indications of the manufacturers objective intent)The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/PEither:The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; orThe HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and:Is for autologous use;Is for allogeneic use in a first-degree or second-degree blood relative; orIs for reproductive use12Due to the ongoing development of new products and clinical trials, the field of FDA regulatory requirements is fluid and evolving. It is the expectation that the respective Medicare Administrative Contractor will continue to follow any guidance and insight as it is brought forward by the FDA.Lack of standard formulation, dose, frequency of administration, and standard of care in treatment with these products further complicates regulation and guidance determinations.Despite this lack of standardization, numerous amniotic and placental-derived products have been released for use in treatment of musculoskeletal conditions. These conditions include, but are not limited to tendon/ligament injuries, musculoskeletal injuries, cartilage damage, osteoarthritis, (or pain related of these conditions) as well as an adjunctive to orthopedic surgical treatments. Due to the lack of component standardization, the remainder of this LCD will use the term amniotic and placental-derived products to mean ANY product derived from ANY combination of amniotic membrane/chorion/placenta/Whartons jelly/umbilical cord/amniotic fluid/umbilical cord blood.Although amniotic and placental-derived products are marketed to treat certain musculoskeletal conditions, there is limited support for safety and efficacy from human clinical trials available.All injectable amniotic and/or placental-derived products fall under FDA section 551 of the Federal Food, Drug, and Cosmetic Act. Promotion relating to novel indication or evidence of new intended use may constitute labeling, adulteration, or misbranding of the drug or device if such dissemination fails to comply with section 551 of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 360aaa) and the requirements of this part. A manufacturers failure to exercise due diligence in submitting the clinical studies are necessary for the approval of a new use as subject of information disseminated under this part or in beginning or completing such clinical studies shall be deemed a failure to comply with section 551 of the act and the requirement of this part. Use of any amniotic and/or placental-derived products that have not met the requirements of section 551 of the Federal Food, Drug, and Cosmetic Act will be denied per Medicare Benefit Policy Manual 100-2 Chapter 15 Section 50.4.1 and associated services will also be denied per Medicare Benefit Policy Manual 100-2 Chapter 16 Section 180.General InformationAssociated InformationN/ASources of InformationN/ABibliographyZakrzewski W, Dobrzynski M, Szymonowicz M, and Rybak Z. Stem Cells: Past, Present, and Future. Stem Cell Research & Therapy 2019 10:68.doi:10.1186/s13287-019-1165-5Dhillon MS, Behera P, Patel S, and Shetty V. Orthobiologics and Platelet Rich Plasma. Indian J of Orthop. 2014 Jan-Feb; 48(1):1-9.doi:10.4103/0019-5413.125477
Local Coverage Determinations, LCD, Local policies, Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound, DL39139	Use this page to view details for the Local Coverage Determination for Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound.	PROPOSED	Proposed LCD - Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound (DL39139)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39138&ver=5	lcd-39138-5-1.txt	1	39138	lcd	5	1	ab95b35b-8cc3-4457-bdd3-31f3a4b60669	General InformationAssociated InformationN/ASources of InformationN/ABibliographyZakrzewski W, Dobrzynski M, Szymonowicz M, and Rybak Z. Stem Cells: Past, Present, and Future. Stem Cell Research & Therapy 2019 10:68.doi:10.1186/s13287-019-1165-5Dhillon MS, Behera P, Patel S, and Shetty V. Orthobiologics and Platelet Rich Plasma. Indian J of Orthop. 2014 Jan-Feb; 48(1):1-9.doi:10.4103/0019-5413.125477Sultan AA, Piuzzi NS, Mont MA. Nonoperative Applications of Placental Tissue Matrix in Orthopaedic Sports Injuries: A Review of Literature. Clin J Sport Med. Jul 2020;30(4):383-389. doi:10.1097/jsm.0000000000000684Gabbe SG, Niebyl JR, Simpson JL, et al. Obstetricsnormal and problem pregnancies. 5th ed. Philadelphia: Churchill Livingstone; 2007.Niknejad H, Peirovi H, Jorjani M, Ahmadiani A, Ghanavi J, Seifalian AM. Properties of the Amniotic Membrane for Potential use in Tissue Engineering. European Cells and Materials. Vol. 15 2008. Pg 88-99.doi:10.22203/ecm.v015a07Huddleston HP, Cohn MR, Haunschild ED, Wong SE, Farr J, Yanke AB. Amniotic Product Treatments: Clinical and Basic Science Evidence. Curr Rev Musculoskelet Med. 2020 Apr;13(2):148-154. PMID: 32076938McIntyre JA, Jones IA, Danilkovich A, Vangsness CT Jr.McIntyre JA, et al. The Placenta: Applications in Orthopaedic Sports Medicine. Am J Sports Med. 2018 Jan;46(1):234-247.
Local Coverage Determinations, LCD, Local policies, Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound, DL39139	Use this page to view details for the Local Coverage Determination for Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound.	PROPOSED	Proposed LCD - Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound (DL39139)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39138&ver=5	lcd-39138-5-1.txt	1	39138	lcd	5	2	dc982d40-5a4c-4053-a76c-232c92ebeda1	Gabbe SG, Niebyl JR, Simpson JL, et al. Obstetricsnormal and problem pregnancies. 5th ed. Philadelphia: Churchill Livingstone; 2007.Niknejad H, Peirovi H, Jorjani M, Ahmadiani A, Ghanavi J, Seifalian AM. Properties of the Amniotic Membrane for Potential use in Tissue Engineering. European Cells and Materials. Vol. 15 2008. Pg 88-99.doi:10.22203/ecm.v015a07Huddleston HP, Cohn MR, Haunschild ED, Wong SE, Farr J, Yanke AB. Amniotic Product Treatments: Clinical and Basic Science Evidence. Curr Rev Musculoskelet Med. 2020 Apr;13(2):148-154. PMID: 32076938McIntyre JA, Jones IA, Danilkovich A, Vangsness CT Jr.McIntyre JA, et al. The Placenta: Applications in Orthopaedic Sports Medicine. Am J Sports Med. 2018 Jan;46(1):234-247.Riboh JC, Saltzman BM, Yanke AB, Cole BJ. Human Amniotic Membrane-Derived Products in Sports Medicine: Basic Science, Early Results, and Potential Clinical Applications. Am J Sports Med. 2016 Sep;44(9):2425-34.Hannon CP, Yanke AB, Farr J. Amniotic Tissue Modulation of Knee Pain-A Focus on Osteoarthritis. J Knee Surg. 2019 Jan;32(1):26-36. doi:10.1055/s-0038-1676370Leal-Marin S, Kern T, Hofmann N, Pogozhykh O, Framme C, Brgel M, Figueiredo C, Glasmacher B, Gryshkov O. Human Amniotic Membrane: A review on tissue engineering, application, and storage. J Biomed Mater Res. 2021;118. doi.org/10.1002/jbm.b.34782Farr J, Gomoll AH, Yanke AB, Strauss EJ, Mowry KC. A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms. J Knee Surg. Nov 2019;32(11):1143-1154. doi:10.1055/s-0039-1696672FDA Guidance for Industry and Food and Drug Administration Staff. Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use. 2020 July.Guidance for Industry Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Small Entity Compliance Guide. U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research. 2007 Aug.Gellhorn A.C., Han A. The use of dehydrated human amnion/chorion membrane allograft injection for the treatment of tendinopathy or arthritis: a case series involving 40 patients.PM&R. 2017;9(12):1236-1243. doi:10.1016/j.pmrj.2017.04.011Buck D. Amniotic umbilical cord particulate for discogenic pain.Am. Osteopath. Assoc.2019;119(12):814-819. doi:10.7556/jaoa.2019.138Ross A, Gambrill V, Main C. Clinical outcomes of amniotic membrane/umbilical cord particulate in spinal disorders: a retrospective study.J Pain Res. 2022;15:3971-3979. doi:10.2147/JPR.S375201, 10.2147/JPR.S375201Ackley JF, Kolosky M, Gurin D, Hampton R, Masin R, Krahe D. Cryopreserved amniotic membrane and umbilical cord particulate matrix for partial rotator cuff tears: A case series. Medicine (Baltimore). Jul 2019;98(30):e16569. doi:10.1097/md.0000000000016569Aufiero, D, Sampson, S, Onishi, K, and Bemden, V. Treatment of medial and lateral elbow tendinosis with an injectable amniotic membrane allografta retrospective case series.J Pain Relief. 2016;5(3):242.Quinet MT, Raghavan M, Morris E, et al. Effectiveness of amniotic fluid injection in the treatment of trigger finger: a pilot study.Journal of Hand Surgery Global Online. 2020;2(5):301-305.Cazzell S., Stewart J., Agnew P.S., et al Randomized controlled trial of micronized dehydrated human amnion/chorion membrane (dHACM) injection compared to placebo for the treatment of plantar fasciitis.Foot Ankle Int. 2018;39(10):1151-1161. doi:10.1177/1071100718788549Zelen C.M., Poka A., Andrews J. Prospective, randomized, blinded, comparative study of injectable micronized dehydrated amniotic/chorionic membrane allograft for plantar fasciitis - A feasibility study.Foot Ankle Int. 2013;34(10):1332-1339. doi:10.1177/1071100713502179Hanselman A.E., Tidwell J.E., Santrock R.D. Cryopreserved human amniotic membrane injection for plantar fasciitis: A randomized, controlled, double-blind pilot study.Foot Ankle Int. 2015;36(2):151-158. doi:10.1177/1071100714552824Matthews M, Betrus CJ, Klein EE, et al. Comparison of Regenerative Injection Therapy and Conventional Therapy for Proximal Plantar Fasciitis.J Foot Ankle Surg. 2022;doi:10.1053/j.jfas.2022.11.010, 10.1053/j.jfas.2022.11.010Nakagawa H, Sung K, Ashkani-Esfahani S, et al. Plantar fasciitis: a comparison of ultrasound-guided fasciotomy with or without amniotic membrane allograft injection.Med. 2022;17(12):931-940. doi:10.2217/rme-2022-0094Werber B: Amniotic tissues for the treatment of chronic plantar fasciosis and Achilles tendinosis.J Sports Med(Hindawi Publ Corp) 2015;2015:219896Lullove E. A flowable placental tissue matrix allograft in lower extremity injuries: a pilot study. 2015;7:e275.Spector JE, Hubbs B, Kot K, et al. Micronized dehydrated human amnion/chorion membrane injection in the treatment of chronic Achilles tendinitis.J Am Podiatr Med Assoc. 2021;111(6)doi:10.7547/19-170, 10.7547/19-170Gomoll A.H., Farr J., Cole B.J., et al. Safety and efficacy of an amniotic suspension allograft injection over 12 months in a single-blinded, randomized controlled trial for symptomatic osteoarthritis of the knee.J. Arthrosc. Relat. Surg.2021;37:22462257. doi: 10.1016/j.arthro.2021.02.044.elik D, oban , Kilioglu . Minimal clinically important difference of commonly used hip-, knee-, foot-, and ankle-specific questionnaires: a systematic review.J Clin Epidemiol. 2019;113:44-57. doi:10.1016/j.jclinepi.2019.04.017McCarthy M Jr, Chang CH, Pickard AS, et al. Visual analog scales for assessing surgical pain.J Am Coll Surg. 2005;201(2):245-252. doi:10.1016/j.jamcollsurg.2005.03.034Landorf KB, Radford JA, Hudson S. Minimal important difference (MID) of two commonly used outcome measures for foot problems.J Foot Ankle Res2010;3(1):7.Gallagher EJ, Liebman M, Bijur PE. Prospective validation of clinically important changes in pain severity measured on a visual analog scale.Ann Emerg Med2001;38(6):633-638.Alden KJ, Harris S, Hubbs B, et al. Micronized dehydrated human amnion chorion membrane injection in the treatment of knee osteoarthritis a large retrospective case series.J Knee Surg. 2021;34(8):841-845. doi:10.1055/s-0039-3400951, 10.1055/s-0039-3400951Castellanos R, Tighe S. Injectable amniotic membrane/umbilical cord particulate for knee osteoarthritis: a prospective, single-center pilot study.Pain Med. 2019;20(11):2283-2291. doi:10.1093/pm/pnz143Mead OG, Mead LP. Intra-articular injection of amniotic membrane and umbilical cord particulate for the management of moderate to severe knee osteoarthritis.Res. Rev.2020;12:161170. doi: 10.2147/ORR.S272980.Natali S, Farinelli L, Screpis D, et al. Human amniotic suspension allograft improves pain and function in knee osteoarthritis: a prospective not randomized clinical pilot study.Clin. Med. 2022;11(12)doi:10.3390/jcm11123295,10.3390/jcm11123295Meadows MC, Elisman K, Nho SJ, et al. A single injection of amniotic suspension allograft is safe and effective for treatment of mild to moderate hip osteoarthritis: a prospective study. 2022;38:325331. doi: 10.1016/j.arthro.2021.04.034.Guimaraes JDS, Arcanjo FL, Leporace G, et al Effects of therapeutic interventions on pain due to plantar fasciitis: A systematic review and meta-analysis.Rehabil. 2022;no pagination. doi:10.1177/02692155221143865Zaffagnini M, Boffa A, Andriolo L, et al. Orthobiologic injections for the treatment of hip osteoarthritis: a systematic review.J Clin Med. 2022;11(22):6663. Published 2022 Nov 10. doi:10.3390/jcm11226663Aratikatla A, Maffulli N, Rodriguez HC, et al. Allogenic perinatal tissue for musculoskeletal regenerative medicine applications: a systematic review protocol. J. Orthop. Surg.2022;17(1):307. doi:10.1186/s13018-022-03197-z,10.1186/s13018-022-03197-zSultan AA, Samuel LT, Roth A, et al. Operative Applications of Placental Tissue Matrix in Orthopaedic Sports Injuries: A Review of the Literature.Surg Technol Int.2019;34:397-402.McIntyre JA, Jones IA, Danilkovich A, Vangsness CT. The placenta: applications in orthopaedic sports medicine.J. Sports Med. 2018;46(1):234-247. doi:10.1177/0363546517697682Tsikopoulos K, Vasiliadis HS, Mavridis D. Injection therapies for plantar fasciopathy ('plantar fasciitis'): A systematic review and network meta-analysis of 22 randomised controlled trials.J. Sports Med. 2016;50(22):1367-1375. doi:10.1136/bjsports-2015-095437Sterne JAC, Savovic J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials.BMJ. 2019;366:l4898. Published 2019 Aug 28. doi:10.1136/bmj.l4898Schnemann H, Brozek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013.The GRADE Working Group, 2013. Available fromguidelinedevelopment.org/handbook.
Local Coverage Determinations, LCD, Local policies, Pneumatic Compression Devices, DL33829	Use this page to view details for the Local Coverage Determination for Pneumatic Compression Devices.	PROPOSED	Proposed LCD - Pneumatic Compression Devices (DL33829)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39169&ver=7	lcd-39169-7-1.txt	1	39169	lcd	7	0	7ef9bcae-8e77-469e-8fe9-68c9b3b59f61	CMS National Coverage PolicyCMS Pub. 100-03, (Medicare National Coverage Determinations Manual), Chapter 1, Section 280.6Coverage Indications, Limitations, and/or Medical NecessityFor any item to be covered by Medicare, it must 1) be eligible for a defined Medicare benefit category, 2) be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member, and 3) meet all other applicable Medicare statutory and regulatory requirements.The purpose of a Local Coverage Determination (LCD) is to provide information regarding reasonable and necessary criteria based on Social Security Act 1862(a)(1)(A) provisions.In addition to the reasonable and necessary criteria contained in this LCD there are other payment rules, which are discussed in the following documents, that must also be met prior to Medicare reimbursement:The LCD-related Standard Documentation Requirements Article, located at the bottom of this policy under the Related Local Coverage Documents section.The LCD-related Policy Article, located at the bottom of this policy under the Related Local Coverage Documents section.Refer to the Supplier Manual for additional information on documentation requirements.Refer to the DME MAC web sites for additional bulletin articles and other publications related to this LCD.For the items addressed in this LCD, the reasonable and necessary criteria, based on Social Security Act 1862(a)(1)(A) provisions, are defined by the following coverage indications, limitations and/or medical necessity.PRESCRIPTIONSPrescriptions for Pneumatic Compression Devices (PCDs) (E0650, E0651, E0652, E0675, E0676) are limited to Physicians (MD, DO, DPM) and physician extenders (NP, PA, CNS) to the extent allowed by their applicable state scope-of-practice and other license requirements. Providers must use care because the treatment of lymphedema, chronic venous insufficiency with ulceration and complications related to the treatment of these conditions by use of PCDs, commonly require consideration of diagnoses and management of systemic conditions. In no event should a provider order PCDs or PCD appliances that are to be used for or are to be applied to areas of the body that fall outside of their state scope of practice and other license limitations.DEFINITIONSFor Medicare DMEPOS reimbursement purposes the following definitions are used in this policy.Edema:Edema is a non-specific term for the accumulation of fluid in tissue, most often in the extremities. There are numerous causes for edema, ranging from systemic disorders (e.g. congestive heart failure) to local conditions (e.g. post-surgery, congenital abnormalities). (Examples are not all-inclusive.)Lymphedema, as discussed below, is just one group of conditions that can be a cause of accumulation of fluid in the tissue. Lymphedema arises from disorders of the lymphatic system. It is essential to rule out other causes of edema in order to diagnose lymphedema. Edema from other causes is not classified as lymphedema for purposes of Medicare reimbursement for PCDs (E0650, E0651, E0652).Primary lymphedema:Primary lymphedema is a disorder of the lymphatic system that occurs on its own. It is inherited and uncommon. Examples (not all-inclusive) are:Congenital lymphedema due to lymphatic aplasia or hypoplasiaMilroy's disease, an autosomal dominant familial form of congenital lymphedemaLymphedema praecoxLymphedema tardaSecondary lymphedema:Secondary lymphedema is a disorder of lymphatic flow that is caused by some other disease or condition. It is more common than primary lymphedema. It is most commonly caused by surgery (especially lymph node dissection, such as for breast cancer), radiation therapy (especially axillary or inguinal), trauma, lymphatic obstruction by tumor, and, in developing countries, lymphatic filariasis. Secondary lymphedema may also result from compression of the lymphatic and venous channels resulting from leakage of fluid into interstitial tissues in patients with chronic venous insufficiency (CVI). (See below)Chronic Venous Insufficiency (CVI)Lymphedema may also be caused by CVI when fluid leaks into the tissues from the venous system. CVI of the lower extremities is a condition caused by abnormalities of the venous wall and valves, leading to obstruction or reflux of blood flow in the veins. Signs of CVI include hyperpigmentation, stasis dermatitis, chronic edema, and venous stasis ulcers. The incidence of lymphedema from CVI is not well established.Peripheral Arterial Disease (PAD)PAD is a circulatory problem in which narrowed arteries reduce blood flow to limbs, resulting in compromised blood flow to the distal tissue and failure to keep up with oxygen demands.GENERALPCDs coded as E0650, E0651, E0652 are used only in the treatment of lymphedema or CVI with venous stasis ulcers. Reimbursement for these items is based upon the criteria in the following sections. PCD coded as E0675 is used in the treatment of PAD. Claims for E0675 will be denied as not reasonable and necessary as outlined below.I - LYMPHEDEMAA PCD coded as E0650 or E0651 is covered for both primary and secondary lymphedema in beneficiaries with chronic and severe lymphedema when all of the following three requirements are met:The beneficiary has a diagnosis of lymphedema as defined above, andThe beneficiary has persistence of chronic and severe lymphedema as identified by the documented presence of at least one of the following clinical findings:Marked hyperkeratosis with hyperplasia and hyperpigmentation,Papillomatosis cutis lymphostatica,Deformity of elephantiasis,Skin breakdown with persisting lymphorrhea,Detailed measurements over time confirming the persistence of the lymphedema with a history evidencing a likely etiology, andIn addition to this documented persistence, the lymphedema is then documented to be unresponsive to other clinical treatment over the course of a required four-week trial. (See below for trial guidelines.)A PCD coded as E0650 or E0651 used to treat lymphedema that does not meet all of the requirements above is not eligible for reimbursement. Claims will be denied as not reasonable and necessary.A PCD coded as E0650 or E0651 used to treat edema from causes other than lymphedema is not eligible for reimbursement. Claims will be denied as not reasonable and necessary.A PCD coded as E0652 is not covered for the treatment of lymphedema of the extremities alone even if the criteria in this section are met. Claims will be denied as not reasonable and necessary. Refer below to the sections III - LYMPHEDEMA EXTENDING ONTO THE CHEST, TRUNK AND/OR ABDOMEN and PCD Code Selection for additional information about the limited coverage for PCD coded as E0652.Four-Week Trial for LymphedemaA four-week trial of conservative therapy demonstrating failed response to treatment is required. The four-week trial of conservative therapy must include all of the following:Regular and compliant use of an appropriate compression bandage system or compression garment to provide adequate graduated compressionAdequate compression is defined as (1) sufficient pressure at the lowest pressure point to cause fluid movement, and (2) sufficient pressure across the gradient (from highest to lowest pressure point) to move fluid from distal to proximal. The compression used must not create a tourniquet effect at any point.The garment may be prefabricated or custom-fabricated but must provide adequate graduated compression starting with a minimum of 30 mmHg distally.Regular exerciseElevation of the limbWhen available, manual lymphatic drainage is a key component of conservative treatment as is appropriate medication treatment when there is concurrent congestive heart failure.At the end of the four-week trial, if there has been improvement, then reimbursement for a PCD is not justified. Where improvement has occurred, the trial of conservative therapy must be continued with subsequent reassessment at intervals at least a week apart. Only when no significant improvement has occurred in the most recent four weeks and the coverage criteria above are still met, may the lymphedema be considered unresponsive to conservative therapy, and coverage for a PCD considered.The medical necessity determination for a PCD by the treating practitioner must include symptoms and objective findings, including measurements, to establish the severity of the condition.The documentation by thetreatingpractitionerof the medical necessity of a PCD must include:The patients diagnosis and prognosis;Symptoms and objective findings, including measurements which establish the severity of the condition;The reason the device is required, including the treatments which have been tried and failed; andThe clinical response to an initial treatment with the deviceAt a minimum, re-assessments conducted for a trial must include detailed measurements, obtained in the same manner and with reference to the same anatomic landmarks, prior to and at the conclusion of the various trials and therapy, with bilateral comparisons where appropriate.The trial of conservative therapy must be documented in the beneficiarys medical record before prescribing any type of PCD (E0650, E0651, E0652). This assessment may be performed by thetreatingpractitioneror any other licensed/certified medical professional (LCMP) directly involved in the beneficiarys lymphedema treatment. The LCMP may not have any financial relationship with the DMEPOS supplier providing the device. If the assessment is performed by an LCMP, thetreatingpractitionermust receive and review the report of the evaluation. In addition, thetreatingpractitionermust sign and date the report, and state concurrence or disagreement with the assessment. The signature date must be on or before the prescription date.II - CHRONIC VENOUS INSUFFICIENCY (CVI) WITH VENOUS STASIS ULCERSA PCD coded as E0650 or E0651 is covered for the treatment of CVI of the lower extremities only if the patient has all of the following:Edema in the affected lower extremityOne or more venous stasis ulcer(s)The ulcer(s) have failed to heal after a six-month trial of conservative therapy directed by thetreatingpractitioner. (See below for trial guidelines.)A PCD coded as E0650 or E0651 used to treat CVI that does not meet all of the requirements above is not eligible for reimbursement. Claims will be denied as not reasonable and necessary.A PCD coded as E0650 or E0651 used to treat ulcers in locations other than the lower extremity or ulcers and wounds from other causes is not eligible for reimbursement. Claims will be denied as not reasonable and necessary.A PCD coded as E0652 is not covered for the treatment of CVI even if the criteria in this section are met. Claims will be denied as not reasonable and necessary. Refer below to the sections III - LYMPHEDEMA EXTENDING ONTO THE CHEST, TRUNK AND/OR ABDOMEN and PCD Code Selection for additional information about the limited coverage for PCD coded as E0652.Six-Month Trial for CVIA six-month trial of conservative therapy demonstrating failed response to treatment is required. The six-month trial of conservative therapy must include all of the following:Compliant use of an appropriate compression bandage system or compression garment to provide adequate graduated compressionAdequate compression is defined as (1) sufficient pressure at the lowest pressure point to cause fluid movement and (2) sufficient pressure across the gradient (from highest to lowest pressure point) to move fluid from distal to proximal. The compression used must not create a tourniquet effect at any point.The garment may be prefabricated or custom-fabricated but must provide adequate graduated compression starting with a minimum of 30 mmHg distally.Medications as appropriate (e.g. diuretics and/or other treatment of congestive heart failure)Regular exerciseElevation of the limbAppropriate wound care for the ulcer (including sharp debridement where appropriate)At the end of the six-month trial, if there has been improvement, then reimbursement for a PCD is not reasonable and necessary. Where improvement has occurred, the trial of conservative therapy must be continued with subsequent reassessments. When no significant improvement has occurred for a continuous period of six months and the coverage criteria above are still met, then the use of a PCD to treat CVI is eligible for reimbursement.The trial of conservative therapy must be documented in the beneficiarys medical record before prescribing any type of PCD (E0650, E0651, E0652). This assessment may be performed by thetreatingpractitioneror any other licensed/certified medical professional (LCMP) directly involved in the beneficiarys CVI treatment. The LCMP may not have any financial relationship with the DMEPOS supplier providing the device. If the assessment is performed by an LCMP, thetreatingpractitionermust receive and review the report of the evaluation. In addition, thetreatingpractitionermust sign and date the report, and state concurrence or disagreement with the assessment. The signature date must be on or before the prescription date.III - LYMPHEDEMA EXTENDING ONTO THE CHEST, TRUNK AND/OR ABDOMENA segmented, calibrated gradient PCD (E0652) is only covered when the individual has unique characteristics which prevent them from receiving adequate satisfactory pneumatic compression treatment using a nonsegmented device along with a segmented appliance or compression device without manual control of the pressure in each chamber.A PCD coded as E0652, is covered for the treatment of lymphedema extending onto the chest, trunk and/or abdomen when all of the following are met:
Local Coverage Determinations, LCD, Local policies, Pneumatic Compression Devices, DL33829	Use this page to view details for the Local Coverage Determination for Pneumatic Compression Devices.	PROPOSED	Proposed LCD - Pneumatic Compression Devices (DL33829)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39169&ver=7	lcd-39169-7-1.txt	1	39169	lcd	7	1	89565652-a393-414e-956a-05cfe3e5b95e	The beneficiary has lymphedema of an extremity as defined aboveThe coverage criteria for an E0650 or E0651 are metThe beneficiary has lymphedema extending onto the chest, trunk and/or abdomen that extends past the limits of a standard compression sleeve, and the chest, trunk and/or abdominal lymphedema has failed to improve with a four-week trial. (See below for trial guidelines.)A PCD coded as E0652 used to treat lymphedema extending onto the chest, trunk and/or abdomen that does not meet all of the requirements above is not eligible for reimbursement. Claims will be denied as not reasonable and necessary.A PCD coded as E0652 used to treat lymphedema not extending onto the chest, trunk and/or abdomen or CVI is not eligible for reimbursement. Claims will be denied as not reasonable and necessary.Four-Week Trial for Lymphedema Extending Onto the Chest, Trunk and/or AbdomenA four-week trial of conservative therapy demonstrating failed response to treatment with and E0650 or E0651 is required. The four-week trial of conservative therapy must include all of the following:At least four weeks of regular, daily, multiple-hour home usage of the E0650 or E0651 after careful, in-person fitting, training and supervision by a technician who is skilled in and who regularly and successfully uses the appliance providedCompliant use of an appropriate compression bandage system or compression garment to provide adequate graduated compressionAdequate compression is defined as (1) sufficient pressure at the lowest pressure point to cause fluid movement and (2) sufficient pressure across the gradient (from highest to lowest pressure point) to move fluid from distal to proximal. The compression used must not create a tourniquet effect at any point.The garment may be prefabricated or custom-fabricated but must provide adequate graduated compression starting with a minimum of 30 mmHg distally.Regular exerciseElevation where appropriateManual lymphatic drainage (where available) and self-manual lymphatic drainage (MLD) for at least 30 minutes per dayEvaluation of diet and implementation of any necessary changeMedications as appropriate (e.g. diuretics and/or other treatment of congestive heart failure)Correction (where possible) of anemia and/or hypoproteinemiaAt the end of the four-week trial, if there has been improvement of the lymphedema extending onto the chest, trunk and/or abdomen, then reimbursement for an E0652 is not justified. Where improvement has occurred, the trial of conservative therapy must be continued with subsequent reassessment at intervals at least a week apart. When and only when no significant improvement has occurred in the most recent four weeks and the coverage criteria above are still met, an E0652 is eligible for reimbursement.The trial of conservative therapy must be documented in the beneficiarys medical record before prescribing any type of PCD (E0650, E0651, E0652). This assessment may be performed by thetreatingpractitioneror any other licensed/certified medical professional (LCMP) directly involved in the beneficiarys lymphedema treatment. The LCMP may not have any financial relationship with the DMEPOS supplier providing the device. If the assessment is performed by an LCMP, thetreatingpractitionermust receive and review the report of the evaluation. In addition, thetreatingpractitionermust sign and date the report, and state concurrence or disagreement with the assessment. The signature date must be on or before the prescription date.IV PERIPHERAL ARTERY DISEASE (PAD)A PCD coded as E0675 to treat PAD is not eligible for reimbursement. There is insufficient evidence to demonstrate that reimbursement is justified. Claims for E0675 will be denied as not reasonable and necessary.V DEEP VENOUS THROMBOSIS (DVT) PREVENTIONA PCD coded as E0676 is used only for prevention of venous thrombosis. Refer to the related Policy Article NON-MEDICAL NECESSITY COVERAGE AND PAYMENT RULES section for information about lack of a Medicare benefit for devices used for prophylaxis of venous thrombosis.ACCESSORIESPCD related accessories (E0655, E0656, E0657, E0660, E0665, E0666, E0667, E0668, E0669, E0670, E0671, E0672, E0673) are eligible for reimbursement only when the appropriate, related base PCDs (E0650, E0651, E0652, E0675) meets the applicable coverage criteria for that type of PCD. If the base PCD is not covered, related accessories are not eligible for reimbursement. Claims for related items will be denied as not reasonable and necessary.PCD CODE SELECTION (E0650, E0651, E0652, E0675, E0676)A PCD coded as E0650 or E0651 is used for lymphedema or CVI. An E0650 compressor with a segmented appliance/sleeve (E0671, E0672, E0673) is considered functionally equivalent to an E0651 compressor with a segmented appliance/sleeve (E0667, E0668, E0669).A segmented, calibrated gradient PCD (E0652) is only covered when the individual has unique characteristics which prevent them from receiving adequate satisfactory pneumatic compression treatment using a nonsegmented device along with a segmented appliance or compression device without manual control of the pressure in each chamber.The only unique characteristics identified in the clinical literature that requires the use of an E0652 device is lymphedema extending onto the chest, trunk and/or abdomen which has remained unresponsive to all other therapies.A PCD coded as E0675 is used only for peripheral artery disease. Other PCD codes are not used for this condition.A PCD coded as E0676 is used only for prevention of venous thrombosis. Refer to the related Policy Article NONMEDICAL NECESSITY COVERAGE AND PAYMENT RULES section for information about lack of a Medicare benefit for devices used for prophylaxis of venous thrombosis.GENERALA Standard Written Order (SWO) must be communicated to the supplier before a claim is submitted. If the supplier bills for an item addressed in this policy without first receiving a completed SWO, the claim shall be denied as not reasonable and necessary.For Durable Medical Equipment, Prosthetics, Orthotics and Supplies (DMEPOS) base items that require a Written Order Prior to Delivery (WOPD), the supplier must have received a signed SWO before the DMEPOS item is delivered to a beneficiary. If a supplier delivers a DMEPOS item without first receiving a WOPD, the claim shall be denied as not reasonable and necessary. Refer to the LCD-related Policy Article, located at the bottom of this policy under the Related Local Coverage Documents section.For DMEPOS base items that require a WOPD, and also require separately billed associated options, accessories, and/or supplies, the supplier must have received a WOPD which lists the base item and which may list all the associated options, accessories, and/or supplies that are separately billed prior to the delivery of the items. In this scenario, if the supplier separately bills for associated options, accessories, and/or supplies without first receiving a completed and signed WOPD of the base item prior to delivery, the claim(s) shall be denied as not reasonable and necessary.An item/service is correctly coded when it meets all the coding guidelines listed in CMS HCPCS guidelines, LCDs, LCD-related Policy Articles, or DME MAC articles. Claims that do not meet coding guidelines shall be denied as not reasonable and necessary/incorrectly coded.Proof of delivery (POD) is a Supplier Standard and DMEPOS suppliers are required to maintain POD documentation in their files. Proof of delivery documentation must be made available to the Medicare contractor upon request. All services that do not have appropriate proof of delivery from the supplier shall be denied as not reasonable and necessary.General InformationAssociated InformationDOCUMENTATION REQUIREMENTSSection 1833(e) of the Social Security Act precludes payment to any provider of services unless "there has been furnished such information as may be necessary in order to determine the amounts due such provider". It is expected that the beneficiary's medical records will reflect the need for the care provided. The beneficiary's medical records include thetreatingpractitionersoffice records, hospital records, nursing home records, home health agency records, records from other healthcare professionals and test reports. This documentation must be available upon request.GENERAL DOCUMENTATION REQUIREMENTSIn order to justify payment for DMEPOS items, suppliers must meet the following requirements:SWOMedical Record Information (including continued need/use if applicable)Correct CodingProof of DeliveryRefer to the LCD-related Standard Documentation Requirements article, located at the bottom of this policy under the Related Local Coverage Documents section for additional information regarding these requirements.Refer to the Supplier Manual for additional information on documentation requirements.Refer to the DME MAC web sites for additional bulletin articles and other publications related to this LCD.POLICY SPECIFIC DOCUMENTATION REQUIREMENTSItems covered in this LCD have additional policy-specific requirements that must be met prior to Medicare reimbursement.Refer to the LCD-related Policy article, located at the bottom of this policy under the Related Local Coverage Documents section for additional information.MiscellaneousAppendicesUtilization GuidelinesRefer to Coverage Indications, Limitations, and/or Medical NecessitySources of InformationN/ABibliography
Local Coverage Determinations, LCD, Local policies, Pneumatic Compression Devices, DL33829	Use this page to view details for the Local Coverage Determination for Pneumatic Compression Devices.	PROPOSED	Proposed LCD - Pneumatic Compression Devices (DL33829)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39169&ver=7	lcd-39169-7-1.txt	1	39169	lcd	7	2	a468a46e-35aa-48e4-aa68-71ebe2585c78	Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FGR. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). European Journal of Vascular and Endovascular Surgery. 2007;33(1): S1-S75. doi: 10.1016/j.ejvs.2006.09.024Schainfeld RM. Management of peripheral arterial disease and intermittent claudication. J Am Board Fam Pract. Nov-Dec 2001;14(6):443-50.Kavros SJ, Delis KT, Turner NS, et al. Improving limb salvage in critical ischemia with intermittent pneumatic compression: a controlled study with 18-month follow-up. J Vasc Surg. Mar 2008;47(3):543-9. doi: 10.1016/j.jvs.2007.11.043Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. Jan 2007;45 Suppl S: S5-67. doi: 10.1016/j.jvs.2006.12.037Oresanya L, Mazzei M, Bashir R, et al. Systematic review and meta-analysis of high-pressure intermittent limb compression for the treatment of intermittent claudication. J Vasc Surg. Feb 2018;67(2):620-628 e2. doi: 10.1016/j.jvs.2017.11.044Alvarez OM, Wendelken ME, Markowitz L, Comfort C. Effect of High-pressure, Intermittent Pneumatic Compression for the Treatment of Peripheral Arterial Disease and Critical Limb Ischemia in Patients Without a Surgical Option. Wounds. Nov 2015;27(11):293-301.Labropoulos N, Leon LR, Jr., Bhatti A, et al. Hemodynamic effects of intermittent pneumatic compression in patients with critical limb ischemia. J Vasc Surg. Oct 2005;42(4):710-6. doi: 10.1016/j.jvs.2005.05.051Louridas G, Saadia R, Spelay J, et al. The ArtAssist Device in chronic lower limb ischemia. A pilot studies. Int Angiol. Mar 2002;21(1):28-35.Berni A, Tromba L, Falvo L, et al. Randomized study on the effects of different strategies of intermittent pneumatic compression for lower limb claudication. G Chir. Jun-Jul 2009;30(6-7):269-73.Kakkos SK, Geroulakos G, Nicolaides AN. Improvement of the walking ability in intermittent claudication due to superficial femoral artery occlusion with supervised exercise and pneumatic foot and calf compression: a randomised controlled trial. Eur J Vasc Endovasc Surg. Aug 2005;30(2):164-75. doi: 10.1016/j.ejvs.2005.03.011Delis KT, Nicolaides AN. Effect of intermittent pneumatic compression of foot and calf on walking distance, hemodynamics, and quality of life in patients with arterial claudication: a prospective randomized controlled study with 1-year follow-up. Ann Surg. Mar 2005;241(3):431-41. doi: 10.1097/01.sla.0000154358.83898.26Ramaswami G, D'Ayala M, Hollier LH, Deutsch R, McElhinney AJ. Rapid foot and calf compression increases walking distance in patients with intermittent claudication: results of a randomized study. J Vasc Surg. May 2005;41(5):794-801. doi: 10.1016/j.jvs.2005.01.045van den Houten MM, Gommans LN, van der Wees PJ, Teijink JA. Minimally Important Difference of the Absolute and Functional Claudication Distance in Patients with Intermittent Claudication. Eur J Vasc Endovasc Surg. Mar 2016;51(3):404-9. doi: 10.1016/j.ejvs.2015.11.008McGinigle KL, Minc SD. Disparities in amputation in patients with peripheral arterial disease. Surgery. Jun 2021;169(6):1290-1294. doi: 10.1016/j.surg.2021.01.025Newhall K, Spangler E, Dzebisashvili N, Goodman DC, Goodney P. Amputation Rates for Patients with Diabetes and Peripheral Arterial Disease: The Effects of Race and Region. Ann Vasc Surg. Jan 2016; 30:292-8 e1. doi: 10.1016/j.avsg.2015.07.040Pandit V, Nelson P, Kempe K, et al. Racial and ethnic disparities in lower extremity amputation: Assessing the role of frailty in older adults. Surgery. Dec 2020;168(6):1075-1078. doi: 10.1016/j.surg.2020.07.015O'Donnell TFX, Powell C, Deery SE, et al. Regional variation in racial disparities among patients with peripheral artery disease. J Vasc Surg. Aug 2018;68(2):519-526. doi: 10.1016/j.jvs.2017.10.090Goodney PP, Holman K, Henke PK, et al. Regional intensity of vascular care and lower extremity amputation rates. J Vasc Surg. Jun 2013;57(6):1471-79, 1480 e1-3; discussion 1479-80. doi: 10.1016/j.jvs.2012.11.068Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC Guideline on the Management of Patients with Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. Mar 21 2017;135(12):e726-e779. doi:10.1161/CIR.0000000000000471Conte MS, Bradbury AW, Kolh P, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. J Vasc Surg. Jun 2019;69(6S):3S-125S e40. doi: 10.1016/j.jvs.2019.02.016Abu Dabrh AM, Steffen MW, Asi N, et al. Nonrevascularization-based treatments in patients with severe or critical limb ischemia. J Vasc Surg. 2015;62(5):1330-9. e13. doi: 10.1016/j.jvs.2015.07.069Andersen CA, Daab LJ, Le TD, Green DM, Tyminski RL, Ponticello M, Marmolejo V. Treatment of Nonreconstructable Critical Limb Ischemia With Ischemic Wounds Utilizing a Noninvasive Intermittent Pneumatic Compression Device Monitored With Fluorescence Angiography. Wounds. 2018 Jul;30(7):191-196.Bin Azizi, ZA. Determining the Optimum Intermittent Pneumatic Compression Stimulus for Lower Limb Venous Emptying Using Direct Pressure Measurements [dissertation]. London, UK: University of London; 1996.Breu FX, Zelikovski A, Loberman Z, Rauh G. Efficacy and safety of a new pneumatic compression device for peripheral arterial disease with intermittent claudication: A prospective, randomized, multi-center clinical trial: a prospective, randomized, multi-center clinical trial. Phlebologie. 2014; 43:5-11Chang ST, Hsu JT, Chu CM, Pan KL, Jang SJ, Lin PC, Hsu HC, Huang KC. Using intermittent pneumatic compression therapy to improve quality of life for symptomatic patients with infrapopliteal diffuse peripheral obstructive disease. Circ J. 2012;76(4):971-6. doi: 10.1253/circj. cj-11-1229.Delis KT. The case for intermittent pneumatic compression of the lower extremity as a novel treatment in arterial claudication. Perspect Vasc Surg Endovasc Ther. 2005 Mar;17(1):29-42.Delis KT, Azizi ZA, Stevens RJ, Wolfe JH, Nicolaides AN. Optimum intermittent pneumatic compression stimulus for lower-limb venous emptying. Eur J Vasc Endovasc Surg. 2000 Mar;19(3):261-9.Delis KT, Husmann MJ, Cheshire NJ, Nicolaides AN. Effects of intermittent pneumatic compression of the calf and thigh on arterial calf inflow: a study of normals, claudicants, and grafted arteriopaths. Surgery. 2001 Feb;129(2):188-95.Delis KT, Husmann MJ, Nicolaides AN, Wolfe JH, Cheshire NJ. Enhancing foot skin blood flux in peripheral vascular disease using intermittent pneumatic compression: controlled study on claudicants and grafted arteriopaths. World J Surg. 2002;26(7):861-866.Delis KT, Husmann MJ, Szendro G, Peters NS, Wolfe JH, Mansfield AO. Haemodynamic effect of intermittent pneumatic compression of the leg after infrainguinal arterial bypass grafting. Br J Surg. 2004 Apr;91(4):429-34.Delis KT, Nicolaides AN, Stansby G. Effect of posture on popliteal artery hemodynamics. Arch Surg. 2000 Mar;135(3):265-9.Delis KT, Nicolaides AN, Wolfe JH, Stansby G. Improving walking ability and ankle brachial pressure indices in symptomatic peripheral vascular disease with intermittent pneumatic foot compression: a prospective controlled study with one-year follow-up. J Vasc Surg. 2000 Apr;31(4):650-61.Delis, KT, Slimani, G, Hafez, HM, Nicolaides, AN. Enhancing Venous Outflow in the Lower Limb with Intermittent Pneumatic Compression. A Comparative Haemodynamic Analysis on the Effect of Foot vs. Calf vs. Foot and Calf Compression. Eur J Vasc Endovasc Surg. 2000 Mar;19(3):250-60.Eton, D, Guolin, Z, Tong, HC, Elsorady, M, Syed, ZA. Enhancing neovascularization in chronic limb-threatening ischemia. J Vasc Surg. 2015; June Suppl: 106SEton D, Yu H. Enhanced cell therapy strategy to treat chronic limb-threatening ischemia. J Vasc Surg. 2010 Jul;52(1):199-204.Eze AR, Cisek PL, Holland BS, Comerota AJ Jr, Verramasuneni R, Comerota AJ. The contributions of arterial and venous volumes to increased cutaneous blood flow during leg compression. Ann Vasc Surg. 1998 Mar;12(2):182-6.Eze AR, Comerota AJ, Cisek PL, Holland BS, Kerr RP, Veeramasuneni R, Comerota AJ Jr. Intermittent calf and foot compression increases lower extremity blood flow. Am J Surg. 1996 Aug;172(2):130-4; discussion 135.Feuerhake IL, Henneberg EW, Hgh A. Intermitterende pneumatisk kompressions-behandling ved underekstremitetsiskmi uden kirurgiske behandlingstilbud [The use of intermittent pneumatic compression for critical limb ischaemia without vascular surgery reconstruction]. Ugeskr Laeger. 2016;178(11): V12150982.Gardner, AMN, Fox, RH. The Return of Blood to the Heart. London: John Libbey; 1989.GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. McMaster University, 2020 (developed by Evidence Prime, Inc.). Available from gradepro.org.Guarneri,G, Tiengo, A. Haemorrologic and Clotting Alterations in the Pathogenesis of the Diabetic Foot. In Faglia, E, Giuffrida, G, Oriani, G, ed. The Ischaemic Diabetic Foot. Milano, Italy: Kurtis. 1999: 17-23.Husmann M, Willenberg T, Keo HH, Spring S, Kalodiki E, Delis KT. Integrity of venoarteriolar reflex determines level of microvascular skin flow enhancement with intermittent pneumatic compression. J Vasc Surg. 2008 Dec;48(6):1509-13.
Local Coverage Determinations, LCD, Local policies, Pneumatic Compression Devices, DL33829	Use this page to view details for the Local Coverage Determination for Pneumatic Compression Devices.	PROPOSED	Proposed LCD - Pneumatic Compression Devices (DL33829)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39169&ver=7	lcd-39169-7-1.txt	1	39169	lcd	7	3	0ff85399-0697-4e51-94ef-924b3a54dfba	Feuerhake IL, Henneberg EW, Hgh A. Intermitterende pneumatisk kompressions-behandling ved underekstremitetsiskmi uden kirurgiske behandlingstilbud [The use of intermittent pneumatic compression for critical limb ischaemia without vascular surgery reconstruction]. Ugeskr Laeger. 2016;178(11): V12150982.Gardner, AMN, Fox, RH. The Return of Blood to the Heart. London: John Libbey; 1989.GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. McMaster University, 2020 (developed by Evidence Prime, Inc.). Available from gradepro.org.Guarneri,G, Tiengo, A. Haemorrologic and Clotting Alterations in the Pathogenesis of the Diabetic Foot. In Faglia, E, Giuffrida, G, Oriani, G, ed. The Ischaemic Diabetic Foot. Milano, Italy: Kurtis. 1999: 17-23.Husmann M, Willenberg T, Keo HH, Spring S, Kalodiki E, Delis KT. Integrity of venoarteriolar reflex determines level of microvascular skin flow enhancement with intermittent pneumatic compression. J Vasc Surg. 2008 Dec;48(6):1509-13.Ishibashi, H, Ohta, T, Hosaka, M, Sugimoto, I, Nehei, T, Kawanishi, J. Intermittent Pneumatic Compression Therapy for Chronically Ischemic Legs. In Iwai, T, Ohta, T, Sasajima, T, Ishibashi, H, and Nishikimi, N, ed. Breakthrough in the Treatment for Critical Limb Ischemia in Japan. Japanese Society for Limb Salvage Research. 2004: 65-71.Jolissaint, J, Shah, SK, Martin, MC, Raffetto, JD, McPhee, JT. Risk Prediction of 30-day mortality after lower extremity major amputation. New England Society for Vascular Surgery. Dec 2019 70(6): 1868-1875.Labropoulos N, Watson WC, Mansour MA, Kang SS, Littooy FN, Baker WH. Acute effects of intermittent pneumatic compression on popliteal artery blood flow. Arch Surg. 1998 Oct;133(10):1072-5.Levin SR, Arinze N, Siracuse JJ. Lower extremity critical limb ischemia: A review of clinical features and management. Trends Cardiovasc Med. 2020 Apr;30(3):125-130.Liu K, Chen LE, Seaber AV, Urbaniak JR. Influences of inflation rate and duration on vasodilatory effect by intermittent pneumatic compression in distant skeletal muscle. J Orthop Res. 1999 May;17(3):415-20.Louridas, G. A Randomized, Placebo-Controlled Limb Salvage Trial Using the ArtAssist Pneumatic Compression Device. Winnipeg Vascular and Endovascular Symposium. Winnipeg, Canada; April 2006.Manfredini F, Malagoni AM, Felisatti M, Mandini S, Lamberti N, Manfredini R, Mascoli F, Basaglia N, Zamboni P. Acute oxygenation changes on ischemic foot of a novel intermittent pneumatic compression device and of an existing sequential device in severe peripheral arterial disease. BMC Cardiovasc Disord. 2014 Mar 31; 14:40.Mehta T, Venkata Subramaniam A, Chetter I, McCollum P. Assessing the validity and responsiveness of disease-specific quality of life instruments in intermittent claudication. Eur J Vasc Endovasc Surg. 2006 Jan;31(1):46-52.Mentias A, Qazi A, McCoy K, Wallace R, Vaughan-Sarrazin M, Girotra S. Trends in Hospitalization, Management, and Clinical Outcomes Among Veterans with Critical Limb Ischemia. Circ Cardiovasc Interv. 2020 Feb;13(2): e008597.Montori VM, Kavros SJ, Walsh EE, Rooke TW. Intermittent compression pump for nonhealing wounds in patients with limb ischemia. The Mayo Clinic experience (1998-2000). Int Angiol. 2002 Dec;21(4):360-6.Moran PS, Teljeur C, Harrington P, Ryan M. A systematic review of intermittent pneumatic compression for critical limb ischaemia. Vasc Med. 2015;20(1):41-50. doi:10.1177/1358863X14552096Pawlaczyk K, Gabriel M, Urbanek T, Dzieciuchowicz L, Krasinski Z, Gabriel Z, Olejniczak-Nowakowska M, Stanisic M. Effects of Intermittent Pneumatic Compression on Reduction of Postoperative Lower Extremity Edema and Normalization of Foot Microcirculation Flow in Patients Undergoing Arterial Revascularization. Med Sci Monit. 2015 Dec 21; 21:3986-92.Pfizenmaier DH 2nd, Kavros SJ, Liedl DA, Cooper LT. Use of intermittent pneumatic compression for treatment of upper extremity vascular ulcers. Angiology. 2005 Jul-Aug;56(4):417-22.Schnemann H, Brozek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from guidelinedevelopment.org/handbook.Sterne JAC, Savovic J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366: l4898. Published 2019 Aug 28. doi:10.1136/bmj. l4898Sultan S, Esan O, Fahy A. Nonoperative active management of critical limb ischemia: initial experience using a sequential compression biomechanical device for limb salvage. Vascular. 2008 May-Jun;16(3):130-9. doi: 10.2310/6670.2008.00021.Sultan S, Hamada N, Soylu E, Fahy A, Hynes N, Tawfick W. Sequential compression biomechanical device in patients with critical limb ischemia and nonreconstructible peripheral vascular disease. J Vasc Surg. 2011 Aug;54(2):440-6; discussion 446-7. doi: 10.1016/j.jvs.2011.02.057.Tawfick WA, Hamada N, Soylu E, Fahy A, Hynes N, Sultan S. Sequential compression biomechanical device versus primary amputation in patients with critical limb ischemia. Vasc Endovascular Surg. 2013 Oct;47(7):532-9.van Bemmelen PS, Mattos MA, Faught WE, Mansour MA, Barkmeier LD, Hodgson KJ, Ramsey DE, Sumner DS. Augmentation of blood flow in limbs with occlusive arterial disease by intermittent calf compression. J Vasc Surg. 1994 Jun;19(6):1052-8.van Bemmelen PS, Weiss-Olmanni J, Ricotta JJ. Rapid intermittent compression increases skin circulation in chronically ischemic legs with infra-popliteal arterial obstruction. Vasa. 2000 Feb;29(1):47-52.van Bemmelen PS, Choudry RG, Salvatore MD, Goldenberg M, Goldman BI, Blebea J. Long-term intermittent compression increases arteriographic collaterals in a rabbit model of femoral artery occlusion. Eur J Vasc Endovasc Surg. 2007 Sep;34(3):340-6.van Bemmelen P, Char D, Giron F, Ricotta JJ. Angiographic improvement after rapid intermittent compression treatment [ArtAssist] for small vessel obstruction. Ann Vasc Surg. 2003 Mar;17(2):224-8.van Bemmelen PS, Gitlitz DB, Faruqi RM, et al. Limb salvage using high-pressure intermittent compression arterial assist device in cases unsuitable for surgical revascularization. Arch Surg. 2001;136(11):1280-1286.Williams KJ, Babber A, Ravikumar R, Davies AH. Non-Invasive Management of Peripheral Arterial Disease. Adv Exp Med Biol. 2017; 906:387-406. doi:10.1007/5584_2016_129Zaki M, Elsherif M, Tawfick W, El Sharkawy M, Hynes N, Sultan S. The Role of Sequential Pneumatic Compression in Limb Salvage in Non-reconstructable Critical Limb Ischemia. Eur J Vasc Endovasc Surg. 2016 Apr;51(4):565-71. doi: 10.1016/j.ejvs.2015.12.025.Zaleska MT, Olszewski WL, Ross J. The long-term arterial assist intermittent pneumatic compression generating venous flow obstruction is responsible for improvement of arterial flow in ischemic legs. PLoS One. 2019 Dec 11;14(12): e0225950.
Local Coverage Determinations, LCD, Local policies, MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer, DL38586	Use this page to view details for the Local Coverage Determination for MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer.	PROPOSED	Proposed LCD - MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer (DL38586)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39347&ver=3	lcd-39347-3-1.txt	1	39347	lcd	3	0	a0215b34-bbd6-40aa-b7bc-53368fc54729	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 1of 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.ORb. The 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 society consensus guidelines (i.e., National Comprehensive Cancer Network [NCCN], American Society of Clinical Oncology [ASCO], Society of Urologic Oncology [SUO], or American Urological Association [AUA]).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 Services 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/ABibliographySiegel 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.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.
Local Coverage Determinations, LCD, Local policies, Genetic Testing for Oncology, DL39365	Use this page to view details for the Local Coverage Determination for Genetic Testing for Oncology.	PROPOSED	Proposed LCD - Genetic Testing for Oncology (DL39365)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39364&ver=23	lcd-39364-23-1.txt	1	39364	lcd	23	0	91bd5b6f-bfce-46e7-81d4-b4aba3e7bebb	CMS National Coverage PolicyThis LCD supplements but does not replace, modify or supersede existing Medicare applicable National Coverage Determinations (NCDs) or payment policy rules and regulations for genetic testing for oncology. Federal statute and subsequent Medicare regulations regarding provision and payment for medical services are lengthy. They are not repeated in this LCD. Neither Medicare payment policy rules nor this LCD replace, modify or supersede applicable state statutes regarding medical practice or other health practice professions acts, definitions and/or scopes of practice. All providers who report services for Medicare payment must fully understand and follow all existing laws, regulations and rules for Medicare payment for genetic testing for oncology and must properly submit only valid claims for them. Please review and understand them and apply the medical necessity provisions in the policy within the context of the manual rules. Relevant CMS manual instructions and policies may be found in the following Internet-Only Manuals (IOMs) published on the CMS Web site:IOM Citations:CMS IOM Publication 100-02,Medicare Benefit Policy Manual,Chapter 15, Section 50.4.5 Off Label Use of Anti-Cancer Drugs and Biologicals, Section 80.1 Clinical Laboratory Services and Section 280 Preventive and Screening ServicesCMS IOM Publication 100-03,Medicare National Coverage Determinations (NCD) Manual,Chapter 1, Part 2, Section 90.2 Next-Generation Sequencing for Patients with Advanced CancerChapter 1, Part 4, Section 210.3 Colorectal Cancer Screening TestsCMS IOM Publication 100-08,Medicare Program Integrity Manual,Chapter 13, Section 13.5.4 Reasonable and Necessary Provisions in an LCDSocial Security Act (Title XVIII) Standard References:Title XVIII of the Social Security Act, Section 1862(a)(1)(A) states that no Medicare payment may be made for items or services which are not reasonable and necessary for the diagnosis or treatment of illness or injury.Code of Federal Regulations (CFR) References:CFR, Title 42, Volume 2, Chapter IV, Part 410.32(d)(3) Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: ConditionsCoverage Indications, Limitations, and/or Medical NecessityCompliance with the provisions in this LCD may be monitored and addressed through post payment data analysis and subsequent medical review audits.History/Background and/or General InformationWith advancement in science and technology comes the ability to incorporate genetic testing for oncology biomarkers into clinical care, with the goal of improved patient outcomes. The scope of this LCD is DNA and RNA genetic testing in the practice of oncology in the Medicare population.As defined by the Food and Drug Administration (FDA) and National Institutes of Health (NIH) Biomarker Working Group, a biomarker is A defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, orbiological responses to an exposure or intervention, including therapeutic interventions, and may include molecular, histologic, radiographic, or physiologic characteristics.1 (p.45)Cancer is a disease caused by changes or alterations to a persons genome. Some genetic changes or alterations can be inherited (also known as germline mutations). About 5-10% of all cancer diagnoses result from germline mutations, and over 50 hereditary cancer syndromes are known. Other cancer-causing (oncogenic) genetic changes or alterations result from acquired genetic damage (also known as somatic mutations). Somatic mutations can arise in numerous scenarios, including exposure to chemicals that alter DNA (carcinogens) or ultraviolet (UV) radiation from the sun.2Biomarker testing is a part of personalized laboratory medicine (also known as precision medicine). Precision medicine is a tailored approach to medical care and treatment. Because each patient has a unique combination of genetic changes, and therefore, a unique pattern of biomarkers, precision medicine for oncology involves the use of biomarker testing to pinpoint the disease management needs of individual patients (and avoid the use of treatments which are unlikely to be successful).3Much of this testing involves direct evaluation of the genetics of the malignancy through various testing methodologies. These methodologies can include high level genetic evaluations such as karyotyping (analysis of chromosomes) to more detailed evaluations such as identifying specific pathogenic point variations (analysis of specific nucleotide changes).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 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, 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: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 (DA59125) 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.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.2016.05.007
Local Coverage Determinations, LCD, Local policies, Genetic Testing for Oncology, DL39365	Use this page to view details for the Local Coverage Determination for Genetic Testing for Oncology.	PROPOSED	Proposed LCD - Genetic Testing for Oncology (DL39365)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39364&ver=23	lcd-39364-23-1.txt	1	39364	lcd	23	1	aa3724b3-1e48-4488-9e07-0eeb574554f2	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.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.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.
Local Coverage Determinations, LCD, Local policies, Genetic Testing for Oncology, DL39367	Use this page to view details for the Local Coverage Determination for Genetic Testing for Oncology.	PROPOSED	Proposed LCD - Genetic Testing for Oncology (DL39367)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39366&ver=10	lcd-39366-10-1.txt	1	39366	lcd	10	0	db94fda9-d55a-40fd-8f87-54ede121a545	CMS National Coverage PolicyThis LCD supplements but does not replace, modify or supersede existing Medicare applicable National Coverage Determinations (NCDs) or payment policy rules and regulations for genetic testing for oncology. Federal statute and subsequent Medicare regulations regarding provision and payment for medical services are lengthy. They are not repeated in this LCD. Neither Medicare payment policy rules nor this LCD replace, modify or supersede applicable state statutes regarding medical practice or other health practice professions acts, definitions and/or scopes of practice. All providers who report services for Medicare payment must fully understand and follow all existing laws, regulations and rules for Medicare payment for genetic testing for oncology and must properly submit only valid claims for them. Please review and understand them and apply the medical necessity provisions in the policy within the context of the manual rules. Relevant CMS manual instructions and policies may be found in the following Internet-Only Manuals (IOMs) published on the CMS Web site:IOM Citations:CMS IOM Publication 100-02,Medicare Benefit Policy Manual,Chapter 15, Section 50.4.5 Off Label Use of Anti-Cancer Drugs and Biologicals, Section 80.1 Clinical Laboratory Services and Section 280 Preventive and Screening ServicesCMS IOM Publication 100-03,Medicare National Coverage Determinations (NCD) Manual,Chapter 1, Part 2, Section 90.2 Next-Generation Sequencing for Patients with Advanced CancerChapter 1, Part 4, Section 210.3 Colorectal Cancer Screening TestsCMS IOM Publication 100-08,Medicare Program Integrity Manual,Chapter 13, Section 13.5.4 Reasonable and Necessary Provisions in an LCDSocial Security Act (Title XVIII) Standard References:Title XVIII of the Social Security Act, Section 1862(a)(1)(A) states that no Medicare payment may be made for items or services which are not reasonable and necessary for the diagnosis or treatment of illness or injury.Code of Federal Regulations (CFR) References:CFR, Title 42, Volume 2, Chapter IV, Part 410.32(d)(3) Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: ConditionsCoverage Indications, Limitations, and/or Medical NecessityCompliance with the provisions in this LCD may be monitored and addressed through post payment data analysis and subsequent medical review audits.History/Background and/or General InformationWith advancement in science and technology comes the ability to incorporate genetic testing for oncology biomarkers into clinical care, with the goal of improved patient outcomes. The scope of this LCD is DNA and RNA genetic testing in the practice of oncology in the Medicare population.As defined by the Food and Drug Administration (FDA) and National Institutes of Health (NIH) Biomarker Working Group, a biomarker is A defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, orbiological responses to an exposure or intervention, including therapeutic interventions, and may include molecular, histologic, radiographic, or physiologic characteristics.1 (p.45)Cancer is a disease caused by changes or alterations to a persons genome. Some genetic changes or alterations can be inherited (also known as germline mutations). About 5-10% of all cancer diagnoses result from germline mutations, and over 50 hereditary cancer syndromes are known. Other cancer-causing (oncogenic) genetic changes or alterations result from acquired genetic damage (also known as somatic mutations). Somatic mutations can arise in numerous scenarios, including exposure to chemicals that alter DNA (carcinogens) or ultraviolet (UV) radiation from the sun.2Biomarker testing is a part of personalized laboratory medicine (also known as precision medicine). Precision medicine is a tailored approach to medical care and treatment. Because each patient has a unique combination of genetic changes, and therefore, a unique pattern of biomarkers, precision medicine for oncology involves the use of biomarker testing to pinpoint the disease management needs of individual patients (and avoid the use of treatments which are unlikely to be successful).3Much of this testing involves direct evaluation of the genetics of the malignancy through various testing methodologies. These methodologies can include high level genetic evaluations such as karyotyping (analysis of chromosomes) to more detailed evaluations such as identifying specific pathogenic point variations (analysis of specific nucleotide changes).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 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, 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: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.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.2016.05.007
Local Coverage Determinations, LCD, Local policies, Genetic Testing for Oncology, DL39367	Use this page to view details for the Local Coverage Determination for Genetic Testing for Oncology.	PROPOSED	Proposed LCD - Genetic Testing for Oncology (DL39367)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39366&ver=10	lcd-39366-10-1.txt	1	39366	lcd	10	1	aaa3253f-51be-49ce-b965-41bf0af615f6	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.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.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.
Local Coverage Determinations, LCD, Local policies, MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer, DL38647	Use this page to view details for the Local Coverage Determination for MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer.	PROPOSED	Proposed LCD - MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer (DL38647)	html	https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39370&ver=4	lcd-39370-4-1.txt	1	39370	lcd	4	0	96451a56-80d7-4905-a6c8-ce58c6ce655c	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/ABibliographySiegel 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.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.

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Dataset Summary

This dataset contains CMS information with local and national coverage document data sets (LCD & NCD),
as Coverage Articles and [Internet-Only Manuals (IOMs)(https://www.cms.gov/medicare/regulations-guidance/manuals/internet-only-manuals-ioms)

A list of Current LCDS, NCDs and Articles is obrained from Medicare Coverage Database.

The data itself was obtainted by scrapping the urls and extracting data from the pdf files listed in current articles and current lcds

CMS Dataset with Medicare Regulations Guidance Manuals

Data is chunked using text-embedding-3-large model tokenizer with chunk size=3000 and overlap=300 applying langchain.text_splitter.RecursiveCharacterTextSplitter

Licensing Information

Licensed under the Apache License, Version 2.0 (the "License"); you may not use this file except in compliance with the License. You may obtain a copy of the License at

 http://www.apache.org/licenses/LICENSE-2.0

Unless required by applicable law or agreed to in writing, software distributed under the License is distributed on an "AS IS" BASIS, WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. See the License for the specific language governing permissions and limitations under the License.

Author

@evekhm Eva Khmelinskaya

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Number of rows:

7,895