(Medicare National Coverage Determinations Manual)

A clinical study seeking Medicare payment for pharmacogenomic testing of CYP2C9 or VKORC1 alleles to predict warfarin responsiveness provided to the Medicare beneficiary who is a candidate for anticoagulation therapy with warfarin pursuant to CED must addr ess one or more aspects of the following question:   Prospectively, in Medicare-aged subjects whose warfarin therapy management includes pharmacogenomic testing of CYP2C9 or VKORC1 alleles to predict warfarin response, what is the frequency and severity of the following outcomes, compared to subjects whose warfarin therapy management does not include pharmacogenomic testing?   Major hemorrhage  Minor hemorrhage  Thromboembolism related to the primary indication for anticoagulation  Other thromboembolic event  Mortality   The study must adhere to the following standards of scientific integrity and relevance to the Medicare population:  a. The principal purpose of the research study is to test whether a particular intervention potentially improves the participants health outcomes.  b. The research study is well -supported by available scientific and medical information or it is intended to clarify or establish the health outcomes of interventions already in common clinical use.  c. The research study does not unjustifiably duplicate existing studies.  d. The research study design is appropriate to answer the research question being asked in the study.  e. The research study is sponsored by an organization or individual capable of executing the proposed study successfully.  f. The research study is in compliance with all applicable Federal regulations concerning the protection of human subjects found in the Code of Federal Regulations (CFR) at 45 CFR Part 46. If a study is regulated by the FDA, it also must be in compliance with  21 CFR Parts 50 and 56.  g. All aspects of the research study are conducted according to the appropriate standards of scientific integrity.   h. The research study has a written protocol that clearly addresses, or incorporates by reference, the Medicare standards.   i. The clinical research study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals. Trials of all medical technologies measuring therapeutic outcomes as one of the objectives meet this standard only if the disease or condition being studied is life-threatening as defined in 21 CFR  312.81(a) and the patient has no other viable treatment options.  j. The clinical research study is registered on the www.ClinicalTrials.gov  website by the principal sponsor/investigator prior to the enrollment of the first study subject.  k. The research study protocol specifies the method and timing of public release of all pre- specified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early. The results must be made public within 24 months of the end of data collection. If a report is planned to be published in a peer- reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors. However, a full report of the outcomes must be made public no later than 3 years after the end of data collection.  l. The research study protocol must explicitly discuss subpopulations affected by the treatment under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria affect enrollment of these po pulations, and a plan for the retention and reporting of said populations on the trial. If the inclusion and exclusion criteria are expected to have a negative effect on the recruitment or retention of underrepresented populations, the protocol must discuss why these criteria are necessary.   m. The research study protocol explicitly discusses how the results are or are not expected to be generalizable to the Medicare population to infer whether Medicare patients may benefit from the intervention. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability or Medicaid eligibility.   Consistent with section 1142 of the Act, the Agency for Healthcare Research and Quality (AHRQ) supports clinical research studies that CMS determines meet the above-listed standards and address the above- listed research questions.  B. Nationally Non-Covered Indications  The CMS believes that the available evidence does not demonstrate that pharmacogenomic testing of CYP2C9  or VKORC1  alleles to predict warfarin responsiveness improves health outcomes in Medicare beneficiaries outside the context of CED, and is therefore not reasonable and necessary under 1862(a)(1)(A) of the Act.   C. Other  This NCD does not determine coverage to identify CYP2C9 or VKORC1 alleles for other purposes, nor does it determine national coverage to identify other alleles to predict warfarin responsiveness.  (This NCD last reviewed August 2009.)  90.2 Next Generation Sequencing (NGS)  for Patients with Somatic (Acquired)  and Germline (Inherited) Cancer  (Rev. 10346, Issued: 09-11-20, Effective: 01-27-20, Implementation: 11-13-20)  A.  General  Clinical laboratory diagnostic tests can include tests that, for example, predict the risk associated with one or more genetic variations.  In addition, in vitro companion diagnostic laboratory tests provide a report of test results of genetic variations a nd are essential for the safe and effective use of a corresponding therapeutic product.  Next Generation Sequencing (NGS) is one technique that can measure one or more genetic variations as a laboratory diagnostic test, such as when used as a companion in vitro diagnostic test.   This National Coverage Determination (NCD) is only applicable to diagnostic lab tests using NGS for somatic (acquired) and germline (inherited) cancer.   Medicare Administrative Contractors (MACs) may determine coverage of diagnostic lab tests using NGS for RNA sequencing and protein analysis.    B. Nationally Covered Indications  1. Somatic (Acquired) Cancer   Effective for services performed on or after March 16, 2018, the Centers for Medicare & Medicaid Services (CMS) has determined that Next Generation Sequencing (NGS) as a diagnostic laboratory test is reasonable and necessary and covered nationally, when performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, when ordered by a treating physician, and when all of the following requirements are met:   a. Patient has:  i. either recurrent, relapsed, refractory, metastatic, or advanced stage III or IV cancer; and  ii. not been previously tested with the same test using NGS for the same cancer genetic content, and iii. decided to seek further cancer treatment (e.g., therapeutic chemotherapy).   b. The diagnostic laboratory test using NGS must have: i. Food & Drug Administration (FDA) approval or clearance as a companion in vitro diagnostic; and, ii. an FDA -approved or - cleared indication for use in that patients cancer; and,  iii. results provided to the treating physician for management of the patient using a report template to specify treatment options.   2. Germline (Inherited) Cancer   Effective for services performed on or after January 27, 2020, CMS has determined that NGS as a diagnostic laboratory test is reasonable and necessary and covered nationally for patients with germline (inherited) cancer, when performed in a CLIA- certified laboratory, when ordered by a treating physician and when all of the following requirements are met:  a. Patient has:  i. ovarian or breast cancer; and, ii. a clinical indication for germline (inherited) testing for hereditary breast or ovarian cancer; and, iii. a risk factor for germline (inherited) breast or ovarian cancer; and  iv. not been previously tested with the same germline test using NGS for the same germline genetic content.   b. The diagnostic laboratory test using NGS must have all of the following: i. FDA -approval or clearance; and,  ii. results provided to the treating physician for management of the patient using a report template to specify treatment options.   C. Nationally Non -Covered  Indications   1. Somatic (Acquired) Cancer   Effective for services performed on or after March 16, 2018, NGS as a diagnostic laboratory test for patients with acquired  (somatic)  cancer are non -covered if the cancer patient does not meet the criteria noted in section B.1., above.   D. Other   1. Somatic (Acquired) Cancer   Effective for services performed on or after March 16, 2018, Medicare Administrative Contractors (MACs) may determine coverage of NGS as a diagnostic laboratory test for patients with  advanced  cancer only when the test is performed in a CLIA -certified laboratory, when  ordered by a treating physician, and when the patient has:   a. either recurrent, relapsed, refractory, metastatic, or advanced stages III or IV cancer; and,  b. not been previously tested with the same test using NGS for the same cancer genetic content, and c. decided to seek further cancer treatment (e.g., therapeu tic chemotherapy).    2. Germline (Inherited) Cancer   Effective for services performed on or after January 27, 2020, MACs may determine coverage of NGS as a diagnostic laboratory test for patients with germline (inherited) cancer only when the test is performed in a CLIA -certified laboratory, when ordered by a treating physician, when results are provided to the treating physician for management of the patient and when the patient has:  a. any cancer diagnosis; and,  b. a clinical indication for germline (inherited) testing of hereditary cancers; and,  c. a risk factor for germline (inherited) cancer; and,  d. not been previously tested with the same germline test using NGS for the same germline genetic content.  (This NCD last reviewed January 2020)   100 - Gastrointestinal System  (Rev. 1, 10-03-03)  100.1 - Bariatric Surgery for Treatment of Co -Morbid Conditions Related to Morbid Obesity (Rev. 158, Issued: 12-23-13, Effective: 09-24-13, Implementation: 12-17-13)  Please note, sections 40.5, 100.8, 100.11, and 100.14 have been removed from the National Coverage Determination (NCD) Manual and incorporated into NCD 100.1  A. General   Obesity may be caused by medical conditions such as hypothyroidism, Cushing's disease, and hypothalamic lesions, or can aggravate a number of cardiac and respiratory diseases as well as diabetes and hypertension.  Non-surgical services in connection with t he treatment of obesity are covered when such services are an integral and necessary part of a course of treatment for one of these medical conditions.  In addition, supplemented fasting is a type of very low calorie weight reduction regimen used to achieve rapid weight loss.  The reduced calorie intake is supplemented by a mixture of protein, carbohydrates, vitamins, and minerals. Serious questions exist about the safety of prolonged adherence for 2 months or more to a very low calorie weight reduction regimen as a general treatment for obesity, because of instances of cardiopathology and sudden death, as well as possible loss of body protein.  Bariatric surgery procedures are performed to treat comorbid conditions associated with morbid obesity. Two types of surgical procedures are employed. Malabsorptive procedures divert food from the stomach to a lower part of the digestive tract where the no rmal mixing of digestive fluids and absorption of nutrients cannot occur. Restrictive procedures restrict the size of the stomach and decrease intake. Surgery can combine both types of procedures.   The following are descriptions of bariatric surgery procedures:   1. Roux- en-Y Gastric Bypass (RYGBP)   The RYGBP achieves weight loss by gastric restriction and malabsorption. Reduction of the stomach to a small gastric pouch (30 cc) results in feelings of satiety following even small meals. This small pouch is connected to a segment of the jejunum, bypassing the duodenum and very proximal small intestine, thereby reducing absorption. RYGBP procedures can be open or laparoscopic.   2. Biliopancreatic Diversion with Duodenal Switch (BPD/DS) or Gastric Reduction Duodenal Switch (BPD/GRDS)   The BPD achieves weight loss by gastric restriction and malabsorption. The stomach is partially resected, but the remaining capacity is generous compared to that achieved with RYGBP. As such, patients eat relatively normal-sized meals and do not need to re strict intake radically, since the most proximal areas of the small intestine (i.e., the duodenum and jejunum) are bypassed, and substantial malabsorption occurs. The partial BPD/DS or BPD/GRDS is a variant of the BPD procedure. It involves resection of the greater curvature of the stomach, preservation of the pyloric sphincter, and transection of the duodenum above the ampulla of Vater with a duodeno- ileal anastomosis and a lower ileo -ileal anastomosis. BPD/DS or BPD/GRDS procedures can be open or laparosc opic.