(Medicare National Coverage Determinations Manual)

o Graft vs. host disease (acute and chronic),  o Other transplant- related adverse events;  o Overall survival; and  o (optional) Quality of life?   All CMS -approved clinical studies and registries must adhere to the below listed standards of scientific integrity and relevance to the Medicare population listed in section g:   g) All CMS -approved clinical studies and registries in sections d, e and f must adhere to the below listed standards of scientific integrity and relevance to the Medicare population:   a. The principal purpose of the study is to test whether the item or service meaningfully improves health outcomes of affected beneficiaries who are repres ented by the enrolled subjects.   b. The rationale for the study is well supported by available s cientific and medical evidence.   c. The study results are not anticipated to unjustifiabl y duplicate existing knowledge.   d. The study design is methodologically appropriate and the anticipated number of enrolled subjects is sufficient to answer the research question(s) being asked in the N ational Coverage Determination.   e. The study is sponsored by an organization or individual capable  of completing it 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 Food and Drug Administration (FDA), it is also in compliance with 21 CFR Parts 50 and 56.  In addition, to further enhance the protection of human subjects in studies conducted under CED, the study must provide and obtain meaningful informed consent from patients regarding the risks associated  with the study items and/or services, and the use and eventual dis position of the collected data.   g. All aspects of the study are conducted according to appropriate standar ds of scientific integrity.   h. The study has a written protocol that clearly demonstrates adherence to the standards listed here as Medicare requirements.   i. The study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals.  Such studies may meet this requirement 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 studies and registries are registered on the www.ClinicalTrials.gov website by the principal sponsor/investigator prior to the enrollment of the first study subject.  Registries are also registered in the Agency for Healthcare Quality (AHRQ) Registr y of Patient Registries (RoPR).   k. The research study protocol specifies the method and timing of public release of all prespecified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early.  The results must be made public within 12 months of the studys primary completion date, which is the date the final subject had final data collection for the primary endpoint, even if the trial does not achieve its primary aim.  The results must include number started/completed, summary results for primary and secondary outcome measures, statistical analyses, and adverse events.  Final results must be reported in a publicly accessibly manner; either in a peer -reviewed scientific journal (in print or on- line), in an on- line publicly accessible registry dedicated to the dissemination of clinical trial information such as ClinicalTria ls.gov, or in journals willing to publish in abbreviated format (e.g., for studies with negative or incomplete results).   l. The study protocol must explicitly discuss beneficiary subpopulations affected by the item or service under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria effect enrollment of  these populations, and a plan for the retention and reporting of said populations in 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 m ust discuss wh y these criteria are necessary.   m. The study protocol explicitly discusses how the results are or are not expected to be generalizable to affected beneficiary subpopulations.  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.  II. Autologous Stem Cell Transplantation (AuSCT)    a) Effective for services performed on or after April 28, 1989, AuSCT is considered reasonable and necessary under l862(a)(1)(A) of the Act for the following conditions and is covered under Medicare for patients with:   1. Acute leukemia in remission who have a high probability of relapse and who have no human leucocyte antigens (HLA) -matched;   2. Resistant non- Hodgkin's lymphomas or those presenting with poor prognostic features following an initial response;   3. Recurrent or refractory neuroblastoma; or,   4. Advanced Hodgkin's disease who have  failed conventional therapy and have no HLA -matched donor.   b) Effective October 1, 2000, single AuSCT is only covered for Durie -Salmon Stage II or III patients that fit the following requirements:    Newly diagnosed or responsive multiple myeloma.  This includes those patients with previously untreated disease, those with at least a partial response to prior chemotherapy (defined as a 50% decrease either in measurable paraprotein [serum and/or urine] or in bone marrow infiltration, sustained for at l east 1 month), and those in responsive relapse; and    Adequate cardiac, renal, pulmonary, and hepatic function.   c) Effective for services performed on or after March 15, 2005, when recognized clinical risk factors are employed to select patients for transplantation, high dose melphalan (HDM) together with AuSCT is reasonable and necessary for Medicare beneficiaries of any age group with primary amyloid light chain (AL) amyloidosis who meet the following criteria:    Amyloid deposition in 2 or fewer organs; and,   Cardiac left ventricular ejection fraction (EF) greater than 45%.   C. Nationally Non -Covered Indications   I. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)   Effective for claims with dates of service on or after May 24, 1996, through  January 26, 2016, allogeneic HSCT is not covered as treatment for multiple myeloma.   II. Autologous Stem Cell Transplantation (AuSCT)   Insufficient data exist to establish definite conclusions regarding the efficacy of AuSCT for the following conditions:   a) Acute leukemia not in remission;  b) Chronic granulocytic leukemia;  c) Solid tum ors (other than neuroblastoma);  d) Up to October 1, 2000, mul tiple myeloma;  e) Tandem transplantation (multiple rounds of AuSCT) for patients with multiple myeloma;  f) Effective October 1, 2000, non primary AL amyloidosis; and,  g) Effective October 1, 2000, through March 14, 2005, primary AL amyloidosis for Medicare beneficiaries age 64 or older.   In these cases, AuSCT is not considered reasonable and necessary within the meaning of l862(a)(1)(A) of the Act and  is not covered under Medicare.   D. Other  All other indications for stem cell transplantation not otherwise noted above as covered or non- covered remain at local Medicare Admini strative Contractor discretion.   (This NCD last reviewed January 2016.)   110.24 Chimeric Antigen Receptor (CAR) T -cell therapy  (Rev. 10891, Issued: 07- 20-21, Effective: 08 -07-19, Implementation: 09- 20-21)  A. General   Cancer is a collection of related diseases of dividing cells that can start almost anywhere in or on the body, evade the immune system, and invade nearby tissues.  Categories of cancer are typically organized by the location in the body and specific type of cell.  The se categories may include carcinoma, sarcoma, leukemia, lymphoma, multiple myeloma, melanoma, and brain and spinal cord tumors.  There are also changes to these cells that are not considered cancer.  These changes include hyperplasiawhen a cell divides fa ster than normal and dysplasia a buildup of extra cells with abnormal shape and disorganization.   A persons immune system contains cells to help fight substances that are foreign to the body, including cancer.  These cells are called white blood cells, most of which are lymphocytes.  The two main types of lymphocytes are B lymphocytes (B -cells) and T lymphocytes (T -cells).  B -cells generate and release antibodies to fight infection, especially bacterial infections, while T -cells employ a number of other mechanisms to fight abnormal cells such as cancer.  One type of therapy that leverages the immune system immunotherapyis Chimeric Antigen Receptor (CAR) T -cell therapy.   CAR T -cells have been genetically altered in order to improve the ability of the T -cells to fight cancer.  The genetic modification creating a CAR can enhance the ability of the T -cell to recognize and attach to a specific protein, called an antigen, on the surface of a cancer cell.    B. Nationally Covered  Indications   A. Effective for services performed on or after August 7, 2019, the Centers for Medicare & Medicaid Services (CMS) covers autologous treatment for cancer with T- cells expressing at least one chimeric antigen receptor (CAR) when administered at healthcare facilities enrolled in the FDA risk evaluation and mitigation strategies (REMS) and used for a medically accepted indication as defined at Social Security Act section 1861(t)(2)  i.e., is used for either an FDA-approved indication (according to the FDA-approved label for that product), or for other uses when the product has been FDA-approved and the use is supported in one or more CMS -approved compendia.   C. Nationally Non- Covered   Effective for services performed on or after August 7, 2019, the use of non- FDA -approved autologous T-cells expressing at least one CAR is non-covered. Autologous treatment for cancer with T- cells expressing at least one CAR is non- covered when the requirements in Section A are not met.     D. Other  Effective for services performed on or after August 7, 2019, routine costs in clinical trials that use CAR T-cell therapy as an investigational agent that meet the requirements listed in NCD 310.1 will be covered.    (This NCD last reviewed August 2019.)  120 - Infectious Diseases  (Rev. 1, 10-03-03)  No coverage determinations  130 - Mental Health  (Rev. 1, 10-03-03)  130.1 - Inpatient Hospital Stays for the Treatment of Alcoholism  (Rev. 173, Issued: 09-04- 14, Effective: Upon Implementation: of ICD -10, Implementation: Upon Implementation of ICD -10)  A.  Inpatient Hospital Stay for Alcohol Detoxification  Many hospitals provide detoxification services during the more acute stages of alcoholism or alcohol withdrawal. When the high probability or occurrence of medical complications (e.g., delirium, confusion, trauma, or unconsciousness) during detoxification for acute alcoholism or alcohol withdrawal necessitates the constant availability of physicians and/or complex medical equipment found only in the hospital setting, inpatient hospital care during this period is considered reasonable and necessary and is therefore covered under the program. Generally, detoxification can be accomplished within two to three days with an occasional need for up to five days where the patients condition dictates.  This limit (five days) may be extended in an individual case where there is a need for a longer period for detoxification for a particular patient.   In such cases, however, there should be documentation by a physician which substantiates that a longer period of detoxification was reasonable and necessary. When the detoxification needs of an individual no longer require an inpatient hospital setting, coverage should be denied on the basis that inpatient hospital care is not reasonable and necessary as required by 1862(a)(l) of the Social Security Act (the Act).  Following detoxification a patient may be transferred to an inpatient rehabilitation unit or discharged to a residential treatment program or outpatient treatment setting.   B.  Inpatient Hospital Stay for Alcohol Rehabilitation  Hospitals may also provide structured inpatient alcohol rehabilitation programs to the chronic alcoholic.  These programs are composed primarily of coordinated educational and psychotherapeutic services provided on a group basis.  Depending on the subject matter, a series of lectures, discussions, films, and group therapy sessions are led by either physicians, psychologists, or alcoholism counselors from the hospital or various outside organizations.  In addition, individual psychotherapy and family counsel ing (see 70.1) may be provided in selected cases.  These programs are conducted under the supervision and direction of a physician. Patients may directly enter an inpatient hospital rehabilitation program after having undergone detoxification in the same hospital or in  another hospital or may enter an inpatient hospital rehabilitation program without prior hospitalization for detoxification.