(Medicare Benefit Policy Manual)

Medicare does not require, for coverage purposes, that a doctor of medicine or osteopathy order the vaccine. Therefore, the beneficiary may receive the vaccine upon request without a physicians order and without physician supervision.  50.4.5 - Off-Label Use of Drugs and Biologicals in an Anti-Cancer Chemotherapeutic Regimen  (Rev. 212, Issued: 11- 06-15, Effective: 08 -12-15, Implementation: 02- 10-16)  A. Overview   Effective January 1, 1994, off-label, medically accepted indications of Food and Drug Administration-(FDA) approved drugs and biologicals used in an anti -cancer chemotherapeutic regimen are identified under the conditions described below.  A regimen is a c ombination of anti-cancer agents clinically recognized for the treatment of a specific type of cancer.  Off-label, medically accepted indications are supported in either one or more of the compendia or in peer-reviewed medical literature.  The contractor may maintain its own subscriptions to the listed compendia or peer-reviewed publications to determine the medically accepted indication of drugs or biologicals used off- label in an anti -cancer chemotherapeutic regimen.  Compendia documentation or peer-reviewed literature supporting off-label use by the treating physician may also be requested of the physician by the contractor.   B. Recent Revisions to the Compendia List   Do not deny coverage based solely on the absence of FDA -approved labeling for the use, if the use is supported by any of the following compendia and the use is not listed as unsupported, not indicated, not recommended, or equivalent terms, in any of the following compendia:   Existing - American Hospital Formulary Service -Drug Information (AHFS -DI)   Effective June 5, 2008 - National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium   Effective June 10, 2008 - Micromedex DrugDex   Effective July 2, 2008 - Clinical Pharmacology   Effective August 12, 2015  Lexi -Drugs   The listed compendia employ various rating and recommendation systems that may not be readily cross -walked from compendium to compendium.  In general, a use is identified by a compendium as medically accepted if the:  1. indication is a Category 1 or 2A in NCCN, or Class I, Class IIa, or Class IIb in DrugDex; or,   2. narrative text in AHFS -DI or Clinical Pharmacology is supportive, or   3. indication is listed in Lexi -Drugs as Use: Off-Label and rated as Evidence Level A   A use is not medically accepted by a compendium if the:   1. indication is a Category 3 in NCCN or a Class III in DrugDex; or,   2. narrative text in AHFS or Clinical Pharmacology is not supportive, or   3. indication is listed in Lexi -Drugs as Use: Unsupported   The complete absence of narrative text on a use is considered neither supportive nor non-supportive.   C. Use Supported by Clinical Research That Appears in Peer -Reviewed Medical Literature   Contractors may also identify off- label uses that are supported by clinical research under the conditions identified in this section.  Peer- reviewed medical literature may appear in scientific, medical, and pharmaceutical publications in which original manuscripts are published, only after having been critically reviewed for scientific accuracy, validity, and reliability by unbiased, independent experts prior to publication.  In-house publications of entities whose business relates to the manufacture, sale, or distribution of pharmaceutical products are excluded from consideration.  Abstracts (including meeting abstracts) are excluded from consideration.   In determining whether an off-label use is supported, the contractors will evaluate the evidence in published, peer-reviewed medical literature listed below.  When evaluating this literature, they will consider (among other things) the following:    Whether the clinical characteristics of the beneficiary and the cancer are adequately represented in the published evidence.    Whether the administered chemotherapy regimen is adequately represented in the published evidence.    Whether the reported study outcomes represent clinically meaningful outcomes experienced by patients.    Whether the study is appropriate to address the clinical question. The contractor will consider:   1. whether the experimental design, in light of the drugs and conditions under investigation, is appropriate to address the investigative question.  (For example, in some clinical studies, it may be unnecessary or not feasible to use randomization, double bli nd trials, placebos, or crossover.);   2. that non-randomized clinical trials with a significant number of subjects may be a basis for supportive clinical evidence for determining accepted uses of drugs; and,   3. that case reports are generally considered uncontrolled and anecdotal information and do not provide adequate supportive clinical evidence for determining accepted uses of drugs.   The contractor will use peer-reviewed medical literature appearing in the regular editions of the following publications, not to include supplement editions privately funded by parties with a vested interest in the recommendations of the authors:   American Journal of Medicine;  Annals of Internal Medicine;  Annals of Oncology;  Annals of Surgical Oncology;  Biology of Blood and Marrow Transplantation;  Blood;  Bone Marrow Transplantation;  British Journal of Cancer;  British Journal of Hematology;  British Medical Journal;  Cancer;  Clinical Cancer Research;  Drugs;  European Journal of Cancer (formerly the European Journal of Cancer and Clinical Oncology);  Gynecologic Oncology;  International Journal of Radiation, Oncology, Biology, and Physics;  The Journal of the American Medical Association;  Journal of Clinical Oncology;  Journal of the National Cancer Institute;  Journal of the National Comprehensive Cancer Network (NCCN);  Journal of Urology;  Lancet;  Lancet Oncology;  Leukemia;  The New England Journal of Medicine; or  Radiation Oncology   D. Generally   FDA -approved drugs and biologicals may also be considered for use in the determination of medically accepted indications for off-label use if determined by the contractor to be reasonable and necessary.   If a use is identified as not indicated by the Centers for Medicare and Medicaid Services (CMS) or the FDA, or if a use is specifically identified as not indicated in one or more of the compendia listed, or if the contractor determines, based on peer -revie wed medical literature, that a particular use of a drug is not safe and effective, the off-label usage is not supported and, therefore, the drug is not covered.  50.4.5.1 - Process for Amending the List of Compendia for Determination of Medically -Accepted Indications for Off -Label Uses of Drugs and Biologicals in an Anti- Cancer Chemotherapeutic Regimen  (Rev. 120, Issued: 01-29-10, Effective: 01-01-10, Implementation: 03-01-10)  A. Background   In the Physician Fee Schedule final rule for calendar year (CY) 2008, the CMS established a process for revising the list of compendia, as authorized under section 1861(t)(2) of the Social Security Act, and also established a definition for compendium.  At 42 CFR 414.930(a), a compendium is defined as a comprehensive listing of FDA-approved drugs and biologicals or a comprehensive listing of a specific subset of drugs and biologicals in a specialty compendium, for example, a compendium of anti- cancer treatment.  A compendium: (1) includes a summary of the pharmacologic characteristics of each drug or biological and may include information on dosage, as well as recommended or endorsed uses in specific diseases; (2) is indexed by drug or biological, and, (3) effective January 1, 2010, pursuant to section 182(b) of the Medicare Improvements for Patients and Providers Act (MIPPA), has a publicly transparent process for evaluating therapies and for identifying potential conflicts of interests.  See 42 CFR 414.930(a); 72 FR 66222, 66404, and 74 FR 61901.  B. Desirable Characteristics of Compendia   CMS increased the transparency of the process by incorporating a list of desirable compendium characteristics outlined by the Medicare Evidence Development and Coverage Advisory Committee (MedCAC) as criteria for decision -making.  The list of desirable com pendium characteristics was developed by the MedCAC during a public session on March 30, 2006.  The goal of this session was to review the evidence and advise CMS on the desirable characteristics of compendia for use in the determination of medically accep ted indications of drugs and biologicals in anti-cancer therapy.  As a result of this meeting, the MedCAC generated the following list of desirable characteristics:    Extensive breadth of listings,  Quick processing from application for inclusion to listing,  Detailed description of the evidence reviewed for every individual listing,  Use of pre-specified published criteria for weighing evidence,  Use of prescribed published process for making recommendations,  Publicly transparent process for evaluating therapies,  Explicit "Not Recommended" listing when validated evidence is appropriate,  Explicit listing and recommendations regarding therapies, including sequential use or combination in relation to other therapies,  Explicit "Equivocal" listing when validated evidence is equivocal, and,   Process for public identification and notification of potential conflicts of interest of the compendias parent and sibling organizations, reviewers, and committee members, with an established procedure to manage recognized conflicts.   Furthermore, the provisions discussed in section 182(b) of MIPPA bring more uniformity in compendia conflict of interest disclosure practices and allow the public the ability to monitor how these policies impact compendia off- label recommendations.   C. Process for Changing List of Compendia  CMS will provide an annual 30-day open request period starting January 15 for the public to submit requests for additions or deletions to the compendia list contained on the CMS Web site at http://www.cms.hhs.gov/CoverageGenInfo/02_compendia.asp.  Complete requests as defined in section 50.4.5.1.D will be posted to the Web site annually by March 15 for public notice and comment.  The request will identify the requestor and the requested action CMS is being asked to make to the list.  Public comments  will be accepted for a 30 -day period beginning on the day the request is posted on the Web site.  In addition to the annual process, CMS may generate a request for changes to the list at any time an urgent action is needed to protect the interests of the Medicare program and its beneficiaries.   D. Content of Requests   For a request to be considered complete, and therefore accepted for review, it must include the following information:    The full name and contact information (including the mailing address, e -mail address, and    telephone number) of the requestor. If the requestor is not an individual person, the information shall identify the officer or other representative who is authori zed to act for the requestor on all matters related to the request.    Full identification of the compendium that is the subject of the request, including name, publisher, edition if applicable, date of publication, and any other information needed for the accurate and precise identification of the specific compendium.    A complete, written copy of the compendium that is the subject of the request. If the complete compendium is available electronically, it may be submitted electronically in place of hard copy. If the compendium is available online, the requestor may provide CMS with electronic access by furnishing at no cost to the Federal Government sufficient accounts for the purposes and duration of the review of the application in place of hard copy.    The specific action that the requestor wishes CMS to take, for example to add or delete a specific compendium.   Detailed, specific documentation that the compendium that is the subject of the request does or does not comply with the conditions of this rule. Broad, nonspecific claims without supporting documentation cannot be efficiently reviewed; therefore, they wil l not be accepted.    A publicly transparent process for evaluating therapies, which includes the following: (1) internal or external request for listing of a therapy recommendation, including criteria used to evaluate the request (the complete application), (2) listing of all the evidentiary materials reviewed or considered for inclusion in the compendium (3) listing of all individuals who substantively participated in the review and development of the request, and (4) minutes and voting records of meetings for the review and d isposition of the request.  The information from an internal or external request for inclusion of a therapy in a compendium are available to the public for a period of not less than 5 years, which includes availability on the compendiums Web site for a pe riod of not less than 3 years, coincident with the compendiums publication.