CMS Pub. 100-02, ch. 15, § 50.4.5.1

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 compendium 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 accepted 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 authorized 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 will 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 disposition 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 compendium’s Web site for a period of not less than 3

years, coincident with the compendium’s publication.

• A publicly transparent process for identifying potential conflicts of interests that provides: (1) direct

or indirect financial relationships, and (2) ownership or investment interests that exist between

individuals or the spouse or minor child of individuals who have substantively participated in the

development or disposition of compendia recommendations, and the manufacturer or seller of the

drug or biological being reviewed by the compendium. This information shall be identified and

made timely available in response to a public request for a period of not less than 5 years, which

includes availability on the compendium’s Web site for a period of not less than 3 years, coincident

with the compendium’s publication.

A request may have only a single compendium as its subject. This will provide greater clarity to the scope

of the Agency’s review of a given request. A requestor may submit multiple requests, each requesting a

different action.

E. Submission of Requests

Requests must be in writing and submitted in one of the following two ways (no duplicates please):

1. Electronic requests are encouraged to facilitate administrative efficiency. Each solicitation will

include the electronic address for submissions.

2. Hard copy requests can be sent to: Centers for Medicare & Medicaid Services, Coverage and

Analysis Group, Mailstop C1–09–06, 7500 Security Boulevard, Baltimore, MD 21244.

Allow sufficient time for hard copies to be received prior to the close of the open request period.

F. Review of Requests

CMS will consider a compendium’s attainment of the desirable characteristics specified in 50.4.5.1.B when

reviewing requests. CMS may consider additional, reasonable factors in making a determination. For

example, CMS may consider factors that are likely to impact the compendium’s suitability for this use, such

as a change in the compendium’s ownership or affiliation, and the standards applicable to the evidence

considered by the compendium. CMS may consider that broad accessibility by the general public to the

information contained in the compendium may assist beneficiaries, their treating physicians, or both, in

choosing among treatment options. CMS will also consider a compendium’s grading of evidence used in

making recommendations regarding off-label uses, and the process by which the compendium grades the

evidence. CMS may, at its discretion, combine and consider multiple requests that refer to the same

compendium, even if those requests are for different actions. This facilitates administrative efficiency in the

review of requests.

G. Publishing Review Results

CMS will publish decisions on the CMS Web site within 90 days after the close of the public comment

period.

(This instruction was last reviewed by CMS in December 2009.)