AMA-DE Compendium Revision Request - CAG-00388

Issue:

Requestor Name(s):          CMS Generated

Formal Request Accepted and Review Initiated:          February 6, 2008

Expected Completion Date:          June 5, 2008

Lead Analyst(s)

Lead Medical Officer(s):          Lori Paserchia, MD

Actions Taken

To:		Administrative File: CAG #00388

From:	Steve Phurrough, MD, MPA
		Director, Coverage and Analysis Group

		Louis Jacques, MD
		Director, Division of Items and Devices

		Kate Tillman, RN, MA
		Analyst

		Brijet Burton, PA-C
		Analyst

		Lori Paserchia, MD
		Lead Medical Officer

Subject:	American Medical Association Drug Evaluations compendium- Request for deletion from the list of compendia
		for the identification of a medically accepted indication for the off label uses of drugs and biologicals in an 
		anticancer chemotherapeutic regimen

Date:		June 5, 2008

Background

Section 1861(t)(2)(B)(ii)(I) of the Social Security Act (the Act), as amended by Section 6001 (f)(1) of the Deficit Reduction Act of 2005, Pub. Law 109-171, recognizes three compendiaAmerican Medical Association Drug Evaluations (AMA-DE), United States Pharmacopoeia-Drug Information (USP-DI) or its successor publication and American Hospital Formulary Service-Drug Information (AHFS-DI)as authoritative sources for use in the determination of a "medically-accepted indication" of drugs and biologicals used off-label in an anticancer chemotherapeutic regimen, unless the Secretary has determined that the use is not medically appropriate or the use is identified as not indicated in one or more such compendia.

Due to changes in the pharmaceutical reference industry, fewer of these statutorily-named compendia are available for our reference (e.g., the AMA- DE and the USP-DI are no longer published; Thomson Micromedex has designated Drug Points as the successor to the USP-DI.). Consequently, CMS received requests from the stakeholder community for a process to revise the list of compendia. In the Physician Fee Schedule final rule for calendar year 2008, CMS established a process for revising the list of compendia, as authorized under section 1861(t)(2) of the Act, and also established a definition for “compendium.” See 72 Fed. Reg. 66222, 66303-66306, 66404 (Nov. 27, 2007). Under 42 C.F.R. §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; (3) differs from a disease treatment guideline, which is indexed by disease. See 42 C.F.R. § 414.930(a); 72 Fed. Reg. 66222, 66304.

In addition, 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.
• Process for public identification and notification of potential conflicts of interest of the compendia's parent and sibling organizations, reviewers, and committee members, with an established procedure to manage recognized conflicts.

We did not in regulation assign relative weights to these characteristics. Nor did we identify any characteristics as optional requirements, as we believe that all are necessary to fulfill the purpose for which this designation is made. However, as provided in regulation, CMS may consider additional reasonable factors in its decision. See 72 Fed. Reg. at 66306.

The drugs and biologicals used in the treatment of cancer are not benign agents. Boxed label “black box” warnings, a special FDA regulatory requirement, are commonly seen in many classes of agents: bevacizumab, rituximab, irinotecan, doxorubicin, busulfan, capecitabine, fludarabine, cetuximab, trastuzumab, gemtuzumab and docetaxel are but a few examples. The interests of Medicare beneficiaries who have cancer are safeguarded not only when appropriate uses of these agents are supported by Medicare payment, but equally so when inappropriate uses of these dangerous agents are discouraged by the absence of Medicare payment. Thus the explicit identification of indications that are not medically accepted is as necessary as the identification of indications that are medically accepted.

We believe the public should have access to such materials as necessary to determine if a compendium’s actions are indeed consistent with its stated policies. As Medicare beneficiaries who have cancer have the greatest personal stake in this issue, indeed their lives may hang in balance, we believe that public access is less meaningful if it is not provided broadly. Thus, as provided in regulation, we will consider broad access of the compendia to the general public as an additional reasonable factor. See 72 Fed. Reg. at 66306.

Request

CMS’ internally generated request for the deletion of the American Medical Association Drug Evaluations compendium from the list of compendia for the identification of a medically accepted indication for the off-label uses of drugs and biologicals in an anticancer chemotherapeutic regimen was posted on February 6, 2008 on the CMS website.

Materials Reviewed

Public Comments

As required under 42 C.F.R. § 414.930(b), CMS opened a 30 calendar day public comment period starting on the date this request was posted to receive feedback on the deletion of the American Medical Association Drug Evaluations compendium from the list of compendia.

CMS received no public comment regarding the deletion of the American Medical Association Drug Evaluations compendium as an authoritative source for use in the determination of a "medically-accepted indication" of drugs and biologicals used off-label in an anticancer chemotherapeutic regimen.

Other Relevant Comments

CMS received a letter from the Senate Finance Committee, signed by Senator Max Baucus, Senator Charles E. Grassley, Senator John D. Rockefeller and Senator Orrin G. Hatch. They expressed a particular interest with the CMS compendia review process, specifically noting “…conflicts of interest on the part of authors who contribute to the compendia.” In the correspondence, it was requested “…that CMS rely solely on compendia that are developed under policies of transparency and financial disclosure….”

American Medical Association Drug Evaluations compendium

As part of the compendium review process CMS requires access to the compendium under review. As this compendium has not been published since 1995, there is no contemporary edition of this compendium to review.

Analysis

1. The product known as the American Medical Association Drug Evaluations compendium is a compendium as defined by CMS in the regulation. However, it is obsolete and no longer in publication.

2. The American Medical Association Drug Evaluations compendium fails to adequately address the MedCAC identified desirable characteristics. Among other obvious deficits, the AMA-DE has no mechanism to receive and act upon applications, to review evidence, or to process timely listings.

3. There was no public comment. We believe that this is reasonably interpreted as the absence of public concern with CMS’ generated request and with the removal of the American Medical Association Drug Evaluations compendium as an authoritative source for use in the determination of a "medically-accepted indication" of drugs and biologicals used off-label in an anticancer chemotherapeutic regimen.

In summary, we have determined that the American Medical Association Drug Evaluations compendium meets the definition of a compendium as defined by 42 C.F.R. § 414.930(a); 72 Fed. Reg. 66222, 66404 but does not meet the criteria created by the MedCAC and referenced in regulation. It is obsolete and no longer in publication.

Conclusion

The American Medical Association Drug Evaluations compendium is no longer an authoritative compendium for such purposes as defined and outlined in 42 C.F.R. § 414.930(a); 72 Fed. Reg. 66222, 66404. Therefore, we are removing the American Medical Association Drug Evaluations compendium from the list of compendia in Chapter 15, section 50.4.5 of the Medicare Benefit Policy Manual, for use in the determination of a "medically-accepted indication" of drugs and biologicals used off-label in an anticancer chemotherapeutic regimen.