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Compendia and Anticancer Therapy Under Medicare FREE

Katherine Tillman, RN, MA; Brijet Burton, PA-C, MS; Louis B. Jacques, MD; and Steve E. Phurrough, MD, MPA
[+] Article and Author Information

From the Centers for Medicare & Medicaid Services, Baltimore, Maryland.


Disclaimer: The opinions expressed by the authors are personal and do not indicate the positions of the Centers for Medicare & Medicaid Services or of the federal government.

Potential Financial Conflicts of Interest:Other: L. Jacques (investigator independence).

Requests for Single Reprints: Katherine Tillman, RN, MA, Centers for Medicare & Medicaid Services, Mailstop C1-09-06, 7500 Security Boulevard, Baltimore, MD 21244; e-mail, katherine.tillman@cms.hhs.gov.

Current Author Addresses: Ms. Tillman, Ms. Burton, and Drs. Jacques and Phurrough: Centers for Medicare & Medicaid Services, Mailstop C1-09-06, 500 Security Boulevard, Baltimore, MD 21244.


Ann Intern Med. 2009;150(5):348-350. doi:10.7326/0003-4819-150-5-200903030-00109
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Abstract

In 1993, Congress directed the Medicare program to refer to 3 existing published compendia, American Medical Association Drug Evaluations (AMA-DE), United States Pharmacopoeia Drug Information for the Health Professional (USP-DI), and American Hospital Formulary Service Drug Information (AHFS-DI), to identify unlabeled but medically accepted uses of drugs and biologicals in anticancer chemotherapy regimens. Public discussion during the preceding years had centered on whether to designate unlabeled uses of anticancer treatments as experimental and thus outside the scope of Medicare benefits. American Medical Association Drug Evaluations and USP-DI subsequently ceased publication, and the Medicare program faced increasing calls to revise the list of acceptable compendia, as authorized in the statute. In 2007, the Centers for Medicare & Medicaid Services used its regulatory authority to establish a publicly transparent process to revise the list. The Centers for Medicare & Medicaid Services considered 5 requests in 2008 and added National Comprehensive Cancer Network Drugs and Biologics Compendium, DRUGDEX, and Clinical Pharmacology to the list of compendia. DrugPoints was not added, and AMA-DE was removed. Because of the potential for conflicts of interest to lead to biased judgments, the 2008 Medicare Improvements for Patients and Providers Act has a provision that explicitly prohibits inclusion of compendia that do not have a publicly transparent process for evaluating therapies and identifying potential conflicts of interest.

In the pharmaceutical industry, a compendium is a comprehensive listing of drugs and biologicals. It typically includes a summary of the pharmacologic characteristics of each listed drug or biological; information on dosage; and, often, recommended uses for specific diseases. Some insurers refer to compendia when making policy decisions, thus creating a strong financial incentive for manufacturers to obtain a favorable compendium recommendation. The Fee-for-Service Medicare program recognizes certain published compendia as authoritative references to identify medically accepted, unlabeled uses of drugs and biologicals in anticancer treatment regimens. We describe the evolution of Medicare's use of compendia and recent updates to the list of compendia that the Centers for Medicare & Medicaid Services (CMS) recognize. Other articles in this issue discuss the related topics of unlabeled prescribing and conflicts of interest. Although these and other compendia may have additional uses, we focus on those related to anticancer treatment, which has recently been the subject of intense interest for policymakers.

A key policy question of the late 1980s and early 1990s was whether medical insurance should cover unlabeled uses of drugs and biologicals (12). Because health insurance policies generally exclude payment for experimental treatments, insurers denied claims for unlabeled uses of drugs and biologicals. After several attempts in the preceding years, Congress, in the Omnibus Budget Reconciliation Act of 1993, amended Title XVIII of the Social Security Act, which governs Medicare, to address this issue. Among other changes, the statute amended the definition of drugs and biologicals in Section 1861(t) to include unlabeled uses of U.S. Food and Drug Administration (FDA)–approved drugs and biologicals in anticancer chemotherapy regimens if they were favorably cited in the compendia. Otherwise, these uses would not fall within the Medicare benefit and would not be payable under the Medicare program. The amended definition would not include indications that the Secretary of Health and Human Services determined to be medically inappropriate or those that 1 or more compendia cited as not indicated. The statute listed the following compendia: American Hospital Formulary Service Drug Information (AHFS-DI), American Medical Association Drug Evaluations (AMA-DE), and United States Pharmacopoeia Drug Information for the Health Professional. (USP-DI). It also explicitly gave the Secretary of Health and Human Services the authority to revise the list.

Since the 1993 Omnibus legislation, the AMA-DE and USP-DI have ceased publication. The CMS heard requests to recognize additional compendia as authoritative in deciding whether an unlabeled indication was medically accepted. The discussion primarily focused on the need to have more than 1 active, recognized compendium. In response, CMS asked the Agency for Healthcare Research and Quality to perform a systematic review of practices and performance of several published compendia. This systematic review appears in this issue (3). The CMS then convened the Medicare Coverage Advisory Committee (MCAC) on 30 March 2006 to recommend desirable characteristics compendia used for the task of identifying medically accepted, unlabeled uses of drugs and biologicals in cancer treatment. Several of the MCAC recommendations address public transparency and conflict-of-interest concerns. The CMS subsequently referenced the following recommendations in its review of individual requests to add or delete compendia from the recognized list: detailed description of the evidence reviewed for every individual listing; use of prespecified published criteria for weighing evidence; use of a prescribed published process for making recommendations; a publicly transparent process for evaluating therapies; and a 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.

In 2007, CMS used its regulatory authority to publish proposed and final rules that established a publicly transparent process to consider requests for revisions to the list of compendia (42 CFR 414.930 Federal Register November 27, 2007, 66404). For each of 5 requests reviewed in early 2008, CMS considered how well the compendium addressed the MCAC-identified desirable characteristics, as well as additional factors. Ultimately, CMS removed AMA-DE from the list and added the National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium, DRUGDEX, and Clinical Pharmacology, while it declined to add DrugPoints. The decision memoranda are available at the CMS Web site (48).

The practices and policies of the compendia vary considerably. For example, each has its own process for receiving, considering, and deciding on requests to recommend an unlabeled indication. External requests come from interested parties, often manufacturers. The AHFS-DI requires applicants to make a monetary contribution to the Foundation for Evidence Based Medicine, which is AHFS-DI's main avenue for external requests. Recommendations included in the NCCN Drugs and Biologics Compendium are based on the NCCN's own clinical guidelines. Gold Standard Clinical Pharmacology relies on its own staff to monitor the medical literature, review evidence, and develop recommendations. The AHFS-DI has its own staff prepare the initial recommendation, which is then subjected to expert panel review. Other compendia rely largely on external expert committees of researchers and physicians, some of whom receive grant funding or clinical income from manufacturers of drugs under consideration or their competitors. Each compendium publisher has its own policies about disclosing conflict of interest and recusing someone with reported conflicts.

The compendia also differ in their accessibility to the public, an important element of transparency. The NCCN Drugs and Biologics Compendium is available online to the public at no charge. The other compendia require subscription.

Compendia publishers are private entities, and the internal deliberations that lead to their ultimate therapeutic recommendations are generally not open to the public, although publishers may, at their discretion, encourage public review of summary materials. This policy sharply contrasts with federal advisory committees, such as the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) (formerly MCAC), which convenes publicly and, in the case of the MEDCAC, posts its documents on the CMS Web site. The degree to which public access enhances or diminishes the quality and the frankness of the deliberations and whether it creates opportunities for self-interested parties to influence the outcome are a matter of debate. Simply eliminating people with conflicts of interest from the compendia editorial process is not sufficient to instill complete confidence in their published recommendations. Other conflict of interest issues may affect the ultimate validity of a compendium's recommendation: Compendia staff cannot be assured full access to all possibly relevant evidence; published, peer-reviewed, original articles do not represent the full scope of evidence on the use of a drug; and important evidence about harmful effects of drugs may remain suppressed or unpublished, to the detriment of public interest. Thus, a compendium's use of unpublished or methodologically weaker evidence may have unpredictable effects on the ultimate validity of its recommendations.

As recent events show, conflicts of interest among members of advisory committees are in the public eye. A 14 February 2008 Senate Finance Committee letter to CMS expressed concern about potential conflicts of interest “on the part of authors who contribute to the compendia.” The letter continued, “Conflicts of interest have been proven in peer-reviewed studies to have a significant impact on scientific outcomes and medical care.” It was requested that “CMS rely solely on compendia that are developed under policies of transparency and financial disclosure.”

Responding to the public's concern, compendium publishers have adopted policies that provide greater public transparency. Thomson Micromedex continued its policy of disclosing individual conflict of interest information on its external advisory board members (9). On 4 June 2008, the NCCN announced the following changes to its conflict of interest reporting policy: “The National Comprehensive Cancer Network (NCCN), an alliance of 21 of the world's leading cancer centers, will expand its current disclosure process and make public all potential conflicts of interest of all individual expert panel members by the end of 2008” (10). Gold Standard expanded the conflict-of-interest policy for Clinical Pharmacology to require annual disclosure of any significant external relationships of individual editorial team members (11).

Most recently, the 2008 Medicare Improvements for Patients and Providers Act explicitly prohibits the inclusion of compendia that do not have a publicly transparent process for evaluating therapies and identifying potential conflicts of interests. Section 182(b) states that “Conflicts of Interest-Section 1861(t)(2)(B) of the Social Security Act (42 U.S.C. 1395x(t(2)(B)) is amended by adding at the end the following new sentence: ‘On and after January 1, 2010, no compendia may be included on the list of compendia under this subparagraph unless the compendia has a publicly transparent process for evaluating therapies and for identifying potential conflicts of interests’” (12).

To sum up, Congress has created 2 separate processes for deciding which anticancer chemotherapy drugs enter the U.S. market and for which drugs CMS will provide payment. The U.S. Food and Drug Administration determines whether there is sufficient evidence of safety and effectiveness for a particular drug and that it will provide some benefit to the American public—a typical efficacy decision. The CMS reviews similar evidence but determines whether the drug is reasonable and necessary for the Medicare population—an effectiveness decision. Congress has provided a broader authority to CMS to pay for anticancer chemotherapy drugs that may have indications that the FDA has not approved (or considered) but that compendia have listed as having some benefit. Given the high stakes involved in cancer chemotherapy, the public should know about the process by which Congress gives compendia the authority to approve specific indications for these drugs.

References

Aronson FR, Ernest ML, Tasch M, Cusack DM.  Insurance coverage for investigational therapy [Letter]. J Natl Cancer Inst. 1990; 82:1434. PubMed
CrossRef
 
McIntosh H.  Unlabeled drug coverage tackled by states. J Natl Cancer Inst. 1990; 82:996-8.
 
Abernethy AP, Raman G, Balk EM, Hammond JM, Orlando LA, Wheeler JL. et al.  Reliability of compendia methods for off-label oncology indications. Ann Intern Med. 2009; 150:336-343.
 
Centers for Medicare & Medicaid Services.  Baltimore: AMA-DE Compendium Revision Request - CAG-00388. Accessed athttp://www.cms.hhs.gov/mcd/ncpc_view_document.asp?id=13on 5 June 2008.
 
Centers for Medicare & Medicaid Services.  Baltimore: Clinical Pharmacology Compendium Revision Request - CAG-00392. Accessed athttp://www.cms.hhs.gov/mcd/ncpc_view_document.asp?id=17on 2 July 2008.
 
Centers for Medicare & Medicaid Services.  Baltimore: NCCN Compendium Revision Request - CAG-00389. Accessed athttp://www.cms.hhs.gov/mcd/ncpc_view_document.asp?id=14on 5 June 2008.
 
Centers for Medicare & Medicaid Services.  Baltimore: Thomson Micromedex DrugPoints Compendium Revision Request - CAG-00390. Accessed athttp://www.cms.hhs.gov/mcd/ncpc_view_document.asp?id=15on 10 June 2008.
 
Centers for Medicare & Medicaid Services.  Baltimore: Thomson Micromedex DrugDex Compendium Revision Request - CAG-00391. Accessed athttp://www.cms.hhs.gov/mcd/ncpc_view_document.asp?id=16on 10 June 2008.
 
Thomson Reuters Healthcare.  New York: Thomson Micromedex Conflict of Interest Policy. Accessed athttp://www.micromedex.com/about_us/editorial/ed_ConflictofInterest.pdfon 30 January 2009.
 
National Comprehensive Cancer Network.  Fort Washington, PA: NCCN Expands Disclosure Policy. Accessed athttp://www.nccn.org/about/news/newsinfo.asp?NewsID=138on 4 June 2008.
 
Clinical Pharmacology.  Tampa, FL: Editorial Policy Summary. Accessed athttp://www.clinicalpharmacology.com/marketing/editorial_policy.htmlon 30 January 2009.
 
Office of Congressional and Government Affairs.  Washington, DC: Medicare Improvements for Patients and Providers Act of 2008, Pub. Law No. 110-275 (15 July 2008).
 

Figures

Tables

References

Aronson FR, Ernest ML, Tasch M, Cusack DM.  Insurance coverage for investigational therapy [Letter]. J Natl Cancer Inst. 1990; 82:1434. PubMed
CrossRef
 
McIntosh H.  Unlabeled drug coverage tackled by states. J Natl Cancer Inst. 1990; 82:996-8.
 
Abernethy AP, Raman G, Balk EM, Hammond JM, Orlando LA, Wheeler JL. et al.  Reliability of compendia methods for off-label oncology indications. Ann Intern Med. 2009; 150:336-343.
 
Centers for Medicare & Medicaid Services.  Baltimore: AMA-DE Compendium Revision Request - CAG-00388. Accessed athttp://www.cms.hhs.gov/mcd/ncpc_view_document.asp?id=13on 5 June 2008.
 
Centers for Medicare & Medicaid Services.  Baltimore: Clinical Pharmacology Compendium Revision Request - CAG-00392. Accessed athttp://www.cms.hhs.gov/mcd/ncpc_view_document.asp?id=17on 2 July 2008.
 
Centers for Medicare & Medicaid Services.  Baltimore: NCCN Compendium Revision Request - CAG-00389. Accessed athttp://www.cms.hhs.gov/mcd/ncpc_view_document.asp?id=14on 5 June 2008.
 
Centers for Medicare & Medicaid Services.  Baltimore: Thomson Micromedex DrugPoints Compendium Revision Request - CAG-00390. Accessed athttp://www.cms.hhs.gov/mcd/ncpc_view_document.asp?id=15on 10 June 2008.
 
Centers for Medicare & Medicaid Services.  Baltimore: Thomson Micromedex DrugDex Compendium Revision Request - CAG-00391. Accessed athttp://www.cms.hhs.gov/mcd/ncpc_view_document.asp?id=16on 10 June 2008.
 
Thomson Reuters Healthcare.  New York: Thomson Micromedex Conflict of Interest Policy. Accessed athttp://www.micromedex.com/about_us/editorial/ed_ConflictofInterest.pdfon 30 January 2009.
 
National Comprehensive Cancer Network.  Fort Washington, PA: NCCN Expands Disclosure Policy. Accessed athttp://www.nccn.org/about/news/newsinfo.asp?NewsID=138on 4 June 2008.
 
Clinical Pharmacology.  Tampa, FL: Editorial Policy Summary. Accessed athttp://www.clinicalpharmacology.com/marketing/editorial_policy.htmlon 30 January 2009.
 
Office of Congressional and Government Affairs.  Washington, DC: Medicare Improvements for Patients and Providers Act of 2008, Pub. Law No. 110-275 (15 July 2008).
 

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