Thomson Micromedex DrugDex® Compendium Revision Request - CAG-00391

March 20, 2008

Centers for Medicare & Medicaid Services
Department of Health and Human Services
Baltimore, MD 21244-8018

Comments Relating to Thomson Micromedex DrugDex Compendium Revision Request - CAG-00391

Dear Sir/Madam:

ASHP represents pharmacists who practice in hospitals and health systems. The Society's more than 30,000 members include pharmacists and pharmacy technicians who practice in a variety of health-system settings, including inpatient, outpatient, home care, and long-term-care settings. ASHP is also the publisher of the American Hospital Formulary Service Drug Information (AHFS DI), a comprehensive, independent reference on the clinical use of medications marketed in the United States.

Thomson Micromedex (Thomson) is requesting that its DrugDex compendia be included by the Centers for Medicare and Medicaid Services (CMS) in the list of compendia appropriate for identifying medically accepted indications for purposes of Medicare Parts A and B. However, Thomson's request is beyond the scope of the sub-regulatory process by which CMS can accept and definitively act on requests to recognize the addition and/or deletion of existing compendia, since this process applies only to Medicare Part B, not Medicare Part A.

Additionally, ASHP has some serious concerns about the prospect of CMS including the DrugDex database in the list of compendia appropriate for identifying medically accepted indications for drugs, particularly issues relating to transparency and conflict of interest. The final rule published in the CY 2008 Physician Fee schedule states that CMS considers the MedCAC characteristic referencing transparency and conflict of interest to be of high priority to preserve the integrity and minimize bias during the review process.

In an October 23, 2003 Wall Street Journal article, a prominent investigative reporter questioned DrugDex's editorial approach to evidence as well as connections with the pharmaceutical industry. Marcia Angell, MD, former editor of the New England Journal of Medicine, also is highly critical of the influence of pharmaceutical manufacturers on DrugDex. One example cited in the Wall Street Journal report was the use by DrugDex of a paid pharmaceutical manufacturer consultant to author the gabapentin [Neurontin] monograph. The policy implications on coverage decisions were substantial, costing state Medicaid programs considerable resources. DrugDex subsequently deleted all author attributions in their database (fall 2005), so it is no longer possible to determine the extent to which such authors have been used and still remain. Unfortunately, neither AHRQ's Technology Assessment nor CMS's MedCAC public meeting on March 30, 2006, probed this editorial record.

ASHP recommends that CMS not include the DrugDex database in its list of compendia used to determine medically accepted indications for drugs and biologicals used in anti-cancer treatment, unless CMS determines that DrugDex meets the MedCAC criteria. Feel free to contact me if you have any questions regarding our comments. I can be reached by telephone at 301-664-8702, or by e-mail at jcoffey@ashp.org.

Sincerely,

Justine Coffey, JD, LLM
Director, Federal Regulatory Affairs

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March 14, 2008

Katherine Tillman, RN, MA
Coverage and Analysis Group
Centers for Medicare & Medicaid Services
7500 Security Boulevard
Mail Stop S3-02-01
Baltimore, MD 21244

Re: Adding Compendia for the Purposes of Making Medicare Coverage Determinations

Dear Ms. Tillman:

The Biotechnology Industry Organization (BIO) appreciates this opportunity to comment on the recent compendium revision requests. BIO believes that compendia serve as a vital source of information regarding novel and life-saving therapies, and we urge CMS to protect beneficiary access to these therapies by recognizing all of the current applicants. BIO is the largest trade organization to serve and represent the biotechnology industry in the United States and around the globe. BIO represents more than 1,100 biotechnology companies, academic institutions, state biotechnology centers, and related organizations in the United States. BIO members are involved in the research and development of health-care, agricultural, industrial and environmental biotechnology products.

As the representative of an industry dedicated to discovering new therapies and ensuring patient access to them, BIO understands that the practice of medicine constantly evolves through the incorporation of new clinical evidence into the standard of care. Specifically, in oncology, the standard of care can change overnight as clinical researchers discover more effective, safer, or more tolerable treatment regimens. These new treatment options often involve the use of drugs and biologicals for indications not initially approved by the Food and Drug Administration (FDA) and offer patients and physicians renewed hope and greater choice in fighting illness. These advances can be particularly important for patients with advanced stages of cancer.¹ As scientific advances are publicized through peer reviewed publications, scientific compendia often incorporate this information before it appears on the FDA label. Thus, compendia are an important resource for physicians when determining the most appropriate treatment regimen for their Medicare beneficiaries.² It is imperative, therefore, that both the Centers for Medicare and Medicare Services (CMS) and Medicare contractors ensure that coverage policies keep up with the pace of innovation and clinical discovery to allow Medicare beneficiaries timely access to the most appropriate treatment options as described in the peer reviewed literature and compendia in their battles against deadly diseases.

I. The Social Security Act Provides for Numerous Compendia

Congress recognized the importance of scientific compendia in expanding treatment options for cancer patients. In 1993, it amended the Social Security Act (SSA)³ to add to the definition of drug for purposes of coverage, ―any drugs or biologicals used in an anticancer chemotherapeutic regimen for a medically accepted indication.‖⁴ The statute further defines medically accepted indication to include:

In amending the SSA, Congress provided Medicare beneficiaries access to state-of-the-art cancer care by requiring coverage of cancer indications listed in one of the statutorily mandated compendia. Congress also intended for CMS to use multiple publications in making coverage decisions. As it considers compendia revision requests, CMS should honor Congress‘s clear intent and continue to recognize at least three compendia.

II. BIO Urges CMS to Recognize the Current Applicants as Recognized Compendia for Purposes of Medicare Coverage

CMS initiated a public process by holding a Medicare Coverage Advisory Committee (MCAC) meeting on March 30, 2006, entitled, ―Compendia for Coverage of Off-label Uses of Drugs and Biologicals in an Anti-Cancer Chemotherapeutic Regimen‖ to discuss evidence and hear presentations regarding the desired characteristics of published authoritative compendia that may be used by CMS to determine medically accepted indications of drugs and biologicals in an anti-cancer chemotherapeutic regimen.⁶ In preparation for the MCAC, CMS reviewed the legal authority governing the addition and removal of compendia and assessed the functionality of the compendia.⁷ The agency recently finalized a public process for adding or subtracting recognized compendia that it now is implementing.⁸

Although Congress clearly intended Medicare contractors to use at least three compendia to allow Medicare beneficiaries access to state-of-the-art cancer care, only one of these statutorily listed compendia – American Hospital Formulary Service-Drug Information (AHFS) – is available today. The American Medical Association Drug Evaluations (AMA-DE) no longer is in publication, and United States Pharmacopoeia-Drug Information (USP-DI) is now published by Thomson Micromedex® under the name DrugPoints®. Fortunately, Congress recognized that available compendia might change over time and included in the statute a provision permitting the Secretary to revise the list of compendia as appropriate for identifying medically accepted indications for drugs.⁹ As noted above, the statute clearly reflects Congress‘s intent for Medicare contractors to use a variety of compendia for coverage determinations. Because only the AHFS is currently in publication, BIO urges CMS to recognize additional compendia – including all of the current applicants – to ensure that Congressional intent is implemented. Recognition of additional compendia will protect beneficiary access to advanced cancer therapies by providing physicians and policymakers with a wider body of evidence to use in making treatment and coverage decisions. Although all of the compendia are evidence-based, the content of the compendia may vary due to differences in publication schedules, priorities, review processes, local practices and methods of describing the evidence for each listing. To improve the chances of a treatment option being recognized by a compendium in a timely manner, we recommend that CMS continue to recognize multiple compendia for use in Medicare‘s coverage decisions and allow each compendium the needed flexibility to add new indications.

As new compendia are added, BIO looks forward to working with you to ensure that implementation is clear and consistent with statutory requirements and Congressional intent. Our overarching goal is that Medicare beneficiaries have timely access to all appropriate treatments, and we would like to meet with you after the addition of each new compendium to ensure this objective is met.

III. Conclusion

BIO urges CMS to add all of the current applicants to the list of recognized compendia. BIO‘s members are at the forefront of cancer care, as we constantly strive to convert cancer from a death sentence to a chronic disease with the ultimate goal of curing all cancer. We firmly believe that by CMS providing greater access to state-of-the-art care listed in a compendia, Medicare beneficiaries have a better chance of surviving a cancer diagnosis. Please feel free to contact John Siracusa at (202) 962-9200 if you have any questions regarding this letter. Thank you for your attention to this very important matter.

Respectfully submitted,

cc: Steve Phurrough, MD

1 Off-Label Use of Anticancer Therapies: Physician Prescribing Trends and the Impact of Payer Coverage Policy, Sept. 2005, at 5, available at http://www.bio.org/speeches/pubs/CovanceReport.pdf.
2 Id. at 6.
3 Section 13553(b) of the Omnibus Budget Reconciliation Act of 1993 entitled, ―Uniform Coverage of ‗Off-Label‘ Anticancer Drugs.‖
4 SSA § 1861(t)(2)(A).
5 SSA § 1861(t)(2)(B).
6 71 Fed. Reg. 4589 (January 27, 2006).
7 The Agency for Healthcare Research and Quality reviewed the six current compendia and issued a technology assessment availableathttps://www.cms.hhs.gov/mcd/viewtecassess.asp?where=index&tid=46.
8 42. C.F.R. § 414.930.
9 SSA § 1861(t).

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April 3, 2008

Louis Jacques, MD
Director, Division of Items and Devices
Centers for Medicare and Medicaid Services
Room 445-G Hubert Humphrey Building
200 Independence Ave., S.W.
Washington, D.C. 20201

Re: Response to Comments on the Applications for DrugPoints and DrugDex

Dear Dr. Jacques:

Earlier this year, Thomson Micromedex submitted a request for the inclusion of our product DrugDex on the list of compendia recognized by the Medicare program for the determination of coverage of off-label use. In addition, the American Society of Clinical Oncologists ("ASCO") has submitted a request for the inclusion of our product DrugPoints as a listed compendium.

We were disappointed to see certain misleading comments filed in response to these requests. We thought it important to clarify the record and note that, under the drug compendia application process described in 42 C.F.R. § 414.930(b)(iii), "CMS may consider additional reasonable factors" in consideration of each compendium.

Clarification Regarding DrugPoints

On February 12, 2008, CMS accepted an application by ASCO to add the DrugPoints compendium to the list of compendia specified in Section 1861(t)(2)(B)(ii)(I) of the Social Security Act. On March 13, 2008, the American Society of Health-System Pharmacists ("ASHP") submitted a comment adverse to the inclusion of DrugPoints as a CMS-recognized drug compendium. The ASHP comment stated that "DrugPoints clearly is not a 'successor' database since it bears little resemblance to the previous [United States Pharmacopoeia Dispensing Information ("USP DI")] database in content or editorial oversight by USP’s Expert Committees, and it existed simultaneously for many years in Thomson’s drug database collection."

Effective July, 2007, Thomson Micromedex is no longer publishing a professional product under the USP DI name and, thus, USP DI is no longer being updated. Thomson Micromedex is publishing its successor product to USP DI, "DrugPoints," and regularly updating this product. Thomson Micromedex believes that the facts and circumstances make clear that, effective July 2007 DrugPoints became the successor compendium to USP DI.

A "successor" is literally that which follows; comes next in time, or replaces another in position. There is ample evidence to support a determination that DrugPoints is the successor publication to USP DI and not a substitute. It is important to recognize that, although Thomson Micromedex has published a product under the name "DrugPoints" for several years, it is not simply replacing USP DI with the prior DrugPoints product. Rather, comprehensive changes have been made to DrugPoints as a consequence of its new role as the successor to USP DI.

Thomson Micromedex enhanced the DrugPoints product as of July, 2007, specifically to ensure that it would succeed the USP DI product in all essential components, such as the inclusion of indication ratings, references, clinical teaching, toxicology information and common synonyms. The name change is the final step in a long, involved process of transitioning USP DI to DrugPoints. This transition occurred over a two year period and is described below.

In September, 1998, Thomson Micromedex purchased the USP DI content and licensed the rights to the “USP DI” trademark from the United States Pharmacopeial Convention, Inc. (USP). In May, 2004, editorial review responsibility transitioned to Thomson Micromedex and USP expert committees were no longer involved in evidence rating reviews. At that time USP and Thomson Micromedex agreed that the license to the USP DI trademark would cease in 2007 and thereafter neither party would use the mark “USP DI.”

Thomson Micromedex continued to develop evidence-based content, as before, following a defined editorial process that utilizes outside experts. In addition, Thomson Micromedex created the Oncology Advisory Board. Like the USP committee members, these experts are well known in their fields and associated with major organizations and healthcare facilities throughout the nation. Consistent with the USP approach to expert review, Thomson Micromedex has found the Oncology Advisory Board members extremely helpful in contributing the combination of practical experience and clinical research to the review process.

The final step in the transition occurred in early 2007 when Thomson Micromedex began notifying USP DI customers of the pending succession of DrugPoints and the name change from USP DI to DrugPoints pursuant to its contractual obligation to cease using the name USP DI. In July, 2007, Thomson Micromedex ceased publication and updating of USP DI.

We would also note that Thomson Micromedex has been briefing CMS and Congress on this transition and the impending name change since at least 2005. Thomson Micromedex actively advocated before Congress to secure inclusion of Section 6001(f)(1) of the Deficit Reduction Act of 2005 ("DRA") and it was understood by lawmakers and staff involved in this amendment that the purpose was to recognize the Thomson Micromedex product that would succeed to USP DI. CMS was also informed of this legislative advocacy and the intent at the time it was underway.

ASHP also asserted that any determination by CMS must be made for DrugDex instead of DrugPoints because "the information contained in DrugPoints is derived from and summarizes more detailed information from Micromedex's DrugDex Information System." While this statement is factually correct regarding the relationship between the two products, CMS is in no way required to take the course of action desired by ASHP. DrugPoints and DrugDex independently meet the definition of a "compendium" as set forth at 42 C.F.R. § 414.930 and may be independently considered for inclusion.

By way of background, DrugDex was first developed over 30 years ago. It contains comprehensive evidence-based drug information including detailed information on dosing, pharmacokinetics, adverse effects, FDA-approved and off-label uses, comparative efficacy, and other critical information on the appropriate use of drugs. The information is referenced to the underlying studies and intended to provide the healthcare professional with both broad and in-depth review of all aspects of prescription drugs. DrugPoints was initially developed approximately ten years ago and has been greatly enhanced during the last two years in anticipation of becoming the successor to USP DI. DrugPoints contains summary drug information aimed at the point of care clinician. Derived from the same core drug information as DrugDex, DrugPoints provides evidence-based information delivered in a concise format to enhance readability and ease of quickly finding needed information. Sections include dosing, adverse effects, FDA-approved and off-label indications, interactions, toxicology, and pharmacokinetics.

Clarification Regarding DrugDex

On February 19, 2008, CMS accepted an application by Thomson Micromedex to add the DrugDex compendium to the list of compendia specified in Section 1861(t)(2)(B)(ii)(I) of the Social Security Act. On March 20, 2008, ASHP submitted a comment adverse to the inclusion of DrugDex as a CMS-recognized drug compendium.

ASHP's comment asserted that "Thomson's request is beyond the scope of the sub-regulatory process by which CMS can accept and definitively act on requests to recognize the addition and/or deletion of existing compendia, since this process applies only to Medicare Part B, not Medicare Part A." To the extent that this comment by ASHP was actually intended as a serious objection, we would note that our request was only for consideration within the scope of this process and the reference to Part A was simply for completeness.

ASHP also referred to an October 23, 2003 article in the Wall Street Journal (which itself contained numerous errors) to allege that we "used a paid pharmaceutical manufacturer consultant to author the gabapentin (Neurontin) monograph." This is a false and misleading statement. A professor by the name of Nina Graves was one of six individuals who reviewed an initial monograph on Neurontin in the early 1990s. However, Ms. Graves work on Neurontin was discontinued prior to her entering into a financial relationship with drug manufacturer Parke-Davis. As detailed in our request for inclusion of DrugDex as a listed compendium, Thomson Micromedex adheres to a conflict of interest policy that is consistent with industry standards. The policy is intended to ensure that individuals involved in literature evaluation and content development are not influenced by financial conflicts of interest. It is a three-tiered policy which provides that, for de-minimis levels, disclosure is not required; for additional levels, disclosure is required but is not deemed to be disqualifying; and, finally, disqualification results in situations where there is a significant potential for conflict due to the size or nature of a financial relationship. Our policy is not only robust, but entirely transparent – it is easily reviewed on our website.

Thomson Micromedex is committed to providing unbiased, evidence-based information. We appreciate this opportunity to clarify the record in this regard.

Sincerely,

Dr. Alan Ying
Chief Medical Officer
Thomson Healthcare Inc.

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