The Social Security Act Section 1861(t)(2)(B)(ii)(I) recognizes the following compendia: American Medical Association Drug Evaluations (AMA-DE), United States Pharmacopoeia-Drug Information (USP-DI) or its successor publication [amended in Section 6001 (f)(1) of the DRA] and American Hospital Formulary Service-Drug Information (AFHS-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. However, AFHS-DI is the only originally named compendium currently in publication.
CMS received a timely complete request for the addition of the Thomson Micromedex compendium DrugPoints (designated by Thomson Micromedex as the successor publication to USP-DI) to the list of compendia for this use.
American Society of Clinical Oncology (ASCO)
View Requestor Letter
|Formal Request Accepted and Review Initiated
February 12, 2008
|Expected Completion Date
June 10, 2008
Kate Tillman, RN, MA
Brijet Burton, MS, PA-C
|Lead Medical Officer(s)
Lori Paserchia, MD
|February 12, 2008
||ASCO requested the formal addition of DrugPoints, designated by Thomson Micromedex as the successor publication to USP-DI, to the list of statutorily named compendia. The public comment period begins the date of this posting and ends after 30-calendar days. CMS considers all public comments, and is particularly interested in your feedback on the addition of DrugPoints to the list of compendia. Formal public comments may be submitted through the highlighted “comment” link located at the top of this web page. Instructions on how to submit a request to revise the list of compendia may be found at http://www.cms.hhs.gov/CoverageGenInfo/02_compendia.asp#TopOfPage
|June 10, 2008
Administrative File: CAG #00390
Steve Phurrough, MD, MPA
Director, Coverage and Analysis Group
Louis Jacques, MD
Director, Division of Items and Devices
Kate Tillman, RN, MA
Brijet Burton, PA-C
Lori Paserchia, MD
Lead Medical Officer
Thomson Micromedex DrugPoints ® - Request for addition to 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
June 10, 2008
Section 1861(t)(2)(B)(ii)(I) of the Social Security Act (the Act) designates certain compendia 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). 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. See 42 C.F.R. § 414.930(a); 72 Fed. Reg. 66222, 66404.
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.
A formal request submitted by the American Society of Clinical Oncology (ASCO) for the addition of Thomson Micromedex DrugPoints ® to the list of compendia for the determination of medically accepted indications for off-label uses of drugs and biologicals in an anticancer therapeutic regimen was posted on February 12, 2008 on the CMS website.
We note for the convenience of the reader that the publisher of DrugPoints ® is referred to variously by commenters and others as Thomson, Thomson Micromedex, and Thomson Healthcare. Thomson also publishes the DrugDex ® compendium.
The application submitted by ASCO includes a detailed description of how Thomson Healthcare believes DrugPoints ® meets the CMS definition of a compendium and each of the ten MedCAC desirable characteristics.
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 addition of Thomson Micromedex DrugPoints ® to the list of compendia.
CMS received a general public comment from the Biotechnology Industry Organization (BIO) in support of the addition of all compendia for which a request to add such publication to 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 has been submitted. BIO stated that it recognizes that the content of each compendium differs “in publication schedules, priorities, review processes, local practices and methods of describing the evidence of each listing”. However, BIO believes that the addition of all these compendia is critical to the improvement of Medicare beneficiaries’ access to time-sensitive cancer treatment options.
CMS received two public comments regarding the addition of Thomson Micromedex DrugPoints ® to the list of statutorily named compendia. The American Society of Health-System Pharmacists (ASHP) commented on the reference to DrugPoints ® as “the successor publication to USP-DI” in the formal request letter submitted by the American Society of Clinical Oncology (ASCO), dated February 11, 2008. ASHP does not believe that DrugPoints ® is a successor because it “bears little resemblance to the previous USP-DI database in content [and lacks] editorial oversight by USP’s Expert Committees.” In addition ASHP stated, “DrugPoints ® information is derived from Thomson Micromedex’s DrugDex ® database”. Thomson Micromedex, publisher of both DrugPoints ® and DrugDex ®, stated that the recommendations in the former are derived from the latter. ASHP stated that CMS should only make a determination on “the parent database”, DrugDex ® since Thomson has filed a separate request for the recognition of DrugDex ®.
The other public comment February 12, 2008, was submitted the Amerihealthmercy health plan – DBA Passport Health plan, regarding the request for the addition of DrugPoints ® by ASCO. According to the commenter, ASCO’s “sponsorships from internal oncology practices as well as Pharma companies” is a conflicted interest. The commenter states that ASCO should not be in the position “to set directions or approvals for medications” by requesting the recognition of a compendium.
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, the Senators requested “…that CMS rely solely on compendia that are developed under policies of transparency and financial disclosure….”
Thomson Healthcare submitted a letter responding to the issues raised by ASHP regarding the designation of DrugPoints ® as the successor to USP-DI. In its response, Thomson stated that as of July 2007, DrugPoints ® includes “indication ratings, references, clinical teachings, toxicology information, and common synonyms”. Similar to the USP Committee, Thomson stated that it has developed the Oncology Advisory Board. Thomson stated that DrugPoints ® is a summarized version of DrugDex ®. However, Thomson stated that it believes that both “DrugDex ® and DrugPoints ® independently meet the [statutory] definition of a ‘compendium’…and may be independently considered for inclusion” to the list of recognized compendia.
Thomson Micromedex DrugPoints ®
As part of the compendium application submission, CMS requires access to the compendium under review. CMS had unlimited access to the Thomson Micromedex DrugPoints ® during the entire review process, which allowed CMS to navigate the compendium database in order to assess its infrastructure and content.
- The product known as Thomson Micromedex DrugPoints ® is a compendium as defined by CMS in the regulation because it includes a summary of the pharmacologic characteristics of each drug or biological, information on dosage, recommended or endorsed uses in specific diseases and is indexed by drug or biological rather than by disease.
Thomson Micromedex DrugPoints ® addresses each of the MedCAC identified desirable characteristics as noted below.
- It provides an extensive breadth of listings by listing more than 2300 drugs and biologics including prescription, non-prescription and investigational products. FDA-approved indications and off-label uses are presented as well.
- It is designed to provide quick processing from application for inclusion to listing by conducting an ongoing editorial review of the world’s primary literature published in thousands of peer-reviewed journals, FDA-approved product labeling, clinical judgment and recommendations, regulatory standards and compliance, national healthcare trends, editorial board suggestions, external requests, and policy changes in health and disease management from professional health organizations. Online updates of the compendium are provided weekly. We note from materials provided by Thomson, the publisher, that these listings flow from its reliance on the DrugDex ® compendium rather than an independent review.
- It provides a detailed description of the evidence reviewed for every individual listing and fully cites specific studies that are the basis for recommendations.
- It provides on the DrugPoints ® website pre-specified published criteria for weighing evidence that focus on the efficacy, strength of recommendation and strength of evidence, which directly guide the process of decision-making leading to recommendations. We note from materials provided by Thomson, the publisher, that these recommendations flow from its reliance on the DrugDex ® compendium rather than from an independent review.
- It uses a prescribed published process for evaluating therapies, which is available for subscribers to see on its website. When formulating recommendations, clinical staff develops drafts, which are reviewed by internal experts and the Chief Medical Officer. The draft may also be reviewed by an Oncology Advisory Board if the subject involves a new FDA-unapproved use related to oncology or a significant ratings change related to oncology. The staff then collates all comments and formulates the final document. We note from materials provided by Thomson, the publisher, that these recommendations flow from its reliance on the DrugDex ® compendium rather than an independent review.
- It presents the process used for evaluating therapies to subscribers via its website including a listing of all involved panel members. There is an opportunity to make an external request for inclusion of information to the compendium; the policy and process regarding an external request is presented to subscribers via the website. We note that these flow from its reliance on the DrugDex ® compendium rather than an independent review.
- It does not explicitly note when the use of a drug or biologic is not recommended (i.e., denoted with a “Class III” rating in DrugDex ®) when validated evidence is appropriate.
- It provides information regarding the appropriate patient population and appropriate circumstance and time for the use of a drug or biologic alone or in combination and therefore provides explicit listing and recommendations regarding therapies, including sequential use or combination in relation to other therapies.
- It does not explicitly note an "Equivocal" listing (i.e., denoted as “Class indeterminate” in DrugDex ®) when validated evidence is equivocal.
- It incorporates a process for identification and notification of potential conflicts of interest of the compendia's parent and sibling organizations, internal and external reviewers and internal and external committee members, with an established procedure to manage recognized conflicts. The policy and process are disclosed to subscribers via its website as is a listing of all potential and real conflicts of interest.
DrugPoints ® is available to subscribers via the internet.
Public comment was divided on this request. We have addressed the points raised by the commenters in the analysis above.
In summary, we have determined that Thomson Micromedex DrugPoints ® meets the definition of a compendium as defined by 42 C.F.R. § 414.930(a); 72 Fed. Reg. 66222, 66404 but fails to satisfactorily address several of the desirable characteristics recommended by the MedCAC and referenced in the regulation. Specifically, DrugPoints ® itself does not explicitly note when the use of a drug or biologic is not recommended, nor does it explicitly note an "Equivocal" listing when validated evidence is equivocal. The publisher notes that these issues are addressed in DrugDex ®, from which DrugPoints ® is derived. However, we note that a user of DrugPoints ® cannot access DrugDex ® from DrugPoints ®. Rather, a user would have to separately obtain access to DrugDex ® for this information.
The process as defined by 42 C.F.R. § 414.930(c)(1)(vi); 72 Fed. Reg. 66222, 66404 includes a provision that a request include “[a] single compendium as its subject.” Thus, we consider DrugPoints ® as the subject of this request and will not credit to its application such information that must be accessed through another compendium
Thomson Micromedex DrugPoints ® is not 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 not adding Thomson Micromedex DrugPoints ® to 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.