Wolters Kluwer Clinical Drug Information Lexi-Drugs Compendium Revision Request - CAG-00443O

Issue:

Requestor Name(s):          Wolters Kluwer Clinical Drug Information
                                            View Requestor Letter

Formal Request Accepted and Review Initiated:          April 21, 2015

Expected Completion Date:          August 19, 2015

Lead Analyst(s)          Cheryl Gilbreath, PharmD, MBA, RPh

Lead Medical Officer(s):          James Rollins, MD, MSHA, PhD

Actions Taken

To:		Administrative File: CAG #00443O

From:	Tamara Syrek Jensen, JD
		Director, Coverage and Analysis Group 

		Joseph Chin, MD, MS
		Deputy Director, Coverage and Analysis Group

		James Rollins, MD, MSHA, PhD
		Director, Division of Items and Devices
		Lead Medical Officer

		Cheryl Gilbreath, PharmD, MBA, RPh
		Lead Analyst
 
Subject:		Wolters Kluwer Lexi-Drugs® - 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

Date:		August 12, 2015

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, recognized three compendia: American 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). 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.

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 & 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:
1. Extensive breadth of listings.
2. Quick processing from application for inclusion to listing.
3. Detailed description of the evidence reviewed for every individual listing.
4. Use of pre-specified published criteria for weighing evidence.
5. Use of prescribed published process for making recommendations.
6. Publicly transparent process for evaluating therapies.
7. Explicit "Not recommended" listing when validated evidence is appropriate.
8. Explicit listing and recommendations regarding therapies, including sequential use or combination in relation to other therapies.
9. Explicit "Equivocal" listing when validated evidence is equivocal.
10. 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.

Based on the process for revising the list of compendia established in 2008, CMS currently recognizes the following four compendia: American Hospital Formulary Service-Drug Information (AHFS-DI), Truven Health Analytics Micromedex DrugDEX (DrugDEX), National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium, and Elsevier/Gold Standard Clinical Pharmacology for use in the determination of medically-accepted indications of drugs/biologicals used off-label in anti-cancer chemotherapeutic regimens.

A formal request submitted by Wolters Kluwer Clinical Drug Information for the addition of Lexi-Drugs® to the list of compendia used by the Medicare program in the determination of a medically accepted indication for off-label uses of drugs and biologicals n an anticancer chemotherapeutic treatment regimen was posted on April 21, 2015 on the CMS website.

As required by CMS, the application submitted by Wolters Kluwer includes a detailed description of how it believes Lexi-Drugs® meets the CMS definition of a compendium and each of the ten MEDCAC desirable characteristics. The letter can be found on our CMS website at http://www.cms.gov/Medicare/Coverage/CoverageGenInfo/downloads/covdoc31.pdf.

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 addition of Wolters Kluwer Lexi-Drugs® to the list of compendia.

CMS received a total of six comments. Four of the six comments supported the addition of Wolters Kluwer Lexi-Drugs® to the list of compendia for the identification of a medically accepted indication for the off-label uses of drugs and biological in an anticancer chemotherapeutic regimen. These commenters included one from the Association of Community Cancer Centers and one from a coordinator of cancer care and two from pharmacy directors. These comments described Lexi-Drugs® as "user friendly, comprehensive," and a "reliable reference and one that pharmacists use regularly."

CMS received one public comment from Highmark, Inc. opposing the addition of Wolters Kluwer Lexi-Drugs® to the list of statutorily named compendia but did not cite a reason why the compendia should not be added. We also received a comment from Triple-S Advantage that stated CMS should consider budget constraints when deciding to add compendia. Further, the commenter added that there is no apparent benefit of adding Lexi-Drugs® to the list since most of its information is duplicative to other compendia currently recognized.

We appreciate the comments. CMS uses the desirable characteristics developed by the MEDCAC to determine whether a compendium should be added to the CMS-recognized compendia list. Neither of the reasons cited by the commenter are characteristics CMS reviews to determine the compendia acceptability (See 72 Fed. Reg. 66222, 66303-66306, 66404).

All comments can be viewed in their entirety at on the CMS website at https://www.cms.gov/medicare-coverage-database/details/mcd-view-public-comments.aspx?MCDId=31&ExpandComments=n&bc=AAAAAAAAACAAAA%3d%3d&

As part of the compendium application submission, CMS requires access to the compendium under review, which would be available to subscribers of the compendium. CMS was provided with unlimited access to the Wolters Kluwer Lexi-Drugs® delivered on the Lexicomp Online™ platform 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 Wolters Kluwer Lexi-Drugs® 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. Specifically, it comprises drug monographs and is searchable by generic drug names, brand names, NDC, keyword, and synonyms.

Wolters Kluwer Lexi-Drugs® addresses each of the ten MEDCAC identified desirable characteristics as noted below:

In summary, CMS has determined that Wolters Kluwer Lexi-Drugs® meets the definition of a compendium as defined by 42 C.F.R. § 414.930(a); 72 Fed. Reg. 66222, 66303-66306, 6640 as well as all of the criteria created by the MEDCAC and referenced in regulation. CMS uses the desirable characteristics developed by the MEDCAC to determine whether a compendium should be added to the CMS-recognized compendia list. CMS considered all public comments in the final determination.

Wolters Kluwer Lexi-Drugs® is 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 adding Wolters Kluwer Lexi-Drugs® 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, 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.

Indications listed in Lexi-Drugs® as "Use: Off-Label" and rated as "Evidence Level A" with a "Strong" recommendation for inclusion will be considered medically accepted indications as described in §1861(t)(2)(B)(ii)(I).

Indications listed in Lexi-Drugs® as "Use: Unsupported" with an "Against" recommendation for inclusion will not be considered medically accepted indications as described in §1861(t)(2)(B)(ii)(I).

Indications listed in Lexi-Drugs® as "Use: Off Label" and rated as "Evidence Level B" or "Evidence Level C" or "Evidence Level G" with an "Equivocal" recommendation for inclusion, are considered neither "supported" nor "identified as not indicated" as described in §1861(t)(2)(B)(ii)(I). Thus, we cannot identify whether such compendia citations are medically accepted indications within the meaning of that section. Medicare contractors, as instructed in subsection D of Chapter 15, section 50.4.5 of the Medicare Benefit Policy Manual, shall consider the peer reviewed medical literature for indications that Lexi-Drugs® lists as "Equivocal".