To: Administrative File: CAG #00352S
From: Steve Phurrough, MD, MPA
Director, Coverage and Analysis Group
Louis Jacques, MD
Division Director
Katherine Tillman, RN, MA
Lead Analyst
Brijet Burton
Analyst
LCDR Tara Turner, PharmD
Analyst
Lori Paserchia, MD
Lead Medical Officer
Subject: Medical Literature for Local Medicare Contractors to Determine Medically accepted Indications for Drugs and
Biologicals used in Anticancer Treatment
Date: October 15, 2007
BACKGROUND
§1861(t)(2)(B)(ii)(II) of the Social Security Act states that "the carrier involved determines, based upon guidance provided by the Secretary to carriers for determining accepted uses of drugs, that such use is medically accepted based on supportive clinical evidence in peer reviewed medical literature appearing in publications which have been identified for purposes of this subclause by the Secretary." Accordingly, Section 50.4.5 of the Medicare Benefit Policy Manual (previously Section 2049.4.C.4 of the Medical Carrier Manual) lists fifteen peer-reviewed journals that a contractor must use to determine "whether there is supportive clinical evidence for a particular use of a drug." These journals are:
- American Journal of Medicine
- Annals of Internal Medicine
- Journal of the American Medical Association
- Journal of Clinical Oncology
- Blood
- Journal of the National Cancer Institute
- New England Journal of Medicine
- British Journal of Cancer
- British Journal of Hematology
- British Medical Journal
- Cancer
- Drugs
- European Journal of Cancer
- Lancet
- Leukemia
In letters dated May 21, 2003 (2003 letter) and May 4, 2006 (2006 letter), the American Society of Clinical Oncology (ASCO) noted that this list was created in 1993 and has not been revised since. Therefore, ASCO formally submitted requests for CMS to revise the list by adding the following fourteen journals:
- Annals of Oncology
- Biology of Blood and Marrow Transplantation
- Bone Marrow Transplantation
- Cancer Investigation
- International Journal of Cancer
- Lancet Oncology
- Gynecologic Oncology
- Lung Cancer
- The Cancer Journal
- Clinical Cancer Research
- Journal of the National Comprehensive Cancer Network (NCCN)
- Journal of Thoracic Oncology
- Breast Cancer Research and Treatment
- International Journal of Radiation Oncology, Biology, Physics
METHODOLOGY
I. Expert Opinion
Oncology experts from the National Cancer Institute (NCI) at the National Institutes of Health and from the Center for Drug Evaluation and Research at the Food and Drug Administration (FDA) were separately contacted to provide opinions about the ASCO-recommended journal lists. Each expert was asked:
- Which of the journals add value?
- Is there an unmentioned journal that should be added to the CMS list?
The minimum criterion for "value" was a journal that contains full-length, peer-reviewed articles about original research in English.
II. Public Comment
Additionally, CAG provided public notice and solicited public comment through a CMS website posting for the time period of October 27, 2006 through December 26, 2006.
FINDINGS
I. Expert Opinion
The NCI experts suggested that CMS add seven ASCO-recommended journals:
- Annals of Oncology
- Biology of Blood and Marrow Transplantation
- Bone Marrow Transplantation
- Gynecologic Oncology
- Clinical Cancer Research
- International Journal of Radiation, Oncology, Biology, and Physics
- Journal of the NCCN
NCI also recommended the addition of four journals not on the ASCO lists:
- Radiation Oncology
- Annals of Surgical Oncology
- Journal of Urology
- Pediatric Oncology and Hematology
The FDA experts selected three journals from the ASCO lists:
- Gynecologic Oncology
- Clinical Cancer Research
- Lancet Oncology
The FDA experts also suggested that two journals (American Journal of Medicine, and Drugs) be deleted from the CMS list.
II. Public Comment
CMS received a total of 44 comments during the public comment period. Eighteen comments (40.9%) were from physicians. Eleven comments (25%) were from pharmaceutical or biotechnology companies or trade organizations. Seven comments (15.9%) were from other professional organizations. Three comments (6.8%) were from journal editors. Two comments (4.5%) were from Medicare contractors. One comment (2.3%) was from a nurse. One comment (2.3%) was from a physician practice group. One comment (2.3%) was from a health policy professional. All of the commenters agreed that it is important to regularly update the list of publications used to provide evidence to support coverage of off-label cancer treatment to ensure these publications reflect the best available clinical evidence regarding new uses of anticancer treatments.
Public comments received as of December 26, 2006, are summarized below:
- Eight comments (18.2%) support all of the journals recommended by ASCO in its 2006 letter.
- Nine comments (20.5%) support all of the journals recommended by ASCO in both its 2003 and 2006 letters.
- Of the journals recommended by ASCO, the following were individually supported by commenters: Annals of Oncology (4 comments); Biology of Blood and Marrow Transplantation (1 comment); Bone Marrow Transplantation (2 comments); Clinical Cancer Research (3 comments); Gynecologic Oncology (6 comments); International Journal of Cancer (2 comments); Journal of the NCCN (3 comments); Journal of Thoracic Oncology (2 comments); Lancet Oncology (2 comments); Lung Cancer (2 comments); Breast Cancer Research and Treatment (2 comments); International Journal of Radiation Oncology, Biology and Physics (3 comments).
- Several additional journals were recommended by commenters as follows: Journal of Supportive Oncology (3 comments); Supportive Care in Cancer (1 comment); Community Oncology (1 comment); Cancer Research (5 comments); Acta Haematologica (3 comments); Annals of Hematology (4 comments); Annals of Oncology (1 comment); European Journal of Hematology (3 comments); Hematology (3 comments); International Journal of Clinical Oncology (3 comments); International Journal of Hematology (3 comments); International Journal of Oncology (3 comments); Leukemia and Lymphoma (5 comments); Leukemia Research (4 comments); Medical Oncology (1 comment); American Journal of Hematology (4 comments); Anticancer Research (3 comments); Clinical Breast Cancer (3 comments); Clinical Lymphoma and Myeloma (2 comments); Haematologica/The Hematology Journal (6 comments); The Oncologist (15 comments); Seminars in Hematology (2 comments); Seminars in Oncology (3 comments); Seminars in Thrombosis and Hemostasis (2 comments); Journal of Clinical Endocrinology and Metabolism (1 comment); European Journal of Cancer (1 comment); Critical Care Medicine (1 comment); Neurology (1 comment).
- Four individuals focused their comments on the criteria used to evaluate journals. Three commenters supported the two criteria for journals requiring clinical trial registration as a condition of publication and requiring publication of conflict-of-interest disclosure information for authors. One commenter recommended that CMS consider adding an additional criterion for inclusion based on the Journal Impact Factor as determined by ISI (Institute for Scientific Information). One commenter disagreed with the above and stated that the application of external criteria not directly related to the quality of the clinical research is off the point of the 1993 legislation.
- Two commenters urged CMS to remind its contractors that the Agency requires them to evaluate the evidence in peer-reviewed medical literature while making coverage decisions. They expressed a belief that many contractors are implementing policies that state that they will not examine peer reviewed medical literature when making coverage decisions.
- Four commenters urged CMS to also consider expanding the list of recognized compendia. They state that both compendia and peer-reviewed journals are important vehicles for supporting beneficiary access to medically accepted cancer treatments.
- One commenter recommended that CMS consider adding certain qualified abstracts to the list of approved publications. The comment states that CMS coverage policies should recognize that the speed with which medical information is disseminated in today's clinical environment now far surpasses the speed of the publication process.
- One commenter discussed the concern that for some journals there may be periodic "Supplements" (some sponsored by specific pharmaceutical companies) which typically are focused on a specific topic (often a specific pharmaceutical) and for which the peer-reviewed standards of article acceptance appear to be less rigorous than the regular publication.
ANALYSIS
We observed a wide variety of opinion on the value of the ASCO-recommended journals. The NCI experts that we queried supported only seven of the fourteen journals from the ASCO lists, and recommended four additional journals, while the FDA experts that we queried supported only three of fourteen journals from the ASCO lists. Of the ASCO-recommended journals selected by the NCI experts and by the FDA experts, only two were the same (Gynecologic Oncology, and Clinical Cancer Research). This is in contrast to the public commenters where twenty percent of commenters supported the addition of all of the journals from the 2003 and 2006 ASCO lists. Smaller percentages of commenters recommended the addition of select journals from the ASCO lists rather than the entire list(s).
A few public commenters advocated for the implementation of certain selection criteria in order to maximize journal article quality by improving transparency and minimizing publication bias. CMS believes that the development of criteria to achieve the goal of maximizing journal article quality has merit not only to determine which journals should be added to the CMS list, but also to determine which journals should be deleted from the CMS list. We invite continued public input on this issue.
Many public commenters suggested the addition of non-ASCO-recommended journals. The most numerous requests were for the following journals: The Oncologist, Haematologica/The Hematology Journal, Cancer Research, and Leukemia and Lymphoma. This has merit and CMS will consider these suggestions once formal selection criteria have been developed.
One public commenter requested that CMS use abstracts in a manner similar to journal articles. A list of criteria was provided to ensure the quality of the abstracts. While the use of abstracts to make coverage decisions involves the same quality issues as that of full journal articles, abstracts also introduce a “quantity of information” concern. CMS will consider the question of the use of abstracts in the future, particularly during the development of formal selection criteria.
We agree that articles appearing in periodic supplements sponsored by parties with interests in the recommendations of the authors are not reliably subject to the same rigorous peer review standards as articles appearing in the regular pages of a journal. Thus we do not believe that Medicare contractors should be required to consider them for the purpose described in this Decision Memorandum.
ACTION
CMS is adding to the current list at Section 50.4.5 of the Medicare Benefit Policy Manual the following journals:
- Annals of Oncology
- Biology of Blood and Marrow Transplantation
- Bone Marrow Transplantation
- Gynecologic Oncology
- Clinical Cancer Research
- International Journal of Radiation, Oncology, Biology, and Physics
- Journal of NCCN
- Radiation Oncology
- Annals of Surgical Oncology
- Journal of Urology
- Lancet Oncology
We are not deleting any of the current journals at this time.
The carrier will use peer-reviewed medical literature appearing in the regular additions of the publications listed in this section, not to include supplement editions privately funded by parties with a vested interest in the recommendations of the authors.
Medical Literature for Local Medicare Contractors to Determine Medically Accepted Indications for Drugs and Biologicals Used Anticancer Treatment
Under section 1861 (t)(2)(B)(ii)(II) of the Social Security Act, Medicare recognizes a “medically accepted indication” for the off-label use of a drug or biological used in an anticancer treatment regimen if the carrier involved determines that the use is “medically accepted based on supportive clinical evidence in peer-reviewed medical literature appearing in publications which have been identified for purposes of this subclause by the Secretary.” CMS lists 15 publications for this purpose in chapter 15, section 50.4.5 of the Medicare Benefit Policy Manual (referred to henceforth as the CMS list).
In May 2003 and May 2006, CMS received requests from the American Society of Clinical Oncology (ASCO) for the addition of several journals to the CMS list. These may be viewed through the following links. The 2003 and 2006 requests overlap partially. CMS is requesting public comments on the existing CMS list and the additions proposed by ASCO. CMS will also receive comments on journals not currently named by CMS or ASCO.
CMS is particularly interested in comments on the appropriateness of the journals for the purpose described in statute. A journal’s use of a rigorous impartial peer review process, lack of publication bias, full and timely public disclosure of potential conflicts of interest of authors, reviewers and editorial staff, reputation for scientific integrity and authoritative stature in the field of cancer treatment are especially important considerations.
With this solicitation we are opening a 30 day public comment period that will close after 30 calendar days. Instructions on submitting comments can be found at https://www.cms.gov/InfoExchange/02_publiccomments.asp#TopOfPage.
