Compendia: Powerful Tools, Wrong Job

Although determining coverage for off-label use of anticancer drugs was the CMS’s primary intent with this law, the importance of CMS’s decision may be magnified if health plans and private payers follow the agency’s guidance and adopt similar practices across both the public and private sectors. Even as some plans embrace compendia as the starting point in expediting coverage determinations for anticancer drugs, those opposed would argue that as “stewards of the healthcare dollar” these fall short of good science and that we should invest the resources to do better. Since the passage of this law, questions as to the feasibility and financial impact of this policy have arisen, which I’ll review briefly here.

The 4 national compendia recognized by CMS include the NCCN Drugs & Biologics Compendium³; DRUGDEX, published by Thomson Micromedex⁴; Clinical Pharmacology⁵; and American Hospital Formulary Service Drug Information (AHFSDI).⁶ An analysis of these compendia (plus 2 others) conducted by the Agency for Healthcare Research and Quality (AHRQ) sought to determine whether the compendia adhered to stated methods concerning evidence-based medicine and whether they provided comprehensive, research-based, and timely information for off-label prescribing of anticancer drugs.^7,8 Of 14 anticancer drug/condition combinations that were considered “off-label” at the time of the analysis, the researchers found great disparities in compendia listings and the evidence cited to support the recommendations. Additionally, there were different lag times in the way that the 6 compendia identified, processed, and updated information.

Among the reasons identified by the AHRQ to explain this variability were that the compendia were unable to keep up with evolving science; used inconsistent methods to critically appraise scientific studies and report levels of evidence; varied in the level of evidence considered to support medically accepted uses; lacked transparent decision-making or systematic ways for including scientific information; and did not always disclose financial ties to pharmaceutical industry and potential conflicts of interest.

In addition to methodological variables with each compendium, there are operational concerns and an unknown cost impact. Health plans are required to follow CMS guidance in applying compendia for Medicare beneficiaries, but they may be reluctant to use this approach in the private sector without due diligence assessing the ongoing reliability and conflicts in evidence. Although health plans want to prevent the creation of a double standard, some plans will opt for creating separate coverage policies for their commercial plans.

Using utilization data from our own plan, we looked at the potential impact in applying different compendia for coverage decisions and estimated a corresponding cost impact. We selected 5 cancer medications (trastuzumab, bortezomib, lapatinib, dasatinib, and nilotinib) and compared the National Comprehensive Cancer Network (NCCN) and DRUGDEX compendia for differences in their listings of “medically accepted” off-label uses for these medications and what the differences would be in terms of coverage determinations and estimated net cost avoidance (in dollars) with the different compendia if applied to real-world claims.

Our findings echoed those of the AHRQ study, with variability for medically accepted off-label uses and in the quality and type of evidence that could be used to support the listing. In dollar terms, identifying uses that were not considered medically acceptable provided an estimated overall cost avoidance of just under $1 million annually.

It is impractical and duplicative for health plans to consult all 4 compendia in rendering coverage determinations for anticancer drugs under Medicare, so most plans select 1 or 2 compendia as their informational resource. Furthermore, subscriptions are costly, depending on the compendia selected and number of users having access, with annual fees ranging from $500 to $22000.

As for the matter of plans applying compendia across both public and private sectors for coverage determinations, it will take time for a consistent method that assures patient access to the best treatment options to emerge. In an ideal world, we would look at the appropriate use of every medication, but that’s just not practical. Instead we need to focus on the drugs with the greatest safety signals and/or are most expensive. It is best to catch these anticancer drugs right out of the gate, building on evidence, rather than trying to plow through hundreds of trials later on. New anticancer drugs that come to market have top-dollar price tags of up to $100000 a year, so it makes sense to focus on these from the outset.

As for compendia, these are only one means by which health plans can understand how prescribers and the expert community plan to use these drugs and determine their relative place among treatment options. However, we can’t stop there—we need to perform due diligence in looking at the underlying science, balancing cost, access, quality of care, and outcomes to put the patient first.

1. Butcher L. CMS’s use of compendia drawing criticism. Oncol Times. 2009;31(7):39-41.
2. Medicare Benefit Policy Manual. 50.4.5. Off-Label Use of Drugs and Biologicals in an Anti-Cancer Chemotherapeutic Regimen (Rev. 96, Issued: 10-24-08,Effective: 06-05-08 NCCN/06-10-08 Thomson Micromedex/07-02-08 Clinical Pharmacology, Implementation: 11-25-08.) US Dept of Health and Human Services publication 100-02.
3. National Comprehensive Cancer Network. NCCN Drugs & Biologics Compendium. www.nccn.org. Accessed September 1, 2009.
4. Thomson Micromedex Healthcare Series. www.thomsonhc.com. Accessed Sept. 1, 2009. 5. Elsevier Gold Standard: Clinical Pharmacology. www.clinicalpharmacology.com. Accessed Sept. 1, 2009.
5. American Society of Health-System Pharmacists. www.ahfsdruginformation.com. Accessed Sept. 1, 2009.
6. Abernethy AP, Raman G, Balk EM, et al. Systematic review: reliability of compendia methods for off-label oncology indications. Ann Intern Med. 2009;150 (5): 336-343.
7. Abernathy AP et al. Compendia for coverage of off-label uses of drugs and biologics in an anticancer chemotherapeutic regimen. Final Report. Rockville, Md: Agency for Healthcare Research and Quality; May 2007. www.cms.hhs.gov/determinationprocess/downloads/id46TA.pdf. Accessed April 26, 2010.