In March 2007, CMS convened its Medicare Evidence Development and Coverage Advisory Committee (MedCAC) to develop “desirable characteristics” for the regular inclusion of additional compendia (see Table 2). By 2008, CMS had added three new compendia to its list of designated review publications: the National Comprehensive Cancer Network Drugs & Biologics Compendium, DrugDex, and Clinical Pharmacology.

Now Medicare is obliged to cover any off -label cancer therapy if its use is supported in one compendium, as long as none of the others advise against it. However, if off -label use is not included in one of the designated compendia, Medicare contractors are also permitted to rely on peer-reviewed research published in one of 26 specified journals. In an effort to maintain a transparent and up-to-date review system, Medicare evaluates requests for compendia changes each year between January 15th and February 15th.

The CMS action has garnered plaudits not only from major cancer organizations but also from watch-dog groups like Accelerate Progress, who view FDA’s ultraconservative drug approval process as a barrier to cancer care for desperately ill people, according to Scott Riccio, Accelerate Progress executive director.

Mr. Riccio told Oncology News International that “we believe that expanding the meaningful and effective use of off -label drugs is driven, in part, by appropriate reimbursement from CMS. Appropriate off -label use of cancer drugs will be fostered by more, not less, communication of clear actionable information.”

The slippery slope
The compendia issue is not without its critics, some of whom contend that listings of off -label indications in drug compendia affect not only reimbursement decisions, but also utilization.

Neal J. Meropol, MD, director of the Gastrointestinal Cancer Program at Fox Chase Cancer Center in Philadelphia, has published several papers on the implications of drug utilization and costs.

“The reality is that much of what oncologists consider as standard care has not yet been approved for specific indications by the lengthy and expensive FDA labeling process,” he told Oncology News International. “That said, there’s no question that there’s a risk that liberal reimbursement policies may influence the utilization patterns of oncologists.”

Discordant recommendations
In order to better inform potential future coverage decisions, CMS commissioned a technology assessment study from the Agency for Healthcare Research and Quality (AHRQ). The study’s lead author was Amy P. Abernethy, MD, program director of the Duke Cancer Care Research Program at Duke University School of Medicine in Durham, N.C.

Six compendia were evaluated to determine how closely they adhered to their stated methods concerning evidence based medicine and the potential impact of non-adherence.

Looking at 14 cancer agent combinations that were off -label at the time of the study, the authors found great disparities in the recommendations among the four compendia and the evidence cited to support the recommendations.

The use of bevacizumab (Avastin) in breast cancer is one example: The NCCN compendium recommends it while DrugDex advises against its use and neither AHFS-DI nor Clinical Pharmacology mentions bevacizumab for breast cancer treatment (AHRQ Technology Assessment Program: “Compendia for coverage of off-label uses of drugs and biologics in an anticancer chemotherapy regimen: Final report,” May 7, 2007).

“To that end, the most observable outcome was that, in many cases, the compendia were not doing what they said they were doing. Considering all of the available information, the most obvious example of that was not adhering to updating cycles,” Dr. Abernethy said.

These discordant recommendations on the same off -label drug most likely had to do with how the information was interpreted as well as the cycle of updates. “We found over and over that there were different lag-times in the way that the six compendia identified and processed information,” she explained.

Bolstering patient care
The clinical information that needs to be interpolated into the decision-making process is comprehensive and constantly changing. Dr. Abernethy stressed that in their AHRQ report, she and her coauthors were not judging the current information in the compendia, but based their analysis on information available in 2006.