Off-Label Targeted Cancer Therapy Review Could Aid Compendia Evaluation

A CMS-sponsored review of the data available to support off-label use of targeted cancer therapies could help evaluate whether the drug compendia used by Medicare as the basis for determining Part B coverage for off-label cancer drugs incorporate the most current data.

The agency currently recognizes four compendia as authoritative references; three were approved last summer under a new regulatory process (¹ 'The Pink Sheet,' July 7, 2008, in Brief). However, CMS may review the selections on an annual basis.

The targeted therapies review is a technology assessment being funded through the Agency for Healthcare Research and Quality and does not include a consideration of the compendia. However, it might provide a basis for looking at how up-to-date the compendia are, specifically with respect to newer therapies.

Being conducted by the Duke Center for Health Policy Research, the study involves a review of Phase II or III clinical trials on monoclonal antibodies and selected small molecule treatments. CMS has not disclosed a target date for release of the analysis.

The Duke research center has already completed a technology assessment, released in 2006, that raised questions about how comprehensive and current the data cited by the compendia are.

Researchers at Duke and Tufts recently updated that technology assessment. Led by Amy Abernethy at Duke, the updated study was published online by the Annals of Internal Medicine Feb. 16.

Questions On Staying Up-To-Date

The group's latest review of drug compendia supports its earlier conclusion that "the compendia we evaluated did not seem to be updated in a timely, regular and explicit manner," according to the report. The update was not funded by CMS.

As a case study for the update, the researchers compared the data cited by the 2006 and 2008 versions of the compendia for off-label use of Lilly's Gemzar (gemcitabine) in bladder cancer.

The compendia reviewed in the study included those recognized by CMS: the American Hospital Formulary Service Drug Information, the National Comprehensive Care Network Drugs and Biologics Compendium, Thomson Micromedex DrugDex and Elsevier Gold Standard's Clinical Pharmacology.

Although an additional 25 reports on the use of Gemzar in bladder cancer became available in the public domain between 2006 and 2007, only one of the compendia, DrugDex, added to its citations for the indication. It increased the citations from three to 11. The others "had little or no change," the paper says.

The Annals of Internal Medicine also posted an article and an editorial questioning whether the drug compendia are up to the task of serving as authoritative references for Medicare.

In the article, Muriel Gillick, Harvard Medical School, suggests that the high cost and potential safety risks of some drugs should lead to another approach - national coverage determinations by CMS.

NCD Process A Better Alternative?

The agency could adapt the NCD to address consideration of coverage for off-label uses of high-cost drugs, she proposes. She suggests $12,000 per year as the cost threshold for determining which drugs should be subject to an NCD.

The editorial, by journal Editor Harold Sox, agrees that the compendia process may not be the best way to go for off-label coverage.

"Compendia play a useful role, but Congress has assigned them a task that requires considerably greater rigor than they are accustomed to using for their main purpose," he says. Sox was the first chair of the Medicare Coverage Advisory Committee, now known as the Medicare Evidence Development and Coverage Advisory Committee.

"Abernethy and colleagues' review strongly suggest that even an enhanced compendia-based system is too weak to deal with the methodological challenges of the evidence base for off-label indications," Sox points out.

He supported the idea that "something like" CMS' national coverage procedures be considered as an alternative.

- Cathy Kelly ([email protected])