November 30, 2006 The Pump Handle 0Comment

by Susan F. Wood

Much has been written about the antibiotic drug, telithromycin, otherwise known as Ketek. It seems to combine a host of concerns all in one place (see also Matthews, AW, WSJ, May 19, 2006:B1). Critically, concerns about safety, from visual effects to fatal liver toxicity, are paired with questions about lack of relative efficacy. These very basic concerns are then confounded with problems in particular safety studies that were carried out fraudulently and the faulty data derived from it provided to the FDA. But FDA leadership/management apparently discounted these problems, did not relay this information to the advisory committee which recommended approval, and approved this new drug in 2004. This past summer more concerns were raised about studies on Ketek in children; these are no longer ongoing, but FDA has yet to take specific action on whether these studies are permissible.

In last week’s New England Journal of Medicine, David Graham points out another weakness in the approval of Ketek(NEJM, 355(21), November 23, 2006, 2260-2261). He reports on the fact that given the fraudulent safety study, FDA used adverse event data from Germany and France where Ketek is marketed. Unfortunately, Dr. Graham’s analysis points out that the data was insufficient to detect a signal for a safety problem, but “the FDA interpreted the absence of a signal of acute liver failure in the overseas data as confirmation of telithromycin’s safety when the data could not be used to identify the problem.”

This is playing out in interesting ways here in Washington – and hopefully will serve as one of the springboards to improved functioning at the FDA, although there is a long way to go. This is an issue that deserves more attention not less.

It’s not just the NEJM and other scientific journals publishing articles on this; the mainstream press has been a major conduit for information about Ketek itself and about the FDA review process.

Senator Charles Grassley has been investigating during the last year raising questions to FDA and interviewing FDA staff repeatedly on the subject. It is thought that perhaps Sen. Grassley, who has been taking a lead role in drug safety issues at FDA, will issue a report on the subject. Indeed it is reported that the current holdup of the confirmation of Andrew von Eschenbach as FDA Commissioner is due to Senator Grassley’s dissatisfaction with FDA response to his investigation of Ketek. Senator Grassley has been investigating from his position as Chair of the Senate Finance Committee, a rather unusual committee to take interest in FDA. However, with the change in Congress, it may fall to the Senate Health, Education, Labor and Pensions Committee (HELP) soon to be chaired by Senator Edward Kennedy to take or leave the Ketek investigation.

Meanwhile FDA seems to be taking a new tack. A joint Advisory Committee meeting, of the Anti-Infective Drug Advisory Committee and the Drug Safety Advisory Committee, will be meeting Dec. 14 and 15 to discuss “the overall benefit to risk considerations for the approved product KETEK (telithromycin),…with the with the current indications of: Acute bacterial exacerbations of chronic bronchitis, acute bacterial sinusitis, and community acquired pneumonia…”. However it seems that only very limited time is being allowed for public comment (this is something that the FDA can expand or limit at will), so it remains to be seen if a real airing of the safety concerns will occur. But it is a 2-day meeting, so it will be one worth watching.

All of this is taking place in the context of the necessity to pass major FDA legislation next year. The Prescription Drug User Fee Act needs to be renewed in order to keep the funding stream of user fees coming into the FDA, specifically into the Center for Drug Evaluation and Research. The amount of funding and how it is to be used is often central to the discussions about the pressures on FDA to approve new drugs and how much priority is placed on safety, postmarket studies and outcomes, and enforcement by FDA. Legislation specifically on drug safety or any other aspect of FDA reform is likely to be included in this “must-pass” legislation.

Susan Wood is Research Professor at George Washington University School of Public Health and Health Services, where she is part of the Project on Scientific Knowledge and Public Policy (SKAPP).

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