FDA Staffers' Letter To Editor Defends Steps Taken Over Time As Regards This Controversial Sanofi-Aventis Antibiotic
(Posted by Tom Lamb at DrugInjuryWatch.com)
In the April 19, 2007 New England Journal of Medicine (NEJM) appears "The FDA and the Case of Ketek", by David B. Ross, M.D., Ph.D., a former FDA staff physician who was involved in the agency's review of the antibiotic Ketek (telithromycin).
In his Ketek article, Dr. David Ross goes through "several lessons to be learned from an examination of the events surrounding the approval of [Ketek]".
As can be expected in a telling of the Ketek approval story, there is considerable discussion of the infamous drug-safety study known as study 3014 and its "issues of data integrity".
The several points made by Dr. David Ross -- who is currently a clinical assistant professor at George Washington University School of Medicine and Health Sciences -- as concerns the FDA's handling of the Ketek case are captured in these two paragraphs from his April 2007 NEJM article:
The review of Ketek was thus marked by pronounced departures from accepted review practices. In addition to the use of fraudulent data, the substitution of uncontrolled postmarket safety reports for controlled clinical trial data, and the acceptance of trials that could not show efficacy, there was also overt internal pressure brought to bear on FDA reviewers to alter their conclusions....
In the face of Congressional subpoenas and unfavorable publicity, reviewers at the FDA were warned at a June 2006 meeting by Andrew von Eschenbach, then the acting FDA commissioner, not to discuss Ketek outside the agency. By this time, 23 cases of acute severe liver injury and 12 cases of acute liver failure, 4 of them fatal, had been linked to Ketek. By the end of 2006, Ketek had been implicated in 53 cases of hepatotoxic effects. The FDA did not relabel Ketek to indicate its possible severe hepatotoxicity until 16 months after the first liver-failure cases became public. The withdrawal of approval for two indications, acute bacterial sinusitis and acute exacerbation of chronic bronchitis, for which Ketek's efficacy had never been demonstrated, did not occur until February 12, 2007 — only a day before the Congressional hearing on Ketek.
The same April 19, 2007 NEJM edition has a letter to the editor seemingly intended as the FDA's response to this Dr. David Ross article about Ketek. This FDA letter, entitled "Ketek -- The FDA Perspective", is written jointly by Janice Soreth, M.D., Edward Cox, M.D., M.P.H., Sandra Kweder, M.D., John Jenkins, M.D., and Steven Galson, M.D., M.P.H., of the FDA's Center for Drug Evaluation and Research.
As for Ketek study 3014, this April 2007 NEJM letter to the editor asserts "there was no intention to deceive the advisory committee or the public regarding our review of study 3014." These FDA staff members conclude their letter with a recap of recent actions by the FDA and Sanofi-Aventis regarding Ketek:
The FDA monitored the safety of Ketek after approval and conducted a 1-year postapproval safety review in the spring of 2005. After three reports of serious hepatotoxicity were published in January 2006, we conducted an analysis of the available safety data that led to the addition of a bolded warning regarding hepatotoxicity in June 2006. After an advisory committee review of Ketek in December 2006, in February 2007 we added a boxed warning and Medication Guide to the label and removed two indications. Although we believe that the potential benefits of Ketek outweigh its risks when it is used according to the current approved label, we continue our safety surveillance and will take further actions if warranted.
We end, however, by going back to the last sentence of Dr. David Ross' April 2007 NEJM Ketek article:
If the case of Ketek leads to important reforms, then the drug may have done some good after all.
No doubt, we have not heard the last about the FDA's handling of this Ketek case.