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Previous Volume 356:1675-1676 April 19, 2007 Number 16 Next

PDF PDA Full Text Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Related Article by Ross, D. B. PubMed Citation

To the Editor: In response to the article by Ross in this issue of the Journal,¹ we wish to clarify how the Food and Drug Administration (FDA) reviewed Ketek (telithromycin). Although there are other statements or suggestions in the article that also need clarification, we address a few key points in the limited space available here.

First, safety concerns were identified by the FDA early in the review process and taken very seriously throughout four years and three review cycles. The FDA's approval decision followed a careful review of the safety data submitted, including foreign postmarketing adverse-event reports that accumulated during the FDA's review of the application. Although the FDA did not rely on study 3014 to support approval, we reviewed the study for safety findings that would have counted "against the drug," as is consistent with good review practice.

Second, there was no intention to deceive the advisory committee or the public regarding our review of study 3014. Before the second advisory committee meeting, the FDA had only preliminary information regarding inspections of a few of over 1800 clinical study sites. Although the findings at one site had raised serious data-integrity concerns and had led to a referral for criminal investigation, we did not know at that time that we would conclude months later, after additional inspections and further review, that the entire study should not be relied upon. The FDA did not discuss data-integrity issues at the second advisory committee meeting to avoid compromising the ongoing investigations, recognizing that the FDA retained the ultimate decision authority.

Finally, noninferiority studies were considered acceptable as the basis for approval for treatment of certain respiratory infections when the Ketek New Drug Application was submitted. Concurrent with the Ketek review, our thinking on noninferiority studies was evolving. Today, noninferiority studies are no longer considered acceptable for two of the three indications for which Ketek was originally approved. We are applying this new regulatory position to more recently submitted and planned applications.

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.

Janice Soreth, M.D.
Edward Cox, M.D., M.P.H.
Sandra Kweder, M.D.
John Jenkins, M.D.
Steven Galson, M.D., M.P.H.
Center for Drug Evaluation and Research
Food and Drug Administration
Silver Spring, MD 20993

References

1. Ross DB. The FDA and the case of Ketek. N Engl J Med 2007;356:1601-1604. [Free Full Text]

PDF PDA Full Text Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Related Article by Ross, D. B. PubMed Citation

This article has been cited by other articles:

• Bolesta, S., Roslund, B. P. (2008). Elevated hepatic transaminases associated with telithromycin therapy: A case report and literature review. Am J Health Syst Pharm 65: 37-41 [Abstract] [Full Text]