Ketek sparks Criticisms of FDA Approval Process

Rockville, MDCritics of the Food and Drug Administration approval process frequently point to Ketek as evidence that the FDA is not properly protecting the safety of American consumers. The process by which Ketek was approved was filled with false data, illegal activity, and omitted information yet still the drug was approved. Some patients died after taking Ketek for relatively mild sinus infections. Now, patients are investigating possible class action lawsuits against Sanofi-Aventis for pushing the approval of Ketek despite allegedly knowing about the life-threatening risks.

Ketek was initially approved to treat sinus infections. It prevents bacteria from growing by interfering with the synthesis of protein. Ketek is metabolized in the liver, mainly through bile. However, in a few cases, Ketek caused serious damage to the patient's liver. Three reports in January 2006 involved liver problems - one case resulted in death, one required a liver transplant, and one involved drug-induced hepatitis. Furthermore, the FDA has identified 23 cases of serious liver injury and 12 cases of acute liver failure. Four cases of acute liver failure resulted in death.

The New England Journal of Medicine (April 19, 2007) published an article by David B. Ross, M.D., Ph.D. that was extremely critical of the FDA and its decision to approve Ketek. Ross was a former FDA physician who was involved in reviewing Ketek. According to Ross, Ketek was reviewed three times. Ross writes, "During the first round, reviewers identified substantial safety concerns..." including drug interactions, vision problems, and an association with hepatitis. Sanofi-Aventis, maker of Ketek, was asked to obtain further safety information.

Sanofi-Aventis then conducted study 3014, an unblended, randomized, controlled trial. Physicians were given up to $400 per patient enrolled in the study, which was conducted over five months. One of the physicians, who is now serving a prison sentence for her actions, committed fraud by falsifying data and fabricating patient enrollment in the study. According to Ross, of ten sites investigated, four were referred for criminal investigation.

Even though FDA managers knew about problems with study 3014, information claiming Ketek was safe was still presented to an FDA advisory committee. The committee voted to recommend Ketek for approval.

A third review was conducted, using postmarketing reports from other countries. Ross notes, "The postmarketing data submitted by Sanofi-Aventis were reviewed by the FDA without any verification of their accuracy or completeness, even though 3 months before the third review, FDA criminal investigators recommended examining whether Sanofi-Aventis had been involved in systematic fraud in connection with Ketek."

The standard by which Ketek was approved showed only that Ketek was better than a placebo, not that it was better than, or even equal to, other drugs on the market. Study 3014 was cited repeatedly as evidence that Ketek was a safe product, despite reports of at least one death associated with the drug. The FDA finally withdrew approval of Ketek for two uses, but that action was only taken one day before a Congressional hearing on Ketek began. Furthermore, Ketek continues to be approved for one condition, pneumonia.

Dr. David Graham, who also issued warnings about Vioxx, spoke with NPR about the FDA's approval process. Regarding how the FDA approved Ketek, Graham said, "The FDA views industry as its client, and that's the only explanation here. FDA saw that it needed to align its interests with the company's, and the company's interest was 'get this drug approved.'"

Although the FDA has reports of numerous patients who suffered serious complications after using Ketek, it is likely that there are more patients out there who became ill but did not realize their problems were associated with the drug.