The article reported one patient at the Carolinas Medical Center in Charlotte, NC, had died after taking Ketek, another required a liver transplant, and a third patient recovered from drug-induced hepatitis after treatment with Ketek was stopped. The Annal's report also said that Sanofi-Aventis reported 7 cases of hepatitis or hepatocellular damage in patients taking Ketek in data from Phase III trials.
On June 9, 2006, drug maker Sanofi-Aventis made the announcement that it had stopped enrolling children in clinical trials for Ketek and said it halted tests to ensure that clinical trials complied with FDA requirements. The company did not mention the heat coming from two powerful Congressional Committees.
As it turns out, the cases above are not the only serious Ketek related adverse events that have been reported to the FDA. According to a review by the staff of the Senate Finance Committee, of reports in the Adverse Event Reporting System between July 2005 and September 2005, the most recent 3 month period available, two deaths, 35 liver adverse events, 44 cardiac adverse events, and 80 visual adverse events have been recorded.
Because it is well-known that only between 1% and 10% of adverse events are ever reported to the FDA, the numbers above would have to be multiplied many times over to establish a true accounting of the adverse events associated with Ketek.
Along with the January 20, Public Announcement, the FDA posted a document titled, "Questions and Answers on Telithromycin (marketed as Ketek), " on its web site, that asked, "What information was known about liver problems related to telithromycin prior to approval?"
In response, the FDA said, "Based on the pre-marketing clinical data it appeared that the risk of liver injury with telithromycin was similar to that of other marketed antibiotics."
Prior to the approval of Ketek, the agency said, the FDA looked extensively at the potential for hepatic toxicity in patients treated with Ketek. The data examined included a 25,000 patient controlled study, as well as information in nearly 4 million postmarketing prescriptions outside the United States.
The release of this public announcement is what initially sent Senator Charles Grassley (R-Iowa), chairman of the Senate Finance Committee, on the warpath. He demanded an explanation as to why the FDA continued to cite Study 3014 without disclosing that the Anti-Effective Drugs Advisory Committee voted to recommend the approval of Ketek, without knowledge that the study was fraudulent.
In a press release on May 1, 2006, Senator Grassley said he was concerned about the FDA 's complicity with the drug maker and subsequent failure to ensure the integrity of a pivotal study about the benefits and risks of Ketek.
On May 16, 2006, he called it "mystifying" that the FDA continued to provide information the agency knew was fraudulent, and said that he 's keeping the pressure on the FDA for more information about the drug's approval and post-market surveillance. He continues to seek a face-to-face interview with the FDA investigator who discovered the fraud and misconduct in Study 3014.
The study began in October 2001, when doctors began enrolling subjects and were paid $100 for each patient they signed up, and another $150 when they submitted study results, as well as a final $150 after all questions were resolved, according to the May 1, 2006 Wall Street Journal.
On July 24, 2002, drug maker Aventis submitted the results of the study to the FDA, but without disclosing the study's integrity problems.
When the AIDAC reviewed the study, the FDA did not disclose that the agency's Division of Scientific Investigation and Office of Criminal Investigation were investigating the integrity of the study.
A memorandum dated March 25, 2004, by the FDA's Division of Scientific Investigations titled, "DSI Recommendations on Data Integrity, " states that Study 3014 involved "multiple instances of fraud " and that "the integrity of data from all sites involved in [the] study ... cannot be assured with any degree of confidence. "
The infractions discovered were not minor. The doctor with the highest number of patients, Dr Anne Campbell, was subsequently charged in a 21 count indictment related to her fraudulent conduct during the study, and in March 2004, she was sentenced to 57 months in prison.