FDA, Ketek and Americans: Breach of Trust

Telithromycin(Ketek) is a ketolide antibiotic(manufactured by Sanofi-Aventis) similar in chemical structure to Erythromycin but more acid stable, as such it can be taken orally and can survive the acid environment of the stomach. It is supposed to be used for upper respiratory infections.

The Story:
Its trials were started 1998 and FDA gave approval in April, 2004. Sanofi-Aventis declared in advertisements that Ketek had the most successful launch of any antibiotic in history. In February 2005, 7 months after the drug was introduced to the U.S. market, the first death from Ketek-associated liver failure was reported to the FDA. FDA kept quiet on the issue. In January 2006 a leading medical journal (Reference # 1 below) published 3 cases of severe liver toxicity associated with the use of antibiotic following which the FDA vowed to confirm the reports. It stayed quiet again. In the first half of July, 2006 controversies began to spill out in the public domain. David Graham, one of the FDA drug safety department official, wrote emails and a couple of internal memorandums to popular magazines and papers like New York Times but that was disregarded by FDA, the insider story being an exposé of the violations in ethical conduct during the drug approval process. The memo also mentioned of some other less fatal side effects including some vision defects and Myasthenia Gravis (a kind of generalized muscle weakness). Only on February 12, 2007(after more than a year) did the FDA respond clearly re-labeling the drug as no more suited for two conditions it previously approved of; acute bacterial sinusitis and acute bacterial infections in cases of Chronic Bronchitis. The label also mentioned, albeit very softly, that patients with Myasthenia Gravis should not use the drug and that it could also cause liver toxicity and all while being aware that the liver toxicity have been fatal in trials.

Link to FDA label warning = (http://www.fda.gov/cder/drug/infopage/telithromycin/default.htm)

Three other FDA officials have been named as critics of the drug: Dr. Charles Cooper, Dr. David Ross and Dr. Rosemary Johann-Liang. Till this date dozens of such fatal and near fatal incidents of liver toxicity have been reported. David Ross in today�â'¬™s (April 18, 2007) issue of New England Journal of Medicine explains how the fraud has been sustained. The story: The FDA managers reportedly employed 400 doctors (some of which without a license and criminal background) and paid them around 400$ for each patient enrolled for the trial of the drug. The FDA inspectors found out that the recruitment of patients for the trial was being conducted in a fabricated way and violations like after-hour recruitment were common place. These disturbing trends were reported to the FDA managers, but even though the integrity of the study was under question (the data on effects etc were obviously being doctored), the drug was approved by the committee with an overwhelming majority of votes. Many officials were being asked and warned to "soften" the data of trials so that the drug looks as "good".

Hear Dr Ross of George Washington University being interviewed by New England Journal of Medicine=
( http://content.nejm.org/cgi/content/full/356/16/1601/DC1 )

The malpractice, according to Dr Ross, issues from the fact that FDA saves resources by expediting the drug approval process as a single drug testing involves millions of dollars in multiple tests it has to go through before it is labeled safe for the American people. In this case the FDA approved the drug only on the basis of very early trials which are by strict standards not the complete test of a drug's safety. Till now more than 50 cases of liver toxicity have occurred and 4 of them have died. The number of deaths only underscores the severe injury people's trust sustained to see a major agency fall from its high moral seat. It seems that the defenders of faith have turned into crusaders of felony. The lives lost can never be brought back but we hope their sacrifice helps bring on a major reform and rebuild the much maligned trust and prevent many more innocent deaths.

Reference: 1) Clay KD et al. (2006). "Brief communication: severe hepatotoxicity of telithromycin: three case reports and literature review.". Annals of Internal Medicine 144(6): 415-420.