I'll bet you haven't heard about this

While the media freak show was going on, the FDA was conspiring with Sanofi-Aventis to kill you. Dr. David Ross tells the apalling, little-known story in the new NEJM, and bless their normally greedy little hearts, this of sufficient public importance that they've made it available free to the common rabble.

I wrote recently that we have a looming crisis of microbial drug resistance, and that the drug companies aren't investing enough in developing new antibiotics. But that didn't stop S-A from getting approval for a useless, dangerous new antibiotic, called Ketek. Initially, FDA reviewers had safety concerns about it, so they asked S-A to conduct a new clinical trial. The company then set up what amounted to a phony trial, one guaranteed to get favorable results, but that wasn't good enough: they conducted the trial fraudulently. One physician involved in the trial, as a matter of fact, is currently doing 57 months in federal prison for fabricating data.

The FDA learned this before presenting the trial results to its advisory committee, but presented them anyway, without mentioning the fraud. They claim they couldn't discuss it because of the ongoing criminal investigation -- but then why present the results at all? Knowing nothing about the fraud, the committee voted to approve the drug. FDA managers realized they might get in trouble in the long run for this, so as Ross writes, they "proposed using foreign postmarketing reports on Ketek as evidence of the product's safety, despite the unreliability of such data. . . The postmarketing data submitted by Sanofi-Aventis were reivewed 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 . . . " The FDA did not investigate.

Not only was Ketek not safe, it was worse than existing alternatives. But the trial design did not require that it be found to be superior. The FDA had already decided that these "non-inferiority trials" no longer be used, but they justified approving Ketek on the basis of such a trial because of prior agreements with the industry. Isn't the welfare of patients more important than inappropriate agreements that may have been made in the past with manufacturers? Not to Bush's FDA.

Seven months after Ketek had what S-A bragged was the "most successful launch of any antibiotic in history," the FDA got a report of the death from liver failure of a patient treated for a mild respiratory tract infection. They did nothing. A year later, they learned that a report was about to be released of 3 deaths associated with Ketek, so they held an emergency meeting of senior managers, which resulted in an announcement that Ketek was safe -- based on the fraudulent study.

Dr. Ross, in February 2006, alerted the FDA to concerns about the Ketek case. The FDA did nothing. They finally got around to removing mention of the fraudulent study from their web site after a congressional hearing. In June, facing subpoenas and bad press (at least a little bit -- as I say, this was largely ignored by the corporate media), FDA Commissioner Andrew von Eschenbach finally took action. Specifically, he forbade FDA reviewers from discussing the matter publicly. By now, there were 23 cases of liver injury, 12 cases of liver failure, and 4 deaths associated with Ketek known to the agency, and by the end of last year, there were 53 known cases. Approval of Ketek for two indications -- indications for which it had never been shown to be effective in the first place -- was withdrawn in February of this year, the day before a congressional hearing.

In the same issue of NEJM, also free to the masses, is a report that has gotten some attention on your teevee, about the decline in breast cancer incidence following the news that hormone replacement therapy (HRT) was dangerous. Now, the approval of HRT wasn't based on outright fraud, but it was based on speculation rather than solid evidence. This report doesn't quite hammer in the final nail, but it's looking pretty solid that the increasing incidence of breast cancer starting in the 1980s -- the increase that had women marching, and blaming everything from pesticides to PCV piping -- was largely caused by drugs prescribed to women by their doctors.

In this case, I think, the manufacturers were more well-meaning, and the approval process was misguided rather than criminal. Nevertheless this should serve as a powerful reminder that we tinker with our bodies' fundamental processes at our peril, and we need to be much more careful, much more diligent, and much more conservative about pharmaceutical intervention. Yes, it does save lives, and relieve suffering, but it also makes big profits, and there is no doubt about it: our regulatory process is deeply corrupted.