Senator "Smells a Coverup" About How FDA Approved Ketek

We previously posted about the ill-fated clinical trial, study 3014, of the antibiotic telithromycin (Ketek) made by Sanofi-Aventis, run by Pharmaceutical Product Development Inc. (PPD). Problems with the trial included fabrication of data at one clinical site, and allegations of manipulation of data at another. The physician in charge of the first site was convicted of mail fraud, and the physician in charge of the second had his license suspended. Although the results of this trial were never published, it still crept into the clinical literature: it was cited in a review article in the New England Journal of Medicine.

The Washington Post just reported on the failed efforts of US Senator Charles Grassley, (R-Iowa), Chair of the Senate Finance Committee, to get more information about how the US Food and Drug Administration (FDA) approved Ketek. The story is certainly colorful:

The agency acknowledges that there were major improprieties in a 25,000-patient clinical trial done for the drug's developer, Aventis. One person has gone to prison for fraud in connection with that trial, data from several other trial sites have been discarded because basic standards were not met, and the agency told the company it could not say anything about the trial results on its product label.

Nonetheless, the FDA allowed Aventis to use much of the data to support the company's contention that the drug is safe. It also allowed Aventis to present the data to an FDA advisory panel without telling its members of the widespread fraud allegations clouding the trial. Documents show that some FDA employees argued that the trial should have been discarded because of the company's inadequate oversight.

Grassley has pressed to speak with an agent in the FDA's Division of Scientific Investigations who, he said, 'is key to understanding what the FDA did when it became clear that the safety study required by the FDA in order to approve the drug was fraudulent and faulty. Did FDA managers turn a blind eye and let the drug maker off too easy, or did the FDA do the right thing?'

In reply, FDA spokeswoman Susan Bro said: 'We would like to do whatever we can to help [Grassley] fulfill his constitutional duty as well as ours to the American people. However, we will not compromise an ongoing investigation.'

After months of trying to get firsthand information from a government official familiar with a controversial new antibiotic, Sen. Charles E. Grassley (R-Iowa) marched into the Department of Health and Human Services headquarters yesterday asserting his congressional right to receive the data.

After a brief meeting with senior HHS and Food and Drug Administration officials, Grassley departed empty-handed and angry.

'This is extraordinary for me,' the senior Republican said outside the headquarters. 'I haven't had to go to an agency like this since 1983 to get information I requested.'

'I smell a coverup.'

'I'm tired of the runaround,' he said after leaving the HHS headquarters. He said that he told the agencies' officials that 'I know it's probably not your intent to protect companies, to cover for companies.'

'But I said that every time that you stand in the way of information getting out that ought to be public, that's the impression you give the American people.'

It is noteworthy how this story has evolved. Originally, it seemed to be about sloppily supervised research whose unpublished results still had influence. Now the story seems to be morphing into one that includes allegations of government cover-ups of information about how questionable commercially sponsored clinical research may be. The moral is that patients and physicians need to be extremely skeptical about the results of commercially sponsored clinical research.

As we have said before, doctors and patients ought to base choices of tests or treatments on honestly done, honestly reported clinical research. Depending on poorly executed or misleadingly reported research will lead to bad decisions and bad outcomes. Furthermore, failure to honestly report the results of clinical research betrays the trust of the human volunteers who willingly participated in the research partly to help add to scientific knowledge and improve clinical care.