Studies on Ketek (Telithromycin) Done by Pharmaceutical Product Development for Sanofi-Aventis
We recently discussed how results of study of Ketek (Telithromycin) done by Pharmaceutical Product Development for Sanofi-Aventis may have been affected by misconduct, including one conviction for fraud, by some of the physicians paid to enroll patients. Although the results of this trial were never published, they have been cited in the clinical literature.
Now Reuters has reported that Sanofi-Aventis is in talks with the US Food and Drug Administration (FDA) about strengthening the warning label on the drug. A report from PharmaLive said that US Senator Charles Grassley (R-Iowa), chair of the Senate Finance Committee, is pressing the FDA for more information on how it handled the approval of Ketek. The letter said,
the Committee continues to investigate the extremely troubling allegations related to , among other things, the approval and post-market [sic] surveillance of telithromycin (Ketek) by the Food and Drug Administartion. One of the most troubling allegations is that the FDA approved Ketek with full knowledge that some of the clinical safety data supporting its approval was beset by systemic data integrity problems. While the FDA takes its time negotiating with Sanofi-Aventis to decide what drug risk information the public should know, it is completely mystifying why a fraudulant clinical trial is reference in safety information on the FDA's web-site.The Disastrous Trial of TGN 1412 Done by Parexel for TeGenero
We have previously posted, most recently here and here, about the disastrous trial, implemented by Parexel International , of a new monoclonal antibody designated TGN 1412, manufactured by TeGenero AG. All six healthy volunteers who got the antibody soon became critically ill. We had previously noted allegations that there was reason to think prior to this trial that TGN 1412 would pose risks to human subjects.
The BBC interviewed several experts who also felt that TGN 1412 should have been regarded as a risky drug from the outset. For example, it quoted Dr David Glover, "it may be that it [the adverse effect] was unpredicted by the tests that were done. I believe from the basic science it was predictable." Professor David Winter, of the Laboratory of Molecular Biology in Cambridge said that "those testing TGN 1412 may have been lulled into a false sense of security by the fact that it did not seem to harm monkeys - but it was wrong to make too many assumptions based on animal experiments." In response, TeGenero "said it was an 'oversimplification' to suggest that the side effects could have been predicted in advance."
Multiple Clinical Trials Done by SFBC International
We have posted before about the troubles of contract research firm SFBC International We started by posting about allegations that private, for-profit clinical research firms, including SFBC International, supervised by for-profit institutional review boards (IRBs), were doing sloppy and shoddy work. We then noted allegations that SFBC International had tried to threaten or intimidate research subjects who talked to reporters about such poor research practices. Furthermore, we discussed how a review commissioned by the company found that a top executive, Jerry Seifer, SFBC International's Vice President for Legal Affairs, threatened participants in clinical studies who had talked to the press with deportation. Seifer, it turns out, had been the subject of past regulatory sanctions by federal regulators. In addition, study participants in a trial of an immunosuppressant drug carried out by the firm's Canadian subsidiary, SFBC Anapharm, acquired tuberculosis after exposure to another participant with active disease, despite their complaints to Anapharm staff. More recently, we noted that Seifer had resigned, and the company's stock price had fallen. Finally, we noted allegations that 20 people, including trial participants and staff at SFBC International's Montreal facility acquired latent tuberculosis after exposure during trials.
Per Bloomberg News, SFBC International just announced it will shut down its facility in Florida that was the location of allegedly sloppy and shoddy research practices noted above. In fact, the Miami-Dade County Unsafe Structures Board gave the company 60 days to "file a permit to demolish its Miami facility.... The company said it would appeal the ruling and may file [for] an injunction." Bloomberg quoted Kenneth Goodman, Director of the University of Miami's bioethics program, who had toured the Miami area facility,
This is going to send a signal through the entire drug industry that human-subject protection is not a nicety or a courtesy, but a bold-faced moral and legal requirement.Summary
What I saw was a research mill where vulnerable poor and uneducated people were being enticed into taking medical risks to make a living. That's a morally flimsy foundation to advance medical knowledge.
The cases of the Ketek trial, the TGN 1412 trial, and various trials done by SFBC International have rarely been juxtaposed, except on Health Care Renewal. However, their juxtaposition suggests
- Physicians and patients should be extremely skeptical of the results of drug research carried out by contract research organizations sponsored by pharmaceutical companies, since the design and implementation of such studies may not be what they seem. Other evidence that commercial research sponsors may manipulate the design of studies, the analysis of their data, and the dissemination of their results should only add to this skepticism (see most recent post here).
- People should be extremely wary about signing up as subjects for such trials, since their risks may be worse than they realize
- We ought to rethink the social desirability of the current relatively unregulated system of having human clinical research sponsored by commercial firms with interests in their results.