Wednesday, September 24, 2008

Brown University Student Journalists Dare to Report on Paxil/ Seroxat, Study 329 and GSK

We have published a few posts about the controversy about the clinical research supporting the use of paroxetine (Paxil, Seroxat in the UK, made by GlaxoSmithKline) in depression (here, here, here, and here.) This controversy includes allegations that clinical research funded by GSK was manipulated, and that the company's marketing for the drug was unsupported by clinical evidence. GSK settled a case alleging fraud in the marketing of Paxil by then NY Attorney General Eliot Spitzer in 2004. A recent article provided arguments and evidence that Study 329, a clinical trial of paroxetine for adolescents, was manipulated , allegedly at least with the acquiescence of Brown University Psychiatry Chair Dr Martin Keller. [Jureidini JN, McHenry LB, Mansfield PR. Clinical trials and drug promotion: selective reporting of study 329. Int J Risk Safety Med 2008; 20: 73-81. Link here.] A book entirely devoted to this controversy, Side Effects by Alison Bass, who started reporting on the case in 1999 for the Boston Globe, was just published.

I am a still proud alumnus of Brown University (undergraduate and medical). I was a full-time faculty member at the University from 1994-2004, and am still a clinical faculty member. Despite Dr Keller's and the University's central role in the case, at least as alleged by Ms Bass and by Jureidini et al, there has only been silence about the case here in Rhode Island.

That just changed. Intrepid reporters from the Brown Daily Herald published two stories on the GSK/ Paxil/ Keller controversy. Both included some important original reporting, as well as providing clear summaries of the issues at hand.

The first article dealt mainly with Keller's alleged conflicts of interest. This article provided confirmation that Senator Charles Grassley (R-Iowa) and the US Senate Finance Committee is, in fact, investigating Dr Keller and Brown University in connection with the controversy. It also included other original reporting, including an acknowledgement from GlaxoSmithKline Director of US Media Relationships Sarah Alspach that the company had provided the committee with full information about the compensation it gave Dr Keller.

The second provided a quite clear explanation of the allegations about the manipulation of Study 329. This article also included results of an interview with Dr Jon Jureidini, the author of an article that dissected study 329, and suggested that it had been manipulated to enhance the apparent benefits of paroxetine, and diminish its apparent risks. The reporters noted that Jureidini was "confident that data in Study 329 were deliberately misrepresented." They were also able to obtain an internal GSK document that acknowledged that study 329 did not prove the efficacy of the drug.

The BDH reporters, Chaz Firestone and Chaz Kelsh, in my opinion, did a fine job, clearly explaining the issues, and digging out some new facts on the case.

Nonetheless, the BDH reporters were not able to get Dr Keller to talk to them, despite several attempts. They were not able to get anyone in the University administration to discuss any substantive aspects of the case. The highest ranking University official who would talk to them was Provost David Kertzer. He asserted that the University "can't discuss particular cases of possible claims of wrongdoing and what we do about them."

In my opinion, and as I said to the reporters, one of the most distressing aspects of this case is the refusal of Dr Keller or anyone in the University to deal with the content of the case. Very serious allegations have been made. If they can be refuted, they should be. If not, stonewalling only increases the impression that the University administration has something to hide.

Furthermore, the case raises important issues about science and clinical medicine. Universities are supposed to be where people can conduct free enquiry. There seems to be no free enquiry at Brown into the issues raised by this case. University administrators should be encouraging free enquiry. Here, they seem to be doing their best to avoid, if not stifle it.

Today, the BDH published its own editorial on the case, suggesting that Dr Keller's "actions directly affect the integrity of the University." If so, the University community should, at the very least, be discussing these actions, how they affect this integrity, and what ought to be done about it. Unfortunately, I am not optimistic that there will be an open discussion of these issues, even after the brave publication of these articles. The University administration seems to have some reason they want to clamp a lid on this case, and I am afraid they will continue to do so. The medical school faculty, lacking tenure and remembering what happened to previous dissenters like Dr David Kern, are likely to be too scared to push that lid away. Woe unto Brown.

See also comments on the Alison Bass Blog, PharmaGossip, and Pharmalot.

ADDENDUM (29 September, 2008) - See also this post on the Alison Bass blog, with links to some of the original documents relevant to study 329.

1 comment:

Charles Denby, M.D. said...

Beyond disclosure of ALL conflicts of interest, including those heretofore not considered "substantial," one wonders what other systemic remedies might be applied to the problem of tainted researchers. Perhaps the methodology of accounting should apply: a body of independent, credentialed "auditors" could be created, funded by assessments on the pharmaceutical and medical device manufacturers; careful scrutiny of each study by a reviewer standing at true "arm's length" to the authors could lead to an opinion validating the results; a Sarbanes-Oxley zeitgeist would apply.

Charles Denby, M.D.
Assistant Clinical Professor (inactive)
Brown University School of Medicine