New York Attorney General Eliot Spitzer has found what must look like another target-rich environment: the pharmaceutical industry. As many readers will have seen, he's initiated a lawsuit against GlaxoSmithKline for their handling of clinical trial data for the antidepressant Paxil (paroxetine). As far as anyone can tell, this suit is the first of its kind.
There's a specific side to this story, and a there's general one about the handling of all clinical trial data. I think I'm going to end up splitting the difference, but first things first: in this case, SmithKline (as it was at the time) ran different studies on the effectiveness of Paxil in adolescent patients. One study (#329) had positive results, and another (#377, slightly later) showed no benefit versus placebo. Spitzer points out that the successful first study was widely publicized, presented at several scientific meetings, and eventually published. SmithKline (and later GSK) made it part of their sales pitch to physicians.
Meanwhile, the 377 study was presented once, at the annual meeting of that same academy, and never showed up as a full paper in the literature. The presentation wasn't SmithKline's idea; they weren't going to publish or present at all. It was suggested by two of their academic collaborators (Robert Milin and Jovan Simeon). And as you can imagine, it has not been a feature of GSK's promotional literature.
All this, in the eyes of Attorney General Spitzer, adds up to an indictment for fraud - and yes, that's exactly the word he uses. Here we have all the elements of a great case: buried information that would have been harmful to a large corporation, and a whistleblower who brought it to light. It sounds more like a screenplay - as you read about it, you can start mentally casting the movie.
But there are complications. For one thing, SmithKline made no objection when Dr. Milin told them of his plans to present the 377 study. I don't know what the terms of the research agreement were in this case, but often enough the company can exercise a veto in such cases, since they paid for the study. And second, Milin himself is, according to Barry Meier's story in the New York Times last week, a strong believer in the use of Paxil in adolescents. He considers the 377 study to have failed because of a flawed design, not because the drug isn't useful. And as for publishing the results in a journal, that would have actually been quite difficult. Inconclusive or negative results are very hard to publish in general, and in this case even the positive study wasn't the easiest thing to get into the literature. According the Times article, the paper probably bounced around a couple of times before finding a home. It ended up in the Journal of the American Academy of Child and Adolescent Psychiatry, and appropriate venue but hardly the highest-impact journal in the world. And finally, GSK provided details of both studies to the FDA, as it is required to do.
So hiding information, which is the basis of the fraud allegation, lies in the way that GSK detailed physicians. I wouldn't expect them to go out of their way to present data showing that the drug didn't work, but if one of the study's own authors felt that it was flawed, then I really wouldn't expect them to talk about it much. I can see what Spitzer's trying to do, all right, and I can see what he thinks he has. But I don't think that's what's really there.
All this, presumably, is supposed to further the cause of releasing clinical trial data. Under the current system, the company can show it only to the FDA (or other regulatory agencies) if it chooses, and if they give up on the compound, no one has to see it at all. There have been calls over the years to establish a clinical trial database, but nothing's ever come together.
And you know, I actually think that a general trial database could be a good idea. (It could also be a disaster, and the industry has chosen to avoid the latter rather than seek the former - we'll go into some of the complications tomorrow.) But I think that Eliot Spitzer may have picked the wrong grandstand to make a speech from, and should have thought twice before striking up the band. Then again, that's not the sort of behavior that got him to where he is now. . .