There's a disturbing article out at the New England Journal of Medicine on studies conducted on Neurontin (gabapentin) for various unapproved indications. Parke-Davis (and later Pfizer) looked at a wide range of possible indications for the drug - migraine, neuropathic pain, bipolar disorder, and more. That in itself isn't unusual, since CNS drugs often have rather broad and poorly defined mechanisms, and it's not like we understand any of them all that well.
What is unusual is the pattern found when comparing the internal reports with the published versions that showed up in the literature. The authors found that:
"More than half the clinical trials that we included in our analysis (11 of 20) were not published as full-length research articles. For 7 of the 9 trials that were published as full-length research articles, a statistically significant primary outcome was reported, and for more than half these trials, the outcome specified in the published report differed from the outcome originally described in the protocol. Three of the four trials with an unchanged primary outcome had statistically significant results for the protocol-specified primary outcome. Secondary outcomes also frequently differed between the protocol and the published report. Thus, trials with findings that were not statistically significant (P≥0.05) for the protocol-defined primary outcome, according to the internal documents, either were not published in full or were published with a changed primary outcome. . .all the changes that took place between what was specified in the protocol, what was known before publication (as presented in the internal company research reports), and what was reported to the public led to a more favorable presentation in the medical literature. . ."
The authors go on to point out that changing a primary outcome after you see the data is, in fact, a statistical sin (although that's not quite the phrase they use!) You really can't go around doing that, because you can end up chasing after random chance (and avoiding that is the whole point of running well-controlled trials). This does not cover Pfizer and Parke-Davis with glory, but it's worth noting that there's plenty of blame to go around when it comes to this practice:
"Our study is based on a relatively small number of trials undertaken to test a single drug manufactured by a single company and its successors. Furthermore, if a major purpose of the studies we examined was to promote off-label uses of gabapentin, the selective reporting we observed could be more extreme than that observed for studies conducted for other reasons. Previous studies in different settings have shown evidence of these same biases, however. Indeed, selective outcome reporting does not appear to be limited to studies funded by drug companies. Chan and colleagues examined published trials funded by the Canadian Institutes of Health Research and found that 40% of stated primary outcomes differed between the protocol and the published report. In addition, we cannot be certain that selective reporting was a decision made by employees of Pfizer and Parke-Davis, since the authors of the published reports included nonemployees. We did not systematically assess the methodologic quality of the included trials as described in the publications we examined. Previous research has indicated that quality scores are higher for trials conducted by the pharmaceutical industry than for trials conducted by not-for-profit entities, although reports from industry-sponsored trials have potentially distorted the scientific record because of other, less easily measured study factors."
That doesn't get the folks who conducted these gabapentin studies off the hook, although I should note that Pfizer disputes the conclusions of this article (as you'd certainly think that they would). And it's also worth noting that some of its authors have done work for the plaintiffs in suits against Pfizer over gabapentin (thus all the familiarity with the internal company documents, which came to light during discovery proceedings). But again, I don't see how that negates the paper's conclusions, and if Pfizer has any hard data that would do so, I think they should produce it with all speed.
And no, it's just a coincidence that this post involve Pfizer, after I've been going on about their merger business all week. Unfortunately, I think that they're probably not the only company that could be pointed at. But we in the industry shouldn't have things like this for others to uncover in the first place. Should we?