Pfizer disputes NEJM findings of skewing data on Neurontin

The world's largest drugmaker, USA-based Pfizer, denies that it may have altered or omitted unfavorable study results relating to potential expanded uses of Neurontin (gabapentin), indicating the medicine worked better than internal company documents showed, as alleged in a report published in the New England Journal of Medicine yesterday.

Researchers from the University of California at San Francisco and the Johns Hopkins Bloomberg School of Public Health, say trials of Pfizer's Neurontin epilepsy treatment for uses that were not yet approved may have been skewed to emphasize favorable results. They noted that there is good evidence of selective outcome reporting in published reports of randomized trials of the drug.

They said that they had identified 20 clinical trials for which internal documents were available from Pfizer and subsidiary Parke-Davis; of these trials, 12 were reported in publications. For eight of the 12 reported trials, the primary outcome defined in the published report differed from that described in the protocol. Sources of disagreement included the introduction of a new primary outcome (in the case of six trials), failure to distinguish between primary and secondary outcomes (two studies), relegation of primary outcomes to secondary outcomes (two trials), and failure to report one or more protocol-defined primary outcomes (five studies).

Trials that presented findings that were not significant (P 0.05) for the protocol-defined primary outcome in the internal documents either were not reported in full or were reported with a changed primary outcome. The primary outcome was changed in the case of five of eight published trials for which statistically significant differences favoring gabapentin were reported, the researchers stated. Of the 21 primary outcomes described in the protocols of the published trials, six were not reported at all and four were reported as secondary outcomes. Of 28 primary outcomes described in the published reports, 12 were newly introduced.

In conclusion, they said: 'We identified selective outcome reporting for trials of off-label use of gabapentin. This practice threatens the validity of evidence for the effectiveness of off-label interventions.'

Pfizer paid $430 million in criminal fines and civil penalties in 2004 for urging doctors to prescribe Neurontin for off-label uses. The drugmaker said the new review isn't credible and the company didn't attempt to mislead the medical community.

Pfizer issued a statement in response to the study, which included the firm attesting that "the suggestion that Pfizer attempted to mislead the medical community about the effectiveness of gabapentin [Neurontin] for certain off-label conditions is untrue. The review recently published in the New England Journal of Medicine, regarding the reporting of industry-sponsored trials for gabapentin for off-label use, was derived from a report created for litigation and co-authored by [a] plaintiffs' expert witness, who was hired to produce opinions to support plaintiffs' arguments. We believe the review suffers from significant bias, insufficient data, poor methodology, and cannot pass the threshold of credible scientific research."