Outcome reporting in industry-sponsored trials of gabapentin for off-label use

N Engl J Med. 2009 Nov 12;361(20):1963-71. doi: 10.1056/NEJMsa0906126.

Abstract

Background: There is good evidence of selective outcome reporting in published reports of randomized trials.

Methods: We examined reporting practices for trials of gabapentin funded by Pfizer and Warner-Lambert's subsidiary, Parke-Davis (hereafter referred to as Pfizer and Parke-Davis) for off-label indications (prophylaxis against migraine and treatment of bipolar disorders, neuropathic pain, and nociceptive pain), comparing internal company documents with published reports.

Results: We identified 20 clinical trials for which internal documents were available from Pfizer and Parke-Davis; of these trials, 12 were reported in publications. For 8 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 6 trials), failure to distinguish between primary and secondary outcomes (2 trials), relegation of primary outcomes to secondary outcomes (2 trials), and failure to report one or more protocol-defined primary outcomes (5 trials). Trials that presented findings that were not significant (P > or = 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 5 of 8 published trials for which statistically significant differences favoring gabapentin were reported. Of the 21 primary outcomes described in the protocols of the published trials, 6 were not reported at all and 4 were reported as secondary outcomes. Of 28 primary outcomes described in the published reports, 12 were newly introduced.

Conclusions: 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.

MeSH terms

  • Amines / therapeutic use*
  • Bipolar Disorder / drug therapy
  • Clinical Protocols
  • Cyclohexanecarboxylic Acids / therapeutic use*
  • Gabapentin
  • Humans
  • Migraine Disorders / drug therapy
  • Off-Label Use* / statistics & numerical data
  • Outcome Assessment, Health Care* / methods
  • Outcome Assessment, Health Care* / standards
  • Pain / drug therapy
  • Publication Bias*
  • Randomized Controlled Trials as Topic / standards
  • Treatment Outcome
  • gamma-Aminobutyric Acid / therapeutic use*

Substances

  • Amines
  • Cyclohexanecarboxylic Acids
  • gamma-Aminobutyric Acid
  • Gabapentin