Outcome Reporting in Industry-Sponsored Trials of Gabapentin for Off-label Use

SLR - April 2010 - Nicholas L. Hugentobler

Reference: 
Vedula, S.S., Bero, L., Scherer, R.W., Dickersin, K. (2009). Outcome reporting in industry-sponsored trials of Gabapentin for off-label use. The New England Journal of Medicine, 361, 20, 1963-1971.

Scientific Literature Reviews

Reviewed by:  Nicholas L. Hugentobler, DPM
Residency Program: Detroit Medical Center

Podiatric Relevance:
Gabapentin has been described for certain off-label uses. In considering the safety and well-being of the patient, one must continue to evaluate the validity of all information presented for the use of medication and treatment modalities. This analysis provides evidence of selective outcome reporting in published reports of randomized trials.

Methods:
This study examined reporting practices for trials of gabapentin funded by Pfizer and Warner-Lambert's subsidiary, Parke-Davis (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: 
Twenty clinical trials are identified 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>/= 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:
Selective outcome reporting is identified for trials of off-label use of gabapentin. This practice threatens the validity of evidence for the effectiveness of off-label interventions.