Harms were detected but not reported in six clinical trials of gabapentin.

OBJECTIVES: We sought to assess and report harms that were observed but not disclosed previously in clinical trials of gabapentin. STUDY DESIGN AND SETTING: We reanalyzed individual participant data from six randomized parallel trials of gabapentin for neuropathic pain, and we conducted meta-analyses. Between 1996 and 2003, adult participants were assigned to gabapentin (600 mg-3,600 mg per day) or placebo for 7-14 weeks. We calculated the proportion of participants with: one or more adverse events (AEs), one or more serious AEs, discontinued, discontinued because AEs. We also estimated effects on AEs at three levels of aggregation using COSTART, a hierarchical system for classifying AEs: body system, midlevel system, preferred term. RESULTS: We found evidence of important harms that were neither included in published trial reports nor included in systematic reviews. Aggregating related harms led to greater confidence that gabapentin might harm the nervous system and possibly the digestive, metabolic and nutritional, respiratory, sensory, and urogenital body systems. Nervous system harms were more common than previous reports suggest. CONCLUSION: Clinical trials identified harms that were not reported publicly, and journal articles overstated uncertainty about harms. Relying on journal articles to evaluate gabapentin's harms could contribute to incomplete and misleading conclusions in systematic reviews and guidelines. To prevent bias arising from the selective nonreporting of results, journal articles should describe how to access data for all harms observed in clinical trials (e.g., by sharing individual participant data).

Duke Scholars

Author Hwanhee Hong Biostatistics & Bioinformatics, Division of Biostatistics