PMID- 37871835 OWN - NLM STAT- MEDLINE DCOM- 20240108 LR - 20240108 IS - 1878-5921 (Electronic) IS - 0895-4356 (Linking) VI - 164 DP - 2023 Dec TI - Harms were detected but not reported in six clinical trials of gabapentin. PG - 76-87 LID - S0895-4356(23)00274-3 [pii] LID - 10.1016/j.jclinepi.2023.10.014 [doi] AB - 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). CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Mayo-Wilson, Evan AU - Mayo-Wilson E AD - Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC, USA; Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA. Electronic address: evan.mayo-wilson@unc.edu. FAU - Qureshi, Riaz AU - Qureshi R AD - Department of Ophthalmology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. FAU - Hong, Hwanhee AU - Hong H AD - Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA. FAU - Chen, Xiwei AU - Chen X AD - Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA. FAU - Li, Tianjing AU - Li T AD - Department of Ophthalmology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20231021 PL - United States TA - J Clin Epidemiol JT - Journal of clinical epidemiology JID - 8801383 RN - 6CW7F3G59X (Gabapentin) SB - IM MH - Adult MH - Humans MH - Gabapentin/adverse effects MH - *Neuralgia/drug therapy MH - Randomized Controlled Trials as Topic OTO - NOTNLM OT - Adverse events OT - Clinical trials OT - Gabapentinoids OT - Harms OT - Meta-analysis OT - Neuropathic pain OT - Systematic reviews COIS- Declaration of competing interest Evan Mayo-Wilson and Tianjing Li previously received support for research about gabapentin from the Patient Centered Outcomes Research Institute (PCORI). All other authors declare they have no competing interests. EDAT- 2023/10/24 00:41 MHDA- 2023/12/17 09:43 CRDT- 2023/10/23 19:30 PHST- 2023/08/18 00:00 [received] PHST- 2023/10/11 00:00 [revised] PHST- 2023/10/19 00:00 [accepted] PHST- 2023/12/17 09:43 [medline] PHST- 2023/10/24 00:41 [pubmed] PHST- 2023/10/23 19:30 [entrez] AID - S0895-4356(23)00274-3 [pii] AID - 10.1016/j.jclinepi.2023.10.014 [doi] PST - ppublish SO - J Clin Epidemiol. 2023 Dec;164:76-87. doi: 10.1016/j.jclinepi.2023.10.014. Epub 2023 Oct 21.