Extremely large outlier treatment effects may be a footprint of bias in trials from less developed countries: randomized trials of gabapentinoids.

OBJECTIVES

Court documents have proven that a manufacturer-orchestrated strategy tried to promote gabapentin by distorting evidence in randomized trials. Given this background, we aimed to assess whether implausibly large treatment effects for gabapentin and for a similar gabapentinoid, pregabalin may have been published.

STUDY DESIGN AND SETTING

We identified meta-analyses on gabapentin or pregabalin on any outcome from Google Scholar, PubMed, and EMBASE. We explored excess of significance in meta-analyses and whether outlier studies with extreme results (differing >0.8 standard deviations from the summary effect of the meta-analysis) were scrutinized.

RESULTS

All 10 evaluated meta-analyses showed statistically significant favorable findings. Heterogeneity I estimates exceeding 90% were noted in four meta-analyses of postoperative pain. In these four meta-analyses, 77 studies had estimates differing >0.8 standard deviations from the summary estimate. Thirty-nine of 77 represented extremely favorable results, and 33 of them came from less developed countries with no tradition of clinical research, 22 reported no information on funding, and 20 reported no conflicts of interest. Conversely, 27 of 38 studies with unfavorable results came from more developed countries.

CONCLUSION

Extremely favorable outlier studies in the meta-analyzed literature of gabapentin and pregabalin may be a footprint of bias in studies done in less developed countries.