Incomplete reporting of adverse events in duloxetine trials: a meta-research survey of randomized controlled trials vs placebo.

BACKGROUND AND

OBJECTIVES

Relying on published data alone might be insufficient for meta-analyses to be reliable and trustworthy since selective outcome reporting is common, especially for adverse events (AEs). We investigated the existence of selective reporting and its potential for bias in a case study exploring AEs of duloxetine in adults.

STUDY DESIGN AND

SETTING

We systematically searched all previous meta-analyses/pooled analyses on duloxetine published on PubMed for seven indications approved by the American and European health authorities. We included all randomized controlled trials (RCTs) vs placebo. For each RCT, we extracted the number of serious adverse events (SAEs), AEs, drop-outs (DOs) and drop-outs for safety reasons (DOSRs) using four information sources: published articles, clinical study registries, clinical study reports and data available in meta-analyses/pooled analyses. To assess the range of differences resulting from these four extraction strategies, we performed 4 meta-analyses using random effect models as well as a complete meta-analysis combining all sources.

RESULTS

A total of 70 RCTs (including 24,330 patients) were included. Of those, SAEs were identified for 42 studies (61%) in published articles, 58 (84%) in study reports (8 study reports were not retrieved), 24 (34.7%) in registries, and 21 (30.4%) in meta-analyses/pooled analyses. For 2 (2.9%), 2 (2.9%), 2 (2.9%) and 1 (1.4%) studies, we found respectively no data on SAEs, AEs, DOs, and DOSRs in any sources. Discrepant results across sources were found in 24 (34.5%), 20 (28.5%), 13 (18.6%), and 9 (12.8%) studies, respectively for SAEs, AEs, DOs, and DOSRs. Despite variations in point estimates and their 95% confidence intervals, we did not find different results in the conclusions of meta-analyses depending on the different information sources used, except for DOs, for which no effect was found using results published in registries, in contrast to other information sources.

CONCLUSION

None of the four information sources provided complete retrieval of safety results for duloxetine in adults across various indications. However, we did not find strong evidence that this underreporting leads to different conclusions in meta-analyses. Nonetheless, this finding remains uncertain, as we were unable to obtain complete information for all studies despite extensive searches.