Abstract
OBJECTIVE: To determine (i) the difference in the frequency of serious adverse events (SAEs) reported in trial registrations and their respective primary publications and (ii) the effect of adding SAE data from registries to a network meta-analysis (NMA) in changing the surface under the cumulative ranking (SUCRA) curve values of interventions. DESIGN: Secondary analysis of primary publications from two NMAs. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomised trials published in English after 2005 that were included in two NMAs of pharmacological interventions for Alzheimer's disease and chronic obstructive pulmonary disease. DATA EXTRACTION: Two reviewers independently searched multiple international trial registries for registration status and abstracted data from the included study publications and ClinicalTrials.gov. RESULTS: Of the 203 randomised trials included, 140 (69.0%) were registered with a trial registry and 72 (35.5%) posted results in the registry. The proportion of registered trials increased over time (38.5% in 2005 vs 78.6% in 2014). Of the publications with results posted in a trial registry, 14 (19.4%) had inconsistent reporting of overall SAEs; 7 (10.4%) studies did not report SAEs in the publication but did in the registry. In the 134 randomised trials with a prespecified primary outcome in the registry, 19 studies (9.4%) had a change in the primary outcome in the publication. Adding SAEs reported in registries to the NMAs did not affect the ranking of interventions. CONCLUSION: We identified inconsistent reporting of SAEs in randomised trials that were included in two NMAs. Findings highlight the importance of including trial registries in the grey literature search and verifying safety data before incorporating it into NMAs. STUDY REGISTRATION: osf.io/mk6dr.