Article Text
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.
- clinical trial registries
- selective reporting
- reporting bias
- randomised trials
- network meta-analysis
- Adverse events
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Footnotes
EKW and CCL contributed equally.
Contributors EKCW, CCL, SES and ACT conceived the study and wrote the manuscript. EKCW, CCL, MJP, JW, AV, SES and ACT revised the manuscript. EKCW, CCL, JW and AV performed data analysis. JW re-analysed the NMA. All authors read and approved the final manuscript.
Funding ACT is funded by a Tier 2 Canada Research Chair in Knowledge Synthesis (No. 17-0126-AWA) and an Ontario Ministry of Research, Innovation, and Science Early Researcher Award (No. 15-0553-AWA); EW is funded through the University of Toronto Department of Medicine Clinician Scientist Training Program and a CIHR Vanier Canada Graduate Scholarship; JW is funded through the University of Toronto Department of Medicine Clinician Scientist Training Program and a CIHR Doctoral Research Award; AAV is funded from the European Union’s Horizon 2020 (No. 754936); MJP is supported by an Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship (1088535) and SES is funded by a Tier 1 Canada Research Chair in Knowledge Translation (No. 17-0245-SUB).
Competing interests CCL is employed at the Canadian Agency for Drugs and Technologies in Health.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request.