Reporting of clinical trial safety results in ClinicalTrials.gov for FDA-approved drugs: A cross-sectional analysis

• Published in: Clinical trials (London, England) Vol. 19; no. 4; pp. 442 - 451
• Main Authors: Chen, Krista Y, Borglund, Erin M, Postema, Emma Charlotte, Dunn, Adam G, Bourgeois, Florence T
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-08-2022; Sage Publications Ltd
• Subjects: Adverse events; Availability; Clinical trials; Completeness; Confidence intervals; Cross-sectional studies; Drugs; FDA approval; Medical research; Mortality; Pharmacovigilance; Rank tests; Regulatory agencies; Reviews; Risk; Safety; Clinical trials; trial registries; post-marketing surveillance; evidence synthesis; drug safety; adverse event reporting
• ISSN: 1740-7745; 1740-7753
• DOI: 10.1177/17407745221093567

Background
Adverse events identified during clinical trials can be important early indicators of drug safety, but complete and timely data on safety results have historically been difficult to access. The aim was to compare the availability, completeness, and concordance of safety results reported in ClinicalTrials.gov and peer-reviewed publications.
Methods
We analyzed clinical trials used in the Food and Drug Administration safety assessment of new drugs approved between 1 July 2018 and 30 June 2019. The key safety outcomes examined were all-cause mortality, serious adverse events, adverse events, and withdrawals due to adverse events. Availability of safety results was measured by the presence and timing of a record of trial-level results in ClinicalTrials.gov and a corresponding peer-reviewed publication. For the subset of trials with available results, completeness was defined as the reporting of safety results for all participants and compared between ClinicalTrials.gov and publications. To assess concordance, we compared the numeric results for safety outcomes reported in ClinicalTrials.gov and publications to results in Food and Drug Administration trial reports.
Results
Among 156 trials studying 52 drugs, 91 (58.3%) trials reported safety results in ClinicalTrials.gov and 106 (67.9%) in peer-reviewed publications (risk difference = −9.6%, 95% confidence interval = −20.3 to 1.0). All-cause mortality was reported sooner in published articles compared with ClinicalTrials.gov (log-rank test, p = 0.01). There was no difference in time to reporting for serious adverse events (p = 0.05), adverse events (p = 0.09), or withdrawals due to adverse events (p = 0.20). Complete reporting of all-cause mortality was similar in ClinicalTrials.gov and publications (74.7% vs 78.3%, respectively; risk difference = −3.6%, 95% confidence interval = −15.5 to 8.3) and higher in ClinicalTrials.gov for serious adverse events (100% vs 79.2%; risk difference = 20.8%, 95% confidence interval = 13.0 to 28.5) and adverse events (100% vs 86.8%; risk difference = 13.2%, 95% confidence interval = 6.8 to 19.7). Withdrawals due to adverse events were less often completely reported in ClinicalTrials.gov (62.6% vs 92.5%; risk difference = −29.8%, 95% confidence interval = −40.1 to −18.7). No difference was found in concordance of results between ClinicalTrials.gov and publications for all-cause mortality, serious adverse events, or withdrawals due to adverse events.
Conclusion
Safety results were available in ClinicalTrials.gov at a similar rate as in peer-reviewed publications, with more complete reporting of certain safety outcomes in ClinicalTrials.gov. Future efforts should consider adverse event reporting in ClinicalTrials.gov as an accessible data source for post-marketing surveillance and other evidence synthesis tasks.