Comparison of Data on Serious Adverse Events and Mortality in ClinicalTrials.gov, Corresponding Journal Articles, and FDA Medical Reviews: Cross-Sectional Analysis
Inconsistencies in data on serious adverse events (SAEs) and mortality in ClinicalTrials.gov and corresponding journal articles pose a challenge to research transparency.
The objective of this study was to compare data on SAEs and mortality from clinical trials reported in ClinicalTrials.gov and corresponding journal articles with US Food and Drug Administration (FDA) medical reviews.
We conducted a cross-sectional study of a randomly selected sample of new molecular entities approved during the study period 1 January 2013 to 31 December 2015. We extracted data on SAEs and mortality from 15 pivotal trials from ClinicalTrials.gov and corresponding journal articles (the two index resources), and FDA medical reviews (reference standard). We estimated the magnitude of deviations in rates of SAEs and mortality between the index resources and the reference standard.
We found deviations in rates of SAEs (30% in ClinicalTrials.gov and 30% in corresponding journal articles) and mortality (72% in ClinicalTrials.gov and 53% in corresponding journal articles) when compared with the reference standard. The intra-class correlation coefficient between the three resources was 0.99 (95% confidence interval [CI] 0.98–0.99) for SAE rates and 0.99 (95% CI 0.97–0.99) for mortality rates.
There are differences in data on rates of SAEs and mortality in randomized clinical trials in both ClinicalTrials.gov and journal articles compared with FDA reviews. Further efforts should focus on decreasing existing discrepancies to enhance the transparency and reproducibility of data reporting in clinical trials.
Compliance with Ethical Standards
No sources of funding were used to assist in the preparation of this study.
Conflicts of interest
Richeek Pradhan and Sonal Singh have no conflicts of interest relevant to the content of this study.
This research was conducted using publicly available data and did not entail any primary data collection from patients. No Independent Review Board approval was sought.
- 1.WHO. Welcome to the WHO ICTRP. http://www.who.int/ictrp/en/. Accessed 10 Jul 2017.
- 2.ClinicalTrials.gov. https://clinicaltrials.gov/. Accessed 10 Jul 2017.
- 12.Center for Drug Evaluation and Research. New drugs at FDA: CDER’s new molecular entities and new therapeutic biological products. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/. Accessed 7 Dec 2017.
- 14.U.S. Food and Drug Administration. IND safety reporting. 21 CFR §312.32(a).Google Scholar
- 15.Drugs@FDA. FDA approved drug products. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed 10 Jul 2017.