Abstract
Introduction
New safety issues concerning US FDA-approved drugs are commonly communicated through safety-related labeling changes. Therefore, to optimize and refine postmarket safety surveillance strategies, it is important to comprehensively characterize the sources of data giving rise to safety-related labeling changes.
Objectives
Our objective was to characterize the sources of data triggering and supporting the identification of new safety risks of FDA-approved drugs communicated through safety-related labeling changes.
Methods
We conducted a retrospective study with a 10-year observation period using FDA’s internal electronic data repositories for all prescription new molecular entities (NME) approved in 2008. We collected and analyzed information on new safety issues, the section of the full prescribing information updated, initiators (FDA, drug manufacturer), and triggering and supporting sources of evidence.
Results
Among 22 NMEs approved in 2008, 189 new safety issues for 18 NMEs were identified. Compared to drug manufacturer, FDA initiated safety-related labeling changes in nine of the ten changes to the Boxed Warnings, 28 of the 52 changes to the Warnings and Precautions, and 43 of the 134 changes to the Adverse Reactions sections of the full prescribing information. The most frequent triggering sources of evidence included the drug manufacturer safety database (32.3%) and FDA Adverse Event Reporting System (FAERS) safety reports (15.3%) for all relevant sections of the full prescribing information, and class-labeling changes (17.5%) for Boxed Warnings and the Warnings and Precautions sections. The most frequent triggering source of evidence was FAERS safety reports (69%) in the first year after drug approval and the drug manufacturer safety database in subsequent years.
Conclusions
Our findings emphasize the continued importance of safety reports from FAERS and drug manufacturer safety databases and a comprehensive drug safety surveillance program throughout a drug’s lifecycle.
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source by full prescribing information section updated. FAERS FDA Adverse Event Reporting System, NOS not otherwise specified, PMC postmarketing commitment, PMR postmarketing requirement
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Acknowledgements
The authors thank Dr. Karen Long for her invaluable assistance with artwork.
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No sources of funding were used to conduct this study or prepare this manuscript.
Conflicts of Interest
David Croteau, Ellen Pinnow, Eileen Wu, Monica Muñoz, Ilynn Bulatao, and Gerald Dal Pan have no conflicts of interest that are directly relevant to the content of this article.
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In addition to the data found on the public FDA websites referred to in this article, the analytic data sets, redacted for drug manufacturer proprietary information, can be made available upon request to the corresponding author.
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The authors contributed sufficiently to the manuscript, with individual contributions as follows: concept and planning of the work described (DC, EP, EW, MM, IB, GDP); acquisition (EP), analysis (DC, EP, EW, MM, IB), and interpretation of the data (DC, EP, EW, MM, IB, GDP); drafting and/or critical revision of the manuscript (DC); and approval of the final submitted version of the manuscript (DC, EP, EW, MM, IB, GDP). Therefore, all authors share collective responsibility and accountability for the manuscript.
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Croteau, D., Pinnow, E., Wu, E. et al. Sources of Evidence Triggering and Supporting Safety-Related Labeling Changes: A 10-Year Longitudinal Assessment of 22 New Molecular Entities Approved in 2008 by the US Food and Drug Administration. Drug Saf 45, 169–180 (2022). https://doi.org/10.1007/s40264-021-01142-3
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DOI: https://doi.org/10.1007/s40264-021-01142-3