(P-362) Post-marketing Drug Safety Sources: An Evaluation of the Fda’s Drug Safety Communications

Background: The United States Food and Drug Administration (FDA) frequently issues Drug Safety Communications (DSCs) to alert healthcare professionals and consumers about the important safety information of marketed pharmaceutical products. Various sources of evidence are used to support regulatory decision-making.

Objectives: To review the type of evidence sources used in DSCs and to investigate their associations with different regulatory actions including label updates.

Methods: Study design: A cross-sectional study of all DSCs published on the FDA website between 2015 and 2020.
Study population: The DSCs characteristics, type of evaluated data sources, and the regulatory actions were collected from the FDA website.
Statistical analyses: Frequencies with percentages were used to summarize the DSCs characteristics, and the univariate logistic regression was performed to examine the association between the FDA actions and sources of evidence.

Results: Seventy-six DSCs were included in the final analysis, most of them were issued in 2015 (22 [29%]). Antidiabetic drugs, analgesics/opioids, and antipsychotics were the most reported therapeutic groups (11 [14.5%], 8 [11.5%], and 6 (7.9%), respectively). The top reported adverse events by system organ class were cardiac disorders 10 (13%). Label update was the most frequent regulatory action (53 [69.7%]), followed by additional investigations (13[17.1%]). The most updated label sections were the warnings/precautions (38[71.7%]), and the boxed warning (12 [22.6%]). Around 79%, 68%, and 34% of DSCs included evidence sources from observational studies, spontaneous reports, and clinical trials, respectively. However, a significant association was found between spontaneous case reports and label updates (OR=2.78, 95%CI 1.02-7.62, P=0.046). More than half of the DSCs (57%) based their actions on a single source of evidence (commonly from spontaneous reports [16 (37%)]). Moreover, we found a significant association between the number of cited evidence and the label update requests (OR=2.39, 95%CI 1.05-5.43, P=0.038).

Conclusions: The most common sources of evidence in FDA’s DSCs are observational studies and spontaneous reports. Future research is needed to evaluate the contribution of these types of evidence to regulatory actions.