Objectives/Goals: To evaluate the incremental value of post-approval adverse event reporting and population exposure in characterizing a drug’s safety profile, using PD-1 inhibitors as a model class to assess how continued clinical experience enhances safety knowledge. Methods/Study Population: Using PD-1 inhibitors as a model, we are exploring FDA Adverse Event Reporting System (FAERS) database to capture real-world post-marketing safety information on drugs in this class approved by FDA since 2014. Findings from FAERS will be compared with the safety profile in the initial package insert used for FDA approval for each of the drugs. The nature of novel adverse events will be characterized and compared with the extent of exposure as determined through the use of marketing databases (e.g., IQVIA, Cortellis). We seek to identify relationships between the observation of novel adverse events and levels of population exposure. We will explore whether the safety experience with older products in this drug class could be predictive of safety outcomes in newer class candidates. Results/Anticipated Results: The findings would aim to inform the development of a “Goldilocks” approach (the value of incremental exposures), to explore how post-marketing exposure impacts changes in the safety profile of drugs in this class. Results will be used to explore whether a particular level of post-approval exposure is predictive of the occurrence of novel adverse events, excluding idiosyncratic events, among PD-1 inhibitors. Discussion/Significance of Impact: The study will guide the understanding of the incremental value of additional population exposure to refining the safety profile within a class of well-defined drugs and may inform a systematic approach towards consistent class labeling.
Ganesan et al. (Wed,) studied this question.