(BSPOT06) Racial diversity and multimodal safety assessments: limitations of spontaneous reports data and the importance of advancing race-based risk stratification capabilities in real world data

Background: Spontaneous reports data are routinely used for drug and vaccine safety surveillance and have known limitations, including incomplete or missing important patient characteristics, such as race. Surveillance strategies that rely primarily on spontaneous reports data are therefore not well-suited for certain types of safety outcomes of interest, such as risks that are specific to certain race groups, particularly in racially diverse countries, where country of the report may not serve as a useful proxy for race.

Objectives: To evaluate the ability to identify a drug-outcome association that is known to differ by race (i.e., angiotensin-converting enzyme (ACE) inhibitors and a higher risk of angioedema among patients who self-identified as Black race compared to other race groups) using a multimodal surveillance approach.

Methods: Among adults > 18 years of age, associations between angioedema and ACE inhibitors were assessed using the Food and Drug Administration’s Adverse Event Reporting System (FAERS), a spontaneous reports database, and separately in the TriNetX Global database derived from de-identified electronic health records (EHR) of a federated network with natural language processing (NLP). Disproportionality analyses with Multi-item Gamma-Poisson Shrinker (MGPS) model were used to evaluate overall associations in FAERS. In TriNetX using a 1-14 day surveillance window post index date, differences by race were assessed with risk ratio (RR) estimates with 95% confidence intervals (CIs). Significant associations overall, and where applicable, significant differences by race, were based on the following criteria: for MGPS, if the lower limit of the 90%CI is higher than 2; for race RRs, the lower bound of the 95%CI is greater than 1.

Results: In real world data (RWD), our findings confirm a known racial difference in the incidence of angioedema among ACE inhibitor-treated patients, where Black patients were found to have a higher risk compared to other race groups (Black versus White: RR=3.8, 95%CI(3.4-4.3); Black versus Asian (RR=5.8, 95%CI(3.7-9.0)). Although race is not available as a structured data element in FAERS, overall, there was a significant association between angioedema and ACE-inhibitors (MGPS=8.2, 90%CI(8.1-8.3)).

Conclusions: These analyses demonstrate the importance of developing a capacity to enable rapid examination of safety outcomes by race using a multimodal surveillance approach. RWD that includes race information, such as de-identified EHR in TriNetX’s Global Network database, with a dashboard that supports rapid data query analyses and default risk estimation by race, may provide insights into risk subgroups for drug- or vaccine-outcome pairs.