(257) Background Rates of Adverse Events of Special Interest for COVID-19 Vaccine Safety Monitoring Among Adults in the United States

Publication Number: 1302

Background: The U.S. Food and Drug Administration Biologics Effectiveness and Safety (BEST) Initiative conducts active surveillance of adverse events of special interest (AESI) after COVID-19 vaccination. Background rates of AESI from historical cohorts are used as comparators to evaluate safety signals.

Objectives: To estimate the incidence rate (IR) of 17 AESI as historical comparators and 3 negative controls.

Methods: We used five administrative claims databases during the study period, January 1, 2019–December 11, 2020: Medicare claims for adults aged ≥65 years and commercial claims (Blue Health Intelligence® [BHI®], HealthCore Integrated Research Database, IBM® MarketScan® Commercial Database, and Optum pre-adjudicated claims) for adults aged 18–64 years. We estimated the IR of 17 AESI and 3 negative control events, overall and by sex, age, race/ethnicity (Medicare), and nursing home residency status (Medicare) in 2019. We also estimated monthly IRs in 2020 to assess the pandemic’s impact on observed rates. IR was defined as the number of incident events among eligible individuals divided by their accumulated person-time during a specific period.

Results: The study population included over 70 million enrollees annually. In 2019, rates of most AESI and all negative control events increased with age. Compared with those aged 18–64 years, Medicare enrollees had lower IRs per 100,000 person-years for anaphylaxis (11 vs 14–19), appendicitis (80 vs 119–155), narcolepsy (38 vs 44–53), and well-care visits (47,877 vs 53,470–69,730). Rates were higher in males than females for most AESI across databases; in Medicare, rates varied by race/ethnicity and nursing home residency status. We observed seasonal patterns for acute myocardial infarction (Medicare) and anaphylaxis (all databases). Although IRs of most AESI across databases were lower in March–May 2020 compared with the same months in 2019, many rates returned to near pre-pandemic levels after May 2020. However, rates of Guillain-Barré syndrome, Bell’s palsy, narcolepsy, hemorrhagic and non-hemorrhagic stroke, and transverse myelitis remained lower in several databases. In contrast, anaphylaxis, disseminated intravascular coagulation, myocarditis/pericarditis, pulmonary embolism, and common and unusual-site thrombosis with thrombocytopenia exhibited higher rates than pre-pandemic levels in some databases after May 2020.

Conclusions: AESI background rates varied by database and demographics and fluctuated during the peri-COVID-19 period. It is critical to select a comparable period and standardize demographics for background rates from the same database when comparing them with post-vaccination AESI rates to evaluate safety signals.