Surveillance of COVID-19 vaccine safety among elderly persons aged 65 years and older

BackgroundMonitoring safety outcomes following COVID-19 vaccination is critical for understanding vaccine safety especially when used in key populations such as elderly persons age 65 years and older who can benefit greatly from vaccination. We present new findings from a nationally representative early warning system that may expand the safety knowledge base to further public trust and inform decision making on vaccine safety by government agencies, healthcare providers, interested stakeholders, and the public. MethodsWe evaluated 14 outcomes of interest following COVID-19 vaccination using the US Centers for Medicare & Medicaid Services (CMS) data covering 30,712,101 elderly persons. The CMS data from December 11, 2020 through Jan 15, 2022 included 17,411,342 COVID-19 vaccinees who received a total of 34,639,937 doses. We conducted weekly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. FindingsFour outcomes met the threshold for a statistical signal following Pfizer-BioNTech vaccination including pulmonary embolism (PE; RR=1.54), acute myocardial infarction (AMI; RR=1.42), disseminated intravascular coagulation (DIC; RR=1.91), and immune thrombocytopenia (ITP; RR=1.44). After further evaluation, only the RR for PE still met the statistical threshold for a signal; however, the RRs for AMI, DIC, and ITP no longer did. No statistical signals were identified following vaccination with either the Moderna or Janssen vaccines. InterpretationThis early warning system is the first to identify temporal associations for PE, AMI, DIC, and ITP following Pfizer-BioNTech vaccination in the elderly. Because an early warning system does not prove that the vaccines cause these outcomes, more robust epidemiologic studies with adjustment for confounding factors, including age and nursing home residency, are underway to further evaluate these signals. FDA strongly believes the potential benefits of COVID-19 vaccination outweigh the potential risks of COVID-19 infection.

Results of safety monitoring of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in U.S. children aged 5-17 years

ImportanceActive monitoring of health outcomes following COVID-19 vaccination offers early detection of rare outcomes that may not be identified in pre-licensure trials. ObjectiveTo conduct near-real time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the U.S. pediatric population aged 5-17 years. DesignWe conducted rapid cycle analysis of 20 pre-specified health outcomes, 13 of which underwent sequential testing and 7 of which were monitored descriptively within a cohort of vaccinated individuals. We tested for increased risk of each health outcome following vaccination compared to a historical baseline, while adjusting for repeated looks at the data as well as claims processing delay. SettingThis is a population-based study in three large commercial claims databases conducted under the U.S. FDA public health surveillance mandate. ParticipantsThe study included over 3 million enrollees aged 5-17 years with BNT162b2 COVID-19 vaccination through mid-2022 in three commercial claims databases. We required continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window to the COVID-19 vaccination. ExposureExposure was defined as receipt of a BNT162b2 COVID-19 vaccine dose. The primary analysis assessed primary series doses together (Dose 1 + Dose 2), and dose-specific secondary analyses were conducted. Follow up time was censored for death, disenrollment, end of risk window, end of study period, or a subsequent vaccine dose. Main Outcome(s) and Measure(s)We monitored 20 pre-specified health outcomes. We performed descriptive monitoring for all outcomes and sequential testing for 13 outcomes. ResultsAmong 13 health outcomes evaluated by sequential testing, 12 did not meet the threshold for a statistical signal in any of the three databases. In our primary analysis, myocarditis/pericarditis signaled following primary series vaccination with BNT162b2 in ages 12-17 years across all three databases. Conclusions and RelevanceConsistent with published literature, our near-real time monitoring identified a signal for only myocarditis/pericarditis following BNT162b2 COVID-19 vaccination in children aged 12-17 years. This method is intended for early detection of safety signals. Our results are reassuring of the safety of the vaccine, and the potential benefits of vaccination outweigh the risks. Key PointsO_ST_ABSQuestionC_ST_ABSDid active monitoring detect potentially elevated risk of health outcomes following BNT162b2 COVID-19 vaccination in the U.S. pediatric population aged 5-17 years? FindingsTwelve of 13 health outcomes did not meet the safety signal threshold following BNT162b2 COVID-19 vaccination in three large commercial claims databases using near real-time monitoring. Myocarditis/pericarditis met the statistical threshold for a signal following primary series vaccination in ages 12-17 years. MeaningResults from near-real time monitoring of health outcomes following BNT162b2 COVID-19 vaccination provide additional reassuring evidence of vaccine safety in the pediatric population. The myocarditis/pericarditis signal is consistent with current evidence and is being further evaluated.