ABSTRACT
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.
ABSTRACT
It is important to assess the extent to which the real-world effectiveness of marketed vaccines is consistent with that observed in the clinical trials, and to characterize how well vaccines prevent COVID-19 symptoms. We conducted a modified test-negative design (TND) to evaluate the RW effectiveness of three COVID-19 vaccines by leveraging data from an on-going, US community-based registry. Vaccine effectiveness was examined in two ways: considering cases who (1) tested positive for COVID-19 (695 cases, 1,786 controls) and who (2) tested positive with at least one moderate/severe COVID-19 symptom (165 cases, 2,316 controls). Any vaccination (full or partial) was associated with a 95% reduction in the odds of having a positive COVID-19 test [adjusted odds ratio (aOR) = 0.05 (95% confidence interval (CI): 0.04, 0.06)]. Full vaccination was associated with an aOR of 0.03 (95% CI: 0.03, 0.05) while partial vaccination had an aOR of 0.08 (95% CI: 0.06, 0.12). Any vaccination was associated with a 71% reduction in the odds of testing positive and having at least one moderate/severe symptom (aOR=0.29 (95% CI: 0.20, 0.40)). High effectiveness was observed across all three vaccine manufacturers both for prevention of positive COVID-19 test results and prevention of moderate/severe COVID-19 symptoms. Clinicaltrials.gov NCT04368065
