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

Abstract

Importance: Active monitoring of health outcomes following COVID-19 vaccination offers early detection of rare outcomes that may not be identified in pre-licensure trials. Objective: To conduct near-real time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the U.S. pediatric population aged 5-17 years. Design: We 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. Setting: This is a population-based study in three large commercial claims databases conducted under the U.S. FDA public health surveillance mandate. Participants: The 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. Exposure: Exposure 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. Results: Among 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 Relevance: Consistent 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.  

Competing Interest Statement

Annemarie Kline and Cheryl McMahill-Walraven worked on grants, subcontracts, or contracts from Harvard Pilgrim Health Care Institute, Brown University (National Institute on Aging/ IMPACT Collaboratory), Reagan Udall Foundation for the FDA, Academy of Managed Care pharmacy's Biologics and Biosimilar Collective Intelligence Consortium (BBCIC), TherapeuticsMD, Reachnet (Louisiana Public Health Institute), IQVIA, Pfizer, Healthcore, and Patient Centered Outcomes Research Institute as employees of CVS Health and report stock or stock options from CVS Health; Danielle Cooper worked on grants, subcontracts, or contracts from Harvard Pilgrim Health Care Institute, Brown University (National Institute on Aging/ IMPACT Collaboratory), Reagan Udall Foundation for the FDA, Academy of Managed Care pharmacy's Biologics and Biosimilar Collective Intelligence Consortium (BBCIC), TherapeuticsMD, Reachnet (Louisiana Public Health Institute), IQVIA, Pfizer, Healthcore, and Westat as an employee of CVS Health and reports stock or stock option from CVS Health; Charlalynn Harris received grants or contracts from Harvard Pilgrim Health Care Institute, Reagan Udall Foundation for the FDA, and Academy of Managed Care pharmacy's Biologics and Biosimilar Collective Intelligence Consortium (BBCIC) as an employee of CVS Health and reports stock or stock options in CVS Health; Robin Clifford and John Seeger report stock or stock options in UnitedHealth Group; Daniel Beachler is an employee of HealthCore, Inc. who has previously contracted with Pfizer Inc. for separate projects. No other authors report relevant disclosures.

Funding Statement

The US Food and Drug Administration provided funding for this study and contributed as follows: led the design of the study, interpretation of the results, writing of the manuscript, decision to submit, and made contributions to the coordination of data collection and analysis of the data.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

We conducted this study within the Biologics Effectiveness and Safety (BEST) Initiative. FDA Amendments Act of 2007 required that FDA develop a national electronic system for monitoring safety of FDA-regulated medical products. FDA built the Sentinel Initiative in response to the congressional requirement, and the BEST Initiative commenced as a Center for Biologics Evaluation and Research (CBER) component of Sentinel. The Office of Human Research Protection (OHRP) determined that the regulations OHRP administers (45 CFR part 46) do not apply to the activities that are included in the FDA's Sentinel Initiative.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

The study protocol was publicly posted as referenced in the manuscript before data analyses and related documents can be made available where needed, by contacting the corresponding author. De-identified participant data will not be shared without approval from the data partners.

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