CERSI Collaborators: University of California San Francisco: Atul Butte, MD PhD (PI); Kendra Radtke, PharmD, PhD; Rohit Vashisht, PhD; Christopher Williams, MD

FDA Collaborators: : Center for Biologics Evaluation & Research/Office of Biostatistics and Pharmacovigilance: Steven Anderson, PhD (FDA Lead); Yun Lu, PhD; Artur Belov, PhD; Barbee Whitaker, PhD; Richard Forshee, PhD

Project Start Date: August 2022

Regulatory Science Challenge

After nearly three years since the first clinical case of severe acute respiratory syndrome-corona virus (SARS-CoV-2) infection, much is still unknown about COVID-19 and the impact of vaccination on disease severity and outcomes in the pediatric population. Medical product development and subsequent regulatory approval for use in children have historically lagged behind adults. While the development of SARS-CoV-2 vaccines for protection against COVID-19 was rapid as compared to historical timelines, regulatory evaluation of pediatric safety and effectiveness took additional time: Emergency Use Authorization (EUA) by the US FDA was granted 6 months after adults in adolescents 12-15 years of age, 11 months after adults in children 5-11 years of age, and 17 months after adults in children 6 months to 5 years of age. As of October 2022, full FDA approval in the pediatric population has been granted to Comirnaty® by Pfizer-BioNTech in individuals 12 years of age and older. In addition, national COVID-19 vaccination rates in individuals under 18 years of age remain low. Analyses of real-world data (RWD) have the potential to generate supportive evidence of vaccine effectiveness and safety in the pediatric population with larger and more diverse populations than could be reasonably obtained with traditional randomized, controlled clinical trials. Additional gaps in knowledge include the impact of prior SARS-CoV-2 infection on clinical outcomes following vaccination and factors associated with vaccine utilization and clinical outcomes such as social determinants of health and patients with chronic health conditions. Assessing the effectiveness and safety of COVID-19 vaccines in a real-world pediatric population can support regulatory decision-making by the FDA. Studies using RWD may assist in addressing the disparity in evidence used to assess pediatric safety and effectiveness. Therefore, this work has a broader scope of informing the role of real-world data for efficient regulatory decision-making in the pediatric population.

Project Description and Goals

Researchers aim to generate real-world evidence (RWE) on the effectiveness and safety of COVID-19 vaccines in children and adolescents under 18 years with a systematic analysis of clinical data from electronic health records (EHR) and linkage to state-wide vaccine records. Researchers will use EHR data from the University of California (UC) Health system, which includes over 1 million richly diverse pediatric patients receiving care across five UC Health centers. These clinical data include SARS-CoV-2 test results, medication orders, vaccination histories, laboratory measurements, medical conditions, patient demographics, and social determinants of health measures. The goals are (1) to link individual patient records with the State of California Department of Public Health COVID-19 vaccine registry and characterize the pediatric population under 18 years of age according to COVID-19 vaccination status and, using these linked records, (2) determine the frequency of unfavorable clinical outcomes (hospitalization, death) and (3) determine the frequency of adverse events of special interest (AESI) among vaccinated and matched unvaccinated individuals in a given time frame. Researchers will consider prior SARS-CoV-2 infection, sex, age, and other characteristics. The results of this work will inform COVID-19 vaccine effectiveness and safety in a large, diverse pediatric population and contribute supporting evidence for regulatory decision-making.