Serious Adverse Events of Special Interest Following mRNA Vaccination in Randomised Trials

Updated: Jul 1

23 Jun 2022


Joseph Fraiman

Louisiana State University - Lallie Kemp Regional Medical Center

Juan Erviti

Navarre Health Service

Mark Jones

Bond University - Institute for Evidence-Based Healthcare

Sander Greenland

University of California, Los Angeles (UCLA) - Jonathan and Karin Fielding School of Public Health

Patrick Whelan

University of California at Los Angeles

Robert M. Kaplan

Stanford University

Peter Doshi

University of Maryland - School of Pharmacy



Abstract

Introduction: In 2020, prior to COVID-19 vaccine rollout, the Coalition for Epidemic Preparedness Innovations and Brighton Collaboration created a priority list, endorsed by the World Health Organization, of potential adverse events relevant to COVID-19 vaccines. We leveraged the Brighton Collaboration list to evaluate serious adverse events of special interest observed in phase III randomised trials of mRNA COVID-19 vaccines. Methods: Secondary analysis of serious adverse events reported in the placebo-controlled, phase III randomised clinical trials of Pfizer and Moderna mRNA COVID-19 vaccines (NCT04368728 and NCT04470427), focusing analysis on potential adverse events of special interest identified by the Brighton Collaboration. Results: Pfizer and Moderna mRNA COVID-19 vaccines were associated with an increased risk of serious adverse events of special interest, with an absolute risk increase of 10.1 and 15.1 per 10,000 vaccinated over placebo baselines of 17.6 and 42.2 (95% CI -0.4 to 20.6 and -3.6 to 33.8), respectively. Combined, the mRNA vaccines were associated with an absolute risk increase of serious adverse events of special interest of 12.5 per 10,000 (95% CI 2.1 to 22.9). The excess risk of serious adverse events of special interest surpassed the risk reduction for COVID-19 hospitalization relative to the placebo group in both Pfizer and Moderna trials (2.3 and 6.4 per 10,000 participants, respectively). Discussion: The excess risk of serious adverse events found in our study points to the need for formal harm-benefit analyses, particularly those that are stratified according to risk of serious COVID-19 outcomes such as hospitalisation or death.


Funding Information: This study had no funding support. Declaration of Interests: JF, JE, MJ, SG, PW, RK: none to declare. PD has received travel funds from the European Respiratory Society (2012) and Uppsala Monitoring Center (2018); grants from the FDA (through University of Maryland M-CERSI; 2020), Laura and John Arnold Foundation (2017-22), American Association of Colleges of Pharmacy (2015), Patient-Centered Outcomes Research Institute (2014-16), Cochrane Methods Innovations Fund (2016-18), and UK National Institute for Health Research (2011-14); was an unpaid IMEDS steering committee member at the Reagan-Udall Foundation for the FDA (2016-2020) and is an editor at The BMJ. The views expressed here are those of the authors and do not necessarily reflect those of their employers.


Results: Pfizer and Moderna mRNA COVID-19 vaccines were associated with an increased risk of serious adverse events of special interest, with an absolute risk increase of 10.1 and 15.1 per 10,000 vaccinated over placebo baselines of 17.6 and 42.2 (95% CI -0.4 to 20.6 and -3.6 to 33.8), respectively. Combined, the mRNA vaccines were associated with an absolute risk increase of serious adverse events of special interest of 12.5 per 10,000 (95% CI 2.1 to 22.9). The excess risk of serious adverse events of special interest surpassed the risk reduction for COVID-19 hospitalization relative to the placebo group in both Pfizer and Moderna trials (2.3 and 6.4 per 10,000 participants, respectively).

Keywords: SARS-CoV-2, COVID-19, Vaccines, COVID-19 vaccines, mRNA vaccines, Pfizer-BioNTech COVID-19 vaccine BNT162b2, Moderna COVID-19 vaccine mRNA-1273, NCT04368728, NCT04470427, serious adverse events, adverse events of special interest, Brighton Collaboration, Coalition for Epidemic Preparedness Innovations, Safety Platform for Emergency vACcines


Suggested Citation:

Fraiman, Joseph and Erviti, Juan and Jones, Mark and Greenland, Sander and Whelan, Patrick and Kaplan, Robert M. and Doshi, Peter, Serious Adverse Events of Special Interest Following mRNA Vaccination in Randomized Trials. Available at SSRN: https://ssrn.com/abstract=4125239


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