Serious Adverse Events of Special Interest Following mRNA COVID-19 Vaccination in Randomized Trials in Adults
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Using the prespecified list of adverse events of special interest (AESI) identified by the Brighton Collaboration, this secondary analysis of phase III randomized trials of mRNA COVID-19 vaccines (Pfizer and Moderna) evaluated serious AESI associated with these vaccines. Compared with placebo, the mRNA vaccines had a combined excess risk of serious AESI of 12.5 per 10,000 individuals vaccinated and a 16% higher risk of serious adverse events.
- These findings from mRNA COVID-19 vaccine trials emphasize the need for validated harm–benefit analysis by demographics, vaccine type, and according to the risk of serious COVID-19 outcomes.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersINTRODUCTION
In 2020, prior to COVID-19 vaccine rollout, the Brighton Collaboration created a priority list, endorsed by the World Health Organization, of potential adverse events relevant to COVID-19 vaccines. We adapted the Brighton Collaboration list to evaluate serious adverse events of special interest observed in mRNA COVID-19 vaccine trials.
METHODS
Secondary analysis of serious adverse events reported in the placebo-controlled, phase III randomized clinical trials of Pfizer and Moderna mRNA COVID-19 vaccines in adults (NCT04368728 and NCT04470427), focusing analysis on Brighton Collaboration adverse events of special interest.
RESULTS
Pfizer and Moderna mRNA COVID-19 vaccines were associated with an excess risk of serious adverse events of special interest 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 excess risk of serious adverse events of special interest of 12.5 per 10,000 vaccinated (95 % CI 2.1 to 22.9); risk ratio 1.43 (95 % CI 1.07 to 1.92). The Pfizer trial exhibited a 36 % higher risk of serious adverse events in the vaccine group; risk difference 18.0 per 10,000 vaccinated (95 % CI 1.2 to 34.9); risk ratio 1.36 (95 % CI 1.02 to 1.83). The Moderna trial exhibited a 6 % higher risk of serious adverse events in the vaccine group: risk difference 7.1 per 10,000 (95 % CI -23.2 to 37.4); risk ratio 1.06 (95 % CI 0.84 to 1.33). Combined, there was a 16 % higher risk of serious adverse events in mRNA vaccine recipients: risk difference 13.2 (95 % CI -3.2 to 29.6); risk ratio 1.16 (95 % CI 0.97 to 1.39).
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. These analyses will require public release of participant level datasets.
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Additional Info
Disclosure statements are available on the authors' profiles:
Serious adverse events of special interest following mRNA COVID-19 vaccination in randomized trials in adults
Vaccine 2022 Sep 22;40(40)5798-5805, J Fraiman, J Erviti, M Jones, S Greenland, P Whelan, RM Kaplan, P DoshiFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Concern regarding mRNA COVID-19 vaccines has again been stoked by a recent paper comparing purported vaccine harms with potential benefits.1 In a dense secondary analysis of industry data submitted to the FDA for emergency use authorization, the authors argue that the risk for serious adverse events existed for vaccine recipients at a rate of about 1 serious adverse event per 800 vaccinees. Caution is recommended, however, in interpreting this paper due to many confidence intervals crossing the null, the need to combine the two vaccines to achieve significance, and the use of counts of adverse events as opposed to participants with adverse events. That said, we should be looking at current vaccine safety issues and trends as they occur in unfiltered general populations, as opposed to re-interpreting old, and incomplete, data while making clinical decisions.
Across more than 600 million COVID-19 vaccine doses provided in the United States — the vast majority being mRNA vaccines — we have witnessed high levels of safety, ongoing and proactive safety monitoring, especially through the Vaccine Safety Datalink,2 and the subsequent detection and reporting of significant safety issues as they have emerged3:
Accordingly, I am more optimistic than the authors in our ability to detect rare events with observational methods. I do strongly support their contention that full transparency of COVID-19 clinical trial data is needed — in near real-time — to assess vaccine safety properly and independently during the early phases of vaccination programs.
References