Serious Adverse Events of Special Interest Following mRNA Vaccination in Randomized Trials
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 randomized trials of mRNA COVID-19 vaccines.
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 (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 hospitalization or death.
Funding Information: This study had no funding support.
BMJ Senior Editor: COVID vaccines more likely to put you in hospital than keep you out
New study shows over 8 per 10,000 net increase in hospitalization following vaccination.
A new paper authored by British Medical Journal Senior Editor Dr. Peter Doshi and colleagues has reached the conclusion that being injected with a COVID vaccine (either Pfizer or Moderna) is more likely to put you in hospital than keep you out of it.
The paper (which has yet to undergo peer review) analyzes "serious adverse events" (SAEs) which were highlighted on a "priority list" compiled by the World Health Organization (WHO) as linked to COVID vaccination - death, a life-threatening event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability, congenital anomaly/birth defect, and a medically important event.
The study found that Pfizer's vaccine was associated with an increased risk of SAEs of 10.1 events per 10,000. The corresponding figure for Moderna's vaccine was 15.1 events per 10,000.
Risk reduction for COVID-19 hospitalization following vaccination with a Pfizer vaccine was 2.3 per 10,000 participants and 6.4 per 10,000 for Moderna's vaccine. Therefore, the Pfizer vaccine resulted in a net increase of serious adverse events of 7.8 per 10,000 people vaccinated, very similar to the figure for Moderna's vaccine, which was 8.7 per 10,000 people.
The study's authors also noted the failure of the FDA to adequately follow up on thousands of participants in the clinical studies for the two products, "of which the large majority had only received one dose" with no reason provided. The FDA allegedly also obfuscated the trial results by counting "people affected" rather than "adverse events," even though there were twice as many people in the vaccine cohorts than in the placebo cohorts who experienced "multiple" serious adverse events.
The authors concluded that:
"A systematic review and meta-analysis using individual participant data should be undertaken to address questions of harm-benefit in various demographic subgroups. Full transparency of the COVID-19 vaccine clinical trial data is needed to properly evaluate these questions. Unfortunately, well over a year after widespread use of COVID-19 vaccines, participant level data remain inaccessible."