A Reanalysis of the FDA's Benefit--Risk Assessment of Moderna's mRNA-1273 COVID Vaccine Based on a Model Incorporating Benefits Derived from Prior COVID Infection

TL;DR

This study reanalyzes the FDA's benefit-risk assessment of Moderna's COVID vaccine for young males by incorporating prior infection, detailed age stratification, and more accurate infection and adverse event rates, finding risks may outweigh benefits under certain conditions.

Contribution

It extends the FDA's model by including prior COVID infection, refined age-specific hospitalization data, and more realistic infection and adverse event rates, providing a more nuanced benefit-risk analysis.

Findings

Vaccine risks may outweigh benefits for 18-25-year-old males under typical infection scenarios.

Incorporating prior infection reduces the estimated benefits of vaccination.

The model's results are validated by subsequent data, supporting its conclusions.

Abstract

The United States Food and Drug Administration (FDA) conducted a benefit-risk assessment for Moderna's COVID vaccine mRNA-1273 prior to its full approval, announced 1/31/2022. The FDA's assessment focused on males of ages 18-64 years because the agency's risk analysis was limited to vaccine-attributable myocarditis/pericarditis (VAM/P) given the excess risk among males. The FDA's analysis concluded that vaccine benefits clearly outweighed risks, even for 18-25-year-old males (those at highest VAM/P risk). We reanalyze the FDA's benefit-risk assessment using information available through the third week of January 2022 and focusing on 18-25-year-old males. We use the FDA's framework but extend its model by accounting for protection derived from prior COVID infection, finer age-stratification in COVID-hospitalization rates, and incidental hospitalizations (those of patients who test positive for COVID but are being treated for something else). We also use more realistic projections of Omicron-infection rates and more accurate rates of VAM/P. With hospitalizations as the principal endpoint of the analysis (those prevented by vaccination vs. those caused by VAM/P), our model finds vaccine risks outweighed benefits for 18-25-year-old males, except in scenarios projecting implausibly high Omicron-infection prevalence. Our assessment suggests that mRNA-1273 vaccination of 18-25-year-old males generated between 8% and 52% more hospitalizations from vaccine-attributable myocarditis/pericarditis alone compared to COVID hospitalizations prevented (over a five-month period of vaccine protection assumed by the FDA). The preceding assessment derives from model inputs based on data available at the time of the FDA's mRNA-1273 assessment. Moreover, these inputs as well as model outputs are validated by subsequently available data.