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

Fuente: arXiv
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Autores principales: Bourdon, Paul S., Duriseti, Ram, Gromoll, H. Christian, Dalton, Dyana K., Bardosh, Kevin, Krug, Allison E.
Formato: Preprint
Publicado: 2024
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author Bourdon, Paul S.
Duriseti, Ram
Gromoll, H. Christian
Dalton, Dyana K.
Bardosh, Kevin
Krug, Allison E.
author_facet Bourdon, Paul S.
Duriseti, Ram
Gromoll, H. Christian
Dalton, Dyana K.
Bardosh, Kevin
Krug, Allison E.
contents 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.
format Preprint
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institution arXiv
publishDate 2024
record_format arxiv
spellingShingle 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
Bourdon, Paul S.
Duriseti, Ram
Gromoll, H. Christian
Dalton, Dyana K.
Bardosh, Kevin
Krug, Allison E.
Quantitative Methods
92-10, 92C50
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.
title 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
topic Quantitative Methods
92-10, 92C50
url https://arxiv.org/abs/2410.11811