Background: The FDA published “Benefit-Risk Assessment for New Drug and Biological Products, Guidance for Industry” in 2022. The draft guidance describes the FDA Benefit-Risk (BR) Framework for identifying, assessing, and communicating the key factors that affect the agency’s regulatory decisions.
Objectives: The objective of this presentation is to describe the FDA BR Framework and how the BR assessment conducted following this framework has been used to support the agency’s decision on the authorization/approval of a COVID-19 vaccine.
Methods: We present the FDA’s BR assessment of Moderna’s mRNA vaccine (MRNA-1273 or Spikevax) for males 18-64 years of age following dimensions of the BR Framework: Analysis of Condition, Current Treatment Options, Benefit, Risk and Risk Management and BR trade-off. We developed a computational model to predict the key benefits, preventable COVID-19 cases, hospitalizations, intensive care unit visits (ICUs), and deaths, in parallel with the key risks, vaccine-related excess myocarditis/pericarditis cases, hospitalizations, and deaths among male 18-64 years of age vaccinated with the primary series of MRNA-1273. The FDA used real-world evidence to inform many of the model inputs and the BR assessment. A sensitivity analysis was conducted for scenarios representing uncertainty associated with the pandemic, vaccine efficacy, and safety.
Results: For the most likely scenario, we used the US COVID-19 incidence in the week of December 25, 2021, and assumed a vaccine efficacy of 30% against cases and 72% against hospitalization. The vaccine-attributable myocarditis/pericarditis rates were estimated using data from FDA’s CBER Biologics Effectiveness and Safety System. As a part of the results, the model predicted vaccinating one million 18–25-year-old males (the high-risk group) would prevent 82,484 COVID-19 cases, 4,766 hospitalizations, 1,144 ICU admissions, and 51 deaths, compared to 128 vaccine-attributable myocarditis/pericarditis cases and 110 related hospitalizations. The model predicted zero ICU admissions and deaths due to vaccine-attributable myocarditis/pericarditis cases.
Conclusions: The FDA’s BR assessment demonstrates that the benefits of MRNA-1273 for 18-64 years-old male individuals clearly outweigh its risks. Even though this BR assessment has limitations due to model assumptions and data uncertainty, it demonstrates the utility of the FDA BR framework in FDA decision-making and the quantitative approach as a tool to support the BR framework for complex regulatory challenges.
