- Using a mathematical model, Massachusetts General Hospital explored the interplay between COVID-19 vaccine efficacy as determined through clinical testing and the optimal design and execution of vaccination programs
- The effects of any COVID-19 vaccine were highly dependent on the severity of the pandemic at the time and place a vaccine was deployed
- Across all severities of the pandemic, a 50% effective disease-modifying vaccine had more impact on mortality and hospitalizations than a 50% effective preventive vaccine
- Vaccination programs that conferred higher levels of protection, even for a smaller fraction of the target population, generally outperformed strategies that conferred lower protection on a broader population
- Pace and coverage were both necessary for large reductions in infections, and these parameters were complementary—high performance on one measure did not fully compensate for low performance on the other
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In June 2020, the FDA published guidance to pharmaceutical companies about forthcoming COVID-19 vaccines. In order to receive emergency use authorization, a vaccine would have to be at least 50% effective on either of two primary endpoints:
- Prevention of transmission: the vaccine's ability to prevent SARS-CoV-2 from spreading from an infected person to a susceptible person
- Disease modification: in people who become infected despite vaccination, the vaccine's ability to prevent progression to moderate or severe COVID-19
The 50% threshold is considerably lower than the efficacy standards for virtually all other widely used vaccines. But in the context of a pandemic with ruinous economic and public health consequences, would a vaccine with more modest effects be acceptable?
Rochelle Walensky, MD, MPH, former chief of the Division of Infectious Diseases at Massachusetts General Hospital, and colleagues demonstrated through mathematical modeling that the population-wide benefits of any COVID-19 vaccine will depend at least as much on how fast and broadly it's implemented and the severity of the epidemic as on the vaccine's efficacy in clinical trials. Their report appears in Health Affairs.
The model considered:
Three vaccine types:
- Composite of the two
Two implementation parameters:
- Pace: the percentage of the population that can be vaccinated on a given day (a measure of manufacturing capacity and logistical preparedness)
- Coverage: the percentage of the population ultimately vaccinated (a measure of public's acceptance)
Three background severities of the pandemic, expressed by the reproduction number (Rt):
- Base case: Rt = 1.8
- Best case: Rt = 1.5, representing strict adherence to risk mitigation strategies such as masking, physical distancing and limitations on large gatherings
- Worst case: Rt = 2.1, reflecting the higher risks associated with winter weather and greater indoor activity
Base Case Results
- Across all values of Rt, a 50% effective disease-modifying vaccine had more impact on mortality and hospitalizations than a 50% effective preventive vaccine
- The impact of the preventive and disease-modifying vaccines on the number of infections was similar at Rt = 2.1, but the disease-modifying vaccine had more impact at Rt = 1.8 or 1.5
- The 50% effective composite vaccine achieved the greatest reduction in infections for any combination of pace and coverage, but its impact was much less than the sum of the impacts of the other two vaccine types
Sensitivity to Vaccine Efficacy
Even 75% effective, vaccines had diminished benefits when they were introduced into a severe epidemic. For example, for all three vaccine types, a 75% effective vaccine implemented at Rt = 2.1 prevented a smaller number of infections and deaths than a 25% effective vaccine implemented at Rt = 1.5.
Vaccination programs that conferred higher levels of protection, even for a smaller fraction of the target population, generally outperformed strategies that conferred lower protection on a broader population. For example, a 75% effective vaccine administered to 50% of the population was superior to a 25% effective vaccine given to 90%.
Sensitivity to Implementation Effectiveness
Pace and coverage were both necessary for large reductions in infections. They were complimentary—high performance on one measure did not fully compensate for low performance on the other.
Deploying Vaccines Wisely
Even vaccines below the 50% efficacy threshold established in the FDA guidance could make valuable contributions to COVID-19 prevention and response. Still, the ultimate success of COVID-19 vaccination will depend on targeting greater financial resources to vaccine production and distribution, redoubling efforts to promote public confidence in COVID-19 vaccines and continuing adherence to other risk mitigation strategies.
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Learn more about research in the Department of Medicine at Mass General