Measuring vaccine protection when the population is mostly vaccinated.

Objectives: This study aims to address limitations in assessing vaccine protection using the classical vaccine effectiveness (VE) measure, especially in contexts where a significant portion of the population is already vaccinated or infected.
Study Design and Setting: We propose using the adjusted number of cases (ANC) as a building block for deriving vaccine effectiveness measures. This approach accounts for biases arising from small and unrepresentative unvaccinated reference groups with incomplete data. We demonstrate the use of these measures for assessing the protection conferred by a booster dose against severe COVID-19 using data from Israel.
Results: The use of ANC and the derived measures reveals a more comprehensive understanding of the complex immunity landscape compared to traditional VE measures. This approach enables meaningful comparisons between different vaccination categories and provides insights to inform policy decisions.
Conclusion: In situations with widespread vaccination and prior infections, traditional VE measures can be limited in their informative value. Using the ANC offers a more robust and insightful assessment of vaccine effectiveness. A demonstration of the evaluation of booster dose protection against severe COVID-19 in Israel underscores the importance of adopting complementary measures to guide public health strategies.
Competing Interests: Declaration of competing interest None.
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