In a recent article, Lewnard et al. ( ) presented a detailed examination of the test-negative design odds ratio. In the test-negative design, vaccine effectiveness is estimated as 1 minus the odds ratio. The authors considered 2 key vaccine protection models: “all-or-nothing,” where a proportion of the vaccinated population is fully protected and the remaining population is fully susceptible, and “leaky,” where the vaccine reduces the rate of infection in all vaccinated individuals. A central conclusion of the authors is that the test-negative design odds ratio is unable to recover an unbiased estimate of vaccine effectiveness under the leaky model.
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