A Double Machine Learning Approach for the Evaluation of COVID-19 Vaccine Effectiveness Under the Test-Negative Design: Analysis of Québec Administrative Data

The test-negative design (TND), which is routinely used for monitoring seasonal flu vaccine effectiveness (VE), has recently become integral to COVID-19 vaccine surveillance, notably in Qu & eacute;bec, Canada. Some studies have addressed the identifiability and estimation of causal parameters under the TND, but efficiency bounds for nonparametric estimators of the target parameter under the unconfoundedness assumption have not yet been investigated. Motivated by the goal of improving adjustment for measured confounders when estimating COVID-19 VE among community-dwelling people aged >= 60$$ \ge 60 $$ years in Qu & eacute;bec, we propose a one-step doubly robust and locally efficient estimator called TNDDR (TND doubly robust), which utilizes cross-fitting (sample splitting) and can incorporate machine learning techniques to estimate the nuisance functions and thus improve control for measured confounders. We derive the efficient influence function (EIF) for the marginal expectation of the outcome under a vaccination intervention, explore the von Mises expansion, and establish the conditions for n$$ \sqrt{n} $$-consistency, asymptotic normality, and double robustness of TNDDR. The proposed estimator is supported by both theoretical and empirical justifications.