A Design and Analytic Strategy for Monitoring Disease Positivity and Biomarker Levels in Accessible Closed Populations

Abstract

We advocate and expand upon a previously described monitoring strategy for efficient and robust estimation of disease prevalence and case numbers within closed and enumerated populations such as schools, workplaces, or retirement communities. The proposed design relies largely on voluntary testing, notoriously biased (e.g., in the case of COVID-19) due to non-representative sampling. The approach yields unbiased and comparatively precise estimates with no assumptions about factors underlying selection of individuals for voluntary testing, building on the strength of what can be a small random sampling component. This component enables the use of a recently proposed “anchor stream” estimator, a well-calibrated alternative to classical capture-recapture (CRC) estimators based on two data streams. We show that this estimator is equivalent to a direct standardization based on “capture”, i.e., selection (or not) by the voluntary testing program, made possible by means of a key parameter identified by design. This equivalency simultaneously allows for novel two-stream CRC-like estimation of general means (e.g., of continuous variables like antibody levels or biomarkers). For inference, we propose adaptations of Bayesian credible intervals when estimating case counts and bootstrapping when estimating means of continuous variables. We use simulations to demonstrate significant precision benefits relative to random sampling alone.