Variable Selection for Infectious Disease Transmission via Penalized Pairwise Accelerated Failure Time Models

Abstract

In infectious disease transmission, regression and variable selection for time-to-event outcomes are complicated by transmission-induced dependence that violates standard independence assumptions. Pairwise survival analysis addresses this dependence by modeling contact intervals in ordered pairs, defined as the time from the onset of infectiousness in the pair's first individual to their first infectious contact with the second individual. We propose a penalized pairwise accelerated failure time model for contact intervals that accommodates simultaneous covariate effects on infectiousness and susceptibility while jointly representing within-population transmission and infection from external sources. For variable selection with many candidate covariates, we develop adaptive LASSO penalized maximum likelihood estimation with a coordinate descent algorithm, treating distributional baseline parameters as unpenalized nuisance parameters. We establish selection consistency and asymptotic normality of the adaptive LASSO estimator under profile-likelihood regularity conditions in a local asymptotic regime in which information accumulates over all ordered pairs that are ever at risk of transmission during follow-up. Simulation studies show accurate variable selection and improved estimation accuracy compared with the unpenalized estimator and the LASSO. We illustrate the method using 2009 household influenza A (H1N1) surveillance data from Los Angeles County, where the adaptive LASSO produces a sparse, interpretable model and improves the precision of selected covariate effect estimates, including the effect of antiviral prophylaxis on susceptibility.