Title:Causal identification of infectious disease intervention effects in a clustered population

Abstract:Causal identification of treatment effects for infectious disease outcomes in interconnected populations is challenging because infection outcomes may be transmissible to others, and treatment given to one individual may affect others' outcomes. Contagion, or transmissibility of outcomes, complicates standard conceptions of treatment interference in which an intervention delivered to one individual can affect outcomes of others. Several statistical frameworks have been proposed to measure causal treatment effects in this setting, including structural transmission models, mediation-based partnership models, and randomized trial designs. However, existing estimands for infectious disease intervention effects are of limited conceptual usefulness: Some are parameters in a structural model whose causal interpretation is unclear, others are causal effects defined only in a restricted two-person setting, and still others are nonparametric estimands that arise naturally in the context of a randomized trial but may not measure any biologically meaningful effect. In this paper, we describe a unifying formalism for defining nonparametric structural causal estimands and an identification strategy for learning about infectious disease intervention effects in clusters of interacting individuals when infection times are observed. The estimands generalize existing quantities and provide a framework for causal identification in randomized and observational studies, including situations where only binary infection outcomes are observed. A semiparametric class of pairwise Cox-type transmission hazard models is used to facilitate statistical inference in finite samples. A comprehensive simulation study compares existing and proposed estimands under a variety of randomized and observational vaccine trial designs.