A General and Robust Estimation Method for the Case-Time-Control Design

The case-time-control design is a tool to control for measured, time-varying covariates that increase montonically in time within each subject while also controlling for all unmeasured covariates that are constant within each subject across time. Until recently, the design was restricted to data with only two timepoints and a single binary covariate, or data with a binary exposure. Sjölander (2017) made an important extension that allows for an arbitrary number of timepoints and covariates and a nonbinary exposure. However, his estimation method requires fairly strong model assumptions, and it may create bias if these assumptions are violated. We propose a novel estimation method for the case-time-control design, which to a large extent relaxes the model assumptions in Sjölander. We show in simulations that this estimation method performs well under a range of scenarios and gives consistent estimates when Sjölander’s estimation does not.