Modeling unmeasured baseline information in observational time-to-event data subject to delayed study entry

Abstract

Unmeasured baseline information in left-truncated data situations frequently occurs in observational time-to-event analyses. For instance, a typical timescale in trials of antidiabetic treatment is “time since treatment initiation”, but individuals may have initiated treatment before the start of longitudinal data collection. When the focus is on baseline effects, one widespread approach is to fit a Cox proportional hazards model incorporating the measurements at delayed study entry. This has been criticized because of the potential time dependency of covariates. We tackle this problem by using a Bayesian joint model that combines a mixed-effects model for the longitudinal trajectory with a proportional hazards model for the event of interest incorporating the baseline covariate, possibly unmeasured in the presence of left truncation. The novelty is that our procedure is not used to account for non-continuously monitored longitudinal covariates in right-censored time-to-event studies, but to utilize these trajectories to make inferences about missing baseline measurements in left-truncated data. Simulating times-to-event depending on baseline covariates we also compared our proposal to a simpler two-stage approach which performed favorably. Our approach is illustrated by investigating the impact of baseline blood glucose levels on antidiabetic treatment failure using data from a German diabetes register.