Sampling designs for rare time-dependent exposures: a comparison of the nested exposure case-control design and exposure density sampling

Abstract

In extensive cohort studies, the ascertainment of covariate information on all individuals can be challenging. In hospital epidemiology, an additional issue is often the time-dependency of the exposure of interest. We revisit and compare two sampling designs constructed for rare time-dependent exposures and possibly common outcomes – the nested exposure case-control design and exposure density sampling. Both designs enable efficient hazard ratio estimation by sampling all exposed individuals but only a small fraction of the unexposed ones. Moreover, they account for time-dependent exposure to avoid immortal time bias. We evaluate and compare their performance using data of patients hospitalised in the neuro-intensive care unit at the Burdenko Neurosurgery Institute in Moscow, Russia. Three different types of hospital-acquired infections with different prevalence are considered. Additionally, inflation factors, a primary performance measure, are discussed. We enhance both designs to allow for a competitive analysis of combined and competing endpoints compared to the full cohort approach while substantially reducing the amount of necessary information. Nonetheless, exposure density sampling outperforms the nested exposure case-control design concerning efficiency and accuracy in most considered settings.

Inverse Probability Weighting Enhances Absolute Risk Estimation in Three Common Study Designs of Nosocomial Infections

“…For example, one could investigate the different effect of a covariate on discharge alive compared to death, which we combined due to simplicity. When interested in the consequences of infection, rather than the risk of infection, the analysis can be expanded for all three study designs as shown nicely by von Cube et al 18 for the case-cohort design, by Feifel et al 28 for the nested-case cohort design and by Doerken et al 23 for the point-prevalence design.…”