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

Epidemiol Infect. 2021 Apr 23:149:e122. doi: 10.1017/S095026882100090X.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bias
  • Case-Control Studies
  • Cohort Studies
  • Cross Infection / epidemiology
  • Environmental Exposure / analysis*
  • Environmental Exposure / statistics & numerical data
  • Humans
  • Intensive Care Units
  • Odds Ratio
  • Proportional Hazards Models
  • Russia
  • Sampling Studies
  • Time Factors