Characterizing Bias Due to Differential Exposure Ascertainment in Electronic Health Record Data

Data derived from electronic health records (EHR) are heterogeneous with availability of specific measures dependent on the type and timing of patients' healthcare interactions. This creates a challenge for research using EHR-derived exposures because gold-standard exposure data, determined by a definitive assessment, may only be available for a subset of the population. Alternative approaches to exposure ascertainment in this case include restricting the analytic sample to only those patients with gold-standard exposure data available (exclusion); using gold-standard data, when available, and using a proxy exposure measure when the gold standard is unavailable (best available); or using a proxy exposure measure for everyone (common data). Exclusion may induce selection bias in outcome/exposure association estimates, while incorporating information from a proxy exposure via either the best available or common data approaches may result in information bias due to measurement error. The objective of this paper was to explore the bias and efficiency of these three analytic approaches across a broad range of scenarios motivated by a study of the association between chronic hyperglycemia and five-year mortality in an EHR-derived cohort of colon cancer survivors. We found that the best available approach tended to mitigate inefficiency and selection bias resulting from exclusion while suffering from less information bias than the common data approach. However, bias in all three approaches can be severe, particularly when both selection bias and information bias are present. When risk of either of these biases is judged to be more than moderate, EHR-based analyses may lead to erroneous conclusions.