Comparing methods for handling missing data in electronic health records for dynamic risk prediction of central-line associated bloodstream infection

Electronic health records (EHR) often contain varying levels of missing data. This study compared different imputation strategies to identify the most suitable approach for predicting central line-associated bloodstream infection (CLABSI) in the presence of competing risks using EHR data. We analyzed 30862 catheter episodes at University Hospitals Leuven (2012-2013) to predict 7-day CLABSI risk using a landmark cause-specific supermodel, accounting for competing risks of hospital discharge and death. Imputation methods included simple methods (median/mode, last observation carried forward), multiple imputation, regression-based and mixed-effects models leveraging longitudinal structure, and random forest imputation to capture interactions and non-linearities. Missing indicators were also assessed alone and in combination with other imputation methods. Model performance was evaluated dynamically at daily landmarks up to 14 days post-catheter placement. The missing indicator approach showed the highest discriminative ability, achieving a mean AUROC of up to 0.782 and superior overall performance based on the scaled Brier score. Combining missing indicators with other methods slightly improved performance, with the mixed model approach combined with missing indicators achieving the highest AUROC (0.783) at day 4, and the missForestPredict approach combined with missing indicators yielding the best scaled Brier scores at earlier landmarks. This suggests that in EHR data, the presence or absence of information may hold valuable insights for patient risk prediction. However, the use of missing indicators requires caution, as shifts in EHR data over time can alter missing data patterns, potentially impacting model transportability.