Moving Beyond Medical Statistics: A Systematic Review on Missing Data Handling in Electronic Health Records

Background: Missing data in electronic health records (EHRs) presents significant challenges in medical studies. Many methods have been proposed, but uncertainty exists regarding the current state of missing data addressing methods applied for EHR and which strategy performs better within specific contexts. Methods: All studies referencing EHR and missing data methods published from their inception until 2024 March 30 were searched via the MEDLINE, EMBASE, and Digital Bibliography and Library Project databases. The characteristics of the included studies were extracted. We also compared the performance of various methods under different missingness scenarios. Results: After screening, 46 studies published between 2010 and 2024 were included. Three missingness mechanisms were simulated when evaluating the missing data methods: missing completely at random (29/46), missing at random (20/46), and missing not at random (21/46). Multiple imputation by chained equations (MICE) was the most popular statistical method, whereas generative adversarial network-based methods and the k nearest neighbor (KNN) classification were the common deep-learning-based or traditional machine-learning-based methods, respectively. Among the 26 articles comparing the performance among medical statistical and machine learning approaches, traditional machine learning or deep learning methods generally outperformed statistical methods. Med.KNN and context-aware time-series imputation performed better for longitudinal datasets, whereas probabilistic principal component analysis and MICE-based methods were optimal for cross-sectional datasets. Conclusions: Machine learning methods show significant promise for addressing missing data in EHRs. However, no single approach provides a universally generalizable solution. Standardized benchmarking analyses are essential to evaluate these methods across different missingness scenarios.