TY  - JOUR
AU  - Ehrig, Molly
AU  - Bullock, Garrett S
AU  - Leng, Xiaoyan Iris
AU  - Pajewski, Nicholas M
AU  - Speiser, Jaime Lynn
PY  - 2025
DA  - 2025/3/13
TI  - Imputation and Missing Indicators for Handling Missing Longitudinal Data: Data Simulation Analysis Based on Electronic Health Record Data
JO  - JMIR Med Inform
SP  - e64354
VL  - 13
KW  - missing indicator method
KW  - missing data
KW  - imputation
KW  - longitudinal data
KW  - electronic health record data
KW  - electronic health records
KW  - EHR
KW  - simulation study
KW  - clinical prediction model
KW  - prediction model
KW  - older adults
KW  - falls
KW  - logistic regression
KW  - prediction modeling
AB  - Background: Missing data in electronic health records are highly prevalent and result in analytical concerns such as heterogeneous sources of bias and loss of statistical power. One simple analytic method for addressing missing or unknown covariate values is to treat missingness for a particular variable as a category onto itself, which we refer to as the missing indicator method. For cross-sectional analyses, recent work suggested that there was minimal benefit to the missing indicator method; however, it is unclear how this approach performs in the setting of longitudinal data, in which correlation among clustered repeated measures may be leveraged for potentially improved model performance. Objectives: This study aims to conduct a simulation study to evaluate whether the missing indicator method improved model performance and imputation accuracy for longitudinal data mimicking an application of developing a clinical prediction model for falls in older adults based on electronic health record data. Methods: We simulated a longitudinal binary outcome using mixed effects logistic regression that emulated a falls assessment at annual follow-up visits. Using multivariate imputation by chained equations, we simulated time-invariant predictors such as sex and medical history, as well as dynamic predictors such as physical function, BMI, and medication use. We induced missing data in predictors under scenarios that had both random (missing at random) and dependent missingness (missing not at random). We evaluated aggregate performance using the area under the receiver operating characteristic curve (AUROC) for models with and with no missing indicators as predictors, as well as complete case analysis, across simulation replicates. We evaluated imputation quality using normalized root-mean-square error for continuous variables and percent falsely classified for categorical variables. Results: Independent of the mechanism used to simulate missing data (missing at random or missing not at random), overall model performance via AUROC was similar regardless of whether missing indicators were included in the model. The root-mean-square error and percent falsely classified measures were similar for models including missing indicators versus those with no missing indicators. Model performance and imputation quality were similar regardless of whether the outcome was related to missingness. Imputation with or with no missing indicators had similar mean values of AUROC compared with complete case analysis, although complete case analysis had the largest range of values. Conclusions: The results of this study suggest that the inclusion of missing indicators in longitudinal data modeling neither improves nor worsens overall performance or imputation accuracy. Future research is needed to address whether the inclusion of missing indicators is useful in prediction modeling with longitudinal data in different settings, such as high dimensional data analysis. 
SN  - 2291-9694
UR  - https://medinform.jmir.org/2025/1/e64354
UR  - https://doi.org/10.2196/64354
DO  - 10.2196/64354
ID  - info:doi/10.2196/64354
ER  -