Prediction Model Performance With Different Imputation Strategies: A Simulation Study Using a North American ICU Registry

OBJECTIVES: To evaluate the performance of pragmatic imputation approaches when estimating model coefficients using datasets with varying degrees of data missingness. DESIGN: Performance in predicting observed mortality in a registry dataset was evaluated using simulations of two simple logistic regression models with age-specific criteria for abnormal vital signs (mentation, systolic blood pressure, respiratory rate, WBC count, heart rate, and temperature). Starting with a dataset with complete information, increasing degrees of biased missingness of WBC and mentation were introduced, depending on the values of temperature and systolic blood pressure, respectively. Missing data approaches evaluated included analysis of complete cases only, assuming missing data are normal, and multiple imputation by chained equations. Percent bias and root mean square error, in relation to parameter estimates obtained from the original data, were evaluated as performance indicators. SETTING: Data were obtained from the Virtual Pediatric Systems, LLC, database (Los Angeles, CA), which provides clinical markers and outcomes in prospectively collected records from 117 PICUs in the United States and Canada. PATIENTS: Children admitted to a participating PICU in 2017, for whom all required data were available. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Simulations demonstrated that multiple imputation by chained equations is an effective strategy and that even a naive implementation of multiple imputation by chained equations significantly outperforms traditional approaches: the root mean square error for model coefficients was lower using multiple imputation by chained equations in 90 of 99 of all simulations (91%) compared with discarding cases with missing data and lower in 97 of 99 (98%) compared with models assuming missing values are in the normal range. Assuming missing data to be abnormal was inferior to all other approaches. CONCLUSIONS: Analyses of large observational studies are likely to encounter the issue of missing data, which are likely not missing at random. Researchers should always consider multiple imputation by chained equations (or similar imputation approaches) when encountering even only small proportions of missing data in their work.

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