Developing Clinical Prediction Models Using Primary Care Electronic Health Record Data: The Impact of Data Preparation Choices on Model Performance

Objective: To quantify prediction model performance in relation to data preparation choices when using electronic health records (EHR). Study Design and Setting: Cox proportional hazards models were developed for predicting the first-ever main adverse cardiovascular events using Dutch primary care EHR data. The reference model was based on a 1-year run-in period, cardiovascular events were defined based on both EHR diagnosis and medication codes, and missing values were multiply imputed. We compared data preparation choices based on (i) length of the run-in period (2- or 3-year run-in); (ii) outcome definition (EHR diagnosis codes or medication codes only); and (iii) methods addressing missing values (mean imputation or complete case analysis) by making variations on the derivation set and testing their impact in a validation set. Results: We included 89,491 patients in whom 6,736 first-ever main adverse cardiovascular events occurred during a median follow-up of 8 years. Outcome definition based only on diagnosis codes led to a systematic underestimation of risk (calibration curve intercept: 0.84; 95% CI: 0.83–0.84), while complete case analysis led to overestimation (calibration curve intercept: −0.52; 95% CI: −0.53 to −0.51). Differences in the length of the run-in period showed no relevant impact on calibration and discrimination. Conclusion: Data preparation choices regarding outcome definition or methods to address missing values can have a substantial impact on the calibration of predictions, hampering reliable clinical decision support. This study further illustrates the urgency of transparent reporting of modeling choices in an EHR data setting.