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Missing covariate data in medical research: To impute is better than to ignore
Authors:Kristel JM Janssen  A Rogier T Donders  Frank E Harrell  Yvonne Vergouwe  Qingxia Chen  Diederick E Grobbee  Karel GM Moons
Institution:1. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands;2. Department of Epidemiology, Biostatistics and Health Technology Assessment, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;3. Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA
Abstract:ObjectiveWe compared popular methods to handle missing data with multiple imputation (a more sophisticated method that preserves data).Study Design and SettingWe used data of 804 patients with a suspicion of deep venous thrombosis (DVT). We studied three covariates to predict the presence of DVT: d-dimer level, difference in calf circumference, and history of leg trauma. We introduced missing values (missing at random) ranging from 10% to 90%. The risk of DVT was modeled with logistic regression for the three methods, that is, complete case analysis, exclusion of d-dimer level from the model, and multiple imputation.ResultsMultiple imputation showed less bias in the regression coefficients of the three variables and more accurate coverage of the corresponding 90% confidence intervals than complete case analysis and dropping d-dimer level from the analysis. Multiple imputation showed unbiased estimates of the area under the receiver operating characteristic curve (0.88) compared with complete case analysis (0.77) and when the variable with missing values was dropped (0.65).ConclusionAs this study shows that simple methods to deal with missing data can lead to seriously misleading results, we advise to consider multiple imputation. The purpose of multiple imputation is not to create data, but to prevent the exclusion of observed data.
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