Proper Use of Multiple Imputation and Dealing with Missing Covariate Data

Background: Missing data is a typical problem in clinical studies, where the value of variables of interest is not measured or collected for some patients. This article aimed to review imputation approaches for missing values and their application in neurosurgery. Methods: We reviewed current practices on detecting missingness patterns and applications of multiple imputation approaches under different scenarios. Statistical considerations and importance of sensitivity analysis were explained. Various imputation methods were applied to a retrospective cohort. Results: For illustration purposes, a retrospective cohort of 609 patients harboring both ruptured and unruptured intracranial aneurysms and undergoing microsurgical clip reconstruction at Erasmus MC University Medical Center, Rotterdam, The Netherlands, between 2000 and 2019 was used. modified Rankin Scale score at 6 months was the clinical outcome, and potential predictors were age, sex, size of aneurysm, hypertension, smoking, World Federation of Neurosurgical Societies grade, and aneurysm location. Associations were investigated using different imputation approaches, and the results were compared and discussed. Conclusions: Missing values should be treated carefully. Advantages and disadvantages of multiple imputation methods along with imputation in small and big data should be considered depending on the research question and specifics of the study.