Handling missing data in clinical research

Because missing data are present in almost every study, it is important to handle missing data properly. First of all, the missing data mechanism should be considered. Missing data can be either completely at random (MCAR), at random (MAR), or not at random (MNAR). When missing data are MCAR, a complete case analysis can be valid. Also when missing data are MAR, in some situations a complete case analysis leads to valid results. However, in most situations, missing data imputation should be used. Regarding imputation methods, it is highly advised to use multiple imputations because multiple imputations lead to valid estimates including the uncertainty about the imputed values. When missing data are MNAR, also multiple imputations do not lead to valid results. A complication hereby is that it not possible to distinguish whether missing data are MAR or MNAR. Finally, it should be realized that preventing to have missing data is always better than the treatment of missing data. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).