Multiple imputation for missing data in a longitudinal cohort study: a tutorial based on a detailed case study involving imputation of missing outcome data

Multiple imputation (MI), a two-stage process whereby missing data are imputed multiple times and the resulting estimates of the parameter(s) of interest are combined across the completed datasets, is becoming increasingly popular for handling missing data. However, MI can result in biased inference if not carried out appropriately or if the underlying assumptions are not justifiable. Despite this, there remains a scarcity of guidelines for carrying out MI. In this paper we provide a tutorial on the main issues involved in employing MI, as well as highlighting some common pitfalls and misconceptions, and areas requiring further development. When contemplating using MI we must first consider whether it is likely to offer gains (reduced bias or increased precision) over alternative methods of analysis. Once it has been decided to use MI, there are a number of decisions that must be made during the imputation process; we discuss the extent to which these decisions can be guided by the current literature. Finally we highlight the importance of checking the fit of the imputation model. This process is illustrated using a case study in which we impute missing outcome data in a five-wave longitudinal study that compared extremely preterm individuals with term-born controls.