Multiple imputation with competing risk outcomes

Abstract

In time-to-event analyses, a competing risk is an event whose occurrence precludes the occurrence of the event of interest. Settings with competing risks occur frequently in clinical research. Missing data, which is a common problem in research, occurs when the value of a variable is recorded for some, but not all, records in the dataset. Multiple Imputation (MI) is a popular method to address the presence of missing data. MI uses an imputation model to generate M (M > 1) values for each variable that is missing, resulting in the creation of M complete datasets. A popular algorithm for imputing missing data is multivariate imputation using chained equations (MICE). We used a complex simulation design with covariates and missing data patterns reflective of patients hospitalized with acute myocardial infarction (AMI) to compare three strategies for imputing missing predictor variables when the analysis model is a cause-specific hazard when there were three different event types. We compared two MICE-based strategies that differed according to which cause-specific cumulative hazard functions were included in the imputation models (the three cause-specific cumulative hazard functions vs. only the cause-specific cumulative hazard function for the primary outcome) with the use of the substantive model compatible fully conditional specification (SMCFCS) algorithm. While no strategy had consistently superior performance compared to the other strategies, SMCFCS may be the preferred strategy. We illustrated the application of the strategies using a case study of patients hospitalized with AMI.