Dealing with missing delirium assessments in prospective clinical studies of the critically ill: a simulation study and reanalysis of two delirium studies.

In longitudinal critical care studies, researchers may be interested in summarizing an exposure over time and evaluating its association with a long-term outcome. For example, the number of days a patient has delirium (i.e., brain dysfunction) during their critical care stay is associated with the presence and severity of long-term cognitive problems. In large pragmatic trials and multicenter observational studies, particularly when electronic medical record data is used, the information on daily exposure status may be available at some time points and not at others. Model-based multiple imputation is a well-established, widely adopted method to deal with missing data. But the uncertainty around multiple imputation for summary exposure variables is whether the imputation is to be performed at the summary level or at the daily assessment level.