Statistical methods to compare functional outcomes in randomized controlled trials with high mortality

Mortality is a common primary endpoint in randomized controlled trials of patients with a high severity of illness, such as critically ill patients. However, researchers are increasingly evaluating functional outcomes, such as quality of life. Importantly, in such trials some patients may die before the assessment of a functional outcome, resulting in the functional outcome being “truncated due to death.” As described in this paper, defining and testing treatment effects on functional outcomes in this setting requires careful consideration. Data from a completed trial of critically ill patients are used to highlight key differences among three statistical approaches used when analyzing such trials.