Integrating Mortality and Morbidity Outcomes: Using Quality-Adjusted Life Years in Critical Care Trials.

Abstract

Purpose: Outcome measures that integrate mortality and morbidity, like quality-adjusted life years (QALYs), have been proposed for critical care clinical trials. We sought to describe the distribution of QALYs in critically-ill patients, and estimate sample size requirements for a hypothetical trial using QALYs as the primary outcome.

METHODS:

We used data from a prospective cohort study of survivors of acute respiratory distress syndrome survivors to generate utility values and calculate QALYs at 6 and 12 months. Utilizing multiple simulations, we estimated the required sample sizes for multiple outcome scenarios in a hypothetical trial, including a base-case where the intervention improved both mortality and QALYs among survivors.

RESULTS:

From 195 enrolled patients, follow-up was sufficient to generate QALY outcomes for 168 (86.2%) at six months and 159 (81.5%) at one year. For a hypothetical intervention that reduced mortality from 48% to 44% and improved QALYs by 0.025 in survivors at six months, the required per-group sample size was 571 (80% power; two-sided alpha=0.05), compared with 2436 patients needed for a comparison focusing on mortality alone. When only mortality or QALY in survivors (but not both) showed improvement by these amounts, 3426 and 1827 patients per group were needed, respectively. When mortality and morbidity effects moved in opposite directions, simulation results became impossible to interpret.

CONCLUSION:

QALYs may be a feasible outcome in critical care trials yielding a patient-centred result, and major gains in statistical power under certain conditions, but this approach is susceptible to several threats, including loss to follow-up.