Development of a New Longitudinal Ordinal Outcome for Clinical Trials in Extracorporeal Membrane Oxygenation Patients

Rationale: Randomized clinical trials in intensive care often prioritize disease-focused outcomes rather than patient-centered outcomes. Objectives: To report and evaluate the DOSE (daily organ support for patients on extracorporeal membrane oxygenation [ECMO]) outcome. This is a new longitudinal ordinal outcome for clinical trials in patients receiving ECMO. Methods: A prospective, multicenter study was conducted at 28 hospitals in Australia and New Zealand. Adult patients admitted to participating ICUs between February 2019 and September 2023 who received any type of ECMO were included. The DOSE outcome was created considering 1) death, 2) receiving ECMO, 3) ventilated but not receiving ECMO, 4) in an ICU but not ventilated, 5) in a hospital ward, and 6) discharged from the hospital. DOSE was developed in collaboration with consumers and other stakeholders and validated against death and new disability at 6 months. Simulations were performed to compare the power obtained against 28-day mortality alone. Measurements and Main Results: Among 1,375 patients who received ECMO (median age, 52 yr; 34% women), at Day 90, 42%, 29%, and 66% of those receiving venoarterial, venovenous ECMO, or extracorporeal cardiopulmonary resuscitation were deceased, respectively. DOSE accurately predicted death and new disability at 6 months (area under the curve > 0.800). With a sample size of 400 patients per arm and an odds ratio of 1.20, DOSE provided 56% more power than an analysis considering 28-day mortality alone (36% vs. 91%) in simulations of a two-arm clinical trial. Conclusions: The DOSE outcome performed well compared with a patient-centered outcome. Compared with 28-day mortality, DOSE provided more statistical power in a simulated two-arm clinical trial.