Development of a New Longitudinal Ordinal Outcome for Clinical Trials in ECMO Patients

Rationale: Randomised clinical trials in intensive care often prioritize disease-focused outcomes rather than patient-centred outcomes. Objective: To report and evaluate the 'Daily Organ Support for patients on extracorporeal membrane oxygenation (ECMO)', the DOSE outcome. This is a new longitudinal ordinal outcome for clinical trials in patients receiving ECMO. Methods: Prospective, multicentre study in 28 hospitals in Australia and New Zealand. Adult patients admitted to a participating ICU between February 2019 and September 2023 and who underwent any type of ECMO were included. The DOSE outcome was created considering: 1) death; 2) on ECMO; 3) ventilated not on ECMO; 4) in ICU but not ventilated; 5) in 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 six months. Simulations were performed to compare the power obtained against 28-day mortality alone. Measurements and Main Results: Among 1375 patients who received ECMO (median age, 52 years; 34% female), at day 90, 42%, 29% and 66% of the patients receiving VA-, VV-ECMO, or eCPR were deceased, respectively. DOSE accurately predicted death and new disability at six months (area under the curve [AUC] > 0.800). With a sample size of 400 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 to a patient-centred outcome. Compared to 28-day mortality, DOSE provided more statistical power in a simulated two-arm clinical trial.