Mortality has historically been the primary outcome of choice for acute and critical care clinical trials. However, undue reliance on mortality can limit the scope of trials that can be performed. Large sample sizes are usually needed for trials powered for a mortality outcome and focusing solely on mortality fails to recognize the importance that reducing morbidity can have patients’ lives. The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for rapid, efficient trials to rigorously evaluate new therapies for hospitalized patients with acute lung injury. Oxygen-free days (OFDs) is a novel outcome for clinical trials that is a composite of mortality and duration of new supplemental oxygen use. It is designed to characterize recovery from acute lung injury in populations with a high prevalence of new hypoxemia and supplemental oxygen use. In these populations, OFDs captures two patient-centered consequences of acute lung injury, including mortality and hypoxemic lung dysfunction. Power to detect differences in OFDs is typically greater than that for other clinical trial outcomes such as mortality and ventilator-free days. OFDs is the primary outcome for the ACTIV-4 Host Tissue platform, which evaluates novel therapies targeting the host response to COVID-19 among adults hospitalized with COVID-19 and new hypoxemia. This manuscript outlines the rationale for use of OFDs as an outcome for clinical trials, proposes a standardized method for defining and analyzing OFDs, and provides a framework for sample size calculations using the OFD outcome.
Copyright © 2022. Published by Elsevier Inc.