Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the Formula: see text ratio. Because of the ceiling effect in oxyhaemoglobin saturation, Formula: see text ratio ceases to reflect pulmonary oxygenation function at high Formula: see text values. We found that the correlation of Formula: see text with the reference standard (Formula: see text/Formula: see text ratio) improves substantially when excluding Formula: see text and refer to this measure as Formula: see text. Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that Formula: see text is predictive of mortality, and compare the sample sizes required for trials using four different outcome measures. We show that a significant difference in outcome could be detected with the smallest sample size using Formula: see text. We demonstrate that Formula: see text is an effective intermediate outcome measure in COVID-19. It is a non-invasive measurement, representative of disease severity and provides greater statistical power.