Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity

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...

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Bibliographic Details
Main Authors: Swets, MC, Kerr, S, Scott-Brown, J, Brown, AB, Gupta, R, Millar, JE, Spata, E, McCurrach, F, Bretherick, AD, Docherty, A, Harrison, D, Rowan, K, Young, N, Groeneveld, GH, Dunning, J, Nguyen-Van-Tam, JS, Openshaw, P, Horby, PW, Harrison, E, Staplin, N, Semple, MG, Lone, N, Baillie, JK
Other Authors: ISARIC4C Investigators
Format: Journal article
Language:English
Published: Springer Nature 2023
Description
Summary: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.