Spirometry thresholds for clinical trial eligibility: time for urgent re-evaluation

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Bokobza,Idan;Le Sayec,Melanie;Bossley,Cara;Brugha,Rossa;Davies,Jane Carolyn;Dawson,Charlotte;Holt,Lucy;Hughes,Dominic A.;Needham,Yasmine;Pao,Caroline;Ruiz,Gary;Safavi,Shahideh;Saunders,Clare;Shafi,Nadia;Simmonds,Nicholas J.;Waller,Michael D.;Watson,Danie;Davies,Gwyneth

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2025

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A common eligibility criterion in respiratory clinical trials is a per cent-predicted forced expiratory volume in 1 second (ppFEV(1)) between 40% and 90%, using the ethnicity-dependent Global Lung Function Initiative (GLI)-2012 spirometry reference equations. International societies now endorse the newer 'race-neutral' GLI-Global equations. We quantify the impact on trial eligibility of switching from GLI-2012 to GLI-Global for the UK Cystic Fibrosis Registry (n=8182). In a future trial with a maximum eligibility threshold of ppFEV(1)=90%, the changes in ppFEV(1) would lead to over 700 people becoming newly ineligible. Urgent review of fixed ppFEV(1) thresholds is required, with an initial recommendation to widen the range to 30-95% ppFEV(1) when GLI-Global is implemented to ensure equitable access for people of all ethnicities. There is also a wider need to review the use of fixed ppFEV(1) spirometry limits for trial eligibility.

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Thorax

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