Spirometry thresholds for clinical trial eligibility: time for urgent re-evaluation
A common eligibility criterion in respiratory clinical trials is a per cent-predicted forced expiratory volume in 1 second (ppFEV<sub>1</sub>) 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<sub>1</sub>=90%, the changes in ppFEV<sub>1</sub> would lead to over 700 people becoming newly ineligible. Urgent review of fixed ppFEV<sub>1</sub> thresholds is required, with an initial recommendation to widen the range to 30-95% ppFEV<sub>1</sub> 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<sub>1</sub> spirometry limits for trial eligibility.
Authors
- I Bokobza
- D.A. Hughes (ORCID: https://orcid.org/0000-0003-0374-3611)
- Cara Bossley (ORCID: https://orcid.org/0000-0002-8551-6094)
- Gary Ruiz (ORCID: https://orcid.org/0000-0001-5164-789X)
- Michael D Waller (ORCID: https://orcid.org/0000-0002-4954-8339)
- Shahideh Safavi (ORCID: https://orcid.org/0000-0001-6306-6662)
- Gwyneth Davies (ORCID: https://orcid.org/0000-0001-7937-2728)
- Y. Needham
- Charlotte Dawson (ORCID: https://orcid.org/0000-0001-5209-3286)
- C. Pao (ORCID: https://orcid.org/0000-0002-1749-5295)
- Jane C. Davies (ORCID: https://orcid.org/0000-0003-3506-1199)
- Danie Watson
- Rossa Brugha (ORCID: https://orcid.org/0000-0002-5647-2424)
- Mélanie Le Sayec (ORCID: https://orcid.org/0000-0001-9590-4165)
- Clare Saunders (ORCID: https://orcid.org/0000-0001-7724-9777)
- Nicholas J. Simmonds (ORCID: https://orcid.org/0000-0002-1705-4780)
- Lucy Holt
- Nadia Shafi
Institutions
- King's College London (GB)
- Barts Health NHS Trust (GB)
- Royal Brompton & Harefield NHS Foundation Trust (GB)
- Great Ormond Street Hospital for Children NHS Foundation Trust (GB)
- MRC Clinical Trials Unit at UCL (GB)
- King's College Hospital NHS Foundation Trust (GB)
- University College London (GB)
- Imperial College London (GB)
Publication Details
- Journal
- Thorax
- Published
- 2025-09-04
- DOI
- https://doi.org/10.1136/thorax-2024-222652
- Citations
- 1
- Primary Topic
- Cystic Fibrosis Research Advances
- Type
- article
- Field-Weighted Citation Impact
- 1.52
Funders
- UK Research and Innovation
- Cystic Fibrosis Trust
- NIHR Imperial Biomedical Research Centre