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

Area of Science:

• Pulmonary Medicine
• Clinical Trial Design
• Spirometry Standards

Background:

• Respiratory clinical trials commonly use per cent-predicted forced expiratory volume in 1 second (ppFEV1) thresholds between 40% and 90% based on ethnicity-dependent GLI-2012 equations.
• International guidelines now recommend newer, 'race-neutral' GLI-Global spirometry reference equations.

Purpose of the Study:

• To quantify the impact of transitioning from GLI-2012 to GLI-Global equations on respiratory clinical trial eligibility.
• To assess the effect on patient access within the UK Cystic Fibrosis Registry.

Main Methods:

• Analysis of spirometry data from the UK Cystic Fibrosis Registry (n=8182).
• Comparison of ppFEV1 values calculated using GLI-2012 and GLI-Global equations.
• Modeling the effect of a 90% ppFEV1 eligibility threshold under the new equations.

Main Results:

• The shift to GLI-Global equations, particularly with a 90% ppFEV1 upper limit, would render over 700 individuals newly ineligible.
• This change highlights potential disparities in trial access based on spirometry equation choice.

Conclusions:

• Urgent review of fixed ppFEV1 thresholds in clinical trial eligibility is required with the adoption of GLI-Global equations.
• An initial recommendation is to widen the ppFEV1 eligibility range to 30-95% to ensure equitable access across ethnicities.
• A broader re-evaluation of fixed ppFEV1 limits for trial participation is necessary to promote inclusivity.