Comparison between the FEV1/FVC lower limit of normal and a fixed threshold of 0.70 for ruling out significant airway obstruction in clinical trials for IPF

<bold>Background:</bold> Clinical trials evaluating therapies for IPF often use a fixed lower limit of 0.70 for the FEV₁/FVC ratio to rule out significant airway obstruction. ATS/ERS recommends using the predicted lower limit of normal (LLN) as the threshold for identifying obstruction¹. <bold>Objective:</bold> To identify differential performance of the predicted FEV₁/FVC_LLN and fixed 0.70 thresholds for airway obstruction exclusion in IPF clinical trials. <bold>Methods:</bold> We examined 906 acceptable quality forced spirometry measurements done at the Screening Visit in 16 clinical trials for IPF, evaluating the FEV₁/FVC ratio against the FEV₁/FVC predicted LLN (GLI 2012) and a fixed threshold of 0.70 for identifying airway obstruction. <bold>Results:</bold> 82 measurements (9.0%) showed a FEV₁/FVC < 0.70. Of these 82 measurements, <bold>the FEV₁/FVC ratio was above the predicted FEV₁/FVC_LLN</bold> in 59 (72%) measurements. The mean age of this group was 74.5 (7.2). The mean FEV₁/FVC was 0.67 (0.02). The mean FEV₁/FVC z-score was -1.09 (0.33). Twenty three (28%) measurements showed the FEV₁/FVC less than the predicted LLN. The mean age of this group was 71.6 (6.5). The mean FEV₁/FVC was 0.60 (0.07), p < 0.001. The mean FEV₁/FVC z-score was -2.21 (0.75). <bold>Conclusions:</bold> 1. Evaluating for significant airway obstruction using a fixed lower threshold of 0.70 does not align with the 2022 ATS/ERS recommended interpretive strategies for spirometry. 2. In a pooled sample of 906 acceptable spirometry measurements made at the Screening Visit in 16 clinical trials for IPF, shifting to the exclusion threshold of FEV₁/FVC < FEV₁/FVC_LLN would reduce spirometric screen failures for airway obstruction by 72%.