Additions to Funding/Support and Role of the Funder/Sponsor Sections

Kawano-Dourado and colleagues propose that poor adherence to antifibrotic drugs may explain the disease trajectories observed in the ISABELA placebo groups.The mean daily doses of pirfenidone were 2201 mg in ISABELA 1 and 2083 mg in ISABELA 2 1 ; the corresponding daily doses for nintedanib were 283 mg and 270 mg.These levels of exposure are comparable with those reported in the ASCEND trial 2 and in the INPULSIS trial. 3 Far from being concerning, as Kawano-Dourado and colleagues suggest, the data from the ISABELA trials 1 provide considerable reassurance.To be able to demonstrate that novel antifibrotic therapies slow the rate of decline of FVC, it is important that clinical trials are enriched for individuals with progressive disease.It seems that in the era of effective antifibrotic therapy, this enrichment is happening spontaneously; encouragingly, then, ongoing phase 3 trials should be sufficiently powered to show a benefit of novel therapies, if such a benefit exists.These findings highlight the critical importance of disseminating data from negative clinical trials.Although the participants in ISABELA 1 and 2 will undoubtedly have been disappointed by the outcome of the trials, 1 their involvement has taught the IPF community important lessons that will help optimize the design of future clinical trials.