Abstract
Background Little is known about generalisability of randomised controlled trials (RCTs) for idiopathic pulmonary fibrosis (IPF). We evaluated eligibility criteria for phase III IPF RCTs to determine their representativeness in clinical registries, and calculated forced vital capacity (FVC) changes according to eligibility criteria.
Methods Common eligibility criteria used in >60% of IPF RCTs were identified from a literature search and applied to patients with IPF from prospective Australian and Canadian registries. Additional pre-specified criteria of 6-min walk distance (6 MWD) and different measures of preceding disease progression were also evaluated. Joint longitudinal-survival modelling was used to compare FVC decline according to eligibility for individual and composite criteria.
Results Of 990 patients with IPF, 527 (53%) met all common RCT eligibility criteria at the first clinic visit, including 343 with definite IPF and 184 with radiological probable usual interstitial pneumonia pattern without histological confirmation (i.e., provisional IPF). The percentages of eligible patients for landmark RCTs of nintedanib and pirfenidone were 19–50%. Adding 6 MWD ≥150 m and different measures of preceding disease progression to the composite common criteria reduced the percentages of patients meeting eligibility to 52% (n=516) and 4–18% (n=12–61), respectively. Patients meeting the composite common criteria had less rapid 1-year FVC decline than those who did not (−90 versus −103 ml, p=0.01). Definite IPF generally had more rapid 1-year FVC decline compared to provisional IPF.
Conclusions Eligibility criteria of previous IPF RCTs have limited generalisability to clinical IPF populations, with FVC decline differing between eligible and ineligible populations.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
- Received November 10, 2022.
- Accepted February 8, 2023.
- Copyright ©The authors 2023. For reproduction rights and permissions contact permissions{at}ersnet.org