Background Lack of reliable and valid measures of disease activity and clinical response in patients with CTD-ILD makes clinical trial design difficult. From a multi-tiered investigation to develop consensus on provisional criteria in both CTD-ILD and idiopathic pulmonary fibrosis (IPF), we report the results of expert voting from a 3-tiered Delphi exercise to identify domains “important” to measure in a one year randomized controlled trial (RCT) in IPF and CTD-ILD.
Methods Using the international consensus organization, Outcome Measures in Rheumatology (OMERACT) methodology, 270 experts nominated 23 “domains” and 616 “instruments” that were assembled into an initial voting survey for a 3-tiered Delphi exercise with survey items anchored by degree of importance on a 9-point Likert scale with as a voting option. All stages of data collection used a custom-designed secure web-site that included related articles and opportunities for participants to upload commentary supporting or refuting importance of each item.
Tier 1 Analysis: A cut-off median <4 was applied to the results. Final review demanded 100% consensus agreement for dismissal of an item based on lack of: 1. Face validity, 2. Content validity (more suited to diagnostic, demographic, or inclusion criteria) and 3. Feasibility in a multicenter trial.
Tiers 2 and 3 Analysis: To protect against bias introduced by using an arbitrary cut-off, cluster analysis was implemented to identify patterns of consensus within the data.
Results 90% of invited experts: 137 pulmonary, 102 rheumatology and 4 cardiology specialists from 32 countries/6 continents participated. 74% and 69% of participants considered ILD and rheumatologic lung disease respectively as their primary field of research or clinical interest. Recidivism after Tier 1 was <1% with each subsequent Tier. Five common domains were identified for CTD-ILD and IPF: DYSPNEA, HEALTH RELATED QUALITY OF LIFE, LUNG IMAGING, LUNG PHYSIOLOGY/FUNCTION and SURVIVAL.
Conclusions Development of valid, discriminatory and feasible outcome measures to assess disease progression and therapeutic responses is essential for performing RCTs in CTD-ILD. This is the first comprehensive, multi-disciplinary, international effort to assess domains for study of ILD. Experts identified a core set of measures focused on radiographic, physiologic and patient-reported outcomes culled from a large number of candidate items. A research agenda focusing on candidate biomarkers and domains requiring instrument development has emerged. Broad participation from a multidisciplinary ILD research community reflects the high perceived need in this area.
Disclosure of Interest L. A. Saketkoo Grant/Research support from: Actelion, United Therapeutics, D. Khanna Speakers Bureau: Actelion, Fibrogen, Gilead, Novartis, Pfizer, Sanofi, Unitied Therapeutics, D. Huscher: None Declared, P. Dellaripa Grant/Research support from: Biogen IDEC, Genentech, K. Flaherty: None Declared, E. Matteson Grant/Research support from: Biogen IDEC, Genentech, C. Oddis Consultant for: Biogen IDEC, Genentech, A. Wells: None Declared, C. Denton Consultant for: Actelion, Glaxo Smith Kline, Pfizer, United Therapeutics, O. Distler Consultant for: Actelion, Active BiotechBristol-Myers Squibb, Fibrogen, Ergonex, Genentech, Novartis, Pfizer, Sanofi, Unitied Therapeutics, 4D Therapeutics, O. Kowal-Bielecka Consultant for: Bayer, Pfizer, N. Sandorfi: None Declared, R. Christmann: None Declared, K. Phillips Grant/Research support from: Actelion, Amgen, Centocor, Merck, Pfizer, Unitied Therapeutics, D. Pittrow Consultant for: Actelion, Pfizer, MSD, Novartis, Bayer, MBiotec, Baxter, V. Strand Consultant for: Actelion, Amgen, Bristol Myers Squibb, Celgene, Fibrogen, Genentech, Novartis, Pfizer, Sanofi, UCB, K. Brown Consultant for: Actelion, Fibrogen, Gilead, Amgen, Genentech, Celgene, J. Seibold Consultant for: Actelion, Fibrogen, Gilead, Genentech, Celgene, MedImmune, Boerhringer-Ingelheim, Sigma Tau