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OP0001 Developing a disease activity and therapeutic response index in connective tissue disease - interstitial lung disease (CTD-ILD): Results from a delphi exercise: Consensus on domains
  1. L.A. Saketkoo1,
  2. D. Khanna2,
  3. D. Huscher3,4,
  4. P. Dellaripa5,
  5. K. Flaherty2,
  6. E. Matteson6,
  7. C. Oddis7,
  8. A. Wells8,
  9. C. Denton9,
  10. O. Distler10,
  11. O. Kowal-Bielecka11,
  12. N. Sandorfi12,
  13. R. Christmann13,
  14. K. Phillips2,
  15. D. Pittrow14,
  16. V. Strand15,
  17. K. Brown16,
  18. J. Seibold17
  1. 1Louisiana State University Health Sciences Center, New Orleans
  2. 2University of Michigan, Ann Arbor, United States
  3. 3German Rheumatism Research Centre
  4. 4Charité Universitaetsmedizin, Berlin, Germany
  5. 5Brigham & Womens Hospital, Boston
  6. 6Mayo Clinic, Rochester
  7. 7University of Pittsburgh, Pittsburgh, United States
  8. 8Royal Brompton Hospital
  9. 9Royal Free Hospital, London, United Kingdom
  10. 10University Hospital Zurich, Zurich, Switzerland
  11. 11Medical University fo Bialystok, Bialystok, Poland
  12. 12Jefferson University, Philadelphia
  13. 13Boston University, Boston, United States
  14. 14University of Dresden, Dresden, Germany
  15. 15Stanford University, Palo Alto
  16. 16National Jewish Health, Denver
  17. 17Scleroderma Research Consultants LLC, Avon, United States

Abstract

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

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