Session Information
Title: Systemic Sclerosis, Fibrosing Syndromes, and Raynaud’s – Clinical Aspects and Therapeutics II
Session Type: Abstract Submissions (ACR)
Background/Purpose: Lack of reliable and valid measures of disease activity and clinical response in patients with connective tissue disease (CTD)-related interstitial lung disease (ILD) makes clinical trial design difficult. From a multi-tiered investigation to develop consensus on criteria in both CTD-ILD and idiopathic pulmonary fibrosis (IPF), we report results of expert voting from a 3-tiered Delphi exercise to identify domains ‘important’ to measure in a 1 year randomized controlled trial (RCT) in IPF and CTD-ILD.
Methods: Using 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
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 with their candidate instruments were identified for CTD-ILD and IPF (Table 1). Three domains identified for CTD-ILD: biomarkers, cough and medications await nominal group decisions.
Conclusion: 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 domains including 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.
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Table 1. Results of Tier 3
DOMAINS |
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(median /mean ratings)
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Candidate Instruments
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Dyspnea CTD-ILD IPF (8.0/7.8) (8.0/8.1) |
Borg Dyspnea Index Dyspnea 12 Medical Research Council (MRC) Breathlessness (Chronic Dyspnea) Scale Modified MRC Dyspnea Scale Borg Dyspnea Index – Pre and Post Exercise
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Health Related Quality of Life (HRQoL) CTD-ILD IPF (8.0/7.7) (8.0/7.8) |
Medical Outcomes Trust Short Form-36 Health Survey St. George’s Dyspnea Respiratory Questionnaire Visual Analogue Scale of Patient Assessment Disease Activity Ability to Carry Out Activities of Daily Living (ADLs) Health Assessment Questionnaire Disability Index (HAQ-DI)
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Lung Imaging CTD-ILD IPF (9.0/8.3) (9.0/8.3) |
Extent of Honeycombing on HRCT Extent of Reticulation on HRCT Extent of Ground Glass Opacities on HRCT Overall Extent of Interstitial Lung Disease on HRCT
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Lung Physiology / Function CTD-ILD IPF (9.0/8.7) (9.0/8.7) |
Supplemental Oxygen Requirement Forced Vital Capacity on Spirometry Diffusion Capacity of Lung for Carbon Dioxide 6 MWT with Maximal Desaturation on Pulse Oximetry 6 MWT for Distance
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Survival CTD-ILD IPF (8.0/8.2) (9.0/8.4)
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Time to Decline in Forced Vital Capacity Progression Free Survival Time to Death |
Disclosure:
L. A. Saketkoo,
United Therapeutics,
2,
Actelion Pharmaceuticals US,
2;
D. Huscher,
None;
D. Khanna,
Actelion, BMS, Gilead, Genentech, ISDIN, and United Therapeutics,
2,
Actelion, BMS, Gilead, Genentech, ISDIN, and United Therapeutics,
5,
Actelion, BMS, Gilead, Genentech, ISDIN, and United Therapeutics,
8;
P. F. Dellaripa,
Novartis Pharmaceutical Corporation,
2,
Stomedix, Inc.,
2,
Intermune, Inc.,
2,
Genentech and Biogen IDEC Inc.,
2;
K. Flaherty,
None;
C. V. Oddis,
NIAMS, NIH,
2;
K. Phillips,
None;
A. U. Wells,
None;
C. P. Denton,
Actelion Pharmaceuticals US,
5,
GlaxoSmithKline,
5,
Pfizer Inc,
5,
United Therapeutics,
5;
O. Distler,
Actelion, Pfizer, Boehringer-Ingelheim, Bayer, Roche, Ergonex, BMS, Sanofi-Aventis, United BioSource Corporation, medac, Biovitrium, Novartis and Active Biotec,
2,
Actelion, Pfizer, Boehringer-Ingelheim, Bayer, Roche, Ergonex, BMS, Sanofi-Aventis, United BioSource Corporation, medac, Biovitrium, Novartis and Active Biotec,
5,
Actelion, Pfizer and Ergonex,
8;
O. M. Kowal-Bielecka,
None;
R. Christmann,
None;
N. Sandorfi,
None;
D. Pittrow,
Actelion Pharmaceuticals US,
8,
Pfizer Inc,
5,
Baxter, Inc,
5,
Mbiotec,
1,
Bayer,
5,
Sanofi-Aventis Pharmaceutical,
5,
MSD Germany,
5,
Novartis Pharmaceutical Corporation,
5;
V. Strand,
None;
J. R. Seibold,
Actelion Pharmaceuticals EU,
5,
United Therapeutics,
5,
Bayer Pharmaceuticals,
5;
K. K. Brown,
Actelion Pharmaceuticals US,
2,
Amgen,
2,
Fibrogen,
2,
gilead,
2,
Genentech and Biogen IDEC Inc.,
2,
Celgene,
2;
E. L. Matteson,
American College of Rheumatology and EULAR grant to develop classification criteria for rheumatoid arthritis.,
2,
Novartis Pharmaceutical Corporation,
2,
Horizon,
5.
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