Development of a Provisional Core Set of Response Measures for Clinical Trials of Systemic Sclerosis

Objective: To develop a provisional core set of response measures for clinical trials of systemic sclerosis (SSc).
Methods: The Scleroderma Clinical Trial Consortium (SCTC) conducted a structured, 3-round Delphi exercise to reach consensus on a core set of measures for clinical trials of SSc. Round 1 asked the SCTC investigators to list items in 11 pre-defined domains that should be incorporated into clinical trials. Round 2 asked respondents to rate the importance of the chosen items and was followed by a meeting during which Steering Committee discussed the feasibility, reliability, and validity of the items. Round 3 of the Delphi exercise sought to obtain broader consensus on the core set measures. Members also voted on items that had data on feasibility, reliability, and validity but lacked data on responsiveness to change and may be useful outcome measures in future clinical trials.
Results: Fifty SCTC investigators participated in Round 1, providing 212 unique items for the 11 domains. Forty-six (92%) participants responded in Round 2 and rated 177 items. The ratings of 177 items were reviewed by the Steering Committee and 31 items from the 11 domains were judged appropriate for inclusion in a multicenter clinical trial (Table 1). Forty SCTC investigators completed the Round 3 exercise and ranked 30 of 31 items as acceptable for inclusion in the core set on a scale of 1 (complete disagreement on the core set measure for a combined measure) to 9 (complete agreement on the core set measure for a combined measure). The Steering Committee also proposed 14 items for a research agenda.
Conclusion: Using Delphi exercise, we developed a provisional core set of measures for assessment of disease activity and severity in clinical trials of SSc.
Table 1: Core set items selected for 11 domains

SKIN		Agreement from Round 3 Median (25th-75th percentile)
1	Modified Rodnan Skin Score	9 (9-9)
2	Visual analog scale (VAS) or /Likert of patient global assessment for skin activity	7 (5.5 -9)
3	VAS or /Likert of physician global assessment for skin activity	7 (6-9)
4	Durometer	7 (6-8)
MUSCULOSKELETAL
1	Tender Joint Count	6 (5-8)
2	Tendon friction rubs assessed by the physician	8(7-9)
3	Serum creatinine phosphokinase, aldolase	7 (6-9)
CARDIAC
1	Cardiac Echocardiogram with doppler	9 (8-9)
2	Right heart catheterization	8(6-9)
3	6-minute walk test	8(7-9)
4	Borg Dyspnea Instrument	7 (6-9)
PULMONARY
1	Pulmonary Function Testing	9 (9-9)
2	Validated measure of dyspnea	8(7-9)
3	Breathing VAS from the Scleroderma Health Assessment Questionnaire (S-HAQ)	7 (6-9)
4	High resolution computer tomography (HRCT): quantifiable scale	9(7-9)
RENAL
1	Calculated creatinine clearance based on serum creatinine (Cockroft-Gault or MDRD formula)	9(7-9)
2	Pre-defined renal crisis (Presence or absence)	9(8-9)
GASTROINTESTINAL
1	Body mass index (BMI)	7 (6-9)
4	Validated gastrointestinal tract VAS scale (part of S-HAQ) or other SSc-Validated GI questionnaire	8(7-9)
HEALTH-RELATED QUALITY OF LIFE AND FUNCTION
1	Health Assessment Questionnaire-Disability Index (HAQ-DI)	9(7-9)
2	VAS-pain scale from the HAQ-DI	7 (6-9)
3	SF-36 version 2	8(7-9)
GLOBAL HEALTH
1	VAS/Likert patient global severity	8(6.5-9)
2	VAS/Likert physician global severity	8(6-9)
3	Scleroderma-related health transition by patient	7 (6-9)
4	Scleroderma-related health transition by physician	7 (5-8)
RAYNAUD''S PHENOMENON
1	Raynaud’s Condition Score	8(7-9)
2	VAS Raynaud''s (part of S-HAQ)	8(6.5-9)
DIGITAL ULCERS
1	Active digital tip ulcer count on the volar surface	9(7-9)
2	VAS digital ulcer (part of S-HAQ)	8(6-9)
BIOMARKERS
1	Acute phase reactant(s)_Erythrocyte sedimentation rate and/or C-reactive protein	8(6-9)

 D. Khanna, None; D.E. Lovell, None; E. Giannini, None; P.J. Clements, None; P.A. Merkel, None; J.R. Seibold, None; M. Matucci-Cerinic, None; C.P. Denton, None; M.D. Mayes, None; V.D. Steen, None; J. Varga, None; D.E. Furst, None.