Development of Patient-Reported Outcome Measures for Early Systemic Sclerosis Across Disease Subtypes.

Abstract

Existing patient-reported outcome (PRO) measures for systemic sclerosis (SSc) have important limitations, including inadequate coverage of early disease and limited inclusion of diffuse cutaneous (dcSSc) and limited cutaneous (lcSSc) subtypes. This paper reports on the development of two PRO measures for early SSc in the Clinical Outcome Assessments for Systemic Sclerosis Clinical Trials (COAST) study, following regulatory guidance for clinical outcome assessments. Concept elicitation interviews were conducted with 42 individuals with dcSSc or lcSSc within 7 years of disease onset. Data were analyzed using a constant comparative approach. The concept prioritization scheme integrated symptom frequency, bother and health-related quality of life ratings, subgroup analyses, and clinical expert input. Priority concepts were mapped to items from item libraries (PROMIS®, FACIT) and SSc-specific measures, with new items developed during measure refinement. The item pool was reduced through expert consensus. Across SSc subtypes, participants reported 52 symptoms and treatment side effects, spanning 16 domains. Raynaud's phenomenon was the most frequently reported symptom (81.0%), followed by swelling and pain (66.7% each); among the five most frequently reported symptoms, fatigue was rated most bothersome (mean=7.20, 0-10 scale). Participants also reported 57 physical function impacts across 8 domains, and 16 socioemotional concerns across 4 domains. Two candidate measures were constructed: COAST Scleroderma Symptom Questionnaire (33 items) and COAST Scleroderma Function and Mood Questionnaire (20 items). The COAST measures address important gaps in SSc measurement, with content validity established through systematic patient input. The measures were designed for use in clinical trials to assess treatment benefit in early SSc.