OBJECTIVES: Pruritus, fatigue and sleep disturbance are common patient-reported outcomes assessed in trials of PBC. To meet regulatory standards, PRO measures assessing trial endpoints should be rigorously validated in the target patient population. This study evaluated the psychometric properties of several NRS items and the 7-day recall version of PBC-40 (a disease-specific measure of HRQoL, previously validated with 4-week recall).

METHODS: This web-based survey recruited individuals with self-reported PBC (with prior/current pruritus) from market research panels in the US, UK and Canada. Participants completed daily 0–10 NRS items (worst itch, fatigue, pruritus-related sleep interference) over 8 days and the 7-day PBC-40 and other select PROs on Days 1 and 8. Measurement properties were assessed using psychometric analyses.

RESULTS: Participants (N=141) were predominantly female (93%), white (87%), aged ≥35 years (93%) with 80% experiencing pruritus for >1 year. At screening, 69% had pruritus with 50% reporting moderate/greater overall itching severity. The WI-NRS showed acceptable test-retest reliability (ICC: 0.78). Convergent validity of all NRS items was evidenced by large, positive correlations with scores of similar concepts from other measures (r≥0.68, all p<0.0001), and known groups validity was confirmed based on groups defined by PGI-S (all p<0.001) and general health item of the PBC-40. The 7-day PBC-40 showed acceptable test-retest and internal consistency reliability across all 6 domains (ICCs: 0.85–0.90; Cronbach’s alpha: 0.73–0.95); convergent validity was demonstrated across similar measures for itch, fatigue, emotional, social and cognitive domains (r>0.61, all p<0.0001) and factor analysis confirmed the domain structure and adequate fit statistics (RMSEA: 0.059; CFI: 0.966).

CONCLUSIONS: NRS items assessing worst itch, sleep interference and fatigue, and the 7-day PBC-40 are valid and reliable PRO measures, strongly supporting their use as assessments for patient-centric trial endpoints, including in the Phase 3 GLISTEN trial (NCT04950127) of linerixibat for pruritus treatment in PBC.

FUNDING: GSK (212144)