Psychometric validation of the Worst Itch Numerical Rating Scale (WI-NRS) and other patient-reported outcome measures for assessing severity and impact of pruritus in patients with primary biliary cholangitis

Abstract

Background: Cholestatic pruritus is common in primary biliary cholangitis (PBC), often leading to sleep disturbances and substantially impairing health-related quality of life (HRQoL). Fatigue, also frequent in PBC, can be exacerbated by sleep interference due to nighttime pruritus. Quantitative numerical rating scales (NRS) are appropriate for assessing unidimensional patient-reported outcome (PRO) concepts and are easily interpreted. The PBC-40 is a disease-specific, patient-derived 40-item tool that assesses HRQoL in patients with PBC. To assess pruritus severity in clinical trials, rigorous validation of PROs in the target patient population is required. This study aimed to validate the NRS items for worst itch (WI-NRS), pruritus-related sleep interference (Sleep Interference NRS), and fatigue (Fatigue NRS), plus the PBC-40 (modified with a 7-day recall), among patients with PBC and pruritus.

Methodology: Data were analyzed from the Phase 2b GLIMMER trial (NCT02966834) of linerixibat and a separate observational study in patients with PBC and pruritus. Pruritus severity was assessed using the 0-10 WI-NRS. Psychometric properties of the WI-NRS, Sleep Interference NRS, Fatigue NRS, and PBC-40 (7-day recall) were evaluated. Additional PRO data were used to support validation analyses. Multiple psychometric methods were used to validate the NRS items and PBC-40 (7-day recall).

Results: Data for 288 patients (n=147 GLIMMER; n=141 observational study) with PBC experiencing pruritus were included. The internal consistency of PBC-40 (7-day recall) was acceptable to excellent and confirmatory factor analysis confirmed its domain structure. All PBC-40 domains showed acceptable test-retest reliability (intraclass correlation coefficients [ICCs]: 0.72-0.90). The WI-NRS showed acceptable test-retest reliability (ICCs: 0.73-0.81 [GLIMMER]; ICC: 0.78 [observational study]). Test-retest reliability was also acceptable for the Sleep Interference (ICC: 0.85 [GLIMMER]; ICC: 0.77 [observational study]) and Fatigue (ICC: 0.88 [GLIMMER]; ICC: 0.78 [observational study]) NRS items. Convergent, discriminant, and known-groups validity were confirmed for all three NRS items and the PBC-40. Additionally, the NRS and PBC-40 Itch domain demonstrated responsiveness by reflecting change in other PROs over time.

Conclusions: The data support the psychometric reliability, validity, and responsiveness of WI-NRS, pruritus-related Sleep Interference NRS, and Fatigue NRS, and PBC-40 (7-day recall) in patients with PBC experiencing pruritus.

Keywords: 5-D itch scale; Cholestatic pruritus; Fatigue; Itch; Numerical rating scale; PBC-40; Patient-reported outcomes; Primary biliary cholangitis; Psychometric validation; Sleep interference.

Fig. 1

Known-groups validity boxplots of key NRS items at week 16 in GLIMMER versus other measures. WI-NRS weekly itch score by (A) 5-D itch scale Degree item and (B) PGI-S. Sleep Interference NRS by (C) 5-D itch scale Sleep item and (D) PGI-S. Fatigue NRS by (E) BDI-II tiredness or fatigue item and (F) PBC-40 Fatigue domain. The numbers above the box plots represent medians. ^aWeekly itch score. 5-D, 5-dimension; BDI-II, Beck Depression Inventory – II; NRS, Numerical rating scale; PBC-40, Primary Biliary Cholangitis – 40 items; PGI-S, Patient Global Impression of Severity; WI-NRS, Worst Itch Numerical Rating Scale