Abstract
Abstract
Background
Psychometric validation of the Angioedema Quality of Life Questionnaire (AE-QoL) was conducted to determine its suitability for assessing health-related quality of life (HRQoL) in patients with hereditary angioedema (HAE).
Methodology
Data were analyzed from 90 participants with HAE in OASIS-HAE (NCT05139810), a randomized, double-blind, placebo-controlled phase 3 study of donidalorsen (DAWNZERA™). Psychometric validation, assessed by post hoc analyses on scores at Baseline and Week 24 visits, included internal consistency reliability, structural and construct validity (convergent, criterion, and known-groups validity), and responsiveness.
Results
Confirmatory factor analysis supported the 17-item AE-QoL measurement model (comparative fit index [CFI], Tucker-Lewis index [TLI], and standardized root mean square residual [SRMR] met thresholds). Internal consistency reliability was strong for the total, functioning, fatigue/mood, and fears/shame domains (Cronbach’s ⍺: 0.81–0.97; McDonald’s ⍵: 0.86–0.98), but weaker for the 2-item nutrition domain (Cronbach’s ⍺: 0.65–0.75; McDonald’s ⍵: 0.64–0.75). At Week 24, AE-QoL total, functioning, and fears/shame scores showed convergent validity with the 28-day Angioedema Activity Score (AAS-28) (n
r
= 0.51, 0.73, and 0.51, respectively) and with the Angioedema Control Test (AECT) (
r
=-0.77, -0.89, and − 0.70, respectively). Criterion validity was supported by moderate-to-strong correlations with HAE attack rate at Week 24 (total:
r
= 0.65; domains:
r
= 0.55–0.78, excluding fatigue/mood). Known-groups validity was demonstrated by significant differences in AE-QoL scores between patients with poor- versus well-controlled disease based on AECT score at Baseline and Week 24 (all
p
d
effect size [ES] range: 0.63–3.65). AE-QoL total, functioning, and fears/shame scores were sensitive to changes in disease activity, with correlations’ absolute values for changes in score from Baseline to Week 24 exceeding 0.30 for AAS-28 and 0.39 for AECT, excluding fatigue/mood and nutrition domains. AE-QoL change scores for total, functioning, fears/shame, and nutrition domains effectively differentiated between subgroups with varying reductions in HAE attack frequency (all
p
Conclusions
The AE-QoL demonstrated strong reliability, validity, and ability to detect change, supporting its use as an important patient-reported outcome measure for evaluating HRQoL in patients with HAE.