Abstract
INTRODUCTION: Chronic Hand Eczema (CHE) is an inflammatory skin disease of the hands. The Hand Eczema Symptom Diary (HESD) is a new patient-reported outcome measure of worst severity of core CHE signs/symptoms. This study aimed to evaluate content and psychometric validity of the HESD. METHODS: The HESD was developed based on the literature and concept elicitation interviews. Qualitative cognitive debriefing interviews were conducted with CHE patients to assess relevance and understanding of items, response options and recall period. Psychometric properties of the HESD (item performance, dimensionality, reliability, validity, responsiveness and estimation of meaningful change thresholds) were then assessed, first using data from a phase 2b trial (NCT03683719), and confirmed using data from the first 280 participants completing the 16-week treatment phase of a phase 3 trial (NCT04871711). RESULTS: Cognitive debriefing supported item refinement and removal of items and confirmed all items were well understood and relevant to patients. Item properties and dimensionality analyses in the phase 2b data supported removal of additional items, resulting in the 6-item HESD included in the phase 3 trial. Unidimensionality was supported by inter-item correlations (all > 0.70) and Rasch analysis. Internal consistency (Cronbach's alpha = 0.96) and test-retest reliability (Intraclass Correlation Coefficient > 0.89) results were very strong. Construct validity was supported by moderate correlations with concurrent measures (0.53-0.64) and significant differences between severity groups (p < 0.001). Large effect sizes for mean change scores in participants that improved and significant differences between change groups indicated the ability to detect change. Anchor-based analyses supported within-individual responder definitions of ≥ 4-points for improvements in 7-day average HESD scores. CONCLUSION: The HESD is the first CHE-specific, patient-reported outcome measure of CHE signs/symptoms developed and validated in line with regulatory guidance. This article provides evidence of strong content validity and psychometric validity and shows improvements of ≥ 4 points on 7-day average HESD scores represent clinically meaningful, important changes. TRIAL REGISTRATION: NCT03683719, NCT04871711.