OBJECTIVES : The Itch Reported Outcome tool for observers (ItchRO[Obs]) was developed specifically to assess the severity of itch-related symptoms in children with cholestatic liver disease, including Alagille syndrome (ALGS). Itch is evaluated daily in the morning (AM) and evening (PM) using a five-point scale of itch severity (0=none, 4=most severe itch). This study evaluated the psychometric properties of the ItchRO(Obs) in the ICONIC study.

METHODS : Data from ICONIC, a maralixibat 48-week phase 2 placebo-controlled, randomized withdrawal study (RW) in children with ALGS were analyzed. Scores were generated by taking the average of the AM or PM responses over a 7- or 28-day period. Validity and reliability analyses of both the AM and PM scores were conducted. Concurrent and known-groups validity of the new ItchRO scores were examined against co-validators (i.e., Clinician Scratch Scale [CSS] and the caregiver-reported Pediatric Quality of Life Inventory [PedsQL]). Distribution-based and anchor-based approaches were used to establish the clinically relevant minimally important difference (MID).

RESULTS : Positive correlations between ItchRO(Obs) and CSS scores indicated convergent validity, with correlations ranging from r = 0.63 to 0.78. Negative correlations between ItchRO and PedsQL scores indicated divergent validity, with correlations ranging from r = -0.1 to -0.96. Known-groups validity analysis showed worse ItchRO(Obs) scores were associated with more damage of the skin due to pruritus, as measured by the CSS, confirming that ItchRO(Obs) scores are consistent with worsening pruritus. Distribution-based analysis for a MID showed the estimated standard error of measurement (SEM) ranged from 0.28 to 0.32. Using a criterion of 2 SEMs as the MID, these results indicated 7- and 28-day AM and PM change scores of -0.56 to -0.64 were indicative of clinically relevant changes in pruritus.

CONCLUSIONS : ItchRO(Obs) is reliable, valid and capable of detecting small clinically meaningful changes in pruritus-related symptoms as reported by caregivers of patients with ALGS.