Abstract
INTRODUCTION: Understanding how patients experience their disease is a vital step in optimal disease management, and patient- and observer-reported outcome (PRO and ObsRO, respectively) measures can add important details to clinical information that is obtained as novel treatments are developed. Instruments that measure meaningful symptoms and impacts from the perspective of pediatric patients with cholestatic liver disease or their caregivers are needed. This study aimed to identify salient concepts in pediatric cholestatic liver disease, develop novel PRO and ObsRO instruments, and establish the instruments' content validity. METHODS: Relevant signs, symptoms, and impacts of cholestatic liver disease were identified through a literature review, interviews with expert clinicians, and concept elicitation interviews with children and caregivers of children who had progressive familial intrahepatic cholestasis (PFIC), Alagille syndrome, biliary atresia, or primary sclerosing cholangitis. Additional cognitive debriefing interviews with patients and caregivers were performed to ensure that participants could understand the instructions, questions, and response scales of the PRO and ObsRO instruments, with modifications made as necessary to improve comprehension and/or usability. RESULTS: A total of 36 interviews with patients and caregivers were conducted. Pruritus and sleep disturbance (e.g., difficulty falling or staying asleep due to itch) were identified as the most problematic symptom and significant impact, respectively, of the pediatric cholestatic liver diseases assessed. The ObsRO and PRO instruments, called PRUCISION, focus on these key disease features in the morning and evening. Several modifications were made to the draft instruments following cognitive interviews. The final PRUCISION PRO and ObsRO measures are designed as an electronic diary to be completed twice daily. The response scales include pictorial, verbal, and numeric scales. CONCLUSION: Novel PRO and ObsRO PRUCISION instruments were created that evaluate the patient experience of cholestatic pruritus in children with PFIC and other cholestatic liver diseases. The content validity of the PRUCISION instruments is established.