Author information
1RTI Health Solutions, The Pavilion, Towers Business Park, Wilmslow Road, Didsbury, Manchester, M20 2LS, UK. ldoward@rti.org.
2Novartis Pharma AG, Basel, Switzerland.
3RTI Health Solutions, The Pavilion, Towers Business Park, Wilmslow Road, Didsbury, Manchester, M20 2LS, UK.
4RTI Health Solutions, Research Triangle Park, NC, USA.
5Global Liver Institute, Washington, DC, USA.
6Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA.
7Translational and Clinical Research Institute, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, UK.
8Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
9Virginia Commonwealth University, Richmond, USA.
#Contributed equally.
Abstract
Background: Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease characterized by excessive liver fat accumulation, inflammation, cell injury, and fibrosis. It is viewed as largely asymptomatic in its earlier (non-cirrhotic) stages, and information on the patient-perceived impact of NASH is scarce.
Objective: This study aimed to develop a NASH-specific patient-reported outcome (PRO) measure (NASH-CHECK) for use as a trial endpoint, using methods compliant with regulatory expectations.
Methods: A NASH conceptual model was developed based on the literature and clinical/patient expert review. The model guided concept elicitation (CE) interviews in patients with non-cirrhotic NASH recruited via a US tertiary care center. NASH-CHECK content was generated via thematic analysis of CE data and review by clinical/patient experts. Cognitive debriefing (CD) interviews with US patients evaluated content validity.
Results: The literature review confirmed that NASH impacts on functioning and health-related quality of life (HRQoL). Overall, 23 CE and 20 CD interviews were conducted. Key symptoms reported in CE interviews included pain in the upper-right abdomen (n = 14), fatigue (n = 18), poor sleep quality (n = 12), impaired memory (n = 13), and reduced focus (n = 11); key HRQoL impacts included impaired physical functioning, reduced ability to conduct daily living tasks, reduced quality of relationships, low mood, anxiety, and self-consciousness. The 52-item first-draft NASH-CHECK was reduced to 31 items based on patient feedback on item relevance, acceptability, and comprehension.
Conclusions: The interviews revealed key symptoms and broad HRQoL impacts of NASH. As a disease-specific PRO measure assessing symptoms and HRQoL, the NASH-CHECK is relevant, comprehensive, and acceptable to patients and clinicians.