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Review
. 2021 Sep;14(5):533-543.
doi: 10.1007/s40271-020-00485-w. Epub 2020 Dec 18.

Development of a Patient-Reported Outcome Measure for Non-Alcoholic Steatohepatitis (NASH-CHECK): Results of a Qualitative Study

Lynda C Doward  1 , Maria-Magdalena Balp  2 , James Twiss  3 , Christina Slota  4 , Donna Cryer  5 , Clifford A Brass  6 , Quentin M Anstee #  7   8 , Arun J Sanyal #  9
Affiliations
Review

Development of a Patient-Reported Outcome Measure for Non-Alcoholic Steatohepatitis (NASH-CHECK): Results of a Qualitative Study

Lynda C Doward et al. Patient. 2021 Sep.

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.

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Conflict of interest statement

This study was completed under a research contract between RTI Health Solutions and Novartis Pharma AG and was funded by Novartis Pharma AG. LCD, JT, and CS are salaried employees of RTI Health Solutions. MMB and CAB are salaried employees of Novartis. DC is a salaried employee of the Global Liver Institute, which received consulting fees from Novartis in support of this research. AJS has received research grants and consulting fees from Novartis, which funded this study. QMA has received research grants and consulting fees from Novartis and is participating in research collaborations with Novartis, which funded this study.

Figures

Fig. 1
Fig. 1
Key symptoms reported by concept elicitation sample (n = 23)
Fig. 2
Fig. 2
Key health-related quality of life (HRQoL) issues reported by concept elicitation sample (n = 23). iADL instrument activities of daily living
Fig. 3
Fig. 3
Final conceptual model for NASH. ADL activity of daily living, BMI body mass index, iADL instrumental ADL, NASH non-alcoholic steatohepatitis
See this image and copyright information in PMC

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