RTI Health Solutions, The Pavilion, Towers Business Park, Wilmslow Road, Didsbury, Manchester, M20 2LS, UK.
Novartis Pharma AG, Basel, Switzerland.
Patient. 2021 Sep;14(5):533-543. doi: 10.1007/s40271-020-00485-w. Epub 2020 Dec 18.
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.
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.
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.
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.
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.
非酒精性脂肪性肝炎（NASH）是一种进展性的非酒精性脂肪性肝病，其特征为肝内脂肪过度蓄积、炎症、细胞损伤和纤维化。在其早期（非肝硬化）阶段，它通常无症状，而关于 NASH 对患者的影响的信息却很少。
本研究旨在开发一种 NASH 特异性的患者报告结局（PRO）测量工具（NASH-CHECK），作为临床试验的终点，使用符合监管要求的方法。
根据文献和临床/患者专家的审查，建立了一个 NASH 概念模型。该模型指导了在通过美国三级保健中心招募的非肝硬化 NASH 患者中进行的概念发掘（CE）访谈。通过对 CE 数据的主题分析和临床/患者专家的审查，生成了 NASH-CHECK 的内容。对美国患者进行认知性访谈（CD）以评估内容的有效性。
文献综述证实，NASH 会影响患者的功能和健康相关生活质量（HRQoL）。CE 访谈共进行了 23 次，CD 访谈共进行了 20 次。CE 访谈中报告的主要症状包括右上腹痛（n=14）、疲劳（n=18）、睡眠质量差（n=12）、记忆力减退（n=13）和注意力不集中（n=11）；主要的 HRQoL 影响包括身体功能受损、日常活动能力下降、人际关系质量下降、情绪低落、焦虑和自我意识。根据患者对项目相关性、可接受性和理解程度的反馈，最初的 52 项 NASH-CHECK 被简化为 31 项。
访谈揭示了 NASH 的主要症状和广泛的 HRQoL 影响。作为一种评估症状和 HRQoL 的疾病特异性 PRO 测量工具，NASH-CHECK 对患者和临床医生而言是相关的、全面的、可接受的。
