BACKGROUND: This study describes the development of NASH-CHECK: a new patient-reported outcome (PRO) measure assessing symptoms and health-related quality of life (HRQOL) in non-alcoholic steatohepatitis (NASH) fibrosis stages F1–F3 (non-cirrhotic) .
METHODS: NASH-CHECK content was generated via concept-elicitation (CE) interviews with NASH patients in the United States (US) . Content validity was assessed via cognitive debriefing (CD) interviews with US NASH patients . NASH-CHECK was translated into 39 languages; in-country CD interviews further confirmed content validity . Data from a randomised, double-blind, placebo-controlled, phase 2 trial in NASH were used to evaluate NASH-CHECK psychometric properties (dimensional structure, reliability, construct validity, and responsiveness) .
RESULTS: CE interviews (n=23: 78%F; mean[SD] age=56[10] yrs) identified key patient symptoms (pain, fatigue, sleep, cognitive impacts) and HRQOL impacts (physical functioning, social, emotional) . US CD interviews (n=20: 55%F; mean[SD] age=51[10] yrs) resulted in minor changes to some instructions/item wording to improve clarity . NASH-CHECK was successfully adapted into 39 languages (29 countries) . CD interviews in 195 NASH patients (5/language: 49%F, mean[SD] age=49[13] yrs) confirmed content validity. Clinical trial data were available for 253 NASH patients (61%F;mean[SD] age=53[12] yrs). Item-level analyses confirmed a final 28-item PRO measure comprising 5 single-symptom items (Abdominal Pain, Abdominal Bloating, Fatigue, Sleep, and Itchy Skin); 1 symptom scale (Cognitive Symptoms, 4 items); and 3 HRQOL scales (Activity Limitations, 8 items; Emotional Impact, 4 items; Social Impact, 7 items) . Analyses supported internal consistency reliability (baseline Cronbach’s alpha values range 0 .77-0 .94), test retest reliability (intraclass correlation range 0 .62-0 .82), construct validity (e .g . differences in all NASH-CHECK scale scores between levels of Patient Global Impression of Severity [PGIS]; (P<0 .0001; Figure 1), and responsiveness (e .g . differences in most NASH-CHECK scale scores between levels of change in PGIS at 12 weeks; P < 0.05) of the final scales.
CONCLUSION: NASH-CHECK is a novel, NASH-specific PROM assessing patient-relevant symptoms and HRQOL . These results demonstrate content validity, dimensional structure, reliability, construct validity and responsiveness in patients with non-cirrhotic NASH: establishing it as a valuable novel PROM of symptoms and HRQOL in NASH.
