Discussion
obesity, NASH
OBESITY
NASH-CHECK is a novel, NASH-specific measure that was developed in accordance with best practice guidance on the development and validation of PRO measures [The patterns of correlations between NASH-CHECK scale scores and scores on comparator measures were as expected, providing support that the NASH-CHECK scales measure their intended concepts. As expected, all NASH-CHECK scores discriminated between patients according to perceived symptom severity, further supporting the construct validity of NASH-CHECK. Furthermore, this association persisted when controlling for BMI, indicating that the relationship between NASH-CHECK scores and NASH symptom severity was not a function of obesity status. NASH-CHECK scores were also able to detect change associated with change in PGIS score over periods of 12 and 48 weeks, and changes in NASH-CHECK scores were correlated as expected with other PRO change scores. These findings suggest that NASH-CHECK will be valuable for quantifying change in patients’ experiences with NASH.Low levels of associations were found between NASH-CHECK scale scores and clinical assessments such as NAS, ELF score, and ALT level. The observed correlations were comparable to those between CLDQ scale scores and the same clinical variables in this study and are consistent with previous research that has demonstrated only weak associations between PRO scores and clinical outcomes in NASH [The weak associations between NASH-CHECK and the clinical outcomes suggest that PRO data capture unique information about the patient experience that is not available from histologic endpoints or serologic biomarkers for NASH. Such information is valuable in clinical trial settings to determine the broader impacts of NASH and its treatment from the patient perspective; this information provides regulators, policy makers, health technology assessment (HTA) authorities, and clinicians with important insights about the patients’ experience. NASH-CHECK also provides clinicians with a way to quantify the impact of NASH from the patient perspective that could be useful in clinical practice.A limitation of this study was the relatively small sample size available for EFA (n = 103). However, the preliminary scales identified through EFA were confirmed through CFA in a separate sample, thus increasing confidence in the robustness of the identified scale structure. Evaluations of the longitudinal properties of NASH-CHECK were limited by the relatively low levels of symptoms and HRQOL impairments in both study samples at baseline, thus reducing the potential for change. Despite this, changes in NASH-CHECK scale scores were associated with changes in other PRO measures and most differed as expected across levels of change in PGIS.