Table 1.
Comparison of selected PRO measurement properties to FDA and COSMIN recommended standards.
| PRO | Content/item source | Items/domains | Recall period | Construct validity and other validity | Reliability | Instrument modification | Main limitation |
|---|---|---|---|---|---|---|---|
| CLDQ-NAFLD | Items were developed using a variety of sources (HRQoL tools, focus groups, patient interviews — 25 patients with NAFLD, among whom 20% had histological cirrhosis. Validated in 104 patients with NAFLD, among whom 15% had compensated cirrhosis |
6 domains (36 items): abdominal symptoms, activity, emotional, fatigue, systemic symptoms, worry | 2 weeks | Construct validity: domains highly correlated with SF-36: activity, emotional, fatigue and systemic symptoms psychometrically evaluated in a group of patients with NAFLD (n = 104). Known-groups validity: worse scores correlated with increased disease severity in all scales; unable to discriminate between cirrhotic and non-cirrhotic patients. Not validated in a cohort of patients with advanced liver cirrhosis; not validated in NASH |
Tested and retested in a small subgroup of patients with NAFLD (n = 27; 5-19 weeks apart) — non-statistically significant. Internal consistency: Cronbach's α 0.74-0.90 |
Modified version of CLDQ | Lack of evidence of content validity within a NASH population |
| LDQoL 1.0 | Developed after conducting focus group interviews with 15 patients awaiting liver transplantation and literature search on HRQoL in liver disease Input from patient focus groups combined with views of gastroenterologists and hepatologists and literature search of HRQoL |
SF-36 + 12 disease-targeted scales (75 items): symptoms of liver disease, effects of liver disease, concentration, memory, quality of social interaction, health distress, sleep problems, loneliness, hopelessness, stigma of Liver disease, sexual functioning, sexual problems | 4 weeks | Psychometrically evaluated in a group of end-stage liver disease patients. Known-groups validity: worse scores correlated with worse Child-Pugh class, worse self-rated liver disease severity and higher number of disability days |
Internal consistency: Cronbach's α 0.62–0.95 | n.a. | The tool is impractical to use given its length; uses maximum recall period recommended for QoL tools |
| LDSI 2.0 | Items were developed in a large group of patients with liver diseases (patient interviews) | 24 items: 9 items measure severity of symptoms (itch, joint pain, pain in the right upper abdomen, sleepiness during the day, worry about family situation, decreased appetite, depression, fear of complication, jaundice); 9 items measure the impact of these symptoms on person's daily activities; 6 items evaluate memory problems, change of personality, financial affairs, change in use of time, reduced sexual activity and reduced sexual interest | 1 week | Construct validity: tested in comparison with SF-36 and the multidimensional fatigue index-20, showed low to moderate correlations indicating a slight to moderate overlap between the information given by the LDSI and the other 2 questionnaires Spearman correlations reported between symptom severity and related hindrance items ranged between 0.52-0.80. Psychometrically evaluated in a general population of patients with chronic liver disease (n = 1,175) |
Test-retest reliability in a small group of patients (n = 34) only 3 days apart. Internal consistency: Cronbach's α>0.79 |
Modified version of LDSI | Lack of evidence of content validity |
| FIS | Developed on the basis of existing fatigue questionnaires in a group of patients with multiple sclerosis (n = 30) (patient interviews) Designed in accordance with the taxonomy on quality of life in clinical trials73 |
3 domains: cognitive functioning, physical functioning, and psychosocial functioning (40 items) | 1 month | Construct validity: statistically significant correlations between the total FIS and sickness impact profile (generic HRQoL measure) score Evaluated in a group of patients referred to the Infectious Disease Unit for investigation of fatigue |
Internal consistency: Cronbach's α 0.98 | n.a. | Not validated in the NASH patient population; maximum recall period recommended for QoL tools |
The table presents the relevant PROs which were evaluated for the review. The PROs have limitations relating to population group, tool practicality, evidence or validation. CLDQ, chronic liver disease questionnaire; FDA, United States Food and Drug Administration; FIS, fatigue impact scale; HRQoL, health-related quality of life; LDQoL, liver disease quality of life questionnaire; LDSI, liver disease symptom index; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; PROs, patient-reported outcomes.