Psychometric Validation of Four Patient-Reported Outcome Instruments in A Diverse Sample of Adults with Chronic Hepatitis C Virus Infection Treated with Simeprevir and Sofosbuvir

To evaluate measurement properties of four patient reported outcome (PRO) instruments used in chronic hepatitis C virus (HCV) infection trials: Fatigue Severity Scale (FSS); Center for Epidemiologic Studies Depression Scale (CES-D); EuroQoL 5 Dimension (EQ-5D-5L); and HCV Symptom and Impact Questionnaire (HCV-SIQv4), a new 33-item measure of symptoms and impact of HCV and its treatment. PRO data were pooled from the IMPACT (Phase IIb) and OPTIMIST 1&2 (Phase III) trials evaluating the safety and efficacy of simeprevir in combination with sofosbuvir for treatment of chronic HCV infection. Scale range adequacy, reliability, validity, responsiveness, and thresholds for clinically important change were assessed for each PRO instrument. Data from 437 patients with HCV-related liver disease severity ranging from no liver fibrosis to decompensated cirrhosis were analyzed. Stage of liver disease was associated with the severity of symptoms and functioning at baseline. For most patients, symptom scores improved during treatment which is consistent with the reduction in HCV-related symptoms reported in the trials. Reliability was acceptable (Cronbach’s α≥0.7, test-retest ICC ≥0.7) for most scores except the HCV-SIQv4 Gastrointestinal and Integumentary domain scores. Convergent validity was observed between PRO scores and concurrent measures of the same concept. Greater symptom severity and worse impact scores were associated with liver cirrhosis, depression, severe fatigue, and health limitations. Patients who achieved SVR12 had better outcomes on all PRO instruments. HCV-SIQv4 symptom and domain scores were responsive to improvements and worsening in health state (effect sizes ≥0.5). Thresholds for change in scores indicating a clinically important improvement (or worsening) were: 8 (8) for HCV-SIQv4 Overall Body System Score; 1 (1) for FSS; 3 (6) for CES-D; and 8 (worsening not studied) for EQ-5D-5L VAS. The FSS, CES-D, EQ-5D-5L, and HCV-SIQv4 are reliable, valid, and responsive measures of HCV treatment outcomes suitable for patients regardless of liver disease stage.