title: Psychometric evaluation of the hepatitis C virus patient-reported outcomes (HCV-PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial.
abstract: OBJECTIVE
  To describe the psychometric properties and identify the minimally important difference (MID) of the hepatitis C virus patient-reported outcomes (HCV-PRO) instrument. Chronic HCV infection and associated treatments negatively affect PROs of function and well-being.
  
  
  METHODS
  In a phase 2 trial, HCV-infected patients received direct-acting antivirals (DAAs) for 12 weeks with peg-interferon/ribavirin (peg-IFN/RBV) for 48 weeks, or placebo plus peg-IFN/RBV. The HCV-PRO total score, SF-36 PCS and MCS scores, EQ-5D-3L, and EQ VAS were measured at baseline, week 8, end of DAA treatment (EODT), end of peg-IFN/RBV treatment (EOT), and posttreatment week 24 (SVR24). Convergent validity of the HCV-PRO was assessed by Pearson's correlation coefficients. Discriminant validity was assessed by analyzing mean HCV-PRO total scores by EQ-5D anxiety/depression and pain/discomfort domain scores (none vs. some) and presence/absence of depression or fatigue adverse events. MID was identified through effect size (ES) and receiver-operating characteristic (ROC) curve analyses (HCV-PRO response vs. SF-36 PCS/MCS and EQ VAS MID thresholds).
  
  
  RESULTS
  In 74 patients (22 % female; 81 % White; 51 % ≥50 years), correlations (0.64-0.96) between HCV-PRO total scores, SF-36 PCS/MCS scores, and EQ VAS scores at all time points supported convergent validity. HCV-PRO total scores were reduced to 10-30 points in patients impaired by depression, pain, or fatigue symptoms. Impact of peg-IFN/RBV regimen on HCV-PRO ES increased over time (EODT -0.76; EOT -0.93). ES and ROC curve analyses indicated an MID of -10 points.
  
  
  CONCLUSIONS
  The HCV-PRO was valid and responsive in the population studied. An MID of -10 points represented a threshold of clinical significance for the HCV-PRO.
authors.affiliation: Hershey Medical Center, Pennsylvania State University, Hershey, PA, USA, rtanders@psu.edu.
authors.forename: Roger T
authors.initials: RT
authors.lastname: Anderson
authors.forename: Robert W
authors.initials: RW
authors.lastname: Baran
authors.forename: Pennifer
authors.initials: P
authors.lastname: Erickson
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Revicki
authors.forename: Birgitta
authors.initials: B
authors.lastname: Dietz
authors.forename: Katherine
authors.initials: K
authors.lastname: Gooch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D001007:Anxiety / Q000150:complications; D003627:Data Interpretation, Statistical; D003863:Depression / Q000150:complications; D004359:Drug Therapy, Combination; D005260:Female; D006305:Health Status Indicators; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000523:psychology*; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D010919:Placebos; D011594:Psychometrics / Q000592:standards*; D011788:Quality of Life; D015203:Reproducibility of Results; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; D010919:Placebos; D012254:Ribavirin
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