title: Psychometric validation of patient-reported outcome measures assessing chronic constipation.
abstract: BACKGROUND
  Measures assessing treatment outcomes in previous CC clinical trials have not met the requirements described in the US Food and Drug Administration's guidance on patient-reported outcomes.
  
  
  OBJECTIVE
  Psychometric analyses using data from one Phase IIb study and two Phase III trials of linaclotide for the treatment of chronic constipation (CC) were conducted to document the measurement properties of patient-reported CC Symptom Severity Measures.
  
  
  METHODS
  Each study had a multicenter, randomized, double-blind, placebo-controlled, parallel-group design, comparing placebo to four doses of oral linaclotide taken once daily for 4 weeks in the Phase IIb dose-ranging study (n=307) and to two doses of linaclotide taken once daily for 12 weeks in the Phase III trials (n=1,272). The CC Symptom Severity Measures addressing bowel function (Bowel Movement Frequency, Stool Consistency, Straining) and abdominal symptoms (Bloating, Abdominal Discomfort, Abdominal Pain) were administered daily using interactive voice-response system technology. Intraclass correlations, Pearson correlations, factor analyses, F-tests, and effect sizes were computed.
  
  
  RESULTS
  The CC Symptom Severity Measures demonstrated satisfactory test-retest reliability and construct validity. Factor analyses indicated one factor for abdominal symptoms and another for bowel symptoms. Known-groups F-tests substantiated the discriminating ability of the CC Symptom Severity Measures. Responsiveness statistics were moderate to strong, indicating that these measures are capable of detecting change.
  
  
  CONCLUSIONS
  In large studies of CC patients, linaclotide significantly improved abdominal and bowel symptoms. These psychometric analyses support the reliability, validity, discriminating ability, and responsiveness of the CC Symptom Severity Measures for evaluating treatment outcomes in the linaclotide clinical studies.
authors.affiliation: RTI Health Solutions, Durham, NC, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Nelson
authors.affiliation: RTI Health Solutions, Durham, NC, USA.
authors.forename: Valerie Sl
authors.initials: VS
authors.lastname: Williams
authors.affiliation: RTI Health Solutions, Durham, NC, USA.
authors.forename: Sheri E
authors.initials: SE
authors.lastname: Fehnel
authors.affiliation: Forest Research Institute, Jersey City, NJ, USA.
authors.forename: Robyn T
authors.initials: RT
authors.lastname: Carson
authors.affiliation: Ironwood Pharmaceuticals, Cambridge, MA, USA.
authors.forename: James
authors.initials: J
authors.lastname: MacDougall
authors.affiliation: Ironwood Pharmaceuticals, Cambridge, MA, USA.
authors.forename: Mollie J
authors.initials: MJ
authors.lastname: Baird
authors.affiliation: Forest Research Institute, Jersey City, NJ, USA.
authors.forename: Stavros
authors.initials: S
authors.lastname: Tourkodimitris
authors.affiliation: Ironwood Pharmaceuticals, Cambridge, MA, USA.
authors.forename: Caroline B
authors.initials: CB
authors.lastname: Kurtz
authors.affiliation: Ironwood Pharmaceuticals, Cambridge, MA, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Johnston
keywords: linaclotide; patient-reported outcomes; psychometric evaluation