title: PRISM, a Patient-Reported Outcome Instrument, Accurately Measures Symptom Change in Refractory Gastroesophageal Reflux Disease.
abstract: Most patients with gastroesophageal reflux disease (GERD) experience relief following treatment with proton pump inhibitors (PPIs) (Vakil et al. in Am J Gastroenterol 101:1900-1920, 2006; Everhart and Ruhl in Gastroenterology 136:376-386, 2009). As many as 17-44% of patients, however, exhibit only partial response to therapy. Most extant GERD patient-reported outcome (PRO) instruments fail to meet development best practices as described by the FDA (Talley and Wiklund in Qual Life Res 14:21-33, 2005; Van Pinxteren et al. in Cochrane Database Syst Rev 18:CD002095, 2004; El-Serag et al. in Aliment Pharmacol Ther 32:720-737, 2010).
  
  
  
  To develop and validate a PRO instrument for clinical trials involving patients with GERD who are PPI partial responders.
  
  
  
  We prepared a systematic literature review, held patient focus groups, convened an expert panel, and conducted cognitive interviews to establish content validity. Eligible participants took PPI therapy for at least 8 weeks, had undergone an upper endoscopy, and scored at least 8 points on the GerdQ [6]. Qualitative data guided development of 26 draft items. Items were reviewed by expert panels and debriefed with patients. The resulting 21-item instrument underwent psychometric evaluation during a Phase IIB trial.
  
  
  
  During the trial, confirmatory factor analysis (n = 220) resulted in a four-factor model displaying the highest goodness of fit. All domains had a high inter-item correlation (Cronbach's α > 0.8). Test-retest reliability and convergent validity were strong, with highly significant (p < 0.01) correlations between average weekly PRISM scores and severity anchors and significant (p < 0.05) correlations with anchor subscales. Cumulative distribution functions revealed significant differences between responders and non-responders.
  
  
  
  Analysis in a clinical trial setting demonstrated strong psychometric properties suggesting validity of PRISM. Developed in line with FDA guidance on PROs, PRISM represents an important new outcome measure for patients with GERD with a partial response to PPI therapy.
authors.affiliation: Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), 116 N. Robertson Blvd.Suite 400, Los Angeles, CA, 90048, USA.
authors.forename: Garth
authors.initials: G
authors.lastname: Fuller
authors.affiliation: Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), 116 N. Robertson Blvd.Suite 400, Los Angeles, CA, 90048, USA.|UCLA Fielding School of Public Health, Los Angeles, CA, USA.|, 1016 Quail Gardens Ct, Encinitas, CA, 92024, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Bolus
authors.affiliation: Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), 116 N. Robertson Blvd.Suite 400, Los Angeles, CA, 90048, USA.|, 44 16th Street, Hermosa Beach, CA, 90254, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Whitman
authors.affiliation: Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), 116 N. Robertson Blvd.Suite 400, Los Angeles, CA, 90048, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Talley
authors.affiliation: M. H. Erder Health Economics, Inc, Livingston, NJ, USA.
authors.forename: M Haim
authors.initials: MH
authors.lastname: Erder
authors.affiliation: Shire, Zählerweg 10, 6300, Zug, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Joseph
authors.affiliation: M. H. Erder Health Economics, Inc, Livingston, NJ, USA.
authors.forename: Debra G
authors.initials: DG
authors.lastname: Silberg
authors.affiliation: Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), 116 N. Robertson Blvd.Suite 400, Los Angeles, CA, 90048, USA. brennan.spiegel@cshs.org.|UCLA Fielding School of Public Health, Los Angeles, CA, USA. brennan.spiegel@cshs.org.|Department of Medicine, Cedars-Sinai Health System, Cedars-Sinai Medical Center, Los Angeles, CA, USA. brennan.spiegel@cshs.org.|VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA. brennan.spiegel@cshs.org.
authors.forename: Brennan
authors.initials: B
authors.lastname: Spiegel
mesh_terms: D000328:Adult; D002986:Clinical Trials as Topic / Q000379:methods; D000068598:Data Accuracy; D004351:Drug Resistance; D005163:Factor Analysis, Statistical; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis / Q000523:psychology / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071066:Patient Reported Outcome Measures; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D011594:Psychometrics / Q000379:methods / Q000592:standards; D036301:Qualitative Research; D011788:Quality of Life; D063189:Symptom Assessment / Q000379:methods / Q000592:standards
chemical_list: D054328:Proton Pump Inhibitors
keywords: Gastroesophageal reflux; Patient-reported outcomes; Proton pump inhibitors; Psychometrics; Qualitative research; US Food and Drug Administration; Validation studies