title: Responder Definition of a Patient-Reported Outcome Instrument for Laryngopharyngeal Reflux Based on the US FDA Guidance.
abstract: BACKGROUND
  Different end-point measures may contribute to inconsistent therapeutic responses in relief of laryngopharyngeal reflux (LPR) symptoms.
  
  
  OBJECTIVE
  We aimed to determine an a priori responder definition for a patient-reported outcome instrument, the Reflux Symptom Index (RSI), using an anchor-based method, to interpret individual treatment benefit in patients with LPR, on the basis of the US Food and Drug Administration guidance.
  
  
  METHODS
  Patients with chronic laryngeal symptoms suggestive of LPR underwent twice-daily 40 mg esomeprazole treatment for 12 weeks. We used a 50% or more reduction in the primary laryngeal symptom at week 12, an empirical criterion, as an anchor to dichotomize the participants into two groups, and to establish a responder definition of the RSI score change. The optimal cutoff point of the RSI score change was determined on the basis of the maximal Youden index of the receiver operating characteristic analysis.
  
  
  RESULTS
  The mean reduction in the RSI score was significantly greater in subjects with a 50% or more reduction in the primary laryngeal symptom than in those without (-11.0 ± 7.8 vs. -3.1 ± 8.3, P < 0.0001). A reduction of six points or more in the RSI score at week 12 was considered to be the responder definition with a sensitivity of 0.79 and a specificity of 0.70.
  
  
  CONCLUSIONS
  We propose an a priori responder definition derived from an empirical criterion according to the Food and Drug Administration guidance: a reduction of six points or more in the RSI score at week 12. This preliminary estimate provides a clinically meaningful change at an individual level, although additional studies and validations across various languages are required.
authors.affiliation: Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Internal Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Public Health, China Medical University, Taichung, Taiwan.
authors.forename: Han-Chung
authors.initials: HC
authors.lastname: Lien
authors.affiliation: Department of Otolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; School of Speech Language Pathology & Audiology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chen-Chi
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Internal Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shou-Wu
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Division of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Jeng-Yuan
authors.initials: JY
authors.lastname: Hsu
authors.affiliation: Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Internal Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hong-Zen
authors.initials: HZ
authors.lastname: Yeh
authors.affiliation: Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Internal Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chung-Wang
authors.initials: CW
authors.lastname: Ko
authors.affiliation: Department of Internal Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Chi-Sen
authors.initials: CS
authors.lastname: Chang
authors.affiliation: Graduate Institute of Biostatistics, China Medical University, Taichung, Taiwan. Electronic address: wmliang@mail.cmu.edu.tw.
authors.forename: Wen-Miin
authors.initials: WM
authors.lastname: Liang
mesh_terms: D000328:Adult; D064098:Esomeprazole / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D057045:Laryngopharyngeal Reflux / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D017410:Practice Guidelines as Topic / Q000592:standards*; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D057566:Self Report / Q000592:standards*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration / Q000592:standards*
chemical_list: D054328:Proton Pump Inhibitors; D064098:Esomeprazole
keywords: anchor-based method; laryngopharyngeal reflux; patient-reported outcome; responder definition