title: Development of responder definitions for fibromyalgia clinical trials.
abstract: OBJECTIVE
  To develop responder definitions for fibromyalgia (FM) clinical trials using key symptom and function domains.
  
  
  METHODS
  Twenty-four candidate responder definitions were developed by expert consensus and were evaluated in 12 randomized, placebo-controlled trials of 4 medications for the treatment of FM. For each definition, the treatment effects of the medication compared with placebo were analyzed using Cochran-Mantel-Haenszel tests or chi-square tests. A meta-analysis of the pooled results for the 4 medications established risk ratios to determine the definitions that best favored medication over placebo.
  
  
  RESULTS
  Two definitions performed best in the analyses. Both definitions included ≥30% reduction in pain and ≥10% improvement in physical function. The definitions differed in that one (≥30% improvement in FM [FM30] short version) included ≥30% improvement in sleep or fatigue, and the other (FM30 long version) required ≥30% improvement in 2 of the following symptoms: sleep, fatigue, depression, anxiety, or cognition. In the analysis of both versions, the response rate was ≥15% for each medication and was significantly greater compared with placebo. The risk ratio favoring drug over placebo in the pooled analysis for FM30 version 3 (short version) was 1.50 (95% confidence interval [95% CI] 1.24-1.82; P ≤ 0.0001); the risk ratio for FM30 version 6 (long version) was 1.60 (95% CI 1.31-1.96; P ≤ 0.00001).
  
  
  CONCLUSIONS
  Among the 24 responder definitions tested, 2 were identified as most sensitive in identifying response to treatment. The identification of responder definitions for FM clinical trials that include assessments of key symptom and function domains may improve the sensitivity of clinical trials to identify meaningful improvements, leading to improved management of FM.
authors.affiliation: Women’s Health Research Program, University of Cincinnati College of Medicine, Cincinnati, OH 45219, USA. Lesley.Arnold@uc.edu
authors.forename: Lesley M
authors.initials: LM
authors.lastname: Arnold
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
authors.forename: James I
authors.initials: JI
authors.lastname: Hudson
authors.forename: Susan A
authors.initials: SA
authors.lastname: Martin
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Clauw
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Crofford
authors.forename: Fujun
authors.initials: F
authors.lastname: Wang
authors.forename: Birol
authors.initials: B
authors.lastname: Emir
authors.forename: Chinglin
authors.initials: C
authors.lastname: Lai
authors.forename: Rong
authors.initials: R
authors.lastname: Zablocki
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
mesh_terms: D023381:Endpoint Determination; D005356:Fibromyalgia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D015201:Meta-Analysis as Topic; D017063:Outcome Assessment, Health Care; D010146:Pain / Q000503:physiopathology; D059408:Pain Management; D010147:Pain Measurement; D017288:Pain Threshold; D015990:Placebo Effect; D020127:Recovery of Function