title: Sensitivity of single-domain versus multiple-domain outcome measures to identify responders in chronic low-back pain: pooled analysis of 2 placebo-controlled trials of etoricoxib.
abstract: OBJECTIVE
  A composite responder index for chronic low-back pain (CLBP) has recently been proposed to evaluate the efficacy of CLBP treatments in clinical trials. We compared the responsiveness of this composite measure with a number of single-item responder definitions.
  
  
  METHODS
  We pooled data from 2 placebo-controlled studies of etoricoxib in CLBP to evaluate 5 response criteria: 30% pain intensity (PI) reduction; 50% PI reduction; 20 mm absolute reduction (100 mm PI visual analog scale); patient global assessment of response to therapy (PGART); and the composite criteria of 30% reduction in PI+30% improvement in PGART of disease status+no worsening in function. We used bootstrap analysis and logistic regression to assess the ability to differentiate etoricoxib and placebo, and the κ coefficient to assess agreement among the responder criteria.
  
  
  RESULTS
  The criterion of a 20 mm improvement in PI resulted in the greatest proportion (71.5%) of patients being classified as responders and all criteria separated etoricoxib from placebo (P≤0.0001). PGART had the highest discriminant ability (odds ratio 5.90), and was significantly (P<0.05) more discriminant than the 20 mm and ≥30% improvements and the composite criteria. After adjusting for all other measures, only PGART continued to show a significant treatment effect for etoricoxib versus placebo (P=0.0003). Kappa values contrasting the composite criteria and the single-item measures ranged from 0.59 to 0.85.
  
  
  CONCLUSIONS
  These findings do not support the superiority of a composite index over single-item ratings of PI and PGART ratings, but do suggest that PGART ratings may be more responsive to treatment, perhaps because they measure something in addition to change in PI.
authors.affiliation: Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98104, USA. mjensen@uw.edu
authors.forename: Mark P
authors.initials: MP
authors.lastname: Jensen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schnitzer
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.forename: Steven S
authors.initials: SS
authors.lastname: Smugar
authors.forename: Paul M
authors.initials: PM
authors.lastname: Peloso
authors.forename: Arnold
authors.initials: A
authors.lastname: Gammaitoni
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D000077613:Etoricoxib; D005260:Female; D006801:Humans; D017116:Low Back Pain / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D011725:Pyridines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity; D013450:Sulfones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014894:Weights and Measures
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011725:Pyridines; D013450:Sulfones; D000077613:Etoricoxib