title: Abdominal pain endpoints currently recommended by the FDA and EMA for adult patients with irritable bowel syndrome may not be reliable in children.
abstract: BACKGROUND
  The Food and Drug Administration (FDA) recommended ≥30% decrease on patient-reported outcomes for pain be considered clinically significant in clinical trials for adults with irritable bowel syndrome. This percent change approach may not be appropriate for children. We compared three alternate approaches to determining clinically significant reductions in pain among children.
  
  
  METHODS
  80 children with functional abdominal pain participated in a study of the efficacy of amitriptyline. Endpoints included patient-reported estimates of feeling better, and pain Visual Analog Scale (VAS). The minimum clinically important difference in pain report was calculated as (i) mean change in VAS score for children reporting being 'better'; (ii) percent changes in pain (≥30% and ≥50%) on the VAS; and (iii) statistically reliable changes on the VAS for 68% and 95% confidence intervals.
  
  
  RESULTS
  There was poor agreement between the three approaches. 43.6% of the children who met the FDA ≥30% criterion for clinically significant change did not achieve a reliable level of improvement (95% confidence interval).
  
  
  CONCLUSIONS
  Children's self-reported ratings of being better may not be statistically reliable. A combined approach in which children must report improvement as better and achieve a statistically significant change may be more appropriate for outcomes in clinical trials.
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Saps
authors.affiliation: Department of Child and Adolescent Psychiatry, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.|Mary Ann and J. Milburn Smith Child Health Research Program, Children's Hospital of Chicago Research Center, Chicago, IL, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: Lavigne
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy* / Q000209:etiology; D000293:Adolescent; D000639:Amitriptyline / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy*; D008297:Male; D010147:Pain Measurement / Q000379:methods*; D063868:Patient Outcome Assessment; D015203:Reproducibility of Results; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D018712:Analgesics, Non-Narcotic; D000639:Amitriptyline
keywords: clinicially significant change; functional abdominal pain; irritable bowel syndrome; patient reported outcomes