title: Steps toward harmonization for clinical development of medicines in pediatric ulcerative colitis-a global scientific discussion, part 1: efficacy endpoints and disease outcome assessments.
abstract: OBJECTIVE
  There is a pressing need for drug development in pediatric ulcerative colitis (UC). Lack of scientific consensus on efficacy endpoints and disease outcome assessments presents a hurdle for global drug development in pediatric UC. Scientists from 4 regulatory agencies convened an International Inflammatory Bowel Disease Working Group (i-IBD Working Group) to harmonize present thinking about various aspects of drug development in pediatric UC globally.
  
  
  METHODS
  The i-IBD Working Group was convened in 2012 by scientists from the US Food and Drug Administration, European Medicines Agency, Health Canada, and the Pharmaceuticals and Medical Devices Agency of Japan. The members of this group considered reasons for differences in their acceptance of efficacy endpoints and disease activity indices used in pediatric UC, reviewed the available literature, and developed consensus opinions regarding approaches for evaluating outcomes in pediatric UC trials.
  
  
  RESULTS
  There is lack of harmonization in using efficacy endpoint and outcome assessments including disease activity indices to assess clinical benefit in pediatric UC trials. Many disease activity indices have been developed, but their biometric properties, such as responsiveness, reliability, and validity, have not been properly validated. Biomarkers, such as fecal calprotectin and lactoferrin, are being investigated for their potential as noninvasive surrogate endpoints in UC.
  
  
  CONCLUSIONS
  Consensus on the efficacy endpoints, disease activity indices, and outcome assessments is needed for globalization of pediatric UC trials. The i-IBD Working Group offers several perspectives to facilitate harmonization across regions. The development of noninvasive biomarkers as reliable surrogate endpoints needs to be explored further.
authors.affiliation: *US Food and Drug Administration, Silver Spring, MD †European Medicines Agency, London, UK ‡Health Canada, Ottawa, Ontario, Canada §Pharmaceuticals and Medical Devices Agency, Tokyo, Japan.
authors.forename: Haihao
authors.initials: H
authors.lastname: Sun
authors.forename: Richard
authors.initials: R
authors.lastname: Vesely
authors.forename: Jan
authors.initials: J
authors.lastname: Taminiau
authors.forename: Peter
authors.initials: P
authors.lastname: Szitanyi
authors.forename: Elektra J
authors.initials: EJ
authors.lastname: Papadopoulos
authors.forename: Maria
authors.initials: M
authors.lastname: Isaac
authors.forename: Agnes
authors.initials: A
authors.lastname: Klein
authors.forename: Shinobu
authors.initials: S
authors.lastname: Uzu
authors.forename: Donna
authors.initials: D
authors.lastname: Griebel
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Mulberg
mesh_terms: D002170:Canada; D002648:Child; D002986:Clinical Trials as Topic; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003299:Cooperative Behavior; D005060:Europe; D006801:Humans; D007564:Japan; D017063:Outcome Assessment, Health Care; D012107:Research Design; D014481:United States