title: Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee.
abstract: OBJECTIVE
  Although paediatric-onset IBD is becoming more common, few medications have a registered paediatric indication. There are multiple hurdles to performing clinical trials in children, emphasising the importance of choosing an appropriate outcome measure, which can facilitate enrolment, and thereby also drug approval. The aim of this consensus statement is to highlight paediatric specific issues and key factors critical for the optimal conduct of paediatric IBD trials.
  
  
  METHODS
  The Paediatric European Crohn's and Colitis Organisation (ECCO) committee has established an international expert panel to determine the best outcome measures in paediatric IBD, following a literature search and a modified Delphi process. All recommendations were endorsed by at least 80% agreement.
  
  
  RESULTS
  Recognising the importance of mucosal healing (MH), the panel defined steroid-free MH as primary outcome measure for all drugs of new category with one or two postintervention endoscopies per trial (at 8-12 weeks and/or 54 weeks). Since endoscopic evaluation is a barrier for recruitment in children, trials with medications already shown to induce MH in children or adults, could use paediatric-specific disease activity scores as primary outcome, including a modified Paediatric Crohn's Disease Activity Index in Crohn's disease and the Paediatric Ulcerative Colitis Activity Index in UC. Secondary outcomes should include safety issues, MR enterography-based damage and inflammatory scores (in Crohn's disease), faecal calprotectin, quality of life scales, and a patient-reported outcome.
  
  
  CONCLUSIONS
  It is crucial to perform paediatric trials early in the development of new drugs in order to reduce off-label use of IBD medication in children. The thoughtful choice of feasible and standardised outcome measures can help move us towards this goal.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France INSERM U989, Institut IMAGINE, Paris, France APHP, Hôpital Necker Enfants Malades, Service de Gastroentérologie pédiatrique, Paris, France.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Ruemmele
authors.affiliation: Connecticut Children's Medical Center, Hartford, Connecticut, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Hyams
authors.affiliation: Division of Pediatric Gastroenterology, IWK Health Centre, Halifax, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Otley
authors.affiliation: The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Griffiths
authors.affiliation: Children's Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Kaija-Leena
authors.initials: KL
authors.lastname: Kolho
authors.affiliation: Hospital S João, Porto, Portugal.
authors.forename: Jorge Amil
authors.initials: JA
authors.lastname: Dias
authors.affiliation: Pediatric Gastroenterology and Nutrition Unit, Wolfson Medical Center, Sackler School of Medicine, Tel Aviv University, Holon, Israel.
authors.forename: Arie
authors.initials: A
authors.lastname: Levine
authors.affiliation: Pediatric Gastroenterology, Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Escher
authors.affiliation: Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Taminiau
authors.affiliation: Ist Dept of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Veres
authors.affiliation: Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Department of Gastroenterology, University Hospital Leuven, Leuven, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Department of Child Life and Health, University of Edinburgh, Scotland, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Wilson
authors.affiliation: The Juliet Keidan Institute for Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Turner
mesh_terms: D015415:Biomarkers / Q000097:blood; D002648:Child; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D003697:Delphi Technique; D004724:Endoscopy; D006801:Humans; D007249:Inflammation / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers
keywords: IBD; IBD CLINICAL; PAEDIATRIC GASTROENTEROLOGY