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Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee
  1. Frank M Ruemmele1,2,3,
  2. Jeffrey S Hyams4,
  3. Anthony Otley5,
  4. Anne Griffiths6,
  5. Kaija-Leena Kolho7,
  6. Jorge Amil Dias8,
  7. Arie Levine9,
  8. Johanna C Escher10,
  9. Jan Taminiau11,
  10. Gabor Veres12,
  11. Jean-Frederic Colombel13,
  12. Séverine Vermeire14,
  13. David C Wilson15,
  14. Dan Turner16
  1. 1Université Paris Descartes, Sorbonne Paris Cité, Paris, France
  2. 2INSERM U989, Institut IMAGINE, Paris, France
  3. 3APHP, Hôpital Necker Enfants Malades, Service de Gastroentérologie pédiatrique, Paris, France
  4. 4Connecticut Children's Medical Center, Hartford, Connecticut, USA
  5. 5Division of Pediatric Gastroenterology, IWK Health Centre, Halifax, Canada
  6. 6The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  7. 7Children's Hospital, University of Helsinki, Helsinki, Finland
  8. 8Hospital S João, Porto, Portugal
  9. 9Pediatric Gastroenterology and Nutrition Unit, Wolfson Medical Center, Sackler School of Medicine, Tel Aviv University, Holon, Israel
  10. 10Pediatric Gastroenterology, Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
  11. 11Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands
  12. 12Ist Dept of Pediatrics, Semmelweis University, Budapest, Hungary
  13. 13Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, USA
  14. 14Department of Gastroenterology, University Hospital Leuven, Leuven, Belgium
  15. 15Department of Child Life and Health, University of Edinburgh, Scotland, UK
  16. 16The Juliet Keidan Institute for Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel
  1. Correspondence to Professor Frank M Ruemmele, Pediatric Gastroenterology, Hôpital Necker-Enfants Malades, INSERM U989, Université Paris Descartes, Sorbonne Paris Cité, 149 Rue de Sèvres, Paris F-75015, France; frank.ruemmele{at}nck.aphp.fr

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.

Design 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.

  • IBD
  • IBD CLINICAL
  • PAEDIATRIC GASTROENTEROLOGY

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