Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee

Gut. 2015 Mar;64(3):438-46. doi: 10.1136/gutjnl-2014-307008. Epub 2014 May 12.

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.

Keywords: IBD; IBD CLINICAL; PAEDIATRIC GASTROENTEROLOGY.

MeSH terms

  • Biomarkers / blood
  • Child
  • Clinical Trials as Topic / methods
  • Clinical Trials as Topic / standards*
  • Delphi Technique
  • Endoscopy
  • Humans
  • Inflammation / pathology
  • Inflammatory Bowel Diseases / blood
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / pathology
  • Intestinal Mucosa / pathology
  • Quality of Life
  • Treatment Outcome

Substances

  • Biomarkers