Outcome measures for clinical trials in paediatric IBD

An evidence-based, expert-driven practical statement paper of the paediatric ECCO committee

Frank M. Ruemmele, Jeffrey S. Hyams, Anthony Otley, Anne Griffiths, Kaija Leena Kolho, Jorge Amil Dias, Arie Levine, Johanna C. Escher, Jan Taminiau, G. Verès, Jean Frederic Colombel, Séverine Vermeire, David C. Wilson, Dan Turner

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)438-446
Number of pages9
JournalGut
Volume64
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

Fingerprint

Colitis
Outcome Assessment (Health Care)
Clinical Trials
Organizations
Pediatrics
Crohn Disease
Leukocyte L1 Antigen Complex
Off-Label Use
Drug Approval
Pharmaceutical Preparations
Endoscopy
Steroids
Quality of Life
Safety

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Outcome measures for clinical trials in paediatric IBD : An evidence-based, expert-driven practical statement paper of the paediatric ECCO committee. / Ruemmele, Frank M.; Hyams, Jeffrey S.; Otley, Anthony; Griffiths, Anne; Kolho, Kaija Leena; Dias, Jorge Amil; Levine, Arie; Escher, Johanna C.; Taminiau, Jan; Verès, G.; Colombel, Jean Frederic; Vermeire, Séverine; Wilson, David C.; Turner, Dan.

In: Gut, Vol. 64, No. 3, 01.03.2015, p. 438-446.

Research output: Contribution to journalArticle

Ruemmele, FM, Hyams, JS, Otley, A, Griffiths, A, Kolho, KL, Dias, JA, Levine, A, Escher, JC, Taminiau, J, Verès, G, Colombel, JF, Vermeire, S, Wilson, DC & Turner, D 2015, 'Outcome measures for clinical trials in paediatric IBD: An evidence-based, expert-driven practical statement paper of the paediatric ECCO committee', Gut, vol. 64, no. 3, pp. 438-446. https://doi.org/10.1136/gutjnl-2014-307008
Ruemmele, Frank M. ; Hyams, Jeffrey S. ; Otley, Anthony ; Griffiths, Anne ; Kolho, Kaija Leena ; Dias, Jorge Amil ; Levine, Arie ; Escher, Johanna C. ; Taminiau, Jan ; Verès, G. ; Colombel, Jean Frederic ; Vermeire, Séverine ; Wilson, David C. ; Turner, Dan. / Outcome measures for clinical trials in paediatric IBD : An evidence-based, expert-driven practical statement paper of the paediatric ECCO committee. In: Gut. 2015 ; Vol. 64, No. 3. pp. 438-446.
@article{5fbcbbad265e435a8e9f82862761fb9b,
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. 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.",
author = "Ruemmele, {Frank M.} and Hyams, {Jeffrey S.} and Anthony Otley and Anne Griffiths and Kolho, {Kaija Leena} and Dias, {Jorge Amil} and Arie Levine and Escher, {Johanna C.} and Jan Taminiau and G. Ver{\`e}s and Colombel, {Jean Frederic} and S{\'e}verine Vermeire and Wilson, {David C.} and Dan Turner",
year = "2015",
month = "3",
day = "1",
doi = "10.1136/gutjnl-2014-307008",
language = "English",
volume = "64",
pages = "438--446",
journal = "Gut",
issn = "0017-5749",
publisher = "BMJ Publishing Group",
number = "3",

}

TY - JOUR

T1 - Outcome measures for clinical trials in paediatric IBD

T2 - An evidence-based, expert-driven practical statement paper of the paediatric ECCO committee

AU - Ruemmele, Frank M.

AU - Hyams, Jeffrey S.

AU - Otley, Anthony

AU - Griffiths, Anne

AU - Kolho, Kaija Leena

AU - Dias, Jorge Amil

AU - Levine, Arie

AU - Escher, Johanna C.

AU - Taminiau, Jan

AU - Verès, G.

AU - Colombel, Jean Frederic

AU - Vermeire, Séverine

AU - Wilson, David C.

AU - Turner, Dan

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84922382262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922382262&partnerID=8YFLogxK

U2 - 10.1136/gutjnl-2014-307008

DO - 10.1136/gutjnl-2014-307008

M3 - Article

VL - 64

SP - 438

EP - 446

JO - Gut

JF - Gut

SN - 0017-5749

IS - 3

ER -