Turner D¹, Griffiths AM², Wilson D³, Mould DR⁴, Baldassano RN⁵, Russell RK⁶, Dubinsky M⁷, Heyman MB⁸, de Ridder L⁹, Hyams J¹⁰, Martin de Carpi J¹¹, Conklin L^12,13, Faubion WA¹⁴, Koletzko S¹⁵, Bousvaros A¹⁶, Ruemmele FM^17,18,19. Gut. 2019 Apr 12. pii: gutjnl-2018-317987. doi: 10.1136/gutjnl-2018-317987. [Epub ahead of print]

Author information

1 Pediatric Gastroenterology Institute, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.

2 Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

3 Child Life and Health, University of Edinburgh and Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK.

4 Projections Research, Phoenixville, Pennsylvania, USA.

5 Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

6 Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children, Glasgow, Scotland, UK.

7 Department of Pediatrics, Susan and Leonard Feinstein IBD Center, Icahn School of Medicine, Mount Sinai, New York, USA.

8 Department of Paediatrics, University of California San Francisco, San Francisco, California, USA.

9 Department of Paediatric Gastroenterology, Sophia Children's Hospital/ Erasmus MC University, Rotterdam, The Netherlands.

10 Connecticut Children's Medical Center, Hartford, Connecticut, USA.

11 Department of Paediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain.

12 Children's National Health System, Washington, DC, USA.

13 ReveraGen BioPharma, LLC, Rockville, MD, USA.

14 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

15 Division of Gastroenterology and Hepatology, Dr v Hauner Children's Hospital, LMU Munich, Munich, Germany.

16 Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.

17 Université Paris-Descartes, Paris-Sorbonne Cité, Paris, France.

18 Assistance Publique-Hopitaux de Paris, Hôpital Necker Enfants Malades, Service de Gastroentérologie pédiatrique, Paris, France.

19 INSTITUT IMAGINE - INSERM 1163, Paris, France.

Abstract

INTRODUCTION: The optimal trial design for assessing novel therapies in paediatric IBD (PIBD) is a subject of intense ongoing global discussions and debate among the different stakeholders. However, there is a consensus that the current situation in which most medications used in children with IBD are prescribed as off-label without sufficient paediatric data is unacceptable. Shortening the time lag between adult and paediatric approval of drugs is of the upmost importance. In this position paper we aimed to provide guidance from the global clinical research network (Pediatric Inflammatory Bowel Disease Network, PIBDnet) for designing clinical trials in PIBD in order to facilitate drug approval for children.

METHODS: A writing group has been established by PIBDnet and topics were assigned to different members. After an iterative process of revisions among the writing group and one face-to-face meeting, all statements have reached consensus of >80% as defined a priori. Next, all core members of PIBDnet voted on the statements, reaching consensus of >80% on all statements. Comments from the members were incorporated in the text.

RESULTS: The commentary includes 18 statements for guiding data extrapolation from adults, eligibility criteria to PIBD trials, use of placebo, dosing, endpoints and recommendations for feasible trials. Controversial issues have been highlighted in the text.

CONCLUSION: The viewpoints expressed in this paper could assist planning clinical trials in PIBD which are both of high quality and ethical, while remaining pragmatic.