Declining Enrolment and Other Challenges in IBD Clinical Trials: Causes and Potential Solutions.


Journal

Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676

Informations de publication

Date de publication:
05 Jul 2023
Historique:
received: 21 11 2022
accepted: 01 02 2023
medline: 6 7 2023
pubmed: 5 2 2023
entrez: 4 2 2023
Statut: ppublish

Résumé

Rates of enrolment in clinical trials in inflammatory bowel disease [IBD] have decreased dramatically in recent years. This has led to delays, increased costs and failures to develop novel treatments. The aim of this work is to describe the current bottlenecks of IBD clinical trial enrolment and propose solutions. A taskforce comprising experienced IBD clinical trialists from academic centres and pharmaceutical companies involved in IBD clinical research predefined the four following levels: [1] study design, [2] investigative centre, [3] physician and [4] patient. At each level, the taskforce collectively explored the reasons for declining enrolment rates and generated an inventory of potential solutions. The main reasons identified included the overall increased demands for trials, the high screen failure rates, particularly in Crohn's disease, partly due to the lack of correlation between clinical and endoscopic activity, and the use of complicated endoscopic scoring systems not reflective of the totality of inflammation. In addition, complex trial protocols with restrictive eligibility criteria, increasing burden of procedures and administrative tasks enhance the need for qualified resources in study coordination. At the physician level, lack of dedicated time and training is crucial. From the patients' perspective, long washout periods from previous medications and protocol requirements not reflecting clinical practice, such as prolonged steroid management and placebo exposures, limit their participation in clinical trials. This joint effort is proposed as the basis for profound clinical trial transformation triggered by investigative centres, contract research organizations, sponsors and regulatory agencies.

Sections du résumé

BACKGROUND BACKGROUND
Rates of enrolment in clinical trials in inflammatory bowel disease [IBD] have decreased dramatically in recent years. This has led to delays, increased costs and failures to develop novel treatments.
AIMS OBJECTIVE
The aim of this work is to describe the current bottlenecks of IBD clinical trial enrolment and propose solutions.
METHODS METHODS
A taskforce comprising experienced IBD clinical trialists from academic centres and pharmaceutical companies involved in IBD clinical research predefined the four following levels: [1] study design, [2] investigative centre, [3] physician and [4] patient. At each level, the taskforce collectively explored the reasons for declining enrolment rates and generated an inventory of potential solutions.
RESULTS RESULTS
The main reasons identified included the overall increased demands for trials, the high screen failure rates, particularly in Crohn's disease, partly due to the lack of correlation between clinical and endoscopic activity, and the use of complicated endoscopic scoring systems not reflective of the totality of inflammation. In addition, complex trial protocols with restrictive eligibility criteria, increasing burden of procedures and administrative tasks enhance the need for qualified resources in study coordination. At the physician level, lack of dedicated time and training is crucial. From the patients' perspective, long washout periods from previous medications and protocol requirements not reflecting clinical practice, such as prolonged steroid management and placebo exposures, limit their participation in clinical trials.
CONCLUSION CONCLUSIONS
This joint effort is proposed as the basis for profound clinical trial transformation triggered by investigative centres, contract research organizations, sponsors and regulatory agencies.

Identifiants

pubmed: 36738443
pii: 7026239
doi: 10.1093/ecco-jcc/jjad020
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1066-1078

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

Mathieu Uzzan (M)

Paris Est Créteil University UPEC, Assistance Publique-Hôpitaux de Paris (AP-HP), Henri Mondor Hospital, Gastroenterology Department, Fédération Hospitalo-Universitaire TRUE InnovaTive theRapy for immUne disordErs, Créteil F-94010, France.

Yoram Bouhnik (Y)

Paris IBD Center, Groupe hospitalier Ambroise Paré - Hartmann 25-27 boulevard Victor Hugo, 92200 Neuilly sur Seine, France.

Maria Abreu (M)

Crohn's & Colitis Center, Miami, FL, USA.

Harris A Ahmad (HA)

Bristol-Myers Squibb Company, Princeton, NJ, USA.

Shashi Adsul (S)

Takeda Pharmaceuticals International AG, Zurich, Switzerland.

Hilde Carlier (H)

Eli Lilly and Company, Global Immunology, Brussels, Belgium.

Marla Dubinsky (M)

Susan and Leonard Feinstein IBD Center, Icahn School of Medicine, Mount Sinai, NY, USA.

Matthew Germinaro (M)

Janssen Research & Development, LLC, Spring House, PA, USA.

Vipul Jairath (V)

Departments of Medicine, Epidemiology and Biostatsistics, Western University, London, Canada.

Irene Modesto (I)

Pfizer Inc., Madrid, Spain.

Eric Mortensen (E)

Regeneron, Fédération Hospitalo-Universitaire TRUE InnovaTive theRapy for immUne disordErs, Gastroenterology Department, Créteil, France.

Neeraj Narula (N)

Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.

Ezequiel Neimark (E)

AbbVie, North Chicago, IL, USA.

Alessandra Oortwijn (A)

Galapagos N.V., Leiden, The Netherlands.

Marijana Protic (M)

Eli Lilly and Company, International Business Unit, Vernier/Geneva, Switzerland.

David T Rubin (DT)

University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA.

Young S Oh (YS)

Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Rd, Ridgefield, CT 06877, USA.

Jolanta Wichary (J)

ICON Clinical Research, Frankfurt, Germany.

Laurent Peyrin-Biroulet (L)

University of Lorraine, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.

Walter Reinisch (W)

Medizinische Universität Wien Klinische Abt. Gastroenterologie & Hepatologie, AKH Wien Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen (CED) Währinger Gürtel 18-20, A-1090 Vienna, Austria.

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Classifications MeSH