Challenges to the design, execution, and analysis of randomized controlled trials for inflammatory bowel disease

Geert D'Haens*, Brian Feagan, Jean Frédéric Colombel, William J. Sandborn, Walter Reinisch, Paul Rutgeerts, Frank Carbonnel, Jean Yves Mary, Silvio Danese, Richard N. Fedorak, Steven Hanauer, Marc Lémann

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Treatment of inflammatory bowel disease has greatly improved with the development of targeted, monoclonal antibody-based therapies. Tumor necrosis factor antagonists are frequently used to treat patients with Crohn's disease or ulcerative colitis, but they have side effects and their efficacy often decreases with use. New, more effective drugs are therefore needed and in development. However, many agents that appeared to be promising in preclinical studies have failed to show efficacy in clinical trials. We discuss possible reasons for the failures of these reagents in trials, which include the high rate of response to placebo, an inadequate range of doses, inappropriate timing of end point measurements, the changing therapeutic environment, and the competitive trial system. We also review regulatory guidelines for end points and trial design and recommend ways to improve trials.

Original languageEnglish (US)
Pages (from-to)1461-1469
Number of pages9
JournalGastroenterology
Volume143
Issue number6
DOIs
StatePublished - Dec 2012

Keywords

  • Clinical Trials
  • Crohn's Disease
  • Inflammatory Bowel Disease
  • Trial Design
  • Ulcerative Colitis

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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