Comparison of the EMA and FDA Guidelines on Ulcerative
Colitis Drug Development
Q26
Walter Reinisch, *
,a
Klaus Gottlieb,
‡,a
Jean-Frederic Colombel,
§
Silvio Danese,
k
Remo Panaccione,
¶
Julian Panes,
#
Laurent Peyrin-Biroulet, ** David Rubin,
‡‡
Bruce E. Sands,
§
Stefan Schreiber,
§§
Severine Vermeire,
kk
Andrew Mulberg,
¶¶
and Bill Sandborn
##
Q1
*Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna,
Austria;
‡
Department of Medicine, George Washington University School of Medicine, Washington, District of Columbia;
§
Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York;
k
Inflammatory Bowel Disease Center, Humanitas University, Milano, Italy;
¶
Division of Gastroenterology and Hepatology,
University of Calgary, Calgary, Canada;
#
Department of Gastroenterology, Faculty of Medicine, University of Barcelona,
Barcelona, Spain; **Inserm U954, Department of Gastroenterology, Nancy University Hospital, Lorraine University, France;
‡‡
Department of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, Illinois;
§§
Klinik für Innere Medizin I, Christian-Albrechts-Universität Kiel, Kiel, Germany;
kk
Department of Clinical and Experimental
Medicine, KU Leuven, Leuven, Belgium;
¶¶
Amicus Therapeutics, Cranbury, New Jersey;
##
University of California San Diego,
La Jolla, California
BACKGROUND & AIMS:
Q5
In 2016, the European Medicines Agency (EMA) and the US Food and Drug Administration
(FDA) released revised EMA and new FDA draft guidelines related to the development of drugs
intended for the treatment of ulcerative colitis. We sought to compare and contrast the EMA
draft guideline with the FDA draft guidance to facilitate further discussion and perhaps
harmonization between the 2 guidelines when they are finalized.
METHODS: A concordance document was created by arranging like or similar topics addressed by the
guidelines side by side in a tabular format. This concordance table served as a source for
writing the narrative. The first draft was subjected to repeated rounds of reviews and revisions
by the authors and outside reviewers, all of them familiar with the subject matter from a
regulatory science and/or academic perspective.
RESULTS: The FDA guidance focuses on end points, whereas the EMA guideline additionally supplies much
useful information for trial design. FDA guidance appears more aspirational, suggesting the
development of entirely new patient-reported outcome instruments and the incorporation of a
not-yet-validated histology instrument into the definition of mucosal healing.
CONCLUSIONS: The guidelines by the FDA and the EMA complement each other and together are aimed to
further practical drug development toward more clinically relevant end points in ulcerative
colitis. Efforts are needed to harmonize the documents.
Keywords: Ulcerative Colitis; Guidelines; Inflammatory Bowel Disease; Drug Development; FDA; EMA.
Q6 Q7
T
he US Food and Drug Administration (FDA)
Guidance on Ulcerative Colitis–Clinical Trial End
points
1
was released in August 2016, coinciding with
the start of the public consultation period for the revised
Committee for Medicinal Products for Human Use/Euro-
pean Medicines Agency (EMA) Ulcerative Colitis Guide-
line.
2
These draft guidelines present slightly different
emphases. The FDA guidance
Q8
focuses on end points,
whereas the EMA CHMP
Q9
guideline is more comprehen-
sive, relating to clinical trial design. Although the
thinking on both sides of the Atlantic seems to be
converging, there are still important differences that
may affect regulatory approval. In this article, we provide
a detailed review of both guidelines, focusing on adult
drug development, and offer some of our viewpoints in
the discussion.
a
Authors share co-first authorship.
Abbreviations used in this paper: EMA, European Medicines Agency; FDA,
US Food and Drug Administration; PGA, physician global assessment;
PRO, patient-reported outcome; UCDAI, Ulcerative Colitis Disease Activity
Index.
© 2018 by the AGA Institute
1542-3565/$36.00
https://doi.org/10.1016/j.cgh.2018.10.032
Clinical Gastroenterology and Hepatology 2018;-:-–-
REV 5.5.0 DTD YJCGH56154_proof 21 November 2018 6:52 pm ce DVC
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