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Plausibility criteria for putative pathophysiological mechanisms in functional gastrointestinal disorders: a consensus of experts

Tack, Jan; Corsetti, Maura; Camilleri, Michael; Quigley, Aaron; Simren, Magnus; Suzuki, Hidekazu; Talley, Nicholas J.; Tornbloom, Hans; Van Oudenhove, Lukas

Plausibility criteria for putative pathophysiological mechanisms in functional gastrointestinal disorders: a consensus of experts Thumbnail


Authors

Jan Tack

MAURA CORSETTI Maura.Corsetti@nottingham.ac.uk
Clinical Associate Professor

Michael Camilleri

Aaron Quigley

Magnus Simren

Hidekazu Suzuki

Nicholas J. Talley

Hans Tornbloom

Lukas Van Oudenhove



Abstract

The functional gastrointestinal disorders (FGIDs), are extremely common conditions associated with a considerable personal, social and health economic burden. Managing FGIDs in clinical practice is challenging because of the uncertainty of symptom-based diagnosis, the high frequency of overlap between these conditions and the limited efficacy of available therapies. It has often been argued that successful drug development and management of FGIDs requires knowledge of the underlying pathophysiology. Numerous and highly variable candidate pathophysiological mechanisms have been implicated in the generation of FGID symptoms, but there is no current consensus on how to best define the relevance of these disturbances. Methods: A group of international experts on FGIDs developed plausibility criteria that should be fulfilled by relevant pathophysiological mechanisms in FGIDs. Results: Five criteria are proposed: 1) presence of the abnormality in a subset of patients; 2) temporal association between proposed mechanism and symptom(s); 3) correlation between the level of impairment of the mechanism and symptom(s); 4) induction of the symptom(s) by provoking the pathophysiological abnormality in healthy subjects and 5) treatment response by a therapy specifically correcting the underlying disorder, or congruent natural history of symptoms and dysfunction in the absence of specific therapy. Based on strength of evidence for these 5 criteria, a plausibility score is proposed. Conclusion: Evaluation of the strength of evidence for candidate pathophysiological abnormalities fulfilling these 5 plausibility criteria will help to identify the most relevant mechanisms to target for novel diagnostic approaches and for the development of new therapies.

Citation

Tack, J., Corsetti, M., Camilleri, M., Quigley, A., Simren, M., Suzuki, H., …Van Oudenhove, L. (in press). Plausibility criteria for putative pathophysiological mechanisms in functional gastrointestinal disorders: a consensus of experts. Gut, https://doi.org/10.1136/gutjnl-2016-312230

Journal Article Type Article
Acceptance Date Jun 9, 2017
Online Publication Date Aug 16, 2017
Deposit Date Jul 18, 2017
Publicly Available Date Aug 16, 2017
Journal Gut
Print ISSN 0017-5749
Electronic ISSN 1468-3288
Publisher BMJ Publishing Group
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1136/gutjnl-2016-312230
Keywords Functional gastrointestinal disorders, Pathophysiological mechanisms, Gastrointestinal motility, Gastroesophageal reflux, Visceral hypersensitivity, Plausibility criteria
Public URL https://nottingham-repository.worktribe.com/output/877837
Publisher URL http://gut.bmj.com/content/early/2017/08/16/gutjnl-2016-312230
Additional Information ©2017 BMJ Publishing Group Ltd & British Society of Gastroenterology
Contract Date Jul 18, 2017