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

Tack J1, Corsetti M2, Camilleri M3, Quigley EM4, Simren M5, Suzuki H6, Talley NJ7, Tornblom H5, Van Oudenhove L1. Gut. 2017 Aug 16. pii: gutjnl-2016-312230. doi: 10.1136/gutjnl-2016-312230. [Epub ahead of print]
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1 Translational Research Center for Gastrointestinal Disorders, KULeuven, Leuven, Belgium. 2 Gastroenterology, University Hospital Nottingham, Nottingham, UK. 3 Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA. 4 Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, Weill Cornell Medical College, Houston, Texas, USA. 5 Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 6 Gastroenterology, Keio University, Tokyo, Japan. 7 Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia.


BACKGROUND AND AIMS: 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) the 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 five criteria according to the Grading of Recommendations Assessment, Development and Evaluation system, a plausibility score can be calculated for each mechanism.

CONCLUSION: Evaluation of the strength of evidence for candidate pathophysiological abnormalities fulfilling these five plausibility criteria will help to identify the most relevant mechanisms to target for novel diagnostic approaches and for the development of new therapies.

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