PT  - JOURNAL ARTICLE
AU  - Jan Tack
AU  - Maura Corsetti
AU  - Michael Camilleri
AU  - Eamonn MM Quigley
AU  - Magnus Simren
AU  - Hidekazu Suzuki
AU  - Nicholas J Talley
AU  - Hans Tornblom
AU  - Lukas Van Oudenhove
TI  - Plausibility criteria for putative pathophysiological mechanisms in functional gastrointestinal disorders: a consensus of experts
AID  - 10.1136/gutjnl-2016-312230
DP  - 2018 Aug 01
TA  - Gut
PG  - 1425--1433
VI  - 67
IP  - 8
4099  - http://gut.bmj.com/content/67/8/1425.short
4100  - http://gut.bmj.com/content/67/8/1425.full
SO  - Gut2018 Aug 01; 67
AB  - 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.