Best practice & research. Clinical gastroenterology vol:18 issue:4 pages:787-96
Although several studies and publications have been devoted to the evaluation of novel pharmacotherapeutic approaches in functional bowel disorders, the number of successful drug development programs has been disappointingly small. The difficulties of adequate drug development are related to the heterogeneity of the functional disorders, the lack of understanding of the underlying pathophysiology, and the lack of short-term mechanistic studies that predict clinical outcome. When drugs address a single pathophysiological mechanism, the heterogeneity has a negative impact on the possible margin when patients are not selected on the basis of the specific pathophysiological disorder. Although mechanistic studies may provide a rationale for drug development, they do not predict symptomatic success and do not identify the most appropriate dose for clinical trials. Further mechanistic studies are badly needed to improve our understanding of the pathophysiological basis of functional disorders. Future studies might aim at the development of non-invasive test that identify relevant pathophysiological mechanisms, at refining assessment of symptom pattern and at the development of short-term therapeutic trials.