Background: Irritable bowel syndrome (IBS) is a prevalent disorder, and although the pharmaceutical industry knows the potential fallout of a successful drug launch in this area, effective drug treatments are rare.
Aim: To give an overview of the main factors interfering with the development of IBS drugs and to provide pertinent methodological indications to improve their investigation in clinical trials.
Results: Developing IBS drugs remains a major challenge, as numerous factors, related or unrelated to the nature of the disease itself, interfere with the demonstration of efficacy : the multiplicity of physiopathological mechanisms, wide variation in symptoms across patients and over time, associated psychological traits and environmental aspects, and a very significant placebo effect. There can be no question of developing drugs to target a single receptor in the hope of thereby impacting the whole range of factors involved in the genesis of IBS symptoms. Drug safety is, moreover, a prime consideration, given that this pathology, while certainly disabling, is not life-threatening. If a significant difference between a new treatment and placebo is to be demonstrated on a clinical trial, inclusion and efficacy criteria and study treatment duration must be predefined very precisely. The primary endpoint is abdominal pain, but the assessment of relief of the patient's symptoms has been also recommended, even if there is as yet no consensus as to its definition. The impact of a new IBS drug on patient's quality of life is an important secondary endpoint.
Conclusion: In IBS more, perhaps, than in other pathologies, study design needs very careful consideration if new IBS drug trials are to be conclusive. However, some critical methodological issues (e.g., definite primary endpoint, interpretation of results, and definition of responders) are still unresolved.