Drug development and IBS drugs: experience from the past, current challenges, and proposal for the future.

Over the past decade, the failed promise of animal models and preclinical pharmacology, and a changing landscape in the regulatory perspectives have impacted the development of drugs for the treatment of irritable bowel syndrome (IBS). In general, animal models have failed to predict efficacy of medications developed for visceral pain. On the contrary, extensive experience with different endpoints in large, randomized, and controlled trials has generated some data on psychometric validation and unprecedented information about responsiveness of binary or global endpoints. However, it has now become necessary to pursue further validation studies in the run-up to or during pivotal trials. Guidance documents from regulatory agencies in Europe and the United States have focused on patient response outcomes (PROs) and associated impact on quality of life. These extra validation steps will undoubtedly result in delays in drug development. Providing relief to patients should galvanize all parties to achieve effective and fair strategies for regulatory approval.