Camilleri Michael
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Program, Mayo Clinic, Rochester, MN 55905, USA.
Curr Opin Pharmacol. 2008 Dec;8(6):671-6. doi: 10.1016/j.coph.2008.06.001. Epub 2008 Jul 9.
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.
在过去十年中，动物模型和临床前药理学未能实现预期，以及监管观念的不断变化，都对治疗肠易激综合征（IBS）药物的研发产生了影响。总体而言，动物模型未能预测针对内脏痛研发药物的疗效。相反，在大型随机对照试验中对不同终点的广泛经验，产生了一些关于心理测量学验证的数据以及有关二元或总体终点反应性的前所未有的信息。然而，现在有必要在关键试验之前或期间开展进一步的验证研究。欧洲和美国监管机构的指导文件聚焦于患者反应结果（PROs）及其对生活质量的相关影响。这些额外的验证步骤无疑将导致药物研发延迟。为患者提供缓解应促使各方达成有效且公平的监管批准策略。
