Young Jared W, Potter William Z, Riley Steve, Groeneveld Geert J, Kinon Bruce J, Egan Mike F, Feltner Douglas E
Dr. Young is with the Department of Psychiatry, University of California San Diego, La Jolla, California, and Research Service, VA San Diego Healthcare System, San Diego, California; Dr. Potter is with the National Institute of Mental Health, Rockville, Maryland; Dr. Riley is with the Department of Clinical Pharmacology, Global Innovative Pharma Business, Pfizer, Inc., Groton, Connecticut; Dr. Groeneveld is with Center for Human Drug Research, The Netherlands; Dr. Kinon is with Lundbeck LLC, Deerfield, Illinois (Dr. Kinon was with Eli Lilly and Company, Indianapolis, Indiana, when this material was presented); Dr. Egan is with Clinical Neuroscience, Merck & Co, Inc, North Wales, Pennsylvania; and Dr. Feltner is with AbbVie Inc. Pharmaceuticals, Chicago, Illinois.
Innov Clin Neurosci. 2015 Mar-Apr;12(3-4):5S-10S.
For decades, there has been a distinct disconnect translating a compound's effects from basic neuroscience into clinical efficacy. This disconnect has not only been in terms of generating approved compounds, but also in rejecting targets. During the drug discovery process there are key points to be adhered to that would strengthen the likelihood of a compound being translated to the clinic. These points include 1) the importance of translational pharmacology whereby preclinical pharmacological data should predict clinical efficacy; 2) rigorous early phase drug evaluation to enhance early go/no-go decisionmaking; 3) using exposure response modeling to predict drug efficacy during proof-of-concept trials; 4) designing and conducting the appropriate proof-of-concept study; and 5) optimizing Phase II studies to set the stage for success in Phase III trials. These topics were covered in The International Society for CNS Clinical Trials and Methodology (ISCTM) Autumn 2013 meeting on the topic of translational and early development strategies and tools led by Drs. Potter and Feltner. This report comprises a review of those proceedings with a concluding summary to advance future clinical trials.
几十年来,将化合物在基础神经科学方面的作用转化为临床疗效一直存在明显脱节。这种脱节不仅体现在获批化合物的产生上,也体现在靶点的摒弃上。在药物研发过程中,有一些关键点需要遵循,这将增加化合物转化为临床应用的可能性。这些关键点包括:1)转化药理学的重要性,即临床前药理学数据应能预测临床疗效;2)进行严格的早期药物评估,以加强早期的“继续/终止”决策;3)在概念验证试验期间使用暴露-反应模型来预测药物疗效;4)设计并开展适当的概念验证研究;5)优化II期研究,为III期试验的成功奠定基础。这些主题在2013年秋季国际中枢神经系统临床试验与方法学会(ISCTM)会议上进行了探讨,该会议主题为转化和早期开发策略与工具,由波特博士和费尔特纳博士主持。本报告对这些会议记录进行了综述,并给出总结结论,以推动未来的临床试验。