Via N. Sauro, 24, 37047, San Bonifacio (VR), Italy.
Curr Opin Pharmacol. 2011 Oct;11(5):528-33. doi: 10.1016/j.coph.2011.05.008. Epub 2011 Jun 23.
Scientific method in drug discovery has centered on generating a hypothesis (target identification) and hypothesis testing (target validation). Traditionally, both processes were performed using animal data, with the basic pharmacologist being pivotal. Many therapeutic areas that rely on human data to validate targets as animal models are seen as poorly predictive. Failures of molecules in Phase III for poor efficacy raise questions about target identification and validation. The clinical pharmacologist, working with the basic pharmacologist can play a major role in aiding target identification and by developing trial designs using small patient populations, mitigating the need for full Phase III studies to test the hypothesis. Technologies such as genomics, non-invasive imaging and proteomics are in the forefront of improving target identification and in some cases in providing paradigms for target validation in man.
药物发现中的科学方法一直集中在生成假设（靶标鉴定）和假设检验（靶标验证）上。传统上，这两个过程都是使用动物数据进行的，基础药理学家是关键。许多依赖于人类数据来验证动物模型靶标的治疗领域被认为预测性很差。在 III 期临床试验中，由于疗效不佳而导致分子失败，这引发了对靶标鉴定和验证的质疑。临床药理学家与基础药理学家合作，可以在帮助鉴定靶标方面发挥重要作用，并通过使用小患者群体设计试验，减少对全 III 期研究的需求来检验假设。基因组学、非侵入性成像和蛋白质组学等技术处于提高靶标鉴定的前沿，在某些情况下，为人类靶标验证提供了范例。
