Schering-Plough Research Institute, Lafayette, New Jersey, USA.
Clin Pharmacol Ther. 2010 Mar;87(3):278-85. doi: 10.1038/clpt.2009.286. Epub 2010 Feb 3.
Proof of concept (POC) may be defined as the earliest point in the drug development process at which the weight of evidence suggests that it is "reasonably likely" that the key attributes for success are present and the key causes of failure are absent. POC is multidimensional but is focused on attributes that, if not addressed, represent a threat to the success of the project in crucial areas such as safety, efficacy, pharmaceutics, and commercial and regulatory issues. The appropriate weight of evidence is assessed through the use of mathematical models and by evaluating the consequences of advancing a candidate drug that is not safe, effective, or commercially viable, vs. failing to advance a candidate that possesses these attributes. Tools for POC include biomarkers, targeted populations, pharmacokinetic (PK)/pharmacodynamic (PD) modeling, simulation, and adaptive study designs. Challenges to the success of POCs include a shortage of skilled personnel, failure to integrate multiple disciplines and information, and the demand made by organizations for certainty.
概念验证（POC）可被定义为药物开发过程中最早的一个时间点，此时证据表明其“极有可能”具有成功的关键属性，并且不存在失败的关键原因。POC 是多维的，但重点关注的是，如果不加以解决，可能会对项目在安全性、疗效、药剂学以及商业和监管问题等关键领域的成功构成威胁的属性。通过使用数学模型和评估推进不安全、有效或在商业上不可行的候选药物的后果，以及不推进具有这些属性的候选药物，来评估适当的证据权重。POC 的工具包括生物标志物、目标人群、药代动力学（PK）/药效动力学（PD）建模、模拟和适应性研究设计。POC 成功的挑战包括熟练人员短缺、未能整合多个学科和信息，以及组织对确定性的要求。
