Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Adv Drug Deliv Rev. 2011 Jun 19;63(7):511-7. doi: 10.1016/j.addr.2010.10.010. Epub 2010 Oct 26.
Exploratory clinical trials provide a strategy for rapid human entry of investigational drugs. Such clinical studies are typically conducted during early clinical development in phase I as first-in-human studies, have no therapeutic intent, are not intended to examine clinical tolerability and involve a small number of human subjects at limited dose/exposure. Early decision data derived from such clinical studies may include PK, PD and/or biomarker-based translational medicine endpoints as well as PK/PD modeling approaches. This review critically discusses the various exploratory clinical trial strategies, their advantages and disadvantages as well as the regulatory safety requirements. In this respect, strategies for exploratory Investigational New Drugs (eIND), exploratory Clinical Trial Applications (eCTA) and microdosing are highlighted and compared in view of the new ICH M3(R2) guideline including options for biotechnology-derived pharmaceuticals such as monoclonal antibodies.
探索性临床试验为研究药物的快速人体试验提供了一种策略。此类临床研究通常在 I 期早期临床开发期间进行，作为首次人体研究，没有治疗意图，不旨在检查临床耐受性，并且涉及少量人类受试者和有限剂量/暴露。此类临床研究中得出的早期决策数据可包括 PK、PD 和/或基于生物标志物的转化医学终点以及 PK/PD 建模方法。本综述批判性地讨论了各种探索性临床试验策略，及其优缺点以及监管安全要求。在这方面，针对探索性新药研究申请（eIND）、探索性临床试验申请（eCTA）和微剂量探索策略进行了强调，并根据新的 ICH M3(R2)指导原则进行了比较，包括生物技术衍生药物（如单克隆抗体）的各种选择。
