Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA.
Clin Cancer Res. 2010 Mar 15;16(6):1710-8. doi: 10.1158/1078-0432.CCR-09-1993. Epub 2010 Mar 9.
Phase I clinical trials represent the first step in bringing promising new treatments from the laboratory to the clinic. Although the importance of phase I clinical trials is widely recognized, there is currently no consensus among the scientific, medical, and statistical communities on how best to do these studies in humans. With the advent of targeted therapies, it has become evident that we need to tailor the design of phase I studies for the particular drug class under investigation and any endpoints that are being defined. The National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) provides broad external scientific and clinical input on the design and prioritization of early-phase clinical trials with agents for which the NCI Cancer Therapy Evaluation Program (CTEP) holds an Investigational New Drug (IND) application through the U.S. Food and Drug Administration (FDA). The IDSC has formed a number of task forces and working groups, including the Clinical Trial Design Task Force and the Biomarker Working Group, many with membership from within the IDSC as well as external experts, including participants from academia, the pharmaceutical industry, and regulatory authorities. The Clinical Trials Design Taskforce sponsored a Phase I Workshop with the primary goal being to develop consensus recommendations for the optimal design of phase I studies. The primary focus included (1) efficient trial designs, (2) phase I drug combinations, and (3) appropriate statistical and correlative endpoints. In this CCR Focus series, articles summarize key aspects and recommendations on phase I studies (including combination trials), such as design, use of biomarkers, the European Union and Japanese perspectives on design, requirements for first-in-human and other phase I studies, and ensuring regulatory and International Conference on Harmonization (ICH) compliance. A final article summarizes recommendations for the design and conduct of phase II studies.
I 期临床试验代表着将有前途的新疗法从实验室推向临床的第一步。尽管 I 期临床试验的重要性已得到广泛认可，但科学界、医学界和统计界目前尚未就如何在人体中进行这些研究达成共识。随着靶向治疗的出现，很明显，我们需要根据所研究的特定药物类别和正在定义的任何终点来调整 I 期研究的设计。国家癌症研究所（NCI）试验药物指导委员会（IDSC）通过美国食品和药物管理局（FDA）为 NCI 癌症治疗评估计划（CTEP）持有的新药临床试验（IND）申请的药物提供广泛的外部科学和临床输入，以设计和优先考虑早期临床试验。IDSC 已经成立了多个工作组和工作组，包括临床试验设计工作组和生物标志物工作组，许多成员来自 IDSC 内部以及外部专家，包括学术界、制药行业和监管机构的参与者。临床试验设计工作组举办了 I 期研讨会，主要目标是为 I 期研究的最佳设计制定共识建议。主要重点包括（1）高效试验设计，（2）I 期药物联合治疗，以及（3）适当的统计和相关终点。在这个 CCR 焦点系列中，文章总结了关于 I 期研究（包括联合试验）的关键方面和建议，如设计、生物标志物的使用、欧盟和日本对设计的看法、对首次人体和其他 I 期研究的要求，以及确保监管和国际协调会议（ICH）合规性。最后一篇文章总结了 II 期研究设计和实施的建议。
