Harrington J A, Hernandez-Guerrero T C, Basu B
Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
Department of Oncology, University of Cambridge, Cambridge, UK; Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
Clin Oncol (R Coll Radiol). 2017 Dec;29(12):770-777. doi: 10.1016/j.clon.2017.10.005. Epub 2017 Nov 3.
The process of anti-cancer drug development is complex, with high attrition rates. Factors that may optimise this process include well-constructed and relevant pre-clinical testing and use of biomarkers for patient selection. However, the design of early phase clinical trials will probably play a vital role in both the robust clinical investigation of new targeted therapies and in streamlining drug development. In this overview, we assess current concepts in phase I clinical trials, highlighting issues and opportunities to improve their meaningfulness. The particular challenge of how to design combination trials is addressed, with focus on the potential of new adaptive and model-based designs.
抗癌药物的研发过程复杂，淘汰率高。可能优化这一过程的因素包括精心构建且相关的临床前测试以及使用生物标志物进行患者选择。然而，早期临床试验的设计可能在新靶向疗法的稳健临床研究以及简化药物研发方面都发挥至关重要的作用。在本综述中，我们评估了I期临床试验的当前概念，突出了改善其意义的问题和机遇。我们探讨了如何设计联合试验这一特殊挑战，重点关注新的适应性设计和基于模型的设计的潜力。
