We congratulate the authors on their comments on innovative approaches to drug development that fall out of the traditional mold and may result in more quickly bringing safe and effective treatments to patients. Changes in the overall clinical development approach are most relevant to “breakthrough” therapies, which have generally yielded exceptional efficacy data in early clinical studies, motivating exploration of accelerated development and regulatory approaches, as well as a potential ethical need for crossover upon progression in randomized controlled studies (Horning et al. Horning, S.J., Haber, D.A., Selig, W.K., Ivy, S.P., Roberts, S.A., Allen, J.D., Sigal, E.V., and Sawyers, C.L. (2013), “Developing Standards for Breakthrough Therapy Designation in Oncology,” Clinical Cancer Research, 19, 4297–4304. doi: 10.1158/1078-0432.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). As is clear from the article, it will be important to develop an understanding of what works well and where the pitfalls in new approaches are. We comment briefly on the four topics mentioned by the authors, combining comments on items 2 and 3: (1) nonproportional hazards, (2) interpretability of extended Phase I trials, (3) single-arm trials as a basis for approval, and (4) recent innovations in trial design.

我们祝贺作者对传统药物所无法提供的创新药物开发方法的评论，并可能更快地为患者提供安全有效的治疗方法。整体临床开发方法的变化与“突破性”疗法最相关，后者在早期临床研究中通常获得了非凡的疗效数据，激发了对加速发展和调节方法的探索，以及潜在的伦理要求，即在随机进展中进行交叉对照研究（Horning等 Horning，SJ，Haber，DA，Selig，WK，Ivy，SP，Roberts，SA，Allen，JD，Sigal，EV和Sawyers，CL（2013），“制定突破性的肿瘤治疗指定标准，”临床癌症研究，19，4297 – 4304。doi：10.1158 / 1078-0432。[Crossref]，[PubMed]，[Web of Science®]， [Google Scholar]）。从文章中可以清楚地看出，重要的是要了解什么有效，以及新方法的缺陷在哪里。我们对作者提到的四个主题进行简要评论，并结合对项目2和3的评论：（1）非比例危险，（2）扩展的I期临床试验的可解释性，（3）单臂试验作为批准的基础，以及（4）试验设计的最新创新。