Center for Personalized Cancer Therapy and the Division of Hematology and Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nat Rev Clin Oncol. 2020 Mar;17(3):140-146. doi: 10.1038/s41571-019-0313-2. Epub 2020 Feb 4.
The traditional regulatory drug approval paradigm comprising discrete phases of clinical testing that culminate in a large randomized superiority trial has historically been predominant in oncology. However, this approach has evolved in the current era of drug development, with multiple other development pathways now being utilized. Indeed, treatment approaches designed on the basis of an improved understanding of cancer biology have led to unprecedented responses in early phase trials, sometimes resulting in drug approvals in the absence of large-scale trials. At the same time, improved molecular diagnostic technologies have led to the identification of ever-smaller patient subgroups for molecularly targeted therapy. Moreover, new FDA regulatory paradigms have enabled the rapid review and accelerated approval of certain drugs in the absence of survival data. Regulatory approvals based on large-cohort trials with surrogate or intermediate clinical end points or on non-inferiority trials, as well as new tumour-agnostic indications, also set important precedents in the field. In this Viewpoint, we asked two leading oncologists involved in clinical drug development, an expert in regulatory science and prescription drug policy and a prominent patient advocate, to provide their opinions on the implications of these changes in regulatory practices for patient care.
传统的监管药物审批模式包括离散的临床测试阶段，最终以大型随机优势试验为高潮，在肿瘤学领域一直占据主导地位。然而，在药物开发的当前时代，这种方法已经发生了演变，现在正在利用多种其他开发途径。事实上，基于对癌症生物学的理解的改进而设计的治疗方法在早期试验中导致了前所未有的反应，有时导致在没有大规模试验的情况下批准药物。与此同时，改进的分子诊断技术导致了针对分子靶向治疗的患者亚组的不断缩小。此外，新的 FDA 监管模式使某些药物能够在没有生存数据的情况下快速审查和加速批准。基于大型队列试验的替代或中间临床终点或非劣效性试验的监管批准，以及新的肿瘤无关的适应症，也在该领域开创了重要的先例。在本观点中，我们邀请了两位参与临床药物开发的领先肿瘤学家、一位监管科学和处方药政策专家以及一位杰出的患者倡导者，就这些监管实践变化对患者护理的影响发表意见。
