Section of Hematology/Oncology, Department of Medicine, and Comprehensive Cancer Center, University of Chicago, 5841 South Maryland Avenue, MC 2115, Chicago, IL 60637-1470, USA.
Nat Rev Clin Oncol. 2011 Dec 6;9(4):208-14. doi: 10.1038/nrclinonc.2011.190.
In the era of cytotoxic therapies, tumor regression has rarely been observed in phase I trials and randomized controlled trials have usually been required to demonstrate modest improvements over prevailing standards of care. In the era of effective targeted therapies, drugs such as vemurafenib and crizotinib have demonstrated convincing efficacy in early clinical testing, raising the question of whether randomized phase III trials are necessary and feasible before drug approval. Since 1992, the FDA has approved a number of drugs without data from confirmatory clinical trials as part of the accelerated approval process. While this initiative has largely been successful in bringing effective drugs to the market more quickly, there is much to be learned from case studies of drugs, such as gefitinib, which subsequently failed to gain full approval. In this Review, we use a number of historical examples to make the case that it may be reasonable to consider foregoing randomized phase III trials for certain drugs before drug approval. We explore the consequences (both good and bad) of foregoing randomized phase III trials and propose criteria that might be used to select drugs for consideration of such an approach.
在细胞毒性疗法时代，I 期试验中很少观察到肿瘤消退，通常需要进行随机对照试验以证明相对于现有治疗标准有适度的改善。在有效的靶向治疗时代，诸如vemurafenib 和 crizotinib 等药物在早期临床测试中表现出令人信服的疗效，这引发了一个问题，即在药物批准之前是否有必要和可行进行随机 III 期试验。自 1992 年以来，FDA 已批准了许多没有确证性临床试验数据的药物，作为加速审批程序的一部分。虽然这一举措在将有效药物更快推向市场方面取得了很大成功，但从 gefitinib 等药物的案例研究中可以吸取很多教训，这些药物随后未能获得完全批准。在这篇综述中，我们使用了一些历史实例来说明，在药物批准之前，对于某些药物，放弃随机 III 期试验可能是合理的。我们探讨了放弃随机 III 期试验的后果（好的和坏的），并提出了可能用于选择考虑这种方法的药物的标准。
