Benefits, challenges and obstacles of adaptive clinical trial designs.
Benefits, challenges and obstacles of adaptive clinical trial designs.
复制标题
DOI：
10.1186/1750-1172-6-79
复制
发表时间：
2011-11-30
影响因子：
3.7
通讯作者：
Corey R
中科院分区：
文献类型：
--
作者：
Chow SC;Corey R
近年来，在药物/临床研究和开发中使用自适应设计方法已变得流行，因为它的灵活性和有效性，以确定潜在的信号，临床受益的测试治疗的调查。然而，灵活性和效率增加了操作偏倚的风险，导致评估所研究的试验治疗的治疗效果的准确性和可靠性降低。在其最近的指南草案中，美国食品药品监督管理局（FDA）表达了对使用自适应设计的临床试验将总体I类错误率控制在预先规定的显著性水平的监管关注。FDA将适应性设计分为理解良好的设计和不太理解的设计。对于那些不太了解的自适应设计，如自适应剂量探索设计和两阶段I/II期（或II/III期）无缝自适应设计，统计方法尚未建立，因此应谨慎使用。在实践中，临床试验中自适应设计方法的滥用是临床科学家和监管机构共同关注的问题。建议减缓在临床试验中使用自适应设计方法的升级势头，以便有时间开发适当的统计方法。
In recent years, the use of adaptive design methods in pharmaceutical/clinical research and development has become popular due to its flexibility and efficiency for identifying potential signals of clinical benefit of the test treatment under investigation. The flexibility and efficiency, however, increase the risk of operational biases with resulting decrease in the accuracy and reliability for assessing the treatment effect of the test treatment under investigation. In its recent draft guidance, the United States Food and Drug Administration (FDA) expresses regulatory concern of controlling the overall type I error rate at a pre-specified level of significance for a clinical trial utilizing adaptive design. The FDA classifies adaptive designs into categories of well-understood and less well-understood designs. For those less well-understood adaptive designs such as adaptive dose finding designs and two-stage phase I/II (or phase II/III) seamless adaptive designs, statistical methods are not well established and hence should be used with caution. In practice, misuse of adaptive design methods in clinical trials is a concern to both clinical scientists and regulatory agencies. It is suggested that the escalating momentum for the use of adaptive design methods in clinical trials be slowed in order to allow time for development of appropriate statistical methodologies.
登录
查看更多内容
影响因子：
1.1
作者：
Gallo, Paul;Chuang-Stein, Christy;Pinheiro, Jose
通讯作者：
Pinheiro, Jose
影响因子：
3.2
作者：
Chow, Shein-Chung;Tu, Yi-Hsuan
通讯作者：
Tu, Yi-Hsuan
影响因子：
1.9
作者：
OBRIEN, PC;FLEMING, TR
通讯作者：
FLEMING, TR
影响因子：
3.7
作者：
Chow SC;Chang M
通讯作者：
Chang M
影响因子：
--
作者：
Maca, Jeff;Bhattacharya, Suman;Krams, Michael
通讯作者：
Krams, Michael