Embracing model-based designs for dose-finding trials.
Embracing model-based designs for dose-finding trials.
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DOI：
10.1038/bjc.2017.186
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发表时间：
2017-07-25
影响因子：
8.8
通讯作者：
Cornelius V
中科院分区：
文献类型：
--
作者：
Love SB;Brown S;Weir CJ;Harbron C;Yap C;Gaschler-Markefski B;Matcham J;Caffrey L;McKevitt C;Clive S;Craddock C;Spicer J;Cornelius V
剂量探索试验对药物开发至关重要，因为它们为后期测试确定推荐剂量。我们的目标是激励更广泛地使用基于模型的剂量发现设计，如持续再评估方法（CRM）。我们对剂量探索设计进行了文献综述，并进行了一项调查，以确定其实施的感知障碍。我们描述了基于模型的设计的好处（灵活性，上级操作特性，扩展范围），他们目前的摄取量，和现有的资源。实施基于模型的设计的最突出障碍是缺乏适当的培训，首席研究员对基于算法的设计的偏好（例如，3+3），以及在资助之前用于研究设计的有限资源。我们用一个真实的例子来说明如何克服这些障碍。有压倒性的证据证明CRM的好处。许多领先的制药公司经常实施基于模型的设计。我们的分析确定了学术统计学家和临床学者在反映行业在试验设计方面取得的进展方面的障碍。来自资助者、监管机构和期刊编辑的统一支持可以为后期测试提供更准确的剂量，并提高临床药物开发的效率和成功率。我们给出了建议，以增加在学术界剂量探索试验的吸收基于模型的设计。
Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM). We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation. We describe the benefits of model-based designs (flexibility, superior operating characteristics, extended scope), their current uptake, and existing resources. The most prominent barriers to implementation of a model-based design were lack of suitable training, chief investigators’ preference for algorithm-based designs (e.g., 3+3), and limited resources for study design before funding. We use a real-world example to illustrate how these barriers can be overcome. There is overwhelming evidence for the benefits of CRM. Many leading pharmaceutical companies routinely implement model-based designs. Our analysis identified barriers for academic statisticians and clinical academics in mirroring the progress industry has made in trial design. Unified support from funders, regulators, and journal editors could result in more accurate doses for later-phase testing, and increase the efficiency and success of clinical drug development. We give recommendations for increasing the uptake of model-based designs for dose-finding trials in academia.
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DOI：
10.1093/jnci/djp079
发表时间：
2009-05-20
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Le Tourneau C;Lee JJ;Siu LL
通讯作者：
Siu LL
影响因子：
2
作者：
Chevret, Sylvie
通讯作者：
Chevret, Sylvie
影响因子：
45.3
作者：
Iasonos, Alexia;Goenen, Mithat;Bosl, George J.
通讯作者：
Bosl, George J.
影响因子：
50.5
作者：
Doussau, A.;Thiebaut, R.;Paoletti, X.
通讯作者：
Paoletti, X.
影响因子：
11.5
作者：
Iasonos, Alexia;Gounder, Mrinal;O'Quigley, John
通讯作者：
O'Quigley, John