论文标题

使用近似贝叶斯计算设计的肿瘤学剂量查找

Oncology Dose Finding Using Approximate Bayesian Computation Design

论文作者

Jin, Huaqing, Du, Wenbin, Yin, Guosheng

论文摘要

在新的癌症治疗的发展中,一个重要的步骤是通过I期临床试验确定最大耐受剂量(MTD)。一般而言,I期试验设计可以归类为基于模型或基于算法的方法。基于模型的I期设计通常通过使用所有观察到的数据来更有效,而模型错误指定的潜在风险可能会导致不可靠的剂量分配和MTD识别不正确。相比之下,大多数基于算法的设计在使用累积信息方面的效率较低,因为它们倾向于专注于当前剂量水平的剂量运动附近观察到的数据。为了更有效地使用数据,没有任何模型假设,我们提出了一种新型的I阶段试验设计贝叶斯计算方法(ABC)方法。 ABC设计不仅没有任何剂量 - 毒性曲线假设,而且还可以汇总试验中剂量分配的所有可用信息。广泛的模拟研究表明,与其他I期设计相比,其稳健性和效率。我们将ABC设计应用于MEK抑制剂Selumetinib试验,以证明其令人满意的性能。提出的设计由于其简单性,效率和鲁棒性,因此对I期临床试验设计的家族可能是有用的补充。

In the development of new cancer treatment, an essential step is to determine the maximum tolerated dose (MTD) via phase I clinical trials. Generally speaking, phase I trial designs can be classified as either model-based or algorithm-based approaches. Model-based phase I designs are typically more efficient by using all observed data, while there is a potential risk of model misspecification that may lead to unreliable dose assignment and incorrect MTD identification. In contrast, most of the algorithm-based designs are less efficient in using cumulative information, because they tend to focus on the observed data in the neighborhood of the current dose level for dose movement. To use the data more efficiently yet without any model assumption, we propose a novel approximate Bayesian computation (ABC) approach for phase I trial design. Not only is the ABC design free of any dose--toxicity curve assumption, but it can also aggregate all the available information accrued in the trial for dose assignment. Extensive simulation studies demonstrate its robustness and efficiency compared with other phase I designs. We apply the ABC design to the MEK inhibitor selumetinib trial to demonstrate its satisfactory performance. The proposed design can be a useful addition to the family of phase I clinical trial designs due to its simplicity, efficiency and robustness.

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