标题： 在第一二阶段肿瘤剂量寻找试验中，将效用定义为不确定情况下的偏好度量 显示英文标题

标题： Defining Utility as a Measure of Preference Under Uncertainty in Phase I-II Oncology Dose Finding Trials

摘要： 剂量寻找试验的主要目标是从候选剂量中找到一个最优剂量以进行进一步研究。 肿瘤学中的试验设计是分阶段进行的，在每个阶段都会做出如何治疗下一组患者的决定，直到达到最终样本量或提前停止试验。 这项工作将贝叶斯决策理论方法应用于该问题，提出了一种基于疗效和毒性的新效用函数，并基于冯·诺伊曼-摩根斯坦（VNM）效用理论。 我们提出的框架通过允许在判断为收益或损失时风险态度的变化，更好地捕捉真实的临床判断，这些判断是相对于一个称为参考点的中间结果定义的。 我们称这种方法为参考依赖决策理论剂量寻找（R2DT）。 一项模拟研究显示，该框架可以表现良好并产生良好的操作特性。 模拟结果表明， R2DT在候选剂量接近最低可接受疗效和最大可接受毒性阈值的场景中，更能检测到最优剂量。 所提出的框架表明，一种更灵活的效用函数，能够更好地捕捉临床医生的信念，可以导致具有良好操作特性的试验，包括找到最优剂量的高概率。 我们的工作展示了该框架的概念验证，应在更广泛的设置中进行评估。 显示英文摘要

摘要： The main objective of dose finding trials is to find an optimal dose amongst a candidate set for further research. The trial design in oncology proceeds in stages with a decision as to how to treat the next group of patients made at every stage until a final sample size is reached or the trial stopped early. This work applies a Bayesian decision-theoretic approach to the problem, proposing a new utility function based on both efficacy and toxicity and grounded in von Neumann-Morgenstern (VNM) utility theory. Our proposed framework seeks to better capture real clinical judgements by allowing attitudes to risk to vary when the judgements are of gains or losses, which are defined with respect to an intermediate outcome known as a reference point. We call this method Reference Dependent Decision Theoretic dose finding (R2DT). A simulation study demonstrates that the framework can perform well and produce good operating characteristics. The simulation results demonstrate that R2DT is better at detecting the optimal dose in scenarios where candidate doses are around minimum acceptable efficacy and maximum acceptable toxicity thresholds. The proposed framework shows that a flexible utility function, which better captures clinician beliefs, can lead to trials with good operating characteristics, including a high probability of finding the optimal dose. Our work demonstrates proof-of-concept for this framework, which should be evaluated in a broader range of settings.