论文标题
肿瘤学剂量调查设计的统计框架具有晚期毒性：评论
Statistical Frameworks for Oncology Dose-Finding Designs with Late-Onset Toxicities: A Review
论文作者
论文摘要
在肿瘤学剂量调查试验中，由于入学率交错，可能希望在存在未决的毒性结果的情况下实时做出剂量分配决策，例如，当剂量限制毒性是较晚的毒性。患者的活动时间信息可能用于促进此类决定。我们回顾了在剂量调查试验中进行事实建模的统计框架，并将现有设计汇总为两个类别：Tite Design和Pod Designs。 Tite设计基于对毒性概率的推断，而POD设计是基于对剂量发现决策的推断。这两类设计包含现有的单个设计作为特殊情况，并引起了新的设计。我们讨论和研究这些设计的理论特性，包括大样本收敛性能，相干原理和基本决策规则。为了促进这些设计在实践中的使用，我们引入了有效的计算算法并审查常见的实际考虑因素，例如安全规则和悬架规则。最后，通过计算机模拟评估和比较了几种设计的操作特性。
In oncology dose-finding trials, due to staggered enrollment, it might be desirable to make dose-assignment decisions in real-time in the presence of pending toxicity outcomes, for example, when the dose-limiting toxicity is late-onset. Patients' time-to-event information may be utilized to facilitate such decisions. We review statistical frameworks for time-to-event modeling in dose-finding trials and summarize existing designs into two classes: TITE designs and POD designs. TITE designs are based on inference on toxicity probabilities, while POD designs are based on inference on dose-finding decisions. These two classes of designs contain existing individual designs as special cases and also give rise to new designs. We discuss and study the theoretical properties of these designs, including large-sample convergence properties, coherence principles, and the underlying decision rules. To facilitate the use of these designs in practice, we introduce efficient computational algorithms and review common practical considerations, such as safety rules and suspension rules. Finally, the operating characteristics of several designs are evaluated and compared through computer simulations.
