论文标题

HI3+3:模型辅助剂量找到设计借用历史数据

Hi3+3: A Model-Assisted Dose-Finding Design Borrowing Historical Data

论文作者

Duan, Yunshan, Wang, Sue-Jane, Ji, Yuan

论文摘要

背景 - 在I期临床试验中,可以通过多区域计划,同一药物的重新制定或同一类中药物的先前试验获得历史数据。从历史数据中借入信息的统计设计可以降低成本,加快药物开发并保持安全性。目的 - 基于部分使用概率模型并部分使用算法规则进行决策的混合设计,我们旨在提高在存在历史数据,维持患者安全性并实现实际应用的简单性的情况下,提高剂量找到试验的效率。方法 - 我们提出了HI3+3设计,其中字母“ H”表示“历史数据”。我们在借用历史数据之前将其应用于权力,并定义先前的有效样本量(ESS)。剂量调查决策规则遵循I3+3设计中的想法,同时通过权力和ESS结合历史数据。拟议的HI3+3设计在试验开始之前就可以很好地进行剂量决定,这是实践中易于应用的理想功能。结果 - 由于从历史数据中借用的信息,HI3+3设计比i3+3设计要好。它能够为试验患者维持高水平的安全性,而无需牺牲识别正确的MTD的能力。在仿真结果中发现了此功能的插图。结论 - 凭借证明的安全性,效率和简单性,HI3+3设计可能是借用历史数据的剂量发现试验的理想选择。

Background -- In phase I clinical trials, historical data may be available through multi-regional programs, reformulation of the same drug, or previous trials for a drug under the same class. Statistical designs that borrow information from historical data can reduce cost, speed up drug development, and maintain safety. Purpose -- Based on a hybrid design that partly uses probability models and partly uses algorithmic rules for decision making, we aim to improve the efficiency of the dose-finding trials in the presence of historical data, maintain safety for patients, and achieve a level of simplicity for practical applications. Methods -- We propose the Hi3+3 design, in which the letter "H" represents "historical data". We apply the idea in power prior to borrow historical data and define the effective sample size (ESS) of the prior. Dose-finding decision rules follow the idea in the i3+3 design while incorporating the historical data via the power prior and ESS. The proposed Hi3+3 design pretabulates the dosing decisions before the trial starts, a desirable feature for ease of application in practice. Results -- The Hi3+3 design is superior than the i3+3 design due to information borrow from historical data. It is capable of maintaining a high level of safety for trial patients without sacrificing the ability to identify the correct MTD. Illustration of this feature are found in the simulation results. Conclusion -- With the demonstrated safety, efficiency, and simplicity, the Hi3+3 design could be a desirable choice for dose-finding trials borrowing historical data.

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