Operating characteristics are needed to properly evaluate the scientific validity of phase I protocols.
Operating characteristics are needed to properly evaluate the scientific validity of phase I protocols.
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需要操作特性来正确评估I期方案的科学有效性。
DOI：
10.1016/j.cct.2021.106517
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发表时间：
2021-09
影响因子：
2.2
通讯作者：
Petroni GR
中科院分区：
文献类型：
--
作者：
Wages NA;Horton BJ;Conaway MR;Petroni GR
拟定临床试验设计的操作特征提供了对安全性和准确性性能的深入了解，使研究团队和审查实体能够确定设计是否适合实现研究的拟定目标。癌症治疗的进展增加了早期临床试验设计的需求。此外，早期试验设计研究的进展导致了广泛的方法的可用性，这些方法显示出对过时方法的巨大改进。三个试验利用3+3决策规则的变化进行了讨论。方案缺乏细节，包括操作特征和偏离3+3决策规则和MTD确定的决策指南。我们提供了一个讨论的统计问题与每一个设计和操作特性的建议设计相比，更适合实现每一个试验的目标的替代品。我们的研究结果说明了操作特性如何影响设计的安全性和准确性。操作特征可以揭示不良行为，例如高比例的参与者暴露于过度毒性剂量，正确识别MTD的可能性低，以及不适当的早期研究终止。早期试验设计的选择对试验实现其目标的能力具有重要意义。操作特性是方案设计和审查的必要组成部分，确定是否可以实现研究目标并记录研究的科学有效性。由于历史上的接受，继续使用过时的方法阻碍了科学的严谨性和通过药物开发过程移动有效药物的努力。
Operating characteristics for proposed clinical trial designs provide insight into performance regarding safety and accuracy, allowing the study team and review entities to determine the design’s suitability to achieve the study’s proposed objectives. Advances in cancer therapeutics have augmented the needs of early phase clinical trial design. Additionally, advances in research on early-phase trial design have led to the availability of a wide range of methods that show vast improvement over outdated approaches. Three trials utilizing variations of the 3+3 decision rule are discussed. The protocols lacked detail, including operating characteristics and guidance for decision-making that deviated from the 3+3 decision rule and MTD determination. We provide a discussion of the statistical issues associated with each design and operating characteristics for the proposed design compared to alternatives better suited to achieve the aims of each trial. Our results illustrate how operating characteristics inform a design’s safety and accuracy. Operating characteristics can unmask poor behavior, such as a high percentage of particiapnts exposed to overly toxic doses, a low probability of correctly identifying the MTD, and inappropriate early study termination. Selection of early-phase trial design has significant implications on a trial’s ability to meet its objectives. Operating characteristics are a necessary component in the design and review of a protocol, determining if the study’s objectives can be achieved and documenting the study’s scientific validity. Continued use of outdated approaches due to historical acceptance hinders scientific rigor and the effort to move effective agents through the drug development process.
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DOI：
10.1158/1078-0432.ccr-18-0203
发表时间：
2019-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Conaway MR;Petroni GR
通讯作者：
Petroni GR
影响因子：
1.1
作者：
Chiuzan C;Shtaynberger J;Manji GA;Duong JK;Schwartz GK;Ivanova A;Lee SM
通讯作者：
Lee SM
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：
2.2
作者：
Guo, Wentian;Wang, Sue-Jane;Ji, Yuan
通讯作者：
Ji, Yuan
影响因子：
2.1
作者：
Mozgunov, Pavel;Jaki, Thomas;Paoletti, Xavier
通讯作者：
Paoletti, Xavier