Designs for phase I trials in heterogeneous groups

在异质组中进行 I 期试验的设计

• 批准号: 9242508
• 负责人: Mark R Conaway
• 金额: $ 31.42万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9242508
• 关键词: Address; Adverse effects; Caring; Characteristics; Clinical; Complex; Cytotoxic agent; Dose; Dose-Limiting; Ethics; Genetic; Goals; Group Structure; Grouping; Lead; Liver Dysfunction; Malignant Neoplasms; Mathematics; Maximum Tolerated Dose; Methods; Modeling; New Agents; Patients; Pharmaceutical Preparations; Probability; Recommendation; Research Personnel; Risk; Running; Toxic effect; Work; base; cancer therapy; design; experience; improved; oncology; phase I trial; public health relevance; trial design

DESCRIPTION (provided by applicant): We propose to develop designs for phase I trials conducted in heterogeneous groups of patients. Phase I trials in oncology are meant to establish the 'maximally tolerated dose' (MTD), the highest dose that can be administered without excessive side effects. In many studies, the group structure is not used in the design. The resulting recommended dose is weighted in favor of the dose for the most frequently occurring group, effectively moving away from 'personalized' dosing for patients. At present, the most common way to include the group structure as part of the design is to conduct a separate phase I trial within each group. This can be inefficient, requiring a large number of patients, and can lead to dose recommendations that run counter to what is known clinically about the groups. In this proposal, we will develop efficient designs for phase I trials in groups that build from our previous work in designs for combinations of agent. Our goal is to develop efficient and more accurate designs for phase I trials in groups of patients that can lead to improved care across the entire range of cancers and cancer therapies.

描述（由申请人提供）：我们建议开发在异质患者群体中进行的I期试验设计。肿瘤学I期试验旨在确定“最大耐受剂量”（MTD），即可以在不产生过多副作用的情况下施用的最高剂量。在许多研究中，在设计中没有使用组结构。由此产生的推荐剂量是加权的，有利于最频繁发生的群体的剂量，有效地摆脱了对患者的“个性化”剂量。目前，将分组结构作为设计的一部分最常见的方法是在每个组中进行单独的I期试验。这可能是低效的，需要大量的病人，而且

项目成果

Dose-finding design for multi-drug combinations.

• DOI: 10.1177/1740774511408748
• 发表时间: 2011-08
• 期刊: Clinical trials (London, England)
• 作者: Wages NA;Conaway MR;O'Quigley J
• 通讯作者: O'Quigley J

Extended model-based designs for more complex dose-finding studies.

• DOI: 10.1002/sim.4024
• 发表时间: 2011-07-30
• 期刊: STATISTICS IN MEDICINE
• 影响因子: 2
• 作者: O'Quigley, John;Conaway, Mark
• 通讯作者: Conaway, Mark

Integrating the escalation and dose expansion studies into a unified Phase I clinical trial.

将升级和剂量扩展研究整合到统一的I期临床试验中。

• DOI: 10.1016/j.cct.2016.06.010
• 发表时间: 2016-09
• 期刊: Contemporary clinical trials
• 影响因子: 2.2
• 作者: Iasonos A;O'Quigley J
• 通讯作者: O'Quigley J

Shift models for dose-finding in partially ordered groups.

• DOI: 10.1177/1740774518801599
• 发表时间: 2019-03
• 期刊: Clinical trials (London, England)
• 作者: Horton BJ;Wages NA;Conaway MR
• 通讯作者: Conaway MR

Performance of toxicity probability interval based designs in contrast to the continual reassessment method.

与持续重新评估方法相反，基于毒性概率间隔设计的性能。

• DOI: 10.1002/sim.7043
• 发表时间: 2017-01-30
• 期刊: Statistics in medicine
• 影响因子: 2
• 作者: Horton BJ;Wages NA;Conaway MR
• 通讯作者: Conaway MR