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: 8843799
• 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 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8843799
• 关键词: Address; Adverse effects; Caring; Characteristics; Complex; Cytotoxic agent; Dose; Dose-Limiting; Ethics; Genetic; Goals; Group Structure; Grouping; Health; Lead; Liver Dysfunction; Malignant Neoplasms; Maximum Tolerated Dose; Methods; Modeling; New Agents; Patients; Pharmaceutical Preparations; Probability; Recommendation; Research Personnel; Risk; Running; Sorting - Cell Movement; Toxic effect; Weight; Work; base; cancer therapy; design; experience; improved; oncology; phase I trial; 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）：我们建议为在异质性患者组中进行的I期试验开发设计。肿瘤学的I期试验旨在确定“最大耐受剂量”（MTD），即可以施用而没有过度副作用的最高剂量。在许多研究中，设计中没有使用组结构。由此产生的推荐剂量被加权以有利于最频繁发生的组的剂量，有效地远离患者的“个性化”给药。目前，将组结构作为设计的一部分的最常见方法是在每组内进行单独的I期试验。这可能是低效的，需要大量的患者， 可能导致剂量建议与临床上已知的有关群体的情况背道而驰。在本提案中，我们将为第一阶段试验开发有效的设计， 从我们以前的工作在设计的组合剂。我们的目标是为I期临床试验开发更有效、更准确的设计，以改善整个癌症和癌症治疗范围内的护理。