Designs for phase I trials in heterogeneous groups

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

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.