Designs for phase I trials in heterogeneous groups

描述(由申请人提供)：我们建议开发在不同患者组中进行的I期试验的设计。肿瘤学的I期试验旨在确定“最大耐受量”(MTD)，这是可以在没有过度副作用的情况下使用的最高剂量。在许多研究中，群体结构并没有在设计中使用。由此产生的推荐剂量被加权，有利于最频繁发生的人群的剂量，有效地远离了对患者的“个性化”剂量。目前，将小组结构作为设计的一部分，最常见的方法是在每个小组内进行单独的第一阶段试验。这可能是低效的，需要大量的患者，并且 可能会导致剂量建议与临床上对这些群体的已知情况背道而驰。在这个提案中，我们将为第一阶段试验开发有效的设计，在小组中建立 从我们以前的工作中设计出适合组合的药剂。我们的目标是为一组患者的I期试验开发更有效和更准确的设计，从而改善整个癌症和癌症治疗范围的护理。

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.