Current Design Issues in Oncology Trials

描述(由申请人提供)：这项建议为遗传学中的剂量发现临床试验和关联研究开发了顺序设计。新方法是在没有现有方法或现有方法效率不高的情况下开发的。下面描述的所有研究项目都是由Lineberger综合癌症中心的一项或多项临床试验推动的。临床设置如下：(1)在第一设置中，进行细胞抑制剂的剂量发现试验。结果是两个变量，毒性和治疗反应。目标是找到最佳的生物安全剂量，该剂量被定义为具有特定毒性比率的最小剂量和具有特定应答率的剂量。(2)在第二个设置中，进行肿瘤学的剂量发现试验，以寻找具有一定剂量限制毒性的剂量。毒性结果是二元的，对患者的毒性进行长时间的跟踪。其目标是为这类试验开发灵活而高效的设计。(3)在第三种情况下，毒性结果是次要的。其目标是开发一项研究设计，以不同毒性等级的比率的目标加权平均值来确定剂量。(4)第四个背景是全基因组关联研究。

DESCRIPTION (provided by applicant): This proposal develops sequential designs for dose-finding clinical trials and association studies in genetics. The new methods are developed in situations where there are no existing methods or existing methods are not efficient. All research projects described below were motivated by one or more clinical trials at the Lineberger Comprehensive Cancer Center. The clinical settings are the following: (1) In the first setting, a dose-finding trial for a cytostatic agent is conducted. The outcome is bivariate binary, toxicity and therapeutic response. The goal is to find the optimal biological safe dose, the dose defined as the minimum of the dose with a specified toxicity rate and the dose with a specified response rate. (2) In the second setting, a dose- finding trial in oncology is conducted to find the dose with a certain rate of dose limiting toxicity. Toxicity outcome is binary and patients are followed for toxicity for a long period of time. The goal is to develop flexible and efficient designs for such trials. (3) In the third setting toxicity outcome is ordinal. The goal is to develop a study design to identify the dose with a target weighted average of the rates of different toxicity grades. (4) The fourth setting is a genome-wide association study.