Curve-free phase I/II clinical trial designs for molecularly targeted agents and immunotherapy

分子靶向药物和免疫治疗的无曲线 I/II 期临床试验设计

• 批准号: 10304652
• 负责人: Yong Zang
• 金额: $ 14万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10304652
• 关键词: Address; Algorithms; Area; Binomial Model; Clinical; Clinical Trials Design; Communities; Complex; Cytotoxic agent; Data; Decision Making; Development; Dimensions; Dose; Drug Combinations; Goals; Immunotherapeutic agent; Immunotherapy; Joints; Lead; Learning; Likelihood Functions; Literature; Maximum Tolerated Dose; Methods; Modeling; Molecular Target; Monitor; Outcome; Patients; Pattern; Performance; Phase; Phase I Clinical Trials; Phase I/II Clinical Trial; Phase I/II Trial; Physicians; Probability; Research; Series; Testing; Therapeutic Effect; Time; Toxic effect; Translations; Weight; base; cancer therapy; clinical practice; cost; design; efficacy outcomes; flexibility; follow-up; interest; mathematical model; novel; response; simulation; targeted agent; trial design; two-dimensional; unpublished works; user-friendly; web app

Project Summary/Abstract The primary goal of this proposal is to develop transparent, flexible and efficient phase I/II clinical trial designs identifying optimal doses for molecularly targeted agents (MTA) and immunotherapy (IT). Conventional phase I/II clinical trial designs often use sophisticated parametric models to characterize the joint toxicity-efficacy distribu- tions and to conduct the trials. However, the parametric models are hard to justify in practice, and misspecification of parametric models can lead to substantially undesirable performances of phase I/II trials. Moreover, it is difficult for the physicians conducting the trials to clinically interpret the parameters of these sophisticated models, and such great learning costs impede the translation of novel statistical designs into real-world trial implementation. To solve these issues, in this proposal we will propose transparent curve-free phase I/II clinical trial designs. The proposed designs make no parametric assumptions on either dose-response relationship or toxicity-efficacy correlation and therefore performs robustly under any clinically meaningful dose-response curves. The concise clinically interpretable model expression and dose-finding algorithm make the proposed designs highly transla- tional from the statistical community to the clinical community. The proposed designs are also highly flexible because they are applicable for both single-agent trial and drug-combination trial with either quickly observable outcomes or delayed outcomes. The preliminary simulation studies show that the proposed designs are highly efficient in optimal dose selection and patient allocation. In addition, we will develop user-friendly web apps to facilitate the widespread application of the proposed designs in clinical practice.

项目总结/文摘