一个贝叶斯潜伏子组平台设计,用于剂量优化
Rongji Mu1, Xiaojiang Zhan2, Rui Sammi Tang2
1Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
项目Optimus将瘤药物开发从最大耐受剂量转移到最佳生物剂量 (OBD). 一个新的主协议平台试验设计有效地识别了跨多种癌症类型的新药和组合的OBD.
科学领域:
- 在瘤学瘤学.
- 临床试验设计 临床试验设计
- 生物统计学 生物统计学
背景情况:
- 美国FDA的项目Optimus旨在改革瘤药物开发中的剂量优化.
- 该倡议促进从最大耐受剂量 (MTD) 转向最佳生物剂量 (OBD).
研究的目的:
- 提出基于主协议的平台试验设计,用于同时识别新药的OBD.
- 为了评估新药组合与护理标准或其他药物在多种适应症.
主要方法:
- 利用贝叶斯潜伏子组模型来解决各种适用症治疗异质性.
- 采用贝叶斯的层次模型,在子组内借用信息.
- 纳入临时分析以更新子组成员资格,剂量毒性/有效性估计和风险-收益效用.
主要成果:
- 拟议的设计在模拟研究中证明了可取的操作特性.
- 它提供了一种灵活有效的方法来优化在瘤药物开发中的剂量.
- 设计方便了对剂量升级/降级作出明智的,特定于手臂的决策.
结论:
- 主协议平台试验设计有效地确定药物组合的最佳生物剂量.
- 这种方法有可能缩短药物开发时间表并降低成本.
- 设计可以通过简化开发过程来加速监管批准.
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