现有的早期阶段剂量检测设计的统计操作特征,在瘤学中具有毒性和有效性
Hao Sun1, Hsin-Yu Lin1, Jieqi Tu2
1Global Biometrics & Data Sciences, Bristol Myers Squibb, Madison, New Jersey, USA.
Journal of biopharmaceutical statistics
|November 17, 2024
概括
新的临床试验设计通过考虑毒性和疗效来确定最佳生物剂量 (OBD). 在早期癌症试验中,STEIN,PRINTE和BOIN12的设计显示出卓越的性能.
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:
- 传统的I期癌症试验重点是使用单一毒性的最大耐受剂量 (MTD).
- 像免疫瘤学和向疗法等新兴疗法挑战了单一剂量反应假设.
- 基于毒性的传统设计对于这些新型药物来说是不够的.
研究的目的:
- 审查和比较模型辅助的早期剂量发现设计,以确定最佳生物剂量 (OBD).
- 评估设计的操作特性,包括BOIN-ET,BOIN12,UBI,TEPI-2,PRINTE,STEIN,UTPI等.
- 在各种剂量反应情景下评估设计性能.
主要方法:
- 模型辅助剂量确定设计的比较审查.
- 广泛的模拟研究评估运行特征.
- 在CAR T细胞治疗I期试验中的案例研究应用.
主要成果:
- 设计性能根据剂量-反应关系和所选择的指标大大不同.
- 没有一个单一的设计在所有场景中普遍优于其他设计.
- 从不同的角度来看,STEIN,PRINTE和BOIN12都表现出了卓越的性能.
结论:
- 选择剂量确定设计是关键的,取决于具体的治疗背景和预期的剂量反应模式.
- 包含毒性和疗效的模型辅助设计对于新型癌症疗法至关重要.
- 建议使用STEIN,PRINTE和BOIN12,因为它们在识别OBD时具有强大的性能.
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