在药物组合试验中,用于剂量发现和优化局部持续再评估方法
Jingyi Zhang1, Fangrong Yan1, Nolan A Wages2
1Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China.
这项研究引入了一种用于寻找最佳癌症药物组合的新方法. 它使用本地数据来改进剂量选择,使其在早期治疗开发中更加稳健和高效.
科学领域:
- 在瘤学瘤学.
- 生物统计学 生物统计学
- 临床试验设计 临床试验设计
背景情况:
- 优化癌症药物组合具有挑战性,因为样本大小小和剂量范围很大.
- 现有的基于模型的设计需要广泛的参数诱导,并且可能因稀疏数据或模型错误规范而不稳定.
研究的目的:
- 在早期癌症临床试验中开发强大的和高效的设计来探索剂量组合.
- 为了减少模型校准的复杂性,并提高设计稳定性.
主要方法:
- 拟议的局部,低参数化模型用于剂量探索,基于部分订购持续重新评估方法.
- 开发了基于本地数据的持续重新评估方法 (LD-CR) 设计,用于识别最大耐受剂量组合 (MTD) 和最佳生物剂量组合 (OBD).
- LD-CR设计仅模拟邻近剂量组合的局部数据,增强灵活性和稳定性.
主要成果:
- 与现有方法相比,模拟研究表明,用于MTD识别的LD-CR设计的性能具有竞争力.
- LD-CR设计显示出优于基于模型的OBD优化方法的优势.
- 局部建模方法对于描述局部剂量探索空间而言是灵活的.
结论:
- 基于本地数据的持续重新评估方法设计为组合癌症疗法中剂量确定提供了强大而有效的替代方案.
- 这种方法简化了模型校准,提高了设计稳定性,特别有利于早期药物开发.
- 该方法对MTD和OBD识别都很有希望,在某些方面表现优于现有的基于模型的策略.
更多相关视频
15:04Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
Published on: January 19, 2019
06:20Irradiator Commissioning and Dosimetry for Assessment of LQ α and β Parameters, Radiation Dosing Schema, and in vivo Dose Deposition
Published on: March 11, 2021
相关概念视频
Rational Dosage Regimen: Maintenance Dose and Loading Dose
In most cases, drugs are administered repetitively or infused continuously to maintain a steady-state concentration in the body. At a steady...
Dosage Regimen: Fixed Dose
Fixed-dose regimens can be used for various routes of administration, including intravenous (IV) injections and oral medications. For IV administration, a predetermined amount of the drug is...
Drug Dosage Regimen: Overview
Typically, the starting dose and dosing interval are guided by the manufacturer's recommendations based on clinical trials conducted during and after drug...
Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
Drug Discovery: Overview
Analysis of Population Pharmacokinetic Data
