通过贝叶斯优化和机器学习替代模型加速虚拟患者生成
1Department of Biological Regulation, Faculty of Medicine, Tottori University, Yonago, Japan.
CPT: pharmacometrics & systems pharmacology
|December 4, 2024
概括
本研究介绍了一种混合贝叶斯优化和机器学习方法,以提高定量系统药理学 (QSP) 模拟的效率. 这种新方法增强了虚拟患者生成,以加快药物开发速度.
科学领域:
- 药理学 药理学是指药理学的学科.
- 计算生物学 计算生物学
- 生物技术是生物技术.
背景情况:
- 基于模型的药物发现和开发 (MID3) 对制药生产率至关重要.
- 量化系统药理 (QSP) 模型整合了生物机制和疾病复杂性,以预测临床结果.
- QSP的应用已经从代谢和心血管疾病扩展到瘤学和免疫治疗.
研究的目的:
- 解决QSP模型验证方面的挑战,特别是临床试验模拟中的参数可变性和高计算成本.
- 开发一种高效的参数选方法,用于生成多样化的虚拟患者 (VPs).
主要方法:
- 为了高效的参数选,开发了一种将贝叶斯优化与机器学习相结合的混合方法.
- 该方法应用于QSP模拟,以生成虚拟患者.
主要成果:
- 混合方法在QSP模拟中实现了27.5%的接受率.
- 这与传统的随机搜索方法 (2.5%的接受率) 相比,是10倍以上的改进.
结论:
- 拟议的混合方法显著提高了QSP模拟中的参数选效率.
- 这一进步促进了更快,更多样化的虚拟患者生成,加速了临床试验模拟和整体药物开发.
相关概念视频
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
56
Pharmacokinetic models are mathematical constructs that represent and predict the time course of drug concentrations in the body, providing meaningful pharmacokinetic parameters. These models are categorized into compartment, physiological, and distributed parameter models.
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
56
Mechanistic Models: Compartment Models in Algorithms for Numerical Problem Solving
40
Mechanistic models play a crucial role in algorithms for numerical problem-solving, particularly in nonlinear mixed effects modeling (NMEM). These models aim to minimize specific objective functions by evaluating various parameter estimates, leading to the development of systematic algorithms. In some cases, linearization techniques approximate the model using linear equations.
In individual population analyses, different algorithms are employed, such as Cauchy's method, which uses a...
In individual population analyses, different algorithms are employed, such as Cauchy's method, which uses a...
40
Improving Translational Accuracy
9.0K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
9.0K
Pharmacokinetic Models: Comparison and Selection Criterion
38
Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
38
Model Approaches for Pharmacokinetic Data: Compartment Models
75
Compartmental analysis is a widely adopted approach to characterizing drug pharmacokinetics. It uses compartment models that conceptualize the body as a collection of reversibly communicating compartments, each representing a group of tissues exhibiting similar drug distribution characteristics. The movement rate of the drug between these compartments is typically described by first-order kinetics.
Two primary types of compartment models are recognized: mammillary and catenary. The more...
Two primary types of compartment models are recognized: mammillary and catenary. The more...
75
Parametric Survival Analysis: Weibull and Exponential Methods
363
Parametric survival analysis models survival data by assuming a specific probability distribution for the time until an event occurs. The Weibull and exponential distributions are two of the most commonly used methods in this context, due to their versatility and relatively straightforward application.
Weibull Distribution
The Weibull distribution is a flexible model used in parametric survival analysis. It can handle both increasing and decreasing hazard rates, depending on its shape parameter...
Weibull Distribution
The Weibull distribution is a flexible model used in parametric survival analysis. It can handle both increasing and decreasing hazard rates, depending on its shape parameter...
363


