全面评估快速启动方案模式:需要什么?

IF 2.2 4区 医学 Q3 PHARMACOLOGY & PHARMACY Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-10-01 Epub Date: 2022-08-13 DOI:10.1007/s10928-022-09820-0
Ioannis P Androulakis
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引用次数: 0

摘要

定量系统药理学(QSP)是一个强大的方法组合,旨在开发综合数学和计算模型,阐明药理学、生理学和疾病之间复杂的相互作用。随着该领域的发展和成熟,其应用范围已超越了研究和开发的界限,并逐渐进入决策和监管领域。然而,要广泛接受并最终采用一种新的建模方法,需要有评估标准和量化指标,以建立可信度并增强对模型预测的信心。QSP 的目标是在治疗干预的背景下提供对病理学的综合理解。由于其雄心勃勃的性质,以及 QSP 是在各组织和学术机构之间开展活动的结果,以不协调的方式出现,因此所使用的工具、方法、计算方法和途径都具有高熵的特点。要最终接受 QSP 模型预测作为向监管机构提出申请的辅助材料,需要考虑两个关键方面:(1) 增强对 QSP 框架的信心,从而推动标准化和评估;(2) 仔细阐明期望值。这两方面都在很大程度上依赖于我们对 QSP 模型进行严格、一致评估的能力。在本手稿中,我们希望结合 QSP 模型的开发,讨论这种评估的意义和目的,并详细阐述 QSP 的不同特点,这些特点使这种努力具有挑战性。我们认为,QSP 建立的是一个概念性的综合框架,而不是一种具体明确的计算方法。QSP 要求使用各种建模和计算方法,并根据具体应用和可用数据模式进行优化,这些方法超过了化学计量学和 PK/PD 模型所使用的数据结构。虽然这些选择范围促进了创造性,并有望大大提高我们合理和优化设计药物干预措施的能力,但我们对 QSP 模型的期望需要明确阐述并达成一致,评估应强调 QSP 研究的范围而不是所使用的方法。不过,QSP 不应被视为一种独立的方法,而应被视为更广泛的计算模型中的一种。
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Towards a comprehensive assessment of QSP models: what would it take?

Quantitative Systems Pharmacology (QSP) has emerged as a powerful ensemble of approaches aiming at developing integrated mathematical and computational models elucidating the complex interactions between pharmacology, physiology, and disease. As the field grows and matures its applications expand beyond the boundaries of research and development and slowly enter the decision making and regulatory arenas. However, widespread acceptance and eventual adoption of a new modeling approach requires assessment criteria and quantifiable metrics that establish credibility and increase confidence in model predictions. QSP aims to provide an integrated understanding of pathology in the context of therapeutic interventions. Because of its ambitious nature and the fact that QSP emerged in an uncoordinated manner as a result of activities distributed across organizations and academic institutions, high entropy characterizes the tools, methods, and computational methodologies and approaches used. The eventual acceptance of QSP model predictions as supporting material for an application to a regulatory agency will require that two key aspects are considered: (1) increase confidence in the QSP framework, which drives standardization and assessment; and (2) careful articulation of the expectations. Both rely heavily on our ability to rigorously and consistently assess QSP models. In this manuscript, we wish to discuss the meaning and purpose of such an assessment in the context of QSP model development and elaborate on the differentiating features of QSP that render such an endeavor challenging. We argue that QSP establishes a conceptual, integrative framework rather than a specific and well-defined computational methodology. QSP elicits the use of a wide variety of modeling and computational methodologies optimized with respect to specific applications and available data modalities, which exceed the data structures employed by chemometrics and PK/PD models. While the range of options fosters creativity and promises to substantially advance our ability to design pharmaceutical interventions rationally and optimally, our expectations of QSP models need to be clearly articulated and agreed on, with assessment emphasizing the scope of QSP studies rather than the methods used. Nevertheless, QSP should not be considered an independent approach, rather one of many in the broader continuum of computational models.

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来源期刊
CiteScore
4.90
自引率
4.00%
发文量
39
审稿时长
6-12 weeks
期刊介绍: Broadly speaking, the Journal of Pharmacokinetics and Pharmacodynamics covers the area of pharmacometrics. The journal is devoted to illustrating the importance of pharmacokinetics, pharmacodynamics, and pharmacometrics in drug development, clinical care, and the understanding of drug action. The journal publishes on a variety of topics related to pharmacometrics, including, but not limited to, clinical, experimental, and theoretical papers examining the kinetics of drug disposition and effects of drug action in humans, animals, in vitro, or in silico; modeling and simulation methodology, including optimal design; precision medicine; systems pharmacology; and mathematical pharmacology (including computational biology, bioengineering, and biophysics related to pharmacology, pharmacokinetics, orpharmacodynamics). Clinical papers that include population pharmacokinetic-pharmacodynamic relationships are welcome. The journal actively invites and promotes up-and-coming areas of pharmacometric research, such as real-world evidence, quality of life analyses, and artificial intelligence. The Journal of Pharmacokinetics and Pharmacodynamics is an official journal of the International Society of Pharmacometrics.
期刊最新文献
Novel endpoints based on tumor size ratio to support early clinical decision-making in oncology drug-development. Translational pharmacokinetic and pharmacodynamic modelling of the anti-ADAMTS-5 NANOBODY® (M6495) using the neo-epitope ARGS as a biomarker. QSP modeling of a transiently inactivating antibody-drug conjugate highlights benefit of short antibody half life. A PopPBPK-RL approach for precision dosing of benazepril in renal impaired patients. Comparison of the power and type 1 error of total score models for drug effect detection in clinical trials.
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