The convergence of pharmacometrics and quantitative systems pharmacology in pharmaceutical research and development

Article Biology

A Quantitative Systems Pharmacology Perspective on the Importance of Parameter Identifiability

Anna Sher et al.

Summary: This article discusses the challenges in model development and assessment in Quantitative Systems Pharmacology (QSP). QSP requires incorporating mathematical descriptions of complex physiology and drug targets into models, while also developing robust and predictive models. However, there is no standard for model development and assessment in QSP, leading to potential miscommunication and misapplication within the modeling community.

BULLETIN OF MATHEMATICAL BIOLOGY (2022)

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Article Pharmacology & Pharmacy

Integrated systems modeling of severe asthma: Exploration of IL-33/ST2 antagonism

Kapil Gadkar et al.

Summary: Asthma is a complex disease with a high unmet medical need. In this study, a computational model of asthma biology was developed to integrate preclinical and clinical data, and a virtual population was created to capture clinical heterogeneity. The model's simulated responses to different therapies aligned with clinical endpoints and biomarkers. The model was used to explore the potential benefits of targeting the IL-33 pathway and to interpret trial results. Sensitivity analyses revealed the mechanisms behind the predicted biomarker changes. This model provides mechanistic insights and supports clinical program design for novel therapies.

CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY (2022)

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Review Medicine, Research & Experimental

Quantitative Clinical Pharmacology of T-Cell Engaging Bispecifics: Current Perspectives and Opportunities

Peter N. Morcos et al.

Summary: T-cell directing/engaging bispecifics (TDBs) activate T-cells through artificial immune synapses, leading to a powerful mode of action. The pharmacological response involves complex inter-relationships among T-cells, tumor cells, and TDBs, with dosing strategy playing a crucial role in determining the therapeutic window of TDBs.

CTS-CLINICAL AND TRANSLATIONAL SCIENCE (2021)

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Article Pharmacology & Pharmacy

Population repeated time-to-event analysis of exacerbations in asthma patients: A novel approach for predicting asthma exacerbations based on biomarkers, spirometry, and diaries/questionnaires

Robin J. Svensson et al.

Summary: This study aimed to characterize the risk of asthma exacerbation based on baseline and time-varying covariates in a population of severe asthma patients. A model was developed using data from a 52-week phase IIb trial, identifying significant time-varying covariates such as diary-based symptom score, rescue medication use, and forced expiratory volume in 1 s. The presence of time-varying covariates, especially with more frequent measurements like daily diary scores, provided valuable insights into treatment effects and exacerbation hazard.

CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY (2021)

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Review Physiology

History and Future Perspectives on the Discipline of Quantitative Systems Pharmacology Modeling and Its Applications

Karim Azer et al.

Summary: This paper reviews the history of mathematical biology and pharmacology models, highlights some gaps and challenges in the development and application of systems pharmacology models, and proposes an integrated strategy to overcome these challenges by leveraging advances in adjacent fields.

FRONTIERS IN PHYSIOLOGY (2021)

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Article Mathematical & Computational Biology