Quantitative systems pharmacology (QSP) is an important approach in pharmaceutical research and development that facilitates in silico generation of quantitative mechanistic hypotheses and enables in silico trials. As demonstrated by applications from numerous industry groups and interest from regulatory authorities, QSP is becoming an increasingly critical component in clinical drug development. With rapidly evolving computational tools and methods, QSP modeling has achieved important progress in pharmaceutical research and development, including for heart failure (HF). However, various challenges exist in the QSP modeling and clinical characterization of HF. Machine/deep learning (ML/DL) methods have had success in a wide variety of fields and disciplines. They provide data-driven approaches in HF diagnosis and modeling, and offer a novel strategy to inform QSP model development and calibration. The combination of ML/DL and QSP modeling becomes an emergent direction in the understanding of HF and clinical development new therapies. In this work, we review the current status and achievement in QSP and ML/DL for HF, and discuss remaining challenges and future perspectives in the field.
Quantitative systems pharmacology (QSP) modeling is applied to address essential questions in drug development, such as the mechanism of action of a therapeutic agent and the progression of disease. Meanwhile, machine learning (ML) approaches also contribute to answering these questions via the analysis of multi-layer ‘omics’ data such as gene expression, proteomics, metabolomics, and high-throughput imaging. Furthermore, ML approaches can also be applied to aspects of QSP modeling. Both approaches are powerful tools and there is considerable interest in integrating QSP modeling and ML. So far, a few successful implementations have been carried out from which we have learned about how each approach can overcome unique limitations of the other. The QSP + ML working group of the International Society of Pharmacometrics QSP Special Interest Group was convened in September, 2019 to identify and begin realizing new opportunities in QSP and ML integration. The working group, which comprises 21 members representing 18 academic and industry organizations, has identified four categories of current research activity which will be described herein together with case studies of applications to drug development decision making. The working group also concluded that the integration of QSP and ML is still in its early stages of moving from evaluating available technical tools to building case studies. This paper reports on this fast-moving field and serves as a foundation for future codification of best practices.
more » « less- NSF-PAR ID:
- 10362659
- Author(s) / Creator(s):
- ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more »
- Publisher / Repository:
- Springer Science + Business Media
- Date Published:
- Journal Name:
- Journal of Pharmacokinetics and Pharmacodynamics
- Volume:
- 49
- Issue:
- 1
- ISSN:
- 1567-567X
- Format(s):
- Medium: X Size: p. 5-18
- Size(s):
- ["p. 5-18"]
- Sponsoring Org:
- National Science Foundation
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