TY - JOUR
T1 - A Quantitative Systems Pharmacology Perspective on the Importance of Parameter Identifiability
AU - Sher, Anna
AU - Niederer, Steven A.
AU - Mirams, Gary R.
AU - Kirpichnikova, Anna
AU - Allen, Richard
AU - Pathmanathan, Pras
AU - Gavaghan, David J.
AU - van der Graaf, Piet H.
AU - Noble, Denis
N1 - Funding Information:
The authors thank all the participants of the UK QSP Satellite meeting on ‘Quantitative Systems Pharmacology: Is there a case for model reduction?’ at the Department of Physiology, Anatomy and Genetics, University of Oxford, and the UK QSP Network for their support. GRM gratefully acknowledges support from a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and Royal Society and a Senior Research Fellowship from the Wellcome Trust (Wellcome Grant Nos. 101222/Z/13/Z and 212203/Z/18/Z). This research was funded in part by the Wellcome Trust [212203/Z/18/Z]. For the purpose of open access, the author (GM) has applied a CC-BY public copyright license to any Author Accepted Manuscript version arising from this submission.
Funding Information:
The authors thank all the participants of the UK QSP Satellite meeting on ?Quantitative Systems Pharmacology: Is there a case for model reduction?? at the Department of Physiology, Anatomy and Genetics, University of Oxford, and the UK QSP Network for their support. GRM gratefully acknowledges support from a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and Royal Society and a Senior Research Fellowship from the Wellcome Trust (Wellcome Grant Nos. 101222/Z/13/Z and 212203/Z/18/Z). This research was funded in part by the Wellcome Trust [212203/Z/18/Z]. For the purpose of open access, the author (GM) has applied a CC-BY public copyright license to any Author Accepted Manuscript version arising from this submission.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/3
Y1 - 2022/3
N2 - There is an inherent tension in Quantitative Systems Pharmacology (QSP) between the need to incorporate mathematical descriptions of complex physiology and drug targets with the necessity of developing robust, predictive and well-constrained models. In addition to this, there is no “gold standard” for model development and assessment in QSP. Moreover, there can be confusion over terminology such as model and parameter identifiability; complex and simple models; virtual populations; and other concepts, which leads to potential miscommunication and misapplication of methodologies within modeling communities, both the QSP community and related disciplines. This perspective article highlights the pros and cons of using simple (often identifiable) vs. complex (more physiologically detailed but often non-identifiable) models, as well as aspects of parameter identifiability, sensitivity and inference methodologies for model development and analysis. The paper distills the central themes of the issue of identifiability and optimal model size and discusses open challenges.
AB - There is an inherent tension in Quantitative Systems Pharmacology (QSP) between the need to incorporate mathematical descriptions of complex physiology and drug targets with the necessity of developing robust, predictive and well-constrained models. In addition to this, there is no “gold standard” for model development and assessment in QSP. Moreover, there can be confusion over terminology such as model and parameter identifiability; complex and simple models; virtual populations; and other concepts, which leads to potential miscommunication and misapplication of methodologies within modeling communities, both the QSP community and related disciplines. This perspective article highlights the pros and cons of using simple (often identifiable) vs. complex (more physiologically detailed but often non-identifiable) models, as well as aspects of parameter identifiability, sensitivity and inference methodologies for model development and analysis. The paper distills the central themes of the issue of identifiability and optimal model size and discusses open challenges.
KW - Model development
KW - Model identifiability
KW - Quantitative systems pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85124322294&partnerID=8YFLogxK
U2 - 10.1007/s11538-021-00982-5
DO - 10.1007/s11538-021-00982-5
M3 - Article
C2 - 35132487
AN - SCOPUS:85124322294
SN - 0092-8240
VL - 84
JO - Bulletin of Mathematical Biology
JF - Bulletin of Mathematical Biology
IS - 3
M1 - 39
ER -