Sobol Sensitivity Analysis: A Tool to Guide the Development and Evaluation of Systems Pharmacology Models

被引:340
作者
Zhang, X-Y [1 ]
Trame, M. N. [1 ]
Lesko, L. J. [1 ]
Schmidt, S. [1 ]
机构
[1] Univ Florida, Coll Pharm, Ctr Pharmacometr & Syst Pharmacol, Dept Pharmaceut, Orlando, FL 32827 USA
关键词
D O I
10.1002/psp4.6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A systems pharmacology model typically integrates pharmacokinetic, biochemical network, and systems biology concepts into a unifying approach. It typically consists of a large number of parameters and reaction species that are interlinked based upon the underlying (patho) physiology and the mechanism of drug action. The more complex these models are, the greater the challenge of reliably identifying and estimating respective model parameters. Global sensitivity analysis provides an innovative tool that can meet this challenge.
引用
收藏
页码:69 / 79
页数:11
相关论文
共 57 条
[1]   Evaluating Systems Pharmacology Models Is Different From Evaluating Standard Pharmacokinetic Pharmacodynamic Models [J].
Agoram, B. .
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, 2014, 3 (02)
[2]   A Systems Pharmacology Perspective on the Clinical Development of Fatty Acid Amide Hydrolase Inhibitors for Pain [J].
Benson, N. ;
Metelkin, E. ;
Demin, O. ;
Li, G. L. ;
Nichols, D. ;
van der Graaf, P. H. .
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, 2014, 3 (01)
[3]   Systems pharmacology of the nerve growth factor pathway: use of a systems biology model for the identification of key drug targets using sensitivity analysis and the integration of physiology and pharmacology [J].
Benson, Neil ;
Matsuura, Tomomi ;
Smirnov, Sergey ;
Demin, Oleg ;
Jones, Hannah M. ;
Dua, Pinky ;
van der Graaf, Piet H. .
INTERFACE FOCUS, 2013, 3 (02)
[4]   Mathematical modeling reveals threshold mechanism in CD95-induced apoptosis [J].
Bentele, M ;
Lavrik, I ;
Ulrich, M ;
Stösser, S ;
Heermann, DW ;
Kalthoff, H ;
Krammer, PH ;
Eils, R .
JOURNAL OF CELL BIOLOGY, 2004, 166 (06) :839-851
[5]   Emergent properties of networks of biological signaling pathways [J].
Bhalla, US ;
Iyengar, R .
SCIENCE, 1999, 283 (5400) :381-387
[6]   Ligand-dependent responses of the ErbB signaling network: experimental and modeling analyses [J].
Birtwistle, Marc R. ;
Hatakeyama, Mariko ;
Yumoto, Noriko ;
Ogunnaike, Babatunde A. ;
Hoek, Jan B. ;
Kholodenko, Boris N. .
MOLECULAR SYSTEMS BIOLOGY, 2007, 3 (1)
[7]   SENSITIVITY AND UNCERTAINTY ANALYSIS OF COMPLEX-MODELS OF DISEASE TRANSMISSION - AN HIV MODEL, AS AN EXAMPLE [J].
BLOWER, SM ;
DOWLATABADI, H .
INTERNATIONAL STATISTICAL REVIEW, 1994, 62 (02) :229-243
[8]   Insulin Signaling in Type 2 Diabetes EXPERIMENTAL AND MODELING ANALYSES REVEAL MECHANISMS OF INSULIN RESISTANCE IN HUMAN ADIPOCYTES [J].
Brannmark, Cecilia ;
Nyman, Elin ;
Fagerholm, Siri ;
Bergenholm, Linnea ;
Ekstrand, Eva-Maria ;
Cedersund, Gunnar ;
Stralfors, Peter .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (14) :9867-9880
[9]   Relevance of the application of pharmacokinetic-pharmacodynamic modelling concepts in drug development - The 'Wooden Shoe' paradigm [J].
Breimer, DD ;
Danhof, M .
CLINICAL PHARMACOKINETICS, 1997, 32 (04) :259-267
[10]  
Chan K., 1997, P 1997 WINT SIM C AT