Methodologies for Quantitative Systems Pharmacology (QSP) Models: Design and Estimation

With the increased interest in the application of quantitative systems pharmacology (QSP) models within medicine research and development, there is an increasing need to formalize model development and verification aspects. In February 2016, a workshop was held at Roche Pharma Research and Early Development to focus discussions on two critical methodological aspects of QSP model development: optimal structural granularity and parameter estimation. We here report in a perspective article a summary of presentations and discussions.

[1]  C. Cobelli,et al.  In Silico Preclinical Trials: A Proof of Concept in Closed-Loop Control of Type 1 Diabetes , 2009, Journal of diabetes science and technology.

[2]  S B Duffull,et al.  Scale Reduction of a Systems Coagulation Model With an Application to Modeling Pharmacokinetic–Pharmacodynamic Data , 2014, CPT: pharmacometrics & systems pharmacology.

[3]  Maria Pia Saccomani,et al.  Examples of testing global identifiability of biological and biomedical models with the DAISY software , 2010, Comput. Biol. Medicine.

[4]  MC Peterson,et al.  FDA Advisory Meeting Clinical Pharmacology Review Utilizes a Quantitative Systems Pharmacology (QSP) Model: A Watershed Moment? , 2015, CPT: pharmacometrics & systems pharmacology.

[5]  B. Hendriks.  Negative Modeling Results: A Dime a Dozen or a Stepping Stone to Scientific Discovery? , 2013, CPT: pharmacometrics & systems pharmacology.

[6]  Ursula Klingmüller,et al.  Structural and practical identifiability analysis of partially observed dynamical models by exploiting the profile likelihood , 2009, Bioinform..

[7]  T. Colatsky,et al.  The Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative - Update on progress. , 2016, Journal of pharmacological and toxicological methods.

[8]  G. Colice,et al.  A Mathematical Modeling Approach to Understanding the Effect of Anti‐Interleukin Therapy on Eosinophils , 2016, CPT: pharmacometrics & systems pharmacology.

[9]  N Benson,et al.  A Systems Pharmacology Perspective on the Clinical Development of Fatty Acid Amide Hydrolase Inhibitors for Pain , 2014, CPT: pharmacometrics & systems pharmacology.

[10]  T. Wajima,et al.  A Comprehensive Model for the Humoral Coagulation Network in Humans , 2009, Clinical pharmacology and therapeutics.