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Project 2 - Structural Identifiability and Indistinguishability in Systems Pharmacology


ESR - David Janzén

Aims

To address the novel development and application of mechanism-based models for capturing dose-response time-data when systematic exposure is lacking in current pharmacological experiments, addressing effectively for the first time the characterisation of dose response data, leading to optimisation of subsequent (pre) clinical protocols, and identifying inter-individual differences.

Supervisor: Mike Chappell (University of Warwick), Neil Evans (University of Warwick)

Co-Supervisors: Mats Jirstrand (FCC, Gothenburg Sweden), James Yates (AstraZeneca, UK)

Project Objectives
  • Consider structural and numerical identifiability for all dose response characteristic models developed with the potential to develop new tools linked to the application of deconvolution techniques.
  • Extend structural identifiability analysis to all models developed across all work packages.
  • Examine the structural distinguishability between all candidates models for each application considered.

Project Update

For an update on the project to date please click here

Publications

Conference Presentations

  • September 2016: Conference oral presentation: Structural identifiability of mixed-effects models: Methods and insights. UK Quantitative Systems Pharmacology Network. Guildford, United Kingdom,
  • September 2015: Structural Identiability in Mixed-Effects Models: Two different approaches, 9th IFAC Symposium on Biological and Medical Systems, Berlin, Germany.

Posters Presented

  • 18th-20th November 2015: Pharmacokinetics UK (PKUK), Chester, United Kingdom. Two approaches to study structural identifiability in mixed-effects models.
  • 5th-7th November 2014: Pharmacokinetics UK (PKUK) Bath. Structural Identifiability in Mixed-Effects Models
  • 5th May 2014: Life Science Engineering, Chalmers University, Sweden. Input Estimation, Dose-Response-Time Modelling and Structural Identifiability as tools for Systems Pharmacology
  • 23rd-25th April 2014: 7th Noordwijkerhout Symposium on Pharmacokinetics, Pharmacodynamics and Systems Pharmacology, Systems Pharmacology in Drug Discovery and Development, The Netherlands. Input Estimation, Dose-Response-Time Modelling and Structural Identifiability as tools for Systems Pharmacology
  • 3rd-4th December 2013: Modelling and Simulation Symposium AstraZeneca Alderley Park, UK. Structural Identifiability and Indistinguishability in Quantitative Systems Pharmacology
  • 30th October - 1st November 2013: Pharmacokinetics UK (PKUK) Harrogate. Structural Identifiability and Indistinguishability in Systems Pharmacology To view David's poster presented at PKUK, 2013 please click here 


Other Presentations

  • 16th July 2014: “Milligan et al. - 2013 - Model-based drug development a rational approach to efficiently accelerate drug development” Journal club presentation and discussion with the Modelling and Simulation group at AstraZeneca.
  • 20th May 2014: “Structural Identifiability analysis of ordinary differential equations” given primarily to the Modelling and Simulation group at AstraZeneca.
  • 9th April 2014: “Modelling and simulation at AstraZeneca” given to primarily Engineering Biology students.
  • 20th March 2014: Presented to the Modelling and Simulation Group at AstraZeneca, Mölndal, Sweden.

Conferences Attended

  • 17th-18th December 2014: Modelling and Simulation Symposium AstraZeneca Mölndal, Sweden.
  • 5th-7th November 2014: Pharmacokinetics UK (PKUK) Bath.
  • 5th May 2014: Life Science Engineering, Chalmers University, Sweden.
  • 23rd-25th April 2014: 7th Noordwijkerhout Symposium on Pharmacokinetics, Pharmacodynamics and Systems Pharmacology, Systems Pharmacology in Drug Discovery and Development, The Netherlands.
  • 3rd-4th December 2013: Modelling and Simulation Symposium AstraZeneca Alderley Park, UK.
  • 30th October - 1st November 2013: Pharmacokinetics UK (PKUK) Harrogate.