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Innovative Modelling for Pharmacological Advances through Collaborative Training

Final Report Summary - IMPACT (Innovative Modelling for Pharmacological Advances through Collaborative Training)

IMPACT (Innovative Modelling for Pharmacological Advances through Collaborative Training) has been an EU FP7-funded Marie Curie Initial Training Network (ITN) project (number 316736) co-ordinated by Dr Mike Chappell from the University of Warwick (UoW) in partnership with AstraZeneca (AZ), Fraunhofer-Chalmers Centre (FCC), Uppsala University and the Swedish University of Agricultural Sciences (SLU). It has trained Early Stage Researchers (ESRs) to develop new tools and techniques to support the emerging field of Quantitative and Systems Pharmacology (QSP) and enabled them to perform research projects at the forefront of international pharmacokinetic (PK) and pharmacodynamic (PD) analysis. The project has built upon extremely strong research and training links already formed between the UoW and AZ (UK) in PK/PD modelling and supported the clearly identified need within AZ worldwide to train more personnel with high-level skills in systems modelling for future drug development.

The most effective drugs are those that produce clinical benefit by modulating disease biology and are given to patients at an optimal dose and schedule. In order to deliver new drugs it is necessary to quantify, translate and simulate from the test tube to the patient. This includes being able to model biological pathways, quantify relationships between dose/exposure, target engagement, efficacy and safety in pre-clinical tests and humans and utilising all relevant information efficiently and quantitatively. The development and application of innovative modelling techniques to tackle current problems in drug development allied to the training of researchers with skills to perform these tasks were key drivers for the project partners.

A unique blend of multidisciplinary training was offered to the ESRs by both partners through well-established, extensive and innovative programmes at their sites with the appointed ESRs registered for PhDs at the UoW. The ESR projects were based on research problems and data generated at AZ. The outcomes of the projects not only maintain the positions of AZ and the UoW at the forefront of international research in PK/PD analysis, they greatly enhance the EU’s worldwide standing in this area, and also improve the future job prospects of those trained within the AZ group worldwide.

The project goal was to develop and apply innovative modelling techniques to tackle problems at the forefront of pharmacological research, to permit step-change advancements in drug development, to support the EU policy on healthcare and pharmaceutical development and to underpin the EU's Innovative Medicines Initiative. This was performed through the formation of an interdisciplinary collaborative partnership between AZ and the UoW to train ESRs in systems modelling tools and techniques to enable them to perform ground-breaking research in the emerging field of QSP, placing Europe as leaders in this field.

The project objectives were achieved through four research work packages (WP), organised into five separate projects, which included innovative training and research of relevance to the pharmaceutical industry worldwide. The work was undertaken by five ESR's co-supervised by academics from the UoW, staff from AZ and associated partners. The four WPs are as follows:
1. WP 1: Modelling Dose - Response time outcome relationships (projects 1 & 2).
2. WP 2: Modelling tissue (lung) target exposure (project 3).
3. WP 3: Modelling Cardiovascular Safety - Target Engagement - Exposure (project 4).
4. WP 4: Deconvolution in non-linear ordinary differential equations for QSP (project 5).

The project began on 1st January 2013. The first ESR was appointed in March 2013 and was based at the AZ headquarters in Mölndal, Sweden, through to October 2013, performing work on their research project linked to Work Package 2. The remaining four ESRs were appointed in July/August 2013 and took up their posts in September 2013. These four ESRs spent the first month of their posts also based at the AZ site at Mölndal in Sweden laying the foundations for their individual projects on Work Packages 1, 3 and 4.

All five ESRs started at the UoW in the UK in October 2013 and were based there until April 2014 when they returned to AZ for six months. They have all undertaken taught modules/course material in subjects relevant to their research projects. The ESRs were all based in the Biomedical & Biological Systems Laboratory within the School of Engineering at the UoW working alongside a cohort of over 20 PhD and postdoctoral researchers engaged on projects in similar fields.

They undertook their 2nd year of taught modules at the UoW from the end of September 2014 through to April 2015, they then returned to AZ to continue the work on their research projects. During this period they attended summer schools organised by the IMPACT project, international conferences and presentations, began disseminating the results of their research and publishing their findings in the appropriate technical journals.

Dissemination Activity Total Produced
Publications 10
Poster Presentations 31
Conference papers/oral presentations 70
Total 111
Full details are on the project website:

Four of the five ESRs have submitted their PhD thesis with the fifth expected very soon. At the time of producing this report two have been awarded their PhD (the remainder are still in the approval stage) and three of the ESRs are now in full-time employment with AZ as PK and PK/PD scientists.

The work of the ITN IMPACT project has engendered the formation of the QSP-UK network, it is jointly funded by the Engineering and Physical Services Research Council (EPSRC) and the Medical Research Council (MRC) with additional involvement and financial support from AZ, Pfizer and GlaxoSmithKline. The aim of QSP-UK is "to bring and nurture this new emerging area of science to the UK research space."

There is a proposal to establish a new Centre for Doctoral Training (CDT) in the area of QSP within the School of Engineering at UoW. The CDT will utilise and dovetail with existing postgraduate training offered by the UoW and builds on the work already successfully completed under the IMPACT project. The formation of this CDT Lite widens the collaboration with the leading pharmaceutical companies and other potentially interested parties, namely AZ, Pfizer, GlaxoSmithKline, Novartis, Merck, Bayer, the Liverpool School of Tropical Medicine, the School of Pharmacy (at the University of Manchester) and The Binding Site.

The partner organisations working on the IMPACT project have submitted a follow-up proposal for a further, much larger project in order to continue the training of Early Stage Researchers and help address the severe shortage that exists within the pharmaceutical industry across the EU and worldwide. If successful this project will be led by UoW with two additional academic partners, three industrial partners, three associate partners and will provide training for 15 ESRs.