A UK Quantitative Systems Pharmacology Network

Drug development is a time consuming and expensive process. From the time a compound is identified as having possible therapeutic benefits through to being available in the clinic, takes not only the order of a decade, but 100's of millions of pounds of investment. Successful testing of a compound in the laboratory does not imply that it will be successful in animal or human trials, and even successful animal tests can lead to failure in human trials - a result of the complexity of biology at different scales. On average only one in nine drug compounds is fully developed and approved by US and European regulatory authorities. This low attrition rate is poor for drug companies, both in terms of time and costs, and ultimately us as a society.

Understanding on the single cell scale does not easily translate to the same behaviour in human tissue, organs, whole humans and the overall population given individual differences. We wish to design drugs for large scale population use whilst accounting for the variation between individuals within a population. One technology available to us for tackling this issue is quantitative methods such as mechanistic mathematical modelling and data analysis. Current knowledge of a biological system can be used to develop mathematical models to identify key laboratory experiments, reduce reliance on animals and identify earlier which compounds are most likely to fail or succeed.

The integration of subcellular information into whole individual mechanistic mathematical models to specifically assist in the development of pharmaco-therapeutics has been termed Quantitative Systems Pharmacology (QSP). "Quantitative" because the area uses quantitated processes and data to make predictions and "Systems" because the approach is holistic across the system (single cell to organ to whole individual). This is a new area of science which will require strong interactions between theoretical modellers (mathematicians, statisticians, engineers) and life and pharmaceutical scientists to ensure its success. Individual researchers from each of these areas can be found in both UK academic institutions and leading biopharmaceutical and biotechnology sectors and need to be brought together to allow this new field to thrive and develop in the UK.

To meet this need we will establish a UK Network in QSP. The network will bring together UK pharmaceutical scientists from industry and academia, with theoretical scientists to exchange knowledge and tackle problems in QSP. The network will be arranged around three workshops (one per year), two of which will share knowledge through talks, poster sessions and group discussion on key topics in this burgeoning field. A third workshop will bring mathematical modelling expertise to bear on QSP problems highlighted by the academic and industrial network members. Satellite meetings will allow participants to further explore ideas generated from the main workshops. Our network already has strong support from biopharmaceutical and biotechnology sectors, with sites in the UK, and leading academic institutions.

The network will lead to: (i) new collaborations; (ii) project applications (grant, studentship, fellowship); (iii) scientific publications; (iv) open access mathematical models and their associated code; (v) greater awareness of QSP in the UK pharmaceutical, life and physical science communities; (vi) education and training for those based in industry (and academia) on modelling tools and techniques to support; (vii) greater public awareness of QSP in the development of new drugs and therapeutic agents; (viii) foster the development of mathematical models as surrogates for the ex-vivo and in-vivo animal systems currently used to extrapolate efficacy and toxicity responses to drugs; and (ix) develop and strengthen international links between the UK and other key international initiatives in Systems Pharmacology research.

The network will impact on research in the biopharmaceutical and biotechnology (short, medium and long term) and public health arenas (medium to longer term). It is unique in terms of its multidisciplinary, academic and industrial components with no other current rivals known to exist (internationally) providing such a novel combination of scientific training and research activity. The network will bring economical and industrial benefits, impact on the strategic competitiveness of UK science, enhance public-private collaborations, allow results developed during the network to be exploited and ensure public impact is achieved through public engagement in science activities.

A mechanistic model driven approach to drug development, can take into account differences between the drivers of a myriad of diseases and is likely to be more successful than empirical approaches that have been used to date. This will add economic competitiveness to those companies involved, with expertise in each of the respective areas (pharmaceutical, biological, mathematical and engineering sciences) close to hand in the UK. The fundamental knowledge generated from innovative tools for drug development and effect at a systems level will significantly help to overcome bottlenecks and the length of time currently taken in drug design and development. The programme of network activities will generate research outcomes, concepts, innovative tools and techniques, technology and novel strategies, that will be of direct relevance to the UK biopharmaceutical and biotechnology industry.

A direct industrial benefit of the network will be to help maintain the UK's (and Europe's) competitive market position in the face of competition from the US and the Far East. Developing innovative modelling tools and techniques in the QSP framework will also place the UK strategically at the forefront of this emerging research area. In general the network will provide innovation in terms of the development methodologies for identifying unknown mathematical relationships in a (nonlinear) pharmacological system leading to more robust tools for drug design and discovery. The network will enhance longstanding collaborations between the Universities involved and drug discovery at major pharmaceutical companies with bases in the UK. It will further facilitate new collaborations with academia and the private sector, including clinical development.