We spoke to our Exploratory Clinical Drug Development 2012 speaker Dr Piet van der Graff from Pfizer regarding his thoughts on the current challenges within pre-clinical drug development. Here's what he had to sayâ¦
Q. What challenges does your organisation face in forming highly predictive pre-clinical models to identify novel concepts relevant to human disease?
Â· Rational and quantitative translation of preclinical models to human (patho)physiology, clinical pharmacology and disease outcome
Â· Identification and implementation of translatable biomarkers
Â· Historical bias towards animal models of âdisease'
Q. What decision criteria is used in your translational science work to ensure the confirmation of a new drug target? And how can new strategies help the improved selection of drug candidates for human testing?
Â· 3 Pillars of Survival (see Morgan, Van der Graaf et al., Drug Discovery Today 2012)
How has new or how would new technologies improve clinical trial design?
Mechanistic PKPD models are now advocated not only by academic and industrial researchers, but also by regulators. A recent development in this area is based on the growing realisation that innovation could be dramatically catalysed by creating synergy at the interface between Systems Biology and PKPD, two disciplines which until now have largely
existed in âparallel universes' with a limited track record of impactful collaboration. This has led to the emergence of systems pharmacology. Broadly speaking, this is the quantitative
analysis of the dynamic interactions between drug(s) and a biological system to understand the behaviour of the system as a whole, as opposed to the behaviour of its individual constituents; thus, it has become the interface between PKPD and systems biology. It applies the concepts of Systems Engineering, Systems Biology, and PKPD to the study of complex biological systems through iteration between computational and/or mathematical modelling and experimentation. Application of systems pharmacology can now impact across all stages of drug research and development, ranging from very early discovery programs to large-scale Phase 3/4 patient studies, and has the potential to become an integral component of a new âenhanced quantitative drug discovery and development' (EQD3) R&D paradigm.
Dr van der Graaf will be speaking at this year's Exploratory Clinical Development World Europe 2012. Check out the programme and see who else is speaking.