To facilitate pharmacometrics enhancement of the PDN, the THD funding
will be used to establish an Australian Centre for Pharmacometrics
(ACP), with the headquarters at the University of South Australia. This
site has been chosen on the basis of its critical mass of expertise in
the field and relationship to the NCRIS supported Large Animal Imaging
Facility, which can offer unique insights into drug disposition.
However, key pharmacometrics groups from across Australia and New
Zealand are jointly involved in the ACP.
The role of the ACP is to facilitate training and education in
pharmacometrics and increase the utilization of such analyses in
biomedical research on a national scale. It will facilitate drug
development and biomedical research nationally by providing high-end
computing facilities and pharmacometric expertise.
The Australian Centre for Pharmacometrics, through a modelling and simulation approach to data analysis, will aggregate:
• In vitro and in silico modelling to provide initial basic pharmacological understanding.
• Small and large animal studies used collectively to provide a
complete pharmacological (pharmacokinetic and pharmacodynamic)
• Pharmacometric analyses throughout the whole drug-development
process to provide a mechanistic and quantitative understanding of the
drug and identify characteristics of an “optimal” formulation, thus
improving the efficiency of development progress, including the optimal
design of the studies themselves.
• This process is integrative and cyclical. Information from each
step is feedback and evaluated for its impact on the development cycle
via pharmacometric input.
Pharmacometrics combines our knowledge base of disease with our
understanding of drug pharmacology, side effects and treatment
variability. This field has often been referred to as “modelling and
simulation” in the past, and can be defined as the science that
coordinates all information about quantifying drugs and drug effects,
the mechanistic processes involved in disease and its treatment, plus
the interpreted results of in vitro, animal and clinical trials. The
combined information encourages efficient and improved drug candidate
selection and formulation development via rational informed
decision-making. Given the ever increasing cost of drug development, it
is important that Australia be at the forefront of “smart drug
The value of pharmacometrics is illustrated by:
• Drug models describing relationships between exposure, response for
both desired and undesired effects, and individual patient
• Disease models describing the relationship between biomarkers and
clinical outcomes, time course of disease and placebo effects.
• The capacity to integrate mechanistic knowledge from prior
understanding, related compounds, chemistry and biology, together with
the ability to include both richly sampled data and more
limited/incomplete data typically unusable in traditional statistical
• The generation of trial models describing trial design, subject
numbers, sampling times, inclusion/exclusion criteria, patient
discontinuation and adherence. Trials are then designed to provide the
most efficient and optimal way to answer the question being asked.
• Improved analyses that are designed, conducted and reviewed in the
context of ongoing development, therapeutic and regulatory decisions.
Recent advances in pharmacometrics provide a clear mechanism to
streamline, facilitate and optimise the pre-clinical development of
pharmacotherapeutic agents. By providing a guided progression, informed
by pharmacometric analyses, the conduct and design of studies will
maximise the efficiency of pre-clinical development. The result is
clear and rational progress of molecules and optimal formulation for
human clinical trials. This process will increase the efficiency of the
present process in Australia in which the progression is often
Importantly it may also lead to increases in efficiency by early culling
of molecules that are unlikely to be clinically useful due to a poor
pharmacokinetic / pharmaceutical properties – this is presently a major
impediment to drug development as it a significant cause of costly drug
failures during the clinical development stages.