A user-friendly tool for analysis of complex in vitro experimental data in drug discovery and development

In vitro-in vivo extrapolation (IVIVE) is a rapidly emerging area in drug development
whereby in vitro experimental pharmacokinetic / pharmacodynamic (PK-PD) data, generated
in tissue homogenates or cells, are analysed and the results incorporated into computer models
to predict the effects of drugs in the whole body.
PK-PD data analysis in whole cell systems is complex and time consuming, yet accurate data
analysis and informed data interpretation are crucial in early drug development as this
information is used to select drugs to be assessed in human trials. Whilst there are many
software tools available for in vitro data analysis, these tools were developed for broad
application and are not specialised for drug development use. The tools do not support
analysis of more complex in vitro experimental systems which are increasingly being used in
an attempt to overcome newer challenges in drug development, lack appropriate statistical
rigour and do not allow IVIVE.
The project will provide a user-friendly software tool to analyse in vitro data describing the
metabolism, transport and receptor binding of drugs in the first instance. The experimental
uncertainty arising from the data analysis will also be determined. The results derived from
the in vitro data analysis and any associated uncertainty will be extrapolated to describe the
behaviour of the drug within the whole body. The tool will enable non-expert users to
determine the quality of the generated in vitro data, and the appropriateness of using the
estimated parameters in the decision making process.
The development and utilisation of this tool will allow consistency in data analysis across the
pharmaceutical industry. Use of the tool will ultimately lead to improved efficiency and
increase the utility of IVIVE and pharmacokinetic / pharmacodynamic understanding in drug
development. In turn, increased use of IVIVE will contribute to reducing and replacing animal
experiments within early drug development.