Exploratory development pharmacodynamics

The term exploratory development (ED) can be defined as the first part of clinical drug development in which tolerability, pharmacokinetics and pharmacodynamic activity are defined in man and in which an early indication of therapeutic efficacy is often obtained . A new active substance (NAS) can be defined as an unlicensed new chemical or biological entity with activity in biological systems whose therapeutic potential is under investigation . The overall aim of ED should be to select appropriate NASs for full development (ED) and to reject those that will not make useful medicines, as early as possible. 

Documentation on assumptions should address those assumptions implicit in the pharmacokinetic or pharmacodynamic model and the statistical methodology chosen to evaluate the data. It should also state the assumed sensitivity of the parameters required to define the model relative to the data space being evaluated as well as any preconceived notions regarding biomarkers or surrogate markers evaluated as responses or covariates in the analysis. Hypotheses should be defined based on what was held a priori as true before the study or analysis, what was developed from preliminary or exploratory data analysis, and what would constitute a difference or equivalence in an effect or outcome, hi some instances the criteria for difference as opposed to equivalence can be defined from a statistical viewpoint independent of the actual study design. This approach does not always confer regulatory acceptance, however. 

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