ABSTRACT
With the increased emphasis of model-based drug development through the FDA criti-
cal path initiative (1), it is increasingly apparent that in addition to gaining
a quantitative understanding of the relationship between dose (exposure or concen-
tration) and response, it is equally important to be able to predict and simulate the
effect of a drug on disease pathophysiology to an extent greater than has been accom-
plished in the past. It is assumed that through these novel processes, a more informed
understanding of the appropriate selection of doses is achieved. To consider the poten-
tial benefits of model-based drug development, it is perhaps necessary to review
whether the current commonly employed designs for Phase I/II studies are adequate approaches to the desired goals and consider the advantages and disadvantages of
some newer designs in the realm of clinical pharmacology and experimental medicine.
