ABSTRACT
Dose-response (effectiveness and toxicity) relationships aid in optimizing the
use of drugs. These relationships can also form the basis for drug approval or
refusal. Several regulatory initiatives emphasize the need for better dose
finding and individualization of drug therapy (1,2). A recent article reported
that 21% of the new molecular entities approved by the FDA during 1980-
1999 underwent a dose-related labeling change (3). Of those, 80% of the
changes represented net reductions in the dosing regimen. It was suggested
that the frequency might be less than 21%, if the definition of “dose change” is
more appropriate (4). Nevertheless, it was generally accepted that the current
dose-finding paradigm is not optimal. It was concluded that the pivotal trials
tend to study relatively high-end doses after inadequate dose-finding efforts.
