When are clinical trials of a given agent vs. placebo no longer appropriate or feasible?

In several situations, placebo-controlled trials may be difficult to conduct. This article discusses the reasons for such difficulty--principally, a belief that the effect of a therapy has already been established or the existence of another therapy already proved effective. In the latter case, an active control equivalence trial may be considered, but this design has important deficiencies in many situations, notably, the lack of assurance of assay sensitivity.

The clinical pharmacologist in drug regulation: the US perspective.

1. Drug development has moved into a new era--a time of particular interest in individualization of treatment and dose-response--that is of particular interest to clinical pharmacologists. 2. Clinical pharmacologists' skills are especially applicable to identifying subgroup differences in pharmacokinetics and the consequences of those differences through such techniques as the pharmacokinetic screen and evaluation of metabolic differences and drug-drug interactions. Clinical pharmacologists also can contribute to the discovery of true differences in pharmacodynamic response. 3. Clinical pharmacologists are trained to take a broad view of drugs, recognizing that they not only have the pharmacologic property of primary interest but often other properties as well, that a 'drug' is really many drugs (isomers, active metabolites) with different properties, and that the properties of drugs should affect how they are dosed and used.