Phase 0 clinical trials: an answer to drug development stagnation?

action, pharmacology, bioavailability, pharmacodynamics, and metabolic microdose assessments. These studies of novel agents expose a small number of patients (perhaps 10 or fewer) to a limited duration (eg, 7 days or less) and dose (in the range of one 100th of the dose required to yield a pharmacologic effect of the test substance with a maximum dose of 100 g). 3 They are conducted before the traditional phase I dose-escalation safety and tolerance studies. By not having the traditional phase I objectives of toxicity and dose finding, phase 0 studies can be conducted early in the development process and are actually considered more of a discovery, rather than development, tool. In early 2006, the FDA published “A Guidance for Industry, Investigators, and Reviewers for Exploratory IND Studies” as part of the agency’s critical path initiative to streamline drug development and improve the understanding of drugs early in the clinical process. 3 There must be several considerations before initiating a phase 0