Ethics at Phase 0: Clarifying the Issues

The Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) recently issued documents encouraging sponsors to consider microdose testing before launching Phase I trials, and many commentators predict that such methodologies will be applied more routinely in drug development. However, exploratory testing has provoked several ethical criticisms. Skeptics question the value and validity of microdose trials, and whether they present a reasonable balance of risks and benefits for subjects. Another major criticism is that such studies serve mainly commercial ends. The present article explores these and other ethical concerns for studies conducted in the oncology setting. It concludes that microdosing is not inconsistent with prevailing practices in Phase I research, and that in principle, such studies could strengthen the ethical basis for Phase I trials by providing them better evidentiary justification.