Phased by Phase 0?

Today, Lancet ran an editorial asking whether Phase 0 trials will become a "platform for drug development." The editorial responds to the first published 'phase 0' study, this June, in Journal of Clinical Oncology (Kummar et al). These studies involve delivering very small quantities of a new drug to test its properties before giving biologically active levels to patients. They promise to improve the efficiency of drug development by screening drug candidates before they are tested in larger, riskier phase 1 trials.

The Lancet editorial notes the potential of phase 0 studies, but raises questions about their ethics: "no therapeutic benefit can be conferred by the small doses in a phase 0 study, and while taking part, patients are not allowed to enrol in a trial with therapeutic intent." As I have argued in Journal of Law, Medicine, and Ethics, however, the former issue is a red herring: normal phase 1 trials routinely, and deliberately, deliver levels of drug that are too low to cause therapeutic response. Moveover, whether phase 1 trials in themselves have "therapeutic intent" is debatable.

There are, of course, many ethical concerns surrounding phase 0 studies. Chief among them is whether patients understand their nontherapeutic nature, and whether results are publicly reported (I predict that if phase 0 methods are taken up by the private sector, many results will languish in filing cabinets). But effective engagement with ethical issues in phase 0 cancer studies requires, in my view, that we take a more careful look at whether "therapeutic intent" is really the litmus that determines whether a study pursued in patients is ethical. (photo credit: w i n t e r t w i n e d 2009)