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)
@Manual{stream2009-93,
title = {Phased by Phase 0?},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2009,
month = jul,
day = 17,
url = {https://www.translationalethics.com/2009/07/17/phased-by-phase-0/}
}
MLA
Jonathan Kimmelman. "Phased by Phase 0?" Web blog post. STREAM research. 17 Jul 2009. Web. 14 May 2024. <https://www.translationalethics.com/2009/07/17/phased-by-phase-0/>
APA
Jonathan Kimmelman. (2009, Jul 17). Phased by Phase 0? [Web log post]. Retrieved from https://www.translationalethics.com/2009/07/17/phased-by-phase-0/
Phase 0 studies are a new class of drug trials that involve delivering tiny doses of a new drug to human volunteers to study how the drug is distributed and metabolized in the human body. Both FDA and its European counterpart, EMEA, have recently issued statements encouraging drug companies to consider ‘phase 0’ studies before going on to phase 1 trials.
I have written elsewhere (Journal of Law, Medicine, and Ethics, 2007) on the ethics of phase 0 studies, and a recent cluster of new articles on their ethics was published in the journal Clinical Cancer Research. In general, I have tended to support such studies as a way of reducing risk and uncertainty in phase 1 studies.
But the August issue of Nature Medicine contains a small news report describing ongoing controversies about whether such studies accurately predict drug behavior at higher doses. One company that is marketing itself as a supplier of equipment for phase 0 studies claims such studies are highly predictive, but according to the report, chemists and others question their validity, and fault the company for not releasing “specific criteria” they use to support their claim that phase 0 studies are predictive.
The upshot seems to be: 1- buyer beware on phase 0 studies, and 2- companies that pursue phase 0 studies should publish results (few probably do– they contain sensitive proprietary information) so that policy makers and others can evaluate their value. (photo credit: e-chan photo of Kusama Yayoi artwork, 2008)
Jonathan Kimmelman. "Fazing Phase 0?" Web blog post. STREAM research. 08 Aug 2008. Web. 14 May 2024. <https://www.translationalethics.com/2008/08/08/fazing-phase-0/>
APA
Jonathan Kimmelman. (2008, Aug 08). Fazing Phase 0? [Web log post]. Retrieved from https://www.translationalethics.com/2008/08/08/fazing-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.
