Pharma’s Cutting Edge

This article is worth reading if you are involved in Phase 1 studies of oncology agents. Joffe disposes of the artificial distinction between therapeutic and non-therapeutic Phase 1 studies in cancer patients and frames the ethical controversy surrounding an appropriate ethical calculus. Unfortunately, Joffe’s prescriptions, which include comparing the expected benefits of investigational therapies with average benefits from his suggested meta-analyses across therapeutic classes of alternative off-label therapies, are unsatisfying in their attempt to improve the situation. Readers interested in a broad discussion of Phase 1 studies beyond those conducted in patients with active disease (i.e. most Phase 1 studies outside of oncology) will likewise be disappointed, as there is none here. Despite these limitations, Joffe should be thanked for keeping the issue of Phase 1 ethics in the spotlight.

An anecdote of relevance: When I was employed at J&JPRD, we had a corporate-wide meeting for clinical scientists to discuss GCP and clinical ethics (I have to give J&J credit here; I attended at least three company-wide meetings where we discussed these important topics over a three-year period). I remember raising the issue of Phase 1 ethics in the context of the (then) newly issued Helsinki Guideline Revision. In an attempt to raise the level of debate, I claimed that most Phase 1 studies should be declared unethical by the standards of these guidelines. Rather than use my declaration as a kick-off point for a reasoned debate on this important subject, the physician who was then in charge of clinical research at J&JPRD and is now CEO of a small pharmaceutical company, used my comment to assert that all of J&JPRD’s Phase 1 studies were ethical and that anyone who believed they were acting unethically should “come to his office to discuss it.” So much for keeping Phase 1 ethics in the spotlight. Fortunately, boneheads like him are the exception in the industry.