Disclosure in Phase 1 Cancer Trials

Followers of this blog may recall my continuing concern with the way informed consent is obtained in phase 1 trials involving patient-volunteers (typically, these patients have exhausted standard care options and enter phase 1 trials as a final shot at managing their disease). Language used by investigators in these studies is often suggestive of therapeutic benefit, even though meta-analyses of phase 1 studies show that chances of major clinical benefit in phase 1 studies are exceedingly low. In previous posts, I described my own experience with an ethics review committee that actually defended giving patients vague and almost meaningless information about the therapeutic benefits of phase 1 trial participation. Meantime, evidence from surveys indicate that phase 1 cancer patient-volunteers tend to overestimate the probability of therapeutic benefit.

In the July-August 2009 edition of the ethics journal IRB, Shlomo Koyfman and co-authors at NIH offer up a "Consent Form Template for Phase I Oncology Trials." Their recommendations are comprehensive and excellent. Among the items they recommend are:

• use of more therapeutically neutral language, like "research agent" instead of "therapy"

• disclosure of dose escalation design; in particular, the authors recommend that patients be informed about risks and benefits relative to the cohort they are entering.

• a statement (where appropriate) that patient-volunteers will not have the option of adjusting their dose assignment in the study

• a statement that "the chances that this agent will... allow you to live longer [is] very low."

One can quibble with various particulars (I think, for example, discussion of subtherapeutic dosing should be more explicit). But on the whole, these recommendations provide an excellent standard– along with NIH Guidance on Informed Consent for Gene Transfer Research– against which typical phase 1 cancer study consent forms should be measured. (photo credit: banlon1964)