By Jennifer Phillips, Ph.D.
Hello readers! I’m here in sunny Ft. Lauderdale attending the Association for Vision Research and Ophthalmology meeting—that’s right the teeming nerd hordes are at it again. But rather than waiting until the end for a long, post-hoc recap as we’ve done with past scientific meetings, this time I thought I’d try to mix it up with some short, pithy daily notes from the event. I realize I’m not exactly known for ‘short and pithy’ around here, but I’ll do my best.
Topic of the day: Ethics of Genetic Applications in Ophthalmology
This was a talk session with presentations by four speakers, a mix of genetic counselors, clinicians, medical ethics specialists, and researchers. One common theme was the psychological and emotional impact of a diagnosis via genetic testing. There was a bit of friendly debate about the benefits vs. the harm of testing and informing children of later-onset genetic diseases and some general recommendations of having qualified genetic counselors—or clinicians with sufficient training in such counseling, be involved in delivering this news to families and following up with them to make sure they had adequate support. We’ve talked quite a bit on this blog about ways to make this clinician-patient-family interface more successful, so this isn’t anything new, but hopefully it will reassure some of you to hear that the problem is being recognized and discussed in this kind of professional setting.
The most interesting point of discussion, though, by which I mean, the one that made me perk up and say “hey, I should totally blog about that!” was put forth in a very nice talk by Bernard Lo, a professor of medicine and director of the medical ethics program at UCSF. He talked generally about the ethics of clinical trials, and specifically used the RPE65 gene therapy story as an example. I’ve described a few clinical trials here, so the basics—random assignment of participants into a control group or an experimental group, reasonable efforts to prevent the patients from knowing which group they’re in until the end of the study, etc.--should be familiar to most readers. However, the ethical conundrum this speaker put forth that attracted my attention was something neither Mark nor I have discussed in our various posts about clinical trials: any participant in a clinical trial, particularly a Phase I trial, is taking a personal risk so that researchers might benefit from new knowledge and so that future patients might benefit from the studied treatment. There is absolutely no guarantee of any personal gain—it’s altruism, pure and simple. Moreover, conducting such studies runs quite counter to the primary goals of most medical professionals, in that treatment is not being personalized and is not designed to improve the condition of the participants.
The RPE65 story was used as an interesting illustration of this ethical morass. As you may recall, the ‘control group’ did not consist of a separate group of people, but instead patients received treatment in one eye, and had ‘sham surgery’ on the other. Is sham surgery, in this case sticking a needle deep into someone’s eye without delivering any potential treatment, ethically justifiable? Thinking about it from a pure research point of view, it is an important control. The placebo effect is a powerful factor in any clinical trial and must be accounted for in order for any results to be meaningful. Even seemingly objective things like eye chart tests can be influenced by patient effort or the belief that he or she should be seeing better after treatment. And interestingly, the more invasive the intervention, the more powerful the placebo effect. Injecting a completely inactive substance elicits a stronger placebo response from patients than orally consuming the same substance. And the placebo response to surgery has been shown to be more powerful still. Thus, it’s pretty important to control for this with any new treatment being tested. That said, sham surgery is a heckuva lot riskier than taking a sugar pill. Is it ethically permissible? And, if so, under what circumstances?
This is an intriguing question, and one that should prompt a bit of reflection about the risks and benefits of participating in a clinical trial. The potential benefits are great, but not necessarily for the participants. The risks are not inconsiderable, and are very personal. Yet people routinely consent to participate in these trials. Just as the clinicians conducting the trials must subvert some basic tenets of their training regarding individualized care for any given condition, the participants are also willing to forego personal gain so that others might benefit from whatever the study shows. That fills me with awe.
So, for those of you who have already participated in trials, and those who are planning or considering participation in upcoming trials, THANK YOU. You are all truly my heroes.