Tuesday, January 22, 2008

Informed Consent in Gene Therapy Trials

The latest issue of Human Gene Therapy has free online Commentaries on informed consent and gene therapy trials. Here are a few samples:

From Arthur Caplan's "Informed Consent and Initial Clinical Trials of Gene Therapy":

We have not come all that far between the deaths of Jesse Gelsinger and Jolee Mohr when it comes to informed consent practices. Despite a lot of rhetoric and hand-wringing about the need to fix human subjects protections, very little has changed in the past decade in the way informed consent is obtained from prospective subjects. Nor has much changed about the process of gaining informed consent.

....There are steps that the gene therapy community could and should take to improve the consent process. Someone not affiliated with the research for which consent is being sought should be made available to prospective subjects to answer their questions and concerns (Emanuel et al., 2003). Whether that is a local physician, a nurse, or a trained subject advocate available by phone or teleconference, someone ought to be made available to ensure that therapeutic misconception—a belief that what is, in actuality, purely experimental is beneficial and therapeutic— does not take root in phase I and II trials in the fuzzy boundary between where a clinician is also a researcher.

From Suzanne Pattee's "Protections for Participants in Gene Therapy Trials:
A Patient’s Perspective":

People who participate in clinical trials are a rare breed.
Those of us with life-threatening diseases know what it feels like to live each day with a serious health condition and an uncertain future. Instead of accepting our lot in life, we choose to help others in the best way we can—by participating in clinical trials. Even if a trial does not provide a direct therapeutic benefit, we still hope that the first trial will be successful and a new product or cure will result that will help people with our disease. Participating in trials is a way we can give something back to society and others with our disease for the benefits we have received from improved medical care and treatments. After all, if others had not participated in clinical trials before me, I would not have benefited from improved CF care and new treatments, such as Pulmozyme, that have enabled me to live this long and remain relatively healthy.

And a brief excerpt from Jeffrey Kahn's piece entitled "Informed Consent in Human Gene Transfer Clinical Trials":

Human gene transfer (HGT) research raises significant issues for informed consent of the subjects who are recruited to participate in trials, calling into question whether and how HGT research can be performed ethically. My brief answer to this question is that while HGT poses challenges for the informed consent process, acceptable informed consent can be achieved through careful attention to the persistent issues that are outlined below. These challenges are hardly unique to HGT, so the analysis to follow, and the suggestions and recommendations that stem from it, apply more widely across areas of clinical research that share aspects with HGT.

....because so-called “first in human” trials for HGT often combine the goals of “traditional” phase I and II research, the terminology used in the informed consent process can only lead to confusion and misunderstanding on the part of subjects. Subjects will understandably perceive the likelihood of efficacy to be greater than is warranted when both toxicity and safety (phase I goals) and efficacy (phase II goals) are described as part of trials that are the first uses of HGT in humans and in very small groups of subjects. Both of these problems contribute to the problem of therapeutic misconception, an issue that has been widely discussed in the medical and bioethics literature (Appelbaum et al., 1982; King et al., 2005). Finally, the combination of therapeutic misconception with the confusion of overlapping roles leads to potential conflicts in the recruitment of subjects into HGT trials. There is no doubt that researchers must and do believe in the importance of their work and the need to validate the science of HGT. But they may also be “true believers” for whom it is difficult if not impossible to be objective in recruitment of subjects into their research. Their commitment to science should be unquestioned, but they are often equally invested in the ongoing success of the research. All this points to the need be more careful in recruitment, and to do better in the informed consent process.