The January 1, 2008 issue (vol. 19, no. 1) of the journal Human Gene Therapy includes an editorial and five commentaries about adverse events and informed consent in human gene transfer trials. See: Debate over Safety of Gene Therapy Trials Focuses on Issue of Informed Consent, by Vicki Cohn, Press Release, Mary Ann Liebert, Inc., January 22, 2008. All of these articles are currently freely accessible:
1) Adverse Events in Gene Transfer Trials and an Agenda for the New Year, by James M. Wilson, the Editor-In-Chief (Human Gene Therapy. January 1, 2008, 19(1): 1-2. doi:10.1089/hum.2008.0104). Excerpts:
The fact is that gene therapy is, and will remain, a highly visible area of translational research with elevated scrutiny.
I encourage the professional gene therapy societies and various related foundations to work together in the new year to undertake a critical review of the conduct of our clinical trials. As you can see in the following commentaries, these are very complex issues and conflicts and biases are at times unavoidable. However, it behooves us to get ahead of this issue and put in place more effective ways to ensure that research subjects who courageously give of themselves can do so with a full and unbiased understanding of the risks and benefits of their participation.
2) Case of Leukaemia Associated with X-Linked Severe Combined Immunodeficiency Gene Therapy Trial in London, by Board of the European Society of Gene and Cell Therapy, Executive Committee of the Clinigene Network of Excellence, and Executive of the Consert Integrated Project (Human Gene Therapy. January 1, 2008, 19(1): 3-4. doi:10.1089/hum.2007.1221). Excerpt:
However, retroviral and lentiviral SIN vectors remain to be proven clinically to provide both efficacy and a lower, ideally negligible, risk of adverse effects, and long-term follow-up of respective clinical trial patients is a clear necessity.
3) If It’s Broken, Shouldn’t It Be Fixed? Informed Consent and Initial Clinical Trials of Gene Therapy, by Arthur L. Caplan (Human Gene Therapy. January 1, 2008, 19(1): 5-6. doi:10.1089/hum.2007.1010). Excerpt:
Nothing can make the death of a subject in a clinical trial anything other than a horrible tragedy. There are, however, steps that could and should be taken to help ensure that when a death or adverse event occurs there is less room for doubt about the adequacy of informed consent.
4) Informed Consent in Human Gene Transfer Clinical Trials, by Jeffrey Kahn (Human Gene Therapy. January 1, 2008, 19(1): 7-8. doi:10.1089/hum.2007.1228). Excerpt:
The challenge of improving informed consent deserves the same attention as the science and medicine of gene transfer, and only when we meet that challenge can we claim that the subjects in HGT research are truly protected.
5) Protections for Participants in Gene Therapy Trials: A Patient’s Perspective, by Suzanne R. Pattee (Human Gene Therapy. January 1, 2008, 19(1): 9-10. doi:10.1089/hum.2007.1214). Excerpt:
Respecting participants by including them in the process respects the gravity of the request made of them – to give selflessly of themselves to benefit others.
6) Human Gene Therapy, Consent, and the Realities of Clinical Research: Is It Time for a Research Subject Advocate?, by Tomas Jose Silber (Human Gene Therapy. January 1, 2008, 19(1): 11-14. doi:10.1089/hum.2007.1217). Excerpt:
A research subject advocate could enhance the protection of participants in gene transfer research by advising the research team about participant concerns, by verifying the appropriateness of the Data Safety Monitoring Plan, by monitoring adverse events, and, most importantly, by the direct interaction with concerned families, stressing availability throughout the study while maintaining a working relationship with and independence from researchers.
For another example of the “elevated scrutiny” that human gene therapy is receiving, see a commentary about the articles listed above, On gene therapy and informed consent, by Alan Milstein, blog.bioethics.net, January 29, 2008. Excerpt:
January’s issue of Human Gene Therapy offers some intriguing commentary on the issue of informed consent in gene transfer trials.
I had represented the Gelsinger family after the death of their son in the experiment sponsored by Dr. Wilson and because I currently represent the family of Jolie Mohr, whose recent death renewed the debate over the informed consent process in this field of research.
See also: A comment from Paul Gelsinger on gene therapy and informed consent, blog.bioethics.net, January 31, 2008. The final sentence:
Anyone considering joining a clinical trial needs to be aware that they are dealing with a system that is seriously flawed.
Clinical trials of human gene therapy are of great interest from a variety of perspectives, including bioethical ones. They also provide an example of an aspect of biomedical and health-related research that’s of interest to many people, in addition to those researchers who are active in the field. Human Gene Therapy, and its publishers, Mary Ann Liebert Inc., should be thanked for providing free access to the thought-provoking articles published in the January 1, 2008 issue.
However, it should also be noted that Mary Ann Liebert, Inc. is listed in the SHERPA/RoMEO database as a publisher that’s non-compliant with the access policies of a variety of funding agencies. There’s a “Liebert Open Option” for Human Gene Therapy [PDF, 74 KB]. Fee: $3,000.
So far, I’ve not been able to find any information about how Mary Ann Liebert, Inc. plans to respond to the recently-revised NIH Public Access Policy.