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Fixing gene therapy trials

When my editor forwarded me a press release yesterday promoting a linkurl:series of articles;http://www.liebertonline.com/toc/hum/0/0 in January's issue of Human Gene Therapy on informed consent, he mentioned that the authors of those pieces were the key players in the death of an 18-year-old in a 1999 gene therapy trial that had called informed consent into question. The issue's editorial was written by James Wilson, the journal's editor-in-chief, and one of the articles was written by Univers

By | January 23, 2008

When my editor forwarded me a press release yesterday promoting a linkurl:series of articles;http://www.liebertonline.com/toc/hum/0/0 in January's issue of Human Gene Therapy on informed consent, he mentioned that the authors of those pieces were the key players in the death of an 18-year-old in a 1999 gene therapy trial that had called informed consent into question. The issue's editorial was written by James Wilson, the journal's editor-in-chief, and one of the articles was written by University of Pennsylvania bioethicist Arthur Caplan. Both had been defendants in the lawsuit brought by the family of Jesse Gelsinger, the teenager who died in 1999 while participating in a gene therapy trial at UPenn for the metabolic liver disease, ornithine transcarbamylase deficiency. The articles addressed the need to fix informed consent procedures for linkurl:gene therapy;http://www.the-scientist.com/article/display/23064/ trials in the wake of recent serious adverse events, including the death of 36-year-old linkurl:Jolee Mohr;http://www.the-scientist.com/news/display/53453/ last summer after receiving an linkurl:experimental therapy;http://www.the-scientist.com/blog/display/53949/ for rheumatoid arthritis. That made us think to call linkurl:Alan Milstein,;http://www.sskrplaw.com/attorneys/milstein/ who represented the Gelsinger family in linkurl:the case,;http://www.sskrplaw.com/links/healthcare2.html which settled out of court in 2000. Milstein also represents the Mohr family. "That's the pot calling the kettle black," Milstein uttered when I told him that that Wilson, the journal's editor-in-chief, had written the issue's editorial. linkurl:Wilson;http://www.the-scientist.com/article/display/20347/ was the lead investigator of the trial in which Gelsinger died, and was accused of several linkurl:ethical breaches;http://www.the-scientist.com/article/display/11900/ in the study. Caplan provided ethical oversight on the study. "The consent form in that trial is in many ways the best example of how these consent forms in gene therapy trials are misrepresenting the nature of the risk," Milstein told me. Apart from the obvious - the form didn't include information on prior adverse events, or results of studies in which monkeys had died from the treatment - it"compared gene therapy to a taxi cab delivering a healthy gene," he said, a description that "sounds fairly innocuous, as opposed to describing it as it really is" - a risky procedure. Milstein contends that informed consent procedures have changed little in the years between Gelsinger's death and Mohr's. "Just the name gene therapy is a misrepresentation," he said. "It's gene transfer, that may or may not provide any therapy." He noted that consent forms walk a difficult line - they have to be simple enough for subjects to understand, but still accurately represent the risks. One way to address that problem, he said, is by using patient advocates who can translate the sophisticated language into terms subjects can understand. linkurl:Wilson;http://www.liebertonline.com/doi/pdfplus/10.1089/hum.2008.0104 , linkurl:Caplan;http://www.liebertonline.com/doi/pdfplus/10.1089/hum.2007.1010 and other authors in the issue bring up many of these same points. Although the aftermath of the Gelsinger study "set into motion major changes in the oversight of clinical research in the United States," Wilson writes, "it appears we have not gone far enough, based on the concerns that have surfaced" in the study in which Mohr died. "I encourage the professional gene therapy societies and various related foundations to work together in the new year to undertake a critical review" to make sure subjects know what they're getting into.
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Comments

Avatar of: Herb Ruhs

Herb Ruhs

Posts: 9

January 23, 2008

little people are mere cannon fodder of "progress."\n\nCorruption always carries a high risk of morbidity and mortality.

January 23, 2008

If the lawyer had the view of the objective scientist, then his cynicism may be understandable. As a compensated adversary, however, it is understandable that the lawyer can't help but point yet another finger.\n\nThe entire 'sci-fi' impression that gene therapy had on many in the past, and in the influence of those who would say gene therapy is akin to 'playing god', casts the issues raised by this blog in the wrong light. The errors made in the protocol in the original unfortunate case were in the site and dosage of delivery, and changing the protocol on the fly is uncalled for by the tenets of good science whether on is considering a gene therapy trial or a trial designed to determine one's preferred cola. The potential consequences of ad-hoc changes in protocol are of course dire in the case of many clinical trial; however, contrary to the positions review, in fact, clinical research HAS evolved for the better w/IRBs and systematic training of clinical researchers in area of ethics, experimental design, and regulatory matters. IRB approval of updates to protocols are required as a matter of routine.\n\nHere we see scientists involved in worst potential breach of ethics, or at best sloppy science, writing an editorial calling for improvement over old practices. I find it refreshing, and evidence that the objectivity that science expects of its practitioners is alive and well, and that science is self-correcting discipline. I see the motives of the editorial as pure and worthy of reading by every first-year resident.\n\nImagine how damaging it would have been, by comparison, for these guys to spend countless hours writing editorial defending their practices.\n\nThe general population's comprehension of science as a way of knowing needs improving.\n\n\n\n\n
Avatar of: alan milstein

alan milstein

Posts: 1

January 25, 2008

Good post.
Avatar of: Herb Ruhs

Herb Ruhs

Posts: 9

January 25, 2008

Though I appreciate being informed of this strikingly ironic example of the kinds of conflicts of interest that increasingly characterize medical research, I am not surprised. A system that uses ruthless competition oriented toward potentially gargantuan rewards could produce nothing else. While the appearance of moral and ethical restraint is valued, the actual practice is punished in service of a maniacal pursuit of wealth and fame. Science tolerates this situation at the risk of becoming just another source of ignorance and intrigue. False pride is worse than no pride at all.

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