Jolee Mohr took part in a gene therapy clinical trial--and died

According to Wikipedia, "death is the permanent end of the life of a biological organism." My younger daughter would consider that a "scientific" definition--lacking humaness and empathy. This approach was also the approach I viewed this morning.

Today's review of the death last July of a young woman participating in a gene therapy trial was webcast and I did manage to get up at 5:00 am to watch all 7 hours of the live video. The meeting and review of gene therapy trials in general and this particular death were definitely "scientific". Even though I am familiar with much of the language of clinical trials, I had trouble following many of the details of the specific gene therapy and rheumatoid arthritis. If anyone doubted that the presentations were factual and unemotional, you only needed to hear the first and last sentence spoken by the victim's husband to get back to reality:

The 36-year-old female you've been discussing was my wife.

Would my wife have been dead now if she hadn't participated in this clinical trial?

Even in these emotional statements, there was no blame, no anger, only deep emotional pain. Having recently suffered through a similar problem, I am overwhelmed by his ability to speak of his wife's death in so public an arena. Right now, there is still no clear cause of death--at least not one that answers Mr. Mohr's question.

I am not qualified to detail or judge the information presented during the webcast. And, I do not know what the Internet and print media will do with the story. One reporter did repeat Mr. Mohr's question for the Recombinant DNA Advisory Committee, but no clear answer is yet available.

So, what did the review accomplish?

The following proposals were made and approved unanimously by the members of the RAC:

1. RAC proposes continued collaboration among all involved entities to identify all available samples.

2. Identify--if possible-- the role of the gene therapy agent, immune response, and gene transfer product.

3. Identify how to accomplish these goals.

Results are to be presented at the Gene Therapy Advisory Boardmeeting in December.

Although no regulations were violated in the gene therapy trial, and many gene therapy trials have been conducted without such serious results, the audience was reminded by Dr. Federoff, head of the RAC, that gene therapy is still to be considered high risk. We may need to impose higher standards for proposed studies and consider the following:

  • The safety of a vector should not be assumed from one Phase I study. [The study in which the patient died was a Phase I/II study which was investigating safety, but also looking for effectiveness of the treatment.]
  • The study should include plans for lots of samples (eg, blood, tissue, etc.) and possibly redundancy of samples.
  • Plan collection, storage, testing of samples ahead of time and clearly identify who can ask for unplanned samples from patient. [In this case, orders at the hospital needed to come from primary care physician and investigator couldn't intervene.] Consider having the patient wear or carry a medical card indicating participation in a clinical trial, with emergency contact numbers and perhaps an Internet address for information.
  • Have plans in place for autopsy, including collecting and proper storage of sufficient samples for thorough analysis.
  • Consider delays in dosing when untoward events occur.
  • Consider delays in dosing until results of laboratory tests prior to dosing have been received.
  • Consider mild symptoms, eg. of infections in immunocompromised patients such as those in rheumatoid arthritis studies, of greater importance than the same symptoms in a "healthy" patient.

In addition to the specific additional recommendations for Informed Consents for gene therapy trials (compared to ordinary drug trials), add a layer of protection for the patient by

  • Giving information well before starting a trial; let patient take it home
  • Having information delivered by neutral person (not clinical trial staff)
  • Avoiding "therapeutic expectation" as much as possible (expected benefit or perception that this is better than existing treatment).
  • Disclosing potential conflicts of interest, eg investigator paid for services or for acquiring patients, to potential trial participants.
  • Working harder to help patient understand risks of participating--benefits are often only for "the public", not the individual.

Although some of these items are included in the typical Informed Consent, expecting that a potential tiral participant will understand everything at once, especially from a 15-page Informed Consent, is unreasonable.

I'm sure there will be plenty of stories about this very unfortunate death and its effect on many. Check out your local newspaper or national newspapers or websites you trust for further information.

If you wish to see any of the proceedings youself, go to the Recombinant DNA Advisory Committee website, select Meetings and Conferences, and select Webcast for Sept. 17, 2007. You will need to have the latest RealPlayer installed to view the webcast. At this time (Monday the 17th at 5 pm PDT, the tape of the webcast has not been posted, but it should be there soon.

The website also tells you a lot more about gene therapy trials and their oversight. Please ask questions of me if you wish.

Marie Godfrey, PhD

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