Since it’s issuance in 1998, Canada’s Tricouncil Policy Statement (Canada’s policy on the ethics of human research) has had an influence on the practice of research ethics that has outsized Canada’s population. The three research councils– CIHR, NSERC, and SSHRC– are presently revising the Tricouncil, and a few days ago, a revised draft was presented on the CIHR web site.
There is much to commend the newest version. There are also a number of disappointments. I won’t dwell on these here, however. Instead, I will focus on Tricouncil’s revised language on phase 1 and gene transfer research.
The revised Tricouncil contains a definition of phase 1 that, in my view, is somewhat outmoded and not much of an improvement on the old version. Both emphasize the role of phase 1 in toxicity and dose determination, but do not encompass the many other purposes to which phase 1 trials are put (e.g. for deciding whether to pursue phase 2, for gathering evidence of biological effects, etc.). On the other hand, the new Tricouncil requires prospective registration of all trials– including phase 1. And it contains a lengthy discussion of “therapeutic misconception,” which it defines as “the tendency of trial participants to believe that the primary intention of research tests and interventions is to provide a therapeutic benefit to the patient-participant.” The document urges research ethics boards and researchers to “emphasize which specific elements of a clinical study are required for research purposes, as well as the differences between research and the standard clinical care they might otherwise receive.” Bravo.
The new Tricouncil also, for the most part, replaces the old language of “gene therapy” with the more neutral “gene transfer.” In a section on “Gene Transfer,” the new draft warns about therapeutic misconception. It shrinks from any ethical statement on germline modification by deferrinng to Canada’s Assisted Human Reproduction Act. The remainder of the text notes the irreversibility of genetic alterations (not quite accurate), the potentially latent nature of gene transfer risks (a point I agree with), and states that research and ethical debate is evolving rapidly (a point I mostly agree with). Somewhat disappointingly, there is no mention of the need for centralized, transparent, or specialized review of such protocols.
On balance, these two sets of modifications are pretty good, though rather than anticipate the issues that are likely to arise in the next 5-10 years while this draft is in force, I worry a little that instead the draft represents a policy that I and others wish we might have had in the previous 5-10 years. Onwards and upwards! (photo credit: Studiolit 2006)
@Manual{stream2008-118,
title = {Northern Lights? Canada and the New Tricouncil Draft},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = dec,
day = 8,
url = {http://www.translationalethics.com/2008/12/08/northern-lights-canada-and-the-new-tricouncil-draft/}
}
MLA
Jonathan Kimmelman. "Northern Lights? Canada and the New Tricouncil Draft" Web blog post. STREAM research. 08 Dec 2008. Web. 29 Apr 2024. <http://www.translationalethics.com/2008/12/08/northern-lights-canada-and-the-new-tricouncil-draft/>
APA
Jonathan Kimmelman. (2008, Dec 08). Northern Lights? Canada and the New Tricouncil Draft [Web log post]. Retrieved from http://www.translationalethics.com/2008/12/08/northern-lights-canada-and-the-new-tricouncil-draft/
One of the most striking themes at the European Society of Gene and Cell Therapy was the extent to which continental European researchers conceptualize first-in-human gene transfer experiments as therapeutic interventions rather than research protocols.
Perhaps the most extreme and explicit expression of this was view was presented by Bonn internest Thomas Heinemann (he also studied philosophy and serves on several ethics committees in Germany). Heinemann advanced the notion of the “controlled individual therapeutic attempt,” for which the primary objective is therapeutic gain; the scientific dimensions of such studies (e.g. collecting safety data) are necessarily secondary. As he put it, research is only justified “ex post facto.”
I found this argument intriguing for several reasons. First, Heinemann justified this claim largely on grounds of autonomy and instrumentalization of desperately ill patients. In contrast, North American bioethicists typically use autonomy and instrumentalization to argue the opposite: that research is primarily intended to serve the ends of others, hence the paramount importance of obtaining consent from volunteers and their guardians, hence the need to be extremely cautious going into a desperately ill population, where autonomy might be compromised.
Second, I was impressed by the speaker’s conviction that first-in-human trials have therapeutic warrant. After almost twenty years of painstaking and at times discouraging research, we seem to have learned two things: first, that first-in-human trials rarely go as expected, and second, that such studies often yield important insights about new interventions. I might have expected a more cautious and seasoned view about the therapeutic merits of first-in-human attempts: does it really enhance the autonomy of volunteers to offer so little by means of therapy, but to foreseeably get so much in terms of social good? (photo credit: virtualais //www.77click.it, Brugge, 2008)
@Manual{stream2008-122,
title = {In Brugge: The Cure},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
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month = nov,
day = 24,
url = {http://www.translationalethics.com/2008/11/24/in-brugge-the-cure/}
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MLA
Jonathan Kimmelman. "In Brugge: The Cure" Web blog post. STREAM research. 24 Nov 2008. Web. 29 Apr 2024. <http://www.translationalethics.com/2008/11/24/in-brugge-the-cure/>
APA
Jonathan Kimmelman. (2008, Nov 24). In Brugge: The Cure [Web log post]. Retrieved from http://www.translationalethics.com/2008/11/24/in-brugge-the-cure/
In the current issue of Bulletin of the World Health Organization, authors Margaret Carrel and Stuart Rennie describe ethical challenges presented by demographic and health surveillance activities performed in low-income countries (“Demographic and Health Surveillance: Longitudinal Ethical Considerations”). What’s the link to translational research and gene transfer?
A number of issues identified in this article represent continuing challenges for fields like gene transfer, and this article offers analysis on these from an entirely different angle and context.
The most prominent example is the problem of distinguishing between research and care. Health surveillance activities inevitably identify health problems that demand intervention. But because surveillance sites are designed to provide information that will predict trends in similar, unmonitored sites, intervening risks diminishing the reliability of information about disease patterns. Some readers of this blog might be aware that I have argued that clear demarcations between research and care are impossible, and ethicists should abandon the project of trying to devise a dichotomous distinction (Hastings Center Report 2007). Health surveillance provides yet another example.
A second parallel is the issue of consent. The authors of this article ask whether new members of a household–children, for example–must provide consent for surveillance activities that their parents agreed to before they were born. This is analogous to issues encountered around germ cell interventions (intentional or otherwise) in gene transfer. Same is true for infertility treatment research.
Finally, a recent entry in this blog describes a paper Alex John London and I published on gene transfer trials in low and middle-income countries. The kinds of surveillance activities described in this article provide the types of information that research sponsors will need to make the case that an intervention they intend to test will be “responsive” to local health needs. Getting the ethics right for this “leg work” will be necessary for getting the ethics right for translational trials. (photo credit: Christian et Cie, 2008).
@Manual{stream2008-142,
title = {You are being (ethically) watched!},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = aug,
day = 6,
url = {http://www.translationalethics.com/2008/08/06/you-are-being-ethically-watched/}
}
MLA
Jonathan Kimmelman. "You are being (ethically) watched!" Web blog post. STREAM research. 06 Aug 2008. Web. 29 Apr 2024. <http://www.translationalethics.com/2008/08/06/you-are-being-ethically-watched/>
APA
Jonathan Kimmelman. (2008, Aug 06). You are being (ethically) watched! [Web log post]. Retrieved from http://www.translationalethics.com/2008/08/06/you-are-being-ethically-watched/
People often enter drug studies in order to access a promising new drug. But clinical trials take place over a set time period. So is it ethical to withhold from prospective trial subjects preliminary data on safety or efficacy that have been gathered from initial volunteers? In the Feb 1, 2008 issue of Journal of Clinical Oncology, Robert Wells argues it isn’t. Biostatistician Steven Piantadosi, in a rebuttal, argues that it is.
Wells argues (I paraphrase) that anything short of total transparency frustrates patient autonomy and breaches scientific and clinical duties. Piantadosi offers two counter-arguments: first, there are no obligations to disclose uninterpretable data, and second, in research, clinical obligations for full disclosure do not “supercede” societal interests in safeguarding the integrity of data.
The debate revolves around the tension between clinical research (which is primarily aimed at serving society) and clinical care (aimed at serving individual patients). Though I agree that the withholding of preliminary data should make us uncomfortable, total transparency in clinical research would necessitate abandoning well established practices– like blinding and placebo use– that maximize the reliability of knowledge gleaned from clinical trials. The key to navigating the ethical tension lies in making sure volunteers recognize that trials are aimed primarily at serving society. (photo credit: Kah Zanon, 2007)
@Manual{stream2008-179,
title = {Can You Keep A Secret?},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = feb,
day = 22,
url = {http://www.translationalethics.com/2008/02/22/can-you-keep-a-secret/}
}
MLA
Jonathan Kimmelman. "Can You Keep A Secret?" Web blog post. STREAM research. 22 Feb 2008. Web. 29 Apr 2024. <http://www.translationalethics.com/2008/02/22/can-you-keep-a-secret/>
APA
Jonathan Kimmelman. (2008, Feb 22). Can You Keep A Secret? [Web log post]. Retrieved from http://www.translationalethics.com/2008/02/22/can-you-keep-a-secret/
Since it’s issuance in 1998, Canada’s Tricouncil Policy Statement (Canada’s policy on the ethics of human research) has had an influence on the practice of research ethics that has outsized Canada’s population. The three research councils– CIHR, NSERC, and SSHRC– are presently revising the Tricouncil, and a few days ago, a revised draft was presented on the CIHR web site. 
