Friday, March 27, 2009

Centralized Revue

In the most recent issue of Molecular Therapy, U Penn researcher Hildegrund Ertl provides a strong and eloquent defense of the Recombinant DNA Advisory Committee (RAC).  RAC was initially formed to evaluate the safety of studies involving recombinant DNA. In the last decade, however, its most visible function has been to provide advise to researchers pursuing novel gene transfer protocols in human beings.

Many researchers resent RAC, viewing it as yet another layer of oversight for their clinical studies. Understandably, they question whether it makes sense to have a separate review track for gene transfer. Other scientists and ethicists might question whether gene transfer is so exceptional as to be singled out for separate review, but would nevertheless argue that the RAC model should be extended to other ethically contentious areas of medical research. Nevertheless, the RAC model of centralized review of trial protocols has yet to be extended to comparably novel and contentious human clinical research areas like cell transfer, embryonic stem cell research, or tissue engineering.

Ertl provides a clear and persuasive description of RAC's role in improving gene transfer trial safety, enhancing scientific value of studies, and ensuring appropriate informed consent practices. But the structure of her argument embeds three assumptions that, in my view, need to be questioned.

1- Why demand solid preclinical evidence? Ertl answers "if such data are not available, the risk outweighs the potential benefit for human volunteers– and that is not acceptable." I would argue that preclinical evidence is of greater use in improving the scientific value of clinical studies. 

2- How are risks justified in early phase studies? In the above quote, Ertl seems to suggest the answer is therapeutic benefit for the volunteer. In my view, risks in first-in-human trials are justified by the potential for scientific gain, not direct medical benefit.

3- What is the purview of ethics? Ertl, like many others, partitions "technical" concerns like study validity / value / preclinical evidence from "ethical" concerns like informed consent and conflict of interest. But why is the former any less ethical than the latter, given that technical questions implicate problems of risk-benefit balance and the ultimate ends of research. In my view, there is no clear division between the technical and ethical, and few if any decisions in designing and executing clinical protocols are devoid of ethical content. (photo credit: 416style, 2005)

No comments: