In this week's PLoS Medicine, Jonathan Kimmelman from McGill University in Montreal, Canada and Alex London from Carnegie Mellon University in Pittsburgh, USA argue that ethical reviewers and decision-makers pay insufficient attention to threats to validity in pre-clinical studies and consult too narrow a set of evidence. They propose a better way for ethical and scientific decision makers to assess early phase studies: first, to attend to reporting and methodological quality in preclinical experiments that support claims of internal, construct, and external validity; and second, to consider evidence on risks and benefits of agents targeting related biological pathways.
In a Perspective article, James Lavery of the University of Toronto (uninvolved in the proposal) provides feedback on this proposal from the point of view of Institutional Review Boards (IRBs) and how they might better consider pre-clinical data in their deliberations. He says that the Kimmelman and London proposal is valuable "because it encourages IRB members, and other reviewers, to engage with less familiar challenges and guard against complacency in reviewing risk and benefit data from pre-clinical studies. But its true potential value likely lies in the extent to which it can forge agreement throughout the research enterprise on the need for more creative approaches to presenting and contextualizing pre-clinical evidence, and on broadening the base of responsibility for these difficult judgements."
Funding: The authors were supported by Canadian Institutes of Health Research (EOG 102823) and a fellowship from the Andrew W. Mellon Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Citation: Kimmelman J, London AJ (2011) Predicting Harms and Benefits in Translational Trials: Ethics, Evidence, and Uncertainty. PLoS Med 8(3): e1001010.doi:10.1371/journal.pmed.1001010
IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001010
CONTACT:
Shilo Raube
Perspective article by James V. Lavery
Funding: No specific funding was received to write this article.
Competing Interests: The author declares he has no competing interests in relation to this article. The author reports that he has conducted an educational session about ethical challenges in international vaccine trials for Sanofi Pasteur, and an educational session and consultation about the effective use of Community Advisory Boards for Pfizer, Inc., and has been paid for these activities.
Citation: Lavery JV (2011) How Can Institutional Review Boards Best Interpret Preclinical Data? PLoS Med 8(3):e1001011. doi:10.1371/journal.pmed.1001011
IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001011
CONTACT:
James V. Lavery
St. Michael's Hospital and University of Toronto
Centre for Research on Inner City Health
Toronto, Ontario M5B 1W8
CANADA
jim.lavery@utoronto.ca
Journal
PLoS Medicine