Less than five percent of promising basic science discoveries that claim clinical relevance lead to approved drugs within a decade, partly because of flawed pre-clinical animal research. A number of recent initiatives seek to improve the quality of such studies, and an article published this week in PLOS Medicine identifies key experimental procedures believed to increase clinical generalizability.
The authors, led by Jonathan Kimmelman of McGill University in Montréal, did a systematic literature search and identified 26 guidelines with 55 different procedures that groups of scientists had proposed to improve the quality and usefulness of preclinical efficacy studies. They then summarized and prioritized the results.
The key recommendations are listed in the new STREAM (Studies of TRanslation, Ethics And Medicine) checklist, and include performance of a power calculation to determine sample size, randomized treatment allocation, and in-depth characterization of disease phenotype in the animal model prior to experimentation.
Preclinical animal research is a critical step in drug development. More rigorous attention to experimental procedures protects patients in subsequent clinical trials and redeems the use of animals. It also promises to reduce the cost and delay in developing drugs.
The researchers suggest that: "Investigators, institutional review boards, journals, and funding agencies should give our prioritized recommendations due consideration when designing, evaluating, and sponsoring translational investigations."
Funding: This work was funded by the Canadian Institutes of Health Research (EOG 111391). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: holds a Canada Research Chair in Health Knowledge Transfer and Uptake. All other authors have declared that no competing interests exist.
Citation: Henderson VC, Kimmelman J, Fergusson D, Grimshaw JM, Hackam DG (2013) Threats to Validity in the Design and Conduct of Preclinical Efficacy Studies: A Systematic Review of Guidelines for In Vivo Animal Experiments. PLoS Med 10(7): e1001489. doi:10.1371/journal.pmed.1001489
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Contact:
Jonathan Kimmelman
McGill University
Biomedical Ethics Unit, Social Studies of Medicine
Montréal, QC H3A 1X1
CANADA
514.398.3306
jonathan.kimmelman@mcgill.ca
Journal
PLoS Medicine