General Experimental Design 2015 Mouse 101 Course Linda G. Byrd, Ph.D. Geneticist Laboratory of Metabolism September 21, 2015
In 1959, W.M.S. Russell and R.L. Burch published a practical strategy of replacement, refinement, and reduction—referred to as the Three Rs—for researchers to apply when considering experimental design in laboratory animal research (Russell and Burch 1959). Over the years, the Three Rs have become an internationally accepted approach for researchers to apply when deciding to use animals in research and in designing humane animal research studies. THE THREE Rs
Refinement refers to modifications of husbandry or experimental procedures to enhance animal well- being and minimize or eliminate pain and distress. Refinement
Reduction involves strategies for obtaining comparable levels of information from the use of fewer animals or for maximizing the information obtained from a given number of animals (without increasing pain or distress) so that in the long run fewer animals are needed to acquire the same scientific information. This approach relies on an analysis of experimental design, applications of newer technologies, the use of appropriate statistical methods, and control of environmentally related variability in animal housing and study areas. Reduction
Animal species Short term/long term Complexity of the question Manipulation of the samples collected Experimental design
# cages x # breeding females/cage x 6 pups (on average)/litter x 1 litter/month x 12 months = number of mice/year Breeding Mice
Justify the number of animals to be used: Whenever possible the animals should be justified statistically, including a justification for the number of animals per group A table or chart is helpful to explain the requested number of animals to organize by experiment Experiments
Choosing group sizes Replication, replication, replication Experiments (cont)
Similar studies Pubmed ( Laboratory practices Institutional memory References
Pilot studies PK studies Drug Metabolism Drug efficacy Tumor studies Xenograft Spontaneous Induced Types of Studies
Scientific method: Statistical errors ( statistical-errors ) statistical-errors Relying on P-values Statistics
Biochim Biophys Acta Jul;1852(7):