title: Reducing sample size in experiments with animals: historical controls and related strategies.
abstract: Reducing the number of animal subjects used in biomedical experiments is desirable for ethical and practical reasons. Previous reviews of the benefits of reducing sample sizes have focused on improving experimental designs and methods of statistical analysis, but reducing the size of control groups has been considered rarely. We discuss how the number of current control animals can be reduced, without loss of statistical power, by incorporating information from historical controls, i.e. subjects used as controls in similar previous experiments. Using example data from published reports, we describe how to incorporate information from historical controls under a range of assumptions that might be made in biomedical experiments. Assuming more similarities between historical and current controls yields higher savings and allows the use of smaller current control groups. We conducted simulations, based on typical designs and sample sizes, to quantify how different assumptions about historical controls affect the power of statistical tests. We show that, under our simulation conditions, the number of current control subjects can be reduced by more than half by including historical controls in the analyses. In other experimental scenarios, control groups may be unnecessary. Paying attention to both the function and to the statistical requirements of control groups would result in reducing the total number of animals used in experiments, saving time, effort and money, and bringing research with animals within ethically acceptable bounds.
authors.affiliation: Statistics Group, Agricultural Research Service, United States Department of Agriculture, 10300 Baltimore Ave., Building 005, Beltsville, MD 20705, U.S.A.
authors.forename: Matthew
authors.initials: M
authors.lastname: Kramer
authors.affiliation: Laboratorio de Etología, Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universidad de Valencia, c/Catedrático José Beltrán 2, 46980, Paterna, Valencia, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Font
mesh_terms: D000818:Animals; D001699:Biometry; D003198:Computer Simulation; D012107:Research Design; D018401:Sample Size
keywords: animal testing; animal welfare; borrowing information; control group; reduction; sample size; statistical power; three Rs