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Comp Med. 2011 Jun;61(3):206-18.

Minimizing animal numbers: the variable-criteria sequential stopping rule.

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Office of Animal Welfare, University of Washington, Seattle, Washington, USA.


The variable-criteria sequential stopping rule (SSR) allows an investigator to use a few subjects at a time to determine whether a planned experiment is worth pursuing without increasing the rate of false discoveries (type I errors). The SSR is appropriate whenever testing a null hypothesis if the experiment can be conducted in stages. The investigator adds a predetermined number of subjects at each stage and tests repeatedly for significance until the experiment is stopped because: (1) a significant effect is detected; (2) the effect is clearly not going to be significant; or (3) the predetermined maximal number of subjects has been reached. Two crucial features of the SSR are that it holds the probability of a type I error constant and maintains excellent power. The method is more efficient than is performing a typical significance test after a power analysis because SSR can require 30% fewer subjects to achieve the same power. The variable-criteria SSR provides a formal method for assuring the use of a minimal number of animals. This article provides practical examples of how to use the SSR in combination with a t test, one-way ANOVA, one-way ANOVA with a planned contrast as the focus of the stopping rule, or, in limited circumstances, multifactorial ANOVA.

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