ATLA::Alternatives to Laboratory Animals

Volume 31, Supplement 1

The role of control groups in mutagenicity studies: matching biological and statistical relevance.

Dieter Hauschke1, Torsten Hothorn2 and Juliane Schäfer3

1Department of Biometry, ALTANA Pharma, 78467 Konstanz, Germany; 2Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany; 3Department of Statistics, University of Munich, 80539 Munich, Germany

SUMMARY

The statistical test of the conventional hypothesis of "no treatment effect" is commonly used in the evaluation of mutagenicity experiments. Failing to reject the hypothesis often leads to the conclusion in favour of safety. The major drawback of this indirect approach is that what is controlled by a prespecified level a is the probability of erroneously concluding hazard (producer risk). However, the primary concern of safety assessment is the control of the consumer risk, i.e. limiting the probability of erroneously concluding that a product is safe. In order to restrict this risk, safety has to be formulated as the alternative, and hazard, i.e. the opposite, has to be formulated as the hypothesis. The direct safety approach is examined for the case when the corresponding threshold value is expressed either as a fraction of the population mean for the negative control, or as a fraction of the difference between the positive and negative controls.

Keywords: biological relevance, Fieller confidence intervals, mutagenicity studies, test on equivalence