Biostatistical issues in the design and analysis of multiple or repeated genotoxicity assays.

Tests for genotoxic or mutagenic effects of chemicals have prompted efficient biostatistical methods for the quantification of dose-response data, especially from the Ames Salmonella/microsome assay. A decision about the genotoxicity of a compound is, however, always based on several assays, and results from multiple or repeated genotoxicity assays have to be combined either qualitatively or, even better, quantitatively. The latter problem is considered here, and issues for design and analysis are addressed. General recommendations for designing genotoxicity assays are given. A long-known methodology for combining quantitative parameters from different experiments is updated and other statistical methods suitable for the combined analyses of multiple assays are presented. Some aspects of design and analysis are elucidated on count data from unscheduled DNA synthesis assays.