title: Two-stage testing of safety: a statistical view.
abstract: Sample sizes given in regulatory guidelines are not based on statistical reasoning. However, from an ethical, scientific, and regulatory point of view, a mutagenicity experiment must have a reasonable chance of supporting the decision as to whether a result is negative or positive. Consequently, the sample size should be based on type I and type II errors, the underlying variability, and the specific size of a treatment effect. A two-stage adaptive interim analysis is presented, which permits an adaptive choice of sample size after an interim analysis of the data from the first stage. Because the sample size of the first stage is considered to be a minimum requirement, this stage can also be regarded as a pilot study.
authors.affiliation: Department of Biometry, ALTANA Pharma, 78467 Konstanz, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Hauschke
authors.forename: Ludwig A
authors.initials: LA
authors.lastname: Hothorn
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D009152:Mutagenicity Tests / Q000379:methods* / Q000592:standards; D012107:Research Design / Q000592:standards / Q000706:statistics & numerical data