title: Poly-k-trend tests for survival adjusted analysis of tumor rates formulated as approximate multiple contrast test.
abstract: In long-term rodent carcinogenicity studies without cause of death information, poly-k-adjusted tumor rates are commonly used to assess the carcinogenic potential of a compound. Testing trend on proportions, global tests such as the Cochran-Armitage test and Williams-type test have been proposed. Here are introduced simultaneous confidence intervals and adjusted p-values for multiple contrasts on poly-k-adjusted tumor rates, based on approximation with the multivariate normal distribution. Williams-type contrasts and Dunnett-type comparisons to control are special cases of this approach. In simulation studies, the acceptable performance for finite sample sizes is demonstrated. The methods are applied to a real data example and are implemented in a package for R.
authors.affiliation: Leibniz University Hannover, Institute of Biostatistics, Hannover, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Schaarschmidt
authors.forename: Martin
authors.initials: M
authors.lastname: Sill
authors.forename: Ludwig A
authors.initials: LA
authors.lastname: Hothorn
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D005054:Eugenol / Q000031:analogs & derivatives / Q000633:toxicity; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000401:mortality; D011336:Probability; D051381:Rats; D018401:Sample Size
chemical_list: C005223:methyleugenol; D005054:Eugenol