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.

Key Words:

• Animal carcinogenicity study
• Cochran–Armitage trend test
• Multiple contrast test
• Poly-3 test

Notes

The ∗ shows the presence of a tumor, and the number in parentheses is the number of affected animals.