A comparison of test procedures for multidose animal carcinogenicity assays under competing risks

Abstract

Four multidose animal carcinogenicity assay trend test procedures based on the chi-square, Hoel-Walburg, log-rank, and Peto procedures are compared under conditions of competing risks. A total of 42 different risk populations are simulated in which a simulated animal can contract one or more of five different tumor types. The risk populations contain such different risks as incidence of tumor increasing with dose, time of death increasing or decreasing with dose, tumor decreasing time of death without necessarily causing death (nonrepresentativeness), and combinations of the above. Each population is analyzed using each of the four procedures for linear dose-response effect for each tumor separately and for all animals with tumors.

Results show the Peto procedure to be the most robust of the four, giving rejection rates near the nominal for all competing risk situations and having the best power to reject when rejection is called for.

Keywords:

• Animal carcinogenicity assay
• Survival analysis
• Log-rank test
• Hoel-Walburg analysis
• Peto analysis