title: Use of historical controls in time-adjusted trend tests for carcinogenicity.
abstract: We develop a method for incorporating historical control information into time-adjusted tests for dose effects in carcinogenicity studies. After discretizing the time scale, we use a multinomial distribution to model the number of animals dying with tumor in each interval. Data from past studies are used to estimate the parameters characterizing the prior. A score test derived from the resulting Dirichlet-multinomial generalizes the test of Tarone (1982, Biometrics 38, 215-220) and reduces, in the limit, to the log-rank test in the case of a diffuse prior. The methodology is illustrated with data from a study of the fire retardant 2,2-Bis(bromomethyl)-1,3-propanediol.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Ibrahim
authors.forename: L M
authors.initials: LM
authors.lastname: Ryan
mesh_terms: D000818:Animals; D001699:Biometry / Q000379:methods*; D015197:Carcinogenicity Tests / Q000379:methods* / Q000706:statistics & numerical data; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D005411:Flame Retardants / Q000008:administration & dosage / Q000633:toxicity; D016013:Likelihood Functions; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced; D051379:Mice; D015233:Models, Statistical; D011409:Propylene Glycols / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D002273:Carcinogens; D005411:Flame Retardants; D011409:Propylene Glycols; C060080:2,2-bis(bromomethyl)-1,3-propanediol