[On the statistical analysis of long-term tests for carcinogenesis by means of the random censorship model (author's transl)].
In Section 1 we discuss the fundamental point that the overall tumour incidence rates observed in long-term tests for carcinogenesis typically are biased by differences in intercurrent mortality. In view of some more recent results from theoretical statistics an application of the random censorship model provides an especially powerful approach to getting along with this difficulty. The main assumptions making up the random censorship model as to be applied to the special case of long-term carcinogenesis assay data are carefully described. A consistent and unbiased method for calculating tumour incidence rates corrected for tumour independent intercurrent mortality from the data of an experiment which satisfies the aforementioned assumptions is provided by the Kaplan-Meier technique. Full computational details of the Kaplan-Meier procedure are presented in Section 2. Section 3 is concerned with significance tests for judging dose effects on standardized tumour induction rates. The stepwise procedure recently developed by Holm is adapted to the multiple comparison of several single doses of a possibly carcinogenic compound to the same control. A significance test specifically designed for the assessment of an increasing dose dependent trend is due to Cox and Tarone. Formulas enabling to an easy performance of the Cox-Tarone test are also explicitly written down. In Section 4 we show how to take advantage of Cox's "proportional hazards model" in establishing approximate dose-response relationships.--In each case the general description of the computational procedure is illustrated by an elaborate real data example from a study (published in the same issue of this journal) on the carcinogenicity of ethylene oxide and 1,2-propylene oxide after subcutaneous administration in mice.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000009:adverse effects; D005027:Ethylene Oxide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced*; D013223:Statistics as Topic; D013997:Time Factors
D004852:Epoxy Compounds; D005027:Ethylene Oxide; C009068:propylene oxide
Zur statistischen Auswertung von Langzeit-Kanzerogenitätstests im Modell der Zufallszensierung.