Attribution of Tumour Lethality and Estimation of the time to Onset of Occult Tumours in the Absence of Cause-of-Death Information
提出一种非参数最大似然估计方法，用于缺乏死因数据的啮齿动物肿瘤实验，估计肿瘤发病和死亡时间分布，并推算致死肿瘤数量，可节省病理学家逐例判断死因的成本。
SUMMARY A new statistical approach is developed for estimating the carcinogenic potential of drugs and other chemical substances used by humans. Improved statistical methods are developed for rodent tumorigenicity assays that have interval sacrifices but not cause-of-death data. For such experiments, this paper proposes a nonparametric maximum likelihood estimation method for estimating the distributions of the time to onset of and the time to death from the tumour. The log-likelihood function is optimized using a constrained direct search procedure. Using the maximum likelihood estimators, the number of fatal tumours in an experiment can be imputed. By applying the procedure proposed to a real data set, the effect of calorie restriction is investigated. In this study, we found that calorie restriction delays the tumour onset time significantly for pituitary tumours. The present method can result in substantial economic savings by relieving the need for a case-by-case assignment of the cause of death or context of observation by pathologists. The ultimate goal of the method proposed is to use the imputed number of fatal tumours to modify Peto’s International Agency for Research on Cancer test for application to tumorigenicity assays that lack cause-of-death data.