Attribution of Tumor Lethality in the Absence of Cause-of-Death Information.pdf

Attribution of Tumor Lethality in the Absence of Cause-of-Death Information.pdf

  1. 1、本文档共22页,可阅读全部内容。
  2. 2、有哪些信誉好的足球投注网站(book118)网站文档一经付费(服务费),不意味着购买了该文档的版权,仅供个人/单位学习、研究之用,不得用于商业用途,未经授权,严禁复制、发行、汇编、翻译或者网络传播等,侵权必究。
  3. 3、本站所有内容均由合作方或网友上传,本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺!文档内容仅供研究参考,付费前请自行鉴别。如您付费,意味着您自己接受本站规则且自行承担风险,本站不退款、不进行额外附加服务;查看《如何避免下载的几个坑》。如果您已付费下载过本站文档,您可以点击 这里二次下载
  4. 4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等,请点击“版权申诉”(推荐),也可以打举报电话:400-050-0827(电话支持时间:9:00-18:30)。
查看更多
Attribution of Tumor Lethality in the Absence of Cause-of-Death Information

Attribution of Tumor Lethality in the Absence of Cause-of-DeathInformationHongshik Ahn1, Ralph L. Kodell2, and Hojin Moon11Department of Applied Mathematics and StatisticsState University of New York at Stony BrookStony Brook, NY 11794-36002Division of Biometry and Risk AssessmentNational Center for Toxicological ResearchFood and Drug AdministrationJe erson, AR 72079AbstractA new statistical approach is developed for estimating the carcinogenic potential of drugsand other chemical substances used by humans. Improved statistical methods are developedfor rodent tumorigenicity assays that have interval sacri ces but not cause-of-death data. Forsuch experiments, this paper proposes a nonparametric maximum likelihood estimation methodfor estimating the distributions of time-to-onset-of and the time-to-death-from the tumor. Thelog-likelihood function is optimized using a constrained direct-search procedure. Using the max-imum likelihood estimators, the number of fatal tumors in an experiment can be imputed. AMonte Carlo Simulation study is conducted for illustration. The accuracy of cause of deathattributed by the proposed method tends to increase as the competing risks survival rate in-creases. By applying the proposed procedure to a real data set, the e ect of calorie restriction isinvestigated. In this study, we found calorie restriction delays the tumor-onset time signi cantlyfor pituitary tumors. The present method can result in substantial economic savings by relievingthe need for case-by-case assignment of cause of death or context of observation by pathologists.The ultimate goal of the proposed method is to use the imputed number of fatal tumors tomodify Petos IARC test for application to tumorigenicity assays that lack cause-of-death data.Keywords: Bioassay; Competing risk; Incidental tumor; Interval sacri ce; Likelihood1 1 IntroductionIn an animal carcinogenicity study, information about onset of a speci c disease is confoundedwith information about the e ect of

文档评论(0)

l215322 + 关注
实名认证
内容提供者

该用户很懒,什么也没介绍

1亿VIP精品文档

相关文档