Zhu Yiliang, Jia Zhihong, Wang Wei, Gift Jeffrey S, Moser Virginia C, Pierre-Louis Bosny J
Department of Epidemiology and Biostatistics, University of South Florida, Tampa, FL 33612, USA.
Regul Toxicol Pharmacol. 2005 Jul;42(2):190-201. doi: 10.1016/j.yrtph.2005.03.007.
Zhu et al. (Zhu, Y., Wessel, M., Liu, T., Moser, V.C., 2005. Analyses of neurobehavioral screening data: dose-time-response modeling of continuous outcomes. Regul. Toxicol. Pharmacol. 41, 240-255) have recently applied dose-time-response models to longitudinal or time-course neurotoxicity data, and have illustrated the modeling process using continuous data from a functional observational battery (FOB). Following the work of these authors, the purpose of this paper is to show that the benchmark dose (BMD) method for single time point dose-response data can be generalized and applied to longitudinal data such as those generated in neurotoxicity studies. We propose a statistical procedure called bootstrap method for computing the lower confidence limits for the BMD. We demonstrate the method using three previously published FOB datasets of triethyltin (Moser, V.C., Becking, G.C., Cuomo, V., Frantik, E., Kulig, B., MacPhail, R.C., Tilson, H.A., Winneke, G., Brightwell, W.S., DeSalvia, M.A., Gill, M.W., Haggerty, G.C., Hornychova, M., Lammers, J., Larsson, J., McDaniel, K.L., Nelson, B.K., Ostergaard, G., 1997a. The IPCS study on neurobehavioral screening methods: results of chemical testing. Neurotoxicology 18, 969-1056.) and the models of Zhu et al. (Zhu, Y., Wessel, M., Liu, T., Moser, V.C., 2005. Analyses of neurobehavioral screening data: dose-time-response modeling of continuous outcomes. Regul. Toxicol. Pharmacol. 41, 240-255).
朱等人（朱，Y.，韦塞尔，M.，刘，T.，莫泽，V.C.，2005年。神经行为筛查数据分析：连续结果的剂量-时间-反应建模。《毒理学与药理学监管》41卷，第240 - 255页）最近将剂量-时间-反应模型应用于纵向或时间进程神经毒性数据，并使用来自功能性观察组合（FOB）的连续数据阐述了建模过程。继这些作者的工作之后，本文的目的是表明单时间点剂量-反应数据的基准剂量（BMD）方法可以推广并应用于纵向数据，如神经毒性研究中产生的数据。我们提出一种称为自助法的统计程序来计算BMD的下限置信限。我们使用三个先前发表的三乙基锡的FOB数据集（莫泽，V.C.，贝金，G.C.，库莫，V.，弗兰蒂克，E.，库利格，B.，麦克菲尔，R.C.，蒂尔森，H.A.，温内克，G.，布赖特韦尔，W.S.，德萨尔维亚，M.A.，吉尔，M.W.，哈格蒂，G.C.，霍尔尼乔娃，M.，拉默斯，J.，拉尔森，J.，麦克丹尼尔，K.L.，纳尔逊，B.K.，奥斯特加德，G.，1997年a。国际化学品安全规划署关于神经行为筛查方法的研究：化学测试结果。《神经毒理学》18卷，第969 - 1056页）以及朱等人的模型（朱，Y.，韦塞尔，M.，刘，T.，莫泽，V.C.，2005年。神经行为筛查数据分析：连续结果的剂量-时间-反应建模。《毒理学与药理学监管》41卷，第240 - 255页）来演示该方法。
