STATISTICAL-ANALYSIS OF SPARSE INFECTION DATA AND ITS IMPLICATIONS FOR RETROVIRAL TREATMENT TRIALS IN PRIMATES
STATISTICAL-ANALYSIS OF SPARSE INFECTION DATA AND ITS IMPLICATIONS FOR RETROVIRAL TREATMENT TRIALS IN PRIMATES
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DOI：
10.1073/pnas.89.16.7581
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发表时间：
1992-08-15
影响因子：
11.1
通讯作者：
SPOUGE, JL
中科院分区：
文献类型：
--
作者：
SPOUGE, JL
关于反转录病毒灵长类动物试验的报道很少发表任何统计分析。目前的统计方法缺乏对这些试验的适当测试，有效地阻碍了定量评估。本文描述了VACMAN背后的理论，VACMAN是一个用户友好的计算机程序，可以计算体外和体内传染性数据的统计数据。VACMAN的分析适用于许多使用静脉注射的逆转录病毒试验。当病毒剂量-反应曲线具有特定的形状时，该曲线是有效的。来自实际静脉注射的统计数据。逆转录病毒试验说明了有效使用动物的一些不为人知的原则：1：10以外的稀释度可以提高滴定的准确性；以尽可能低的剂量感染滴定动物可以降低挑战剂量；最后，在小规模试验中挑战病毒比控制更多的试验动物可以防止虚假成功，“重复使用”动物，并加强实验结论。提出的理论还解释了病毒饱和的重要概念，这一现象可能导致体外和体内滴定对一些逆转录病毒株是一致的，而对另一些逆转录病毒株是不一致的。
Reports on retroviral primate trials rarely publish any statistical analysis. Present statistical methodology lacks appropriate tests for these trials and effectively discourages quantitative assessment. This paper describes the theory behind VACMAN, a user-friendly computer program that calculates statistics for in vitro and in vivo infectivity data. VACMAN's analysis applies to many retroviral trials using i.v. challenges and is valid whenever the viral dose-response curve has a particular shape. Statistics from actual i.v. retroviral trials illustrate some unappreciated principles of effective animal use: dilutions other than 1:10 can improve titration accuracy; infecting titration animals at the lowest doses possible can lower challenge doses; and finally, challenging test animals in small trials with more virus than controls safeguards against false successes, "reuses" animals, and strengthens experimental conclusions. The theory presented also explains the important concept of viral saturation, a phenomenon that may cause in vitro and in vivo titrations to agree for some retroviral strains and disagree for others.