Continuous Readout versus Titer-Based Assays of Influenza Vaccine Trials: Sensitivity, Specificity, and False Discovery Rates.
Continuous Readout versus Titer-Based Assays of Influenza Vaccine Trials: Sensitivity, Specificity, and False Discovery Rates.
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流感疫苗试验的连续读数与基于滴度的测定：敏感性、特异性和错误发现率。
DOI：
10.1155/2019/9287120
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发表时间：
2019
影响因子：
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通讯作者：
Zand,MartinS
中科院分区：
文献类型：
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作者：
Li,Dongmei;Wang,Jiong;Garigen,Jessica;Treanor,JohnJ;Zand,MartinS
目前衡量流感病毒抗体免疫的金标准依赖于血凝素抑制试验(HAI)，这是一项有80年历史的技术，以及微量中和试验(MN)。这两种分析方法都使用系列稀释法，为每个样本提供8-14个类别滴定值的离散、分级读数。与产生连续读数的其他测量疫苗抗体水平的方法(即mPLEX-Flu和ELISA)不同，滴定方法引入了不精确度，并增加了错误发现率(FDR)。在本文中，我们评估这种统计误差的程度，首先通过模拟研究比较流感疫苗研究组比较分析中的连续数据和滴度数据，然后通过分析流感疫苗试验的实际样本数据。我们的结果显示了使用连续的，而不是离散的读出分析的优越性。与连续读数分析相比，滴定分析具有较低的统计精度和较高的FDR。结果表明，在流感疫苗试验的不同治疗手段的比较中，传统的滴定分析可能会导致II型错误的增加。这些统计问题与基于滴度的分析的数学性质有关，我们在模拟研究中详细研究了这一点。连续读数分析没有这个问题，因此，研究小组的比较可能会用这两种方法得出不同的结果，就像我们在案例研究中所显示的那样。
The current gold standard for measuring antibody‐based immunity to influenza viruses relies on the hemagglutinin inhibition assay (HAI), an 80‐year‐old technology, and the microneutralization assay (MN). Both assays use serial dilution to provide a discrete, ranked readout of 8–14 categorical titer values for each sample. In contrast to other methods of measuring vaccine antibody levels that produce a continuous readout (i.e., mPLEX‐Flu and ELISA), titering methods introduce imprecision and increase false discovery rates (FDR). In this paper, we assess the degree of such statistical errors, first with simulation studies comparing continuous data with titer data in influenza vaccine study group comparison analyses and then by analyzing actual sample data from an influenza vaccine trial. Our results show the superiority of using continuous, rather than discrete, readout assays. Compared to continuous readout assays, titering assays have a lower statistical precision and a higher FDR. The results suggested that traditional titering assays could lead to increased Type‐II errors in the comparison of different therapeutic arms of an influenza vaccine trial. These statistical issues are related to the mathematical nature of titer‐based assays, which we examine in detail in the simulation studies. Continuous readout assays are free of this issue, and thus it is possible that comparisons of study groups could provide different results with these two methods as we have shown in our case study.