Durazo-Arvizu Ramon A, Tian Lu, Brooks Stephen P J, Sarafin Kurtis, Cashman Kevin D, Kiely Mairead, Merkel Joyce, Myers Gary L, Coates Paul M, Sempos Christopher T
Loyola University Chicago, Department of Public Health Sciences, Chicago, IL.
Stanford University, Department of Biomedical Data Science, Palo Alto, CA.
J AOAC Int. 2017 Sep 1;100(5):1234-1243. doi: 10.5740/jaoacint.17-0196. Epub 2017 Jul 18.
Low concentrations of total 25-hydroxyvitamin D [25(OH)D], the principal biological measure of vitamin D status, have been associated with clinical and public health outcomes. The determination of levels under which there is an increase in the risk of disease, as well as comparisons across populations, have been difficult to establish due the large assay variability in measuring 25(OH)D. Accordingly, the Vitamin D Standardization Program (VDSP) includes the retrospective standardization of existing 25(OH)D values collected by epidemiological and clinical studies, as well as clinical trials, as one of its main objectives. We introduce methodology developed by the VDSP that can be used to standardize the measurement of time-stable analytes, including 25(OH)D, in samples that have been banked and maintained appropriately. Sample size estimation formulae are first applied to calculate the required number of banked blood samples to be reanalyzed using either of two approaches. In the first approach, existing samples are remeasured using the current measurement procedure, and an equation relating "old" to "current" measurements is obtained. A second set of sera, usually 40-50 single-donor serum samples, are measured with the current measurement procedure and an assay traceable to a reference measurement procedure and/or certified reference materials, which yields a second calibration equation. These two equations are combined to produce standardized levels from the original old values. This approach is necessary when study restrictions prevent serum samples from being shipped to an external laboratory and is illustrated with samples from the Canadian Health Measures Survey. When serum samples are permitted to be shared with other laboratories, or the study investigators can carry out the measurements with a traceable assay, a single calibration equation method is used. Existing samples are selected and remeasured using the available traceable assay. We outline the statistical theory supporting the VDSP protocol and provide implementation examples. The methods proposed are generalizable to any instance in which banked specimens have been properly prepared and stored and the analyte of interest is stable under those conditions.
低浓度的总25-羟基维生素D[25(OH)D]是维生素D状态的主要生物学指标，它与临床和公共卫生结果相关。由于测量25(OH)D时存在较大的检测变异性，因此难以确定疾病风险增加时的浓度水平，也难以在不同人群之间进行比较。因此，维生素D标准化计划(VDSP)将对流行病学和临床研究以及临床试验收集的现有25(OH)D值进行回顾性标准化作为其主要目标之一。我们介绍了VDSP开发的方法，该方法可用于对已妥善保存的样本中的时间稳定分析物（包括25(OH)D）进行标准化测量。首先应用样本量估计公式，使用两种方法之一来计算需要重新分析的储存血样数量。在第一种方法中，使用当前测量程序对现有样本进行重新测量，并获得一个将“旧”测量值与“当前”测量值相关联的方程。用当前测量程序以及可溯源至参考测量程序和/或有证参考物质的检测方法对第二组血清（通常为40-50个单供体血清样本）进行测量，从而得出第二个校准方程。将这两个方程结合起来，根据原始的旧值得出标准化水平。当研究限制阻止血清样本被运送到外部实验室时，这种方法是必要的，加拿大健康措施调查的样本对此进行了说明。当允许血清样本与其他实验室共享，或者研究人员可以使用可溯源的检测方法进行测量时，则使用单一校准方程法。选择现有样本并使用可用的可溯源检测方法进行重新测量。我们概述了支持VDSP方案的统计理论，并提供了实施示例。所提出的方法可推广到任何已妥善制备和储存储存样本且感兴趣的分析物在这些条件下稳定的情况。
