Linnet Kristian, Kondratovich Marina
Laboratory of Clinical Biochemistry, Psychiatric University Hospital, Risskov, Denmark.
Clin Chem. 2004 Apr;50(4):732-40. doi: 10.1373/clinchem.2003.029983. Epub 2004 Feb 5.
According to recent International Organization for Standardization (ISO) standards, the limit of detection (LoD) of an assay should be estimated taking both type I (alpha) and II (beta) errors into account. The suggested procedure, however, supposes gaussian distributions of both blank and sample measurements and a linear calibration curve. In clinical chemistry, asymmetric, nongaussian blank distributions are common, and the calibration curve may be nonlinear. We present a partly nonparametric procedure that takes these aspects into account.
Using theoretical distribution models and simulation studies, we developed a LoD estimation procedure suitable for the field of clinical chemistry that is partly based on nonparametric statistics.
For sample size n, the nonparametrically determined 95th percentile of the blank measurements obtained as the value of the [n(95/100) + 0.5]th ordered observation defines the limit for results significantly exceeding zero [limit of blank (LoB)]. The LoD is the lowest value that is likely to yield a result exceeding the LoB. LoD is estimated as: LoB + cbeta x SDS, where SDS is the analytical SD of a sample with a low concentration; cbeta = z(1 - beta)/[1 - 1/(4 x f)]; z(1 - beta) is the standard normal deviate; and f is the number of degrees of freedom for estimation of SD(S). c(beta) is approximately equal to 1.65 for a type II error of 5%. Approaches and needed tabular values for calculation of confidence limits are presented as well as sample size. Worked examples are given to illustrate estimation and verification of the limit of detection. Simulation results are used to document performance.
The proposed procedure appears useful for application in the field of clinical chemistry and promotes a standardized approach for estimating LoDs of clinical chemistry assays.
根据国际标准化组织（ISO）的最新标准，检测限（LoD）的估计应同时考虑I型（α）和II型（β）错误。然而，建议的程序假定空白和样品测量值均呈高斯分布且校准曲线为线性。在临床化学中，非对称、非高斯的空白分布很常见，并且校准曲线可能是非线性的。我们提出了一种考虑到这些方面的部分非参数程序。
使用理论分布模型和模拟研究，我们开发了一种适用于临床化学领域的检测限估计程序，该程序部分基于非参数统计。
对于样本量n，通过第[n(95/100)+0.5]个有序观测值获得的非参数确定的空白测量值的第95百分位数定义了显著超过零的结果的限值[空白限（LoB）]。检测限是可能产生超过空白限结果的最低值。检测限估计为：LoB + cbeta x SDS，其中SDS是低浓度样品的分析标准差；cbeta = z(1 - beta)/[1 - 1/(4 x f)]；z(1 - beta)是标准正态偏差；f是用于估计SD(S)的自由度数量。对于5%的II型错误，cbeta约等于1.65。还介绍了计算置信限的方法和所需的表格值以及样本量。给出了实例以说明检测限的估计和验证。使用模拟结果来记录性能。
所提出的程序似乎适用于临床化学领域的应用，并促进了一种标准化的方法来估计临床化学检测的检测限。
