从几个德国和意大利医学中心的实验室数据基础中得出的血浆和血清促甲状腺激素（TSH）浓度的间接参考区间。

Indirect reference intervals of plasma and serum thyrotropin (TSH) concentrations from intra-laboratory data bases from several German and Italian medical centres.

机构信息

Institut für Statistik, Universität Bremen, Bremen, Germany.

出版信息

Clin Chem Lab Med. 2011 Apr;49(4):659-64. doi: 10.1515/CCLM.2011.114. Epub 2011 Feb 23.

DOI:10.1515/CCLM.2011.114

PMID:21342020

Abstract

BACKGROUND

The dogma of establishing intra-laboratory reference limits (RLs) and their periodic review cannot be fulfilled by most laboratories due to the expenses involved. Thus, most laboratories adopt external sources for their RLs, often neglecting the problems of transferability. This is particularly problematic for analytes with a large diversity of existing RLs, as for example thyrotropin (TSH). Several attempts were taken to derive RLs from the large data pools stored in modern laboratory information systems. These attempts were further developed to a more sophisticated indirect procedure. The new approach can be considered a combined concept because it pre-excludes some subjects by direct criteria a-posterior. In the current study, the applicability of the new concept for modern protein bindings assays was examined for estimating RLs of serum and plasma TSH with data sets from several German and Italian laboratories.

METHODS

A smoothed kernel density function was estimated for the distribution of the total mixed data of the sample group (combined data of non-diseased and diseased subjects). It was assumed that the "central" part of the distribution of all data represents the non-diseased ("healthy") population. The central part was defined by truncation points using an optimisation method, and was used to estimate a Gaussian distribution of the values of presumably non-diseased subjects after Box-Cox transformation of the empirical data. This distribution was now considered as the distribution of the non-diseased subgroup. The percentiles of this parametrical distribution were calculated to obtain RLs.

RESULTS

RLs determined by the indirect combined decomposition technique led to similar RLs as found by several recent study reports using a direct method according to international recommendations. Furthermore, the RLs obtained from 13 laboratories in two different European regions reflected the well-known differences of various analytical procedures. Stratification for gender and age was necessary in contrast to earlier reports. With increasing age, an increase of the upper RL and the reference range was observed. Hospitalisation also affected the RLs. Common RLs appeared acceptable only within the same analytical systems. Some laboratories used RLs which were not appropriate for the population served.

CONCLUSIONS

The proposed strategy of combining exclusion criteria with a resolution technique led to retrospective RLs from intra-laboratory data pools for TSH which were comparable with directly determined RLs. Differences between laboratories were due primarily to the well-known bias of the different analytical procedures and to the status of the population.

摘要

背景

由于费用问题，大多数实验室无法遵循建立实验室内部参考范围（RL）并定期进行审查的教条。因此，大多数实验室采用外部来源的 RL，常常忽略了可转移性的问题。对于 TSH 等 RL 种类繁多的分析物来说，这尤其成问题。已经有几次尝试从现代实验室信息系统中存储的大型数据池中得出 RL。这些尝试进一步发展为更复杂的间接方法。新方法可以被认为是一种综合概念，因为它通过直接的后验标准预先排除了一些研究对象。在本研究中，检查了该新概念在使用来自几个德国和意大利实验室的数据组估计血清和血浆 TSH 的 RL 时对现代蛋白质结合测定的适用性。

方法

对样本组的总混合数据分布（非患病和患病受试者的组合数据）进行平滑核密度函数估计。假设所有数据分布的“中心”部分代表非患病（“健康”）人群。使用优化方法通过截断点定义中心部分，并使用 Box-Cox 转换经验数据后，对假定非患病受试者的值进行高斯分布估计。现在，该分布被视为非患病亚组的分布。计算该参数分布的百分位数以获得 RL。

结果

间接综合分解技术确定的 RL 与使用国际建议的直接方法的几项最近研究报告得出的 RL 相似。此外，来自两个不同欧洲地区的 13 个实验室获得的 RL 反映了各种分析程序的已知差异。与早期报告相反，需要按性别和年龄进行分层。随着年龄的增长，上 RL 和参考范围增加。住院治疗也会影响 RL。只有在相同的分析系统中，常见的 RL 才是可以接受的。一些实验室使用的 RL 不适合所服务的人群。