Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Postal Zone E2-P, P.O. Box 9600, 2300 RC Leiden, TheNetherlands, Phone: +31 71 526 2278.
Diagnost-IQ, Expert Centre for Clinical Chemistry, Purmerend, TheNetherlands.
Clin Chem Lab Med. 2018 Dec 19;57(1):42-56. doi: 10.1515/cclm-2018-0462.
Background External quality assessment (EQA) programs for general chemistry tests have evolved from between laboratory comparison programs to trueness verification surveys. In the Netherlands, the implementation of such programs has reduced inter-laboratory variation for electrolytes, substrates and enzymes. This allows for national and metrological traceable reference intervals, but these are still lacking. We have initiated a national endeavor named NUMBER (Nederlandse UniforMe Beslisgrenzen En Referentie-intervallen) to set up a sustainable system for the determination of standardized reference intervals in the Netherlands. Methods We used an evidence-based 'big-data' approach to deduce reference intervals using millions of test results from patients visiting general practitioners from clinical laboratory databases. We selected 21 medical tests which are either traceable to SI or have Joint Committee for Traceability in Laboratory Medicine (JCTLM)-listed reference materials and/or reference methods. Per laboratory, per test, outliers were excluded, data were transformed to a normal distribution (if necessary), and means and standard deviations (SDs) were calculated. Then, average means and SDs per test were calculated to generate pooled (mean±2 SD) reference intervals. Results were discussed in expert meetings. Results Sixteen carefully selected clinical laboratories across the country provided anonymous test results (n=7,574,327). During three expert meetings, participants found consensus about calculated reference intervals for 18 tests and necessary partitioning in subcategories, based on sex, age, matrix and/or method. For two tests further evaluation of the reference interval and the study population were considered necessary. For glucose, the working group advised to adopt the clinical decision limit. Conclusions Using a 'big-data' approach we were able to determine traceable reference intervals for 18 general chemistry tests. Nationwide implementation of these established reference intervals has the potential to improve unequivocal interpretation of test results, thereby reducing patient harm.
背景 电解质、底物和酶等常规化学检验的室间质量评价（EQA）项目已从实验室间比对方案发展为准确度验证调查。在荷兰，此类方案的实施降低了实验室间的电解质、底物和酶的变异。这使得能够建立全国范围内和计量可溯源的参考区间，但这些参考区间仍然缺乏。我们发起了一项名为 NUMBER（荷兰统一决策界限和参考区间）的全国性努力，旨在建立一个可持续的系统，以确定荷兰标准化参考区间。
方法 我们使用循证的“大数据”方法，从临床实验室数据库中来自全科医生就诊患者的数百万个检测结果中推断出参考区间。我们选择了 21 项可溯源至 SI 或具有联合委员会对实验室医学溯源性（JCTLM）列出的参考物质和/或参考方法的检测。对于每个实验室和每个检测，剔除离群值，数据转换为正态分布（如果需要），并计算均值和标准差（SD）。然后，计算每个检测的平均均值和 SD，以生成汇总（均值±2 SD）参考区间。结果在专家会议上进行了讨论。
结果 全国 16 家精心挑选的临床实验室提供了匿名检测结果（n=7,574,327）。在三次专家会议上，与会者根据性别、年龄、基质和/或方法，就 18 项检测的计算参考区间以及必要的子类别划分达成共识。对于两项检测，认为有必要进一步评估参考区间和研究人群。对于葡萄糖，工作组建议采用临床决策限。
结论 使用“大数据”方法，我们能够确定 18 项常规化学检测的可溯源参考区间。这些已建立的参考区间在全国范围内的实施有可能改善对检测结果的明确解释，从而减少患者伤害。
