Evaluation of uncertainty of serum total bilirubin in calibration curve method by Monte Carlo method

doi:10.3969/j.issn.1673-8640.2022.07.015

Abstract

Abstract:

Objective To evaluate the uncertainty process for total bilirubin reference measurement procedure which was recommended by the Joint Committee for Traceability in Laboratory Medicine（JCTLM） used by the Monte Carlo method（MCM） through optimizing. To realize quantity traceability about the uncertainty evaluation of serum total bilirubin under reference laboratory conditions. Methods Applying Doumas method which was recommended by JCTLM,sample A and sample B from external quality assessment scheme for reference laboratories of the International Federation of Clinical Chemistry and Laboratory Medicine（IFCC） in 2014 were determined. Based on software MATLAB,the uncertainty of total bilirubin determination was evaluated by MCM. Results The uncertainty model which was evaluated by the Guide to the Expression of Uncertainty in Measurement（GUM）was established. Parameters related to the calibration curve were as follows：slope（b） was 0.007 531 6,the standard deviation of slope was 0.000 025 51,mean concentration was 87.284 4 mg/L,the standard deviation of mean concentration was 0.196 5,mean absorbance（$\bar{y}$） was 0.657 917,the standard deviation of mean absorbance was 0.000 365 4,intercept（a） was 0.000 525 16,and the standard deviation of intercept was 0.002 699. The results of total bilirubin determination under laboratory conditions were as follows：the concentration of sample A x was 39.368 8 mg/L,the standard uncertainty of sample A synthesis（u） was 0.603 2,95% confidence interval（CI） was 38.188 0-40.553 5,the concentration of sample B x was 18.703 1 mg/L,the standard uncertainty of sample B synthesis（u）was 0.296 4,and 95%CI was 18.122 5-19.284 4. Output quantity of MCM presented skewed normal distribution,showing peak fat-tail. The GUM uncertainty framework（GUF） inclusion interval was verified with adaptive MCM. The absolute deviation d_low and d_high values of the 2 groups were greater than the numerical tolerance 0.05. The results of GUF did not pass the MCM verification. Conclusions With the help of visual software MATLAB,MCM can optimize calculation process,improve the accuracy of inspection results highly compared with the classical GUF.

Key words: Monte Carlo method, Uncertainty, Total bilirubin, Standard curve

CLC Number:

R446.1

MENG Shuting, ZHOU Weiping, DAI Huifen, DONG Deping, DONG Yefeng, GE Renmei, WANG Huimin. Evaluation of uncertainty of serum total bilirubin in calibration curve method by Monte Carlo method[J]. Laboratory Medicine, 2022, 37(7): 674-679.

Figures/Tables 9

References 14

[1]	郑松柏, 庄俊华, 张秀明. 临床酶学参考系统研究进展[J]. 临床检验杂志, 2008, 26(4): 309-311.
[2]	International Organization for Standardization. In vitro diagnostic medical devices-measurement of quantities in biological samples-metrological traceability of values assigned to calibrators and control materials[S]. ISO 17511,ISO, 2020.
[3]	王丽, 权翠侠, 牛璐璐, 等. 新鲜血清赋值传递提高不同生化检测系统检验结果的可比性[J]. 临床检验杂志, 2008, 26(4):294-296.
[4]	戴绘芬, 王惠民, 王建新, 等. 参考测量程序测定血清总胆红素浓度的不确定度评定[J]. 检验医学, 2016, 31(5):368-372.
[5]	Evaluation of measurement data-supplement 1 to the “Guide to the expression of uncertainty in measurement”-propagation of distributions using a Monte Carlo method[Z]. JCGM 101: 2008.
[6]	王惠民, 沈蕾, 王艳秋, 等. 蒙特卡洛法对参考测量程序测定γ-谷氨酰基转移酶活性浓度不确定度的评价[J]. 中华检验医学杂志, 2013, 36(9):836-838.
[7]	孟舒婷, 张忠印, 董业峰, 等. 蒙特卡洛法对血清淀粉酶活性不确定度的评定[J]. 临床与病理杂志, 2019, 39(3):615-622.
[8]	周卫平, 戴绘芬, 陶赟, 等. GUF评定血清TB参考测量程序测量不确定度初探[J]. 检验医学, 2019, 34(11):1032-1037.
[9]	国家质量监督检验检疫总局. JJF 1059.2-2011 用蒙特卡洛法评定测量不确定度[S]. 北京: 国家质量监督检验检疫总局, 2011.
[10]	周卫平, 陶赟, 戴绘芬, 等. GUF法和蒙特卡洛法在TBil参考测量程序测量结果不确定度评定中的应用[J]. 南通大学学报(医学版), 2019, 39(6):455-459.
[11]	International Organization for Standardization. Medical laboratories-calculation and expression of measurement uncertainty[S]. ISO/PDTS 25680.8,ISO, 2008.
[12]	DOUMAS B T, KWORK-CHEUNG P P, PERRY B W, et al. Candidate reference method for determination of total bilirubin in serum:development and validation[J]. Clin Chem, 1985, 31(11):1779-1789. DOI URL
[13]	朱丽红. 扩展校准曲线法在环境监测中的应用[J]. 广东科技, 2009, 18(14):5-6.
[14]	邢彪, 宋太亮, 曹军海, et al. Research on equipment support activity process simulation based on Monte Carlo method[J]. Journal of Shanghai Jiaotong University (Science), 2018, 23(2):250-255. DOI URL

项目	样本A			样本B
项目	空白管	测定管	A₁-A₀	空白管	测定管	A₁-A₀
第1次	0.067 90	0.367 9	0.300 0	0.066 90	0.206 1	0.139 2
第2次	0.067 90	0.358 9	0.291 0	0.064 70	0.206 6	0.141 9
第3次	0.071 10	0.363 6	0.292 5	0.062 80	0.204 4	0.141 6
第4次	0.068 00	0.362 5	0.294 5	0.065 40	0.205 3	0.139 9
第5次	0.067 50	0.369 0	0.301 5	0.062 10	0.208 4	0.146 3
第6次	0.068 50	0.365 0	0.296 5	0.064 70	0.207 2	0.142 5
第7次	0.066 80	0.361 4	0.294 6	0.063 50	0.204 8	0.141 3
第8次	0.067 60	0.363 3	0.295 7	0.063 90	0.204 9	0.141 0
第9次	0.067 70	0.365 3	0.297 6	0.064 50	0.207 3	0.142 8
第10次	0.067 70	0.373 9	0.306 2	0.064 60	0.204 0	0.139 4
均值	0.068 07	0.365 1	0.297 0	0.064 31	0.205 9	0.141 6
标准差	0.001 148	0.004 281	0.004 527	0.001 346	0.001 448	0.002 065
变异系数/%	1.686	1.173	1.524	2.093	0.703 1	1.458

项目	样本A			样本B
项目	空白管	测定管	A₁-A₀	空白管	测定管	A₁-A₀
第1次	0.067 90	0.367 9	0.300 0	0.066 90	0.206 1	0.139 2
第2次	0.067 90	0.358 9	0.291 0	0.064 70	0.206 6	0.141 9
第3次	0.071 10	0.363 6	0.292 5	0.062 80	0.204 4	0.141 6
第4次	0.068 00	0.362 5	0.294 5	0.065 40	0.205 3	0.139 9
第5次	0.067 50	0.369 0	0.301 5	0.062 10	0.208 4	0.146 3
第6次	0.068 50	0.365 0	0.296 5	0.064 70	0.207 2	0.142 5
第7次	0.066 80	0.361 4	0.294 6	0.063 50	0.204 8	0.141 3
第8次	0.067 60	0.363 3	0.295 7	0.063 90	0.204 9	0.141 0
第9次	0.067 70	0.365 3	0.297 6	0.064 50	0.207 3	0.142 8
第10次	0.067 70	0.373 9	0.306 2	0.064 60	0.204 0	0.139 4
均值	0.068 07	0.365 1	0.297 0	0.064 31	0.205 9	0.141 6
标准差	0.001 148	0.004 281	0.004 527	0.001 346	0.001 448	0.002 065
变异系数/%	1.686	1.173	1.524	2.093	0.703 1	1.458

编号	浓度/ （mg/L）	不确定度		对照管A值		测定管A值
编号	浓度/ （mg/L）	相对值/%	绝对值/（mg/L）	均值	标准差	均值	标准差
x₀	0	0	0	0.034 000	0.000 173	0.036 030	0.000 306
x₁	20.474 6	0.418 8	0.085 75	0.034 967	0.000 058 0	0.190 23	0.000 603
x₂	50.591 0	0.424 9	0.215 0	0.035 733	0.000 153	0.421 87	0.000 709
x₃	100.190	0.465 7	0.466 6	0.037 767	0.000 058 0	0.780 37	0.001 01
x₄	150.418	0.472 7	0.711 0	0.038 767	0.000 473	1.175 6	0.000 100
x₅	202.032	0.388 1	0.784 1	0.040 767	0.001 06	1.565 4	0.001 19

编号	浓度/ （mg/L）	不确定度		对照管A值		测定管A值
编号	浓度/ （mg/L）	相对值/%	绝对值/（mg/L）	均值	标准差	均值	标准差
x₀	0	0	0	0.034 000	0.000 173	0.036 030	0.000 306
x₁	20.474 6	0.418 8	0.085 75	0.034 967	0.000 058 0	0.190 23	0.000 603
x₂	50.591 0	0.424 9	0.215 0	0.035 733	0.000 153	0.421 87	0.000 709
x₃	100.190	0.465 7	0.466 6	0.037 767	0.000 058 0	0.780 37	0.001 01
x₄	150.418	0.472 7	0.711 0	0.038 767	0.000 473	1.175 6	0.000 100
x₅	202.032	0.388 1	0.784 1	0.040 767	0.001 06	1.565 4	0.001 19

[1]	WU Jie, LI Zenghe, CHEN Baorong, KONG Xujing. Establishment of traceable steroid hormone standard curve for dried blood spot samples [J]. Laboratory Medicine, 2023, 38(5): 489-493.
[2]	WANG Zhifang, LI Yabo, LIANG Man, AN Shuqi, HAN Yanlin. Adaptive Monte Carlo method for top-down assessment of measurement uncertainty [J]. Laboratory Medicine, 2022, 37(4): 382-386.
[3]	YU Ting, SHEN Min, QU Shoufang, SUN Nan, SUN Jing, HUANG Jie. Development of the national standard materials of total bilirubin in frozen human serum [J]. Laboratory Medicine, 2021, 36(9): 957-961.
[4]	ZHANG Weiwei, JING Rongrong, JI Huoyan, WANG Jianxin, WANG Feng, WANG Huimin. Isotope dilution mass spectrometry applied in measurement uncertainty of serum creatinine concentration [J]. Laboratory Medicine, 2021, 36(3): 263-269.
[5]	WU Qun, SHEN Junfei, WU Wenhao, WANG Beili, PAN Baishen, GUO Wei. Establishment of reference intervals of total bilirubin and direct bilirubin by indirect method [J]. Laboratory Medicine, 2020, 35(8): 749-752.
[6]	ZHENG Gaoming, SU Xiaoru. Correlation of serum bilirubin and CK-MB mass with age in newborns [J]. Laboratory Medicine, 2020, 35(10): 1025-1027.
[7]	YU Shuping, YUAN Dandan, CUI Ming, JING Rongrong, WANG Huimin. Development of BCR-ABL1 candidate reference material and evaluation of measurement uncertainty [J]. Laboratory Medicine, 2019, 34(8): 752-757.
[8]	ZHOU Weiping, DAI Huifen, TAO Yun, WANG Huimin, WANG Jianxin, JI Huoyan, CHEN Feng. Evaluation on the uncertainty of TB reference measurement procedure by GUF [J]. Laboratory Medicine, 2019, 34(11): 1032-1037.
[9]	DING Ning, CHEN Changqiang, FAN Qishi. Correlations of RDW and TB with coronary heart disease and the extent of coronary atherosclerosis [J]. Laboratory Medicine, 2019, 34(10): 889-893.
[10]	PAN Xilong, LIU Xiaodong, HUANG Shaofen. Measurement uncertainties for the determinations of serum K⁺,Na⁺ and Cl^- and their quality improvement [J]. Laboratory Medicine, 2017, 32(7): 642-646.
[11]	GUO Xiaojun, ZHU Lingfeng, XU Chong, JU Yi. Conventional statistics and robust statistics for proficiency testing in laboratory medicine [J]. Laboratory Medicine, 2017, 32(5): 435-439.
[12]	FENG Renfeng. Role of sigma validation for the analysis performance of determination systems among clinical laboratories [J]. Laboratory Medicine, 2017, 32(10): 837-843.
[13]	LI Xin, WANG Di, YANG Chun, XU Jiancheng. Reference intervals of serum bilirubin for Han children in Changchun [J]. Laboratory Medicine, 2016, 31(8): 640-646.
[14]	DAI Huifen, WANG Huimin, WANG Jianxin, JI Huoyan, MENG Shuting. Evaluation on measurement uncertainty of serum total bilirubin concentration by reference procedure [J]. Laboratory Medicine, 2016, 31(5): 368-372.
[15]	HAN Genliang, XU Feng, XU Ling, SHEN Min, GUO Huitao, ZHANG Hong. Performance of improved uricase determination procedure and comparison with chromatography-mass spectrometry reference determination procedure [J]. Laboratory Medicine, 2016, 31(5): 399-404.