The Asian project for collaborative derivation of reference intervals: (2) results of non-standardized analytes and transference of reference intervals to the participating laboratories on the basis of cross-comparison of test results

Kiyoshi Ichihara; Ferruccio Ceriotti; Mori Kazuo; Yang-Yang Huang; Yoshihisa Shimizu; Haruki Suzuki; Masami Kitagawa; Kazuyoshi Yamauchi; Sadao Hayashi; Chia-Chun Tsou; Yoshikazu Yamamoto; Shigeo Ishida; Linda Leong; Michitaka Sano; Hwan Sub Lim; Akira Suwabe; Hee-Yeon Woo; Keiya Kojima; Yoshio Okubo

doi:10.1515/cclm-2012-0422

Article

The Asian project for collaborative derivation of reference intervals: (2) results of non-standardized analytes and transference of reference intervals to the participating laboratories on the basis of cross-comparison of test results

Kiyoshi Ichihara , Ferruccio Ceriotti , Mori Kazuo , Yang-Yang Huang , Yoshihisa Shimizu , Haruki Suzuki , Masami Kitagawa , Kazuyoshi Yamauchi , Sadao Hayashi , Chia-Chun Tsou , Yoshikazu Yamamoto , Shigeo Ishida , Linda Leong , Michitaka Sano , Hwan Sub Lim , Akira Suwabe , Hee-Yeon Woo , Keiya Kojima and Yoshio Okubo

Published/Copyright: February 23, 2013

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From the journal Clinical Chemistry and Laboratory Medicine Volume 51 Issue 7

Abstract

Background: The 2009 Asian multicenter study for derivation of reference intervals (RIs) featured: 1) centralized measurements to exclude reagent-dependent variations; 2) inclusion of non-standardized analytes (hormones, tumor makers, etc.) in the target; and 3) cross-check of test results between the central and local laboratories. Transferability of centrally derived RIs for non-standardized analytes based on the cross-check was examined.

Methods: Forty non-standardized analytes were centrally measured in sera from 3541 reference individuals recruited by 63 laboratories. Forty-four laboratories collaborated in the cross-check study by locally measuring aliquots of sera from 9 to 73 volunteers (average 22.2). Linear relationships were obtained by the major-axis regression. Error in converting RIs using the regression line was expressed by the coefficient of variation of slope b [CV(b)]. CV(b) <10% was set as the cut-off value allowing the conversion. The significance of factors for partitioning RIs was determined similarly as in the first report.

Results: Significant sex-, age-, and region-related changes in test results were observed in 17, 15, and 11 of the 40 analytes, respectively. In the cross-comparison study, test results were not harmonized in the majority of immunologically measured analytes, but their average CV(b)s were <10% except for total protein, cystatin C, CA19-9, free thyroxine, and triiodothyronine. After conversion, 74% of centrally derived RIs were transferred to each local laboratory.

Conclusions: Our results point to the feasibility of: 1) harmonizing test results across different laboratories; and 2) sharing centrally derived RIs of non-standardized analytes by means of comparative measurement of a set of commutable specimens.

Keywords: harmonization; immunoassays; multicenter study; standardization

Corresponding author: Kiyoshi Ichihara, MD, PhD, Faculty of Health Sciences, Department of Clinical Laboratory Sciences, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube 755-8505, Japan, Phone: +81 836 222884, Fax: +81 836 355213

This research was planned collaboratively by the: 1) Committee on Plasma Proteins (C-PP) and Committee on Reference Intervals and Decision Limits (C-RIDL) of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC); 2) the Scientific Committee of the Asia-Pacific Federation for Clinical Biochemistry (APFCB); 3) the Working Group on the Guideline for Common Reference Interval in the Japan Society of Laboratory Medicine (JSLM), and 4) the Committee on Plasma Protein of the Japan Society of Clinical Chemistry (JSCC). This study was also supported by the C-RIDL of the IFCC.

Research funds used included a Scientific Research Fund (No. 21406015: 2009–2011) provided by Japan Society for the Promotion of Science; a Research Promotion Project Fund of the JSLM (2008–2009); and a Scientific Research Fund of the APFCB.

The clinical laboratories taking part in this cross-comparison study belong to the following institutions:

Outside Japan: 1) Gangnam Severance Hospital, Yonsei University, Seoul; 2) Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul; 3) Myongji Hospital, Kwandong University College of Medicine, Gyeonggi-do; 4) Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong; 5) Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau; 6) Mackay Memorial Hospital, Taipei; 7) Cathay General Hospital, Taipei; 8) Yuan Ching Clinical Laboratory, Taipei; 9) National Cheng Kung University, Tainan; 10) Chi-Mei Medical Center, Tainan; 11) National Heart Institute, Kuala Lumpur; 12) Gleneagles Intan Medical Centre, Kuala Lumpur; and 13) Medic-Lab, Ho Chi Minh City.

Inside Japan: 14) Keiyu Corp. Yoshida Hospital, Asahikawa; 15) Hokkaido University, Sapporo; 16) Kishimoto Clinical Laboratory, Tomakomai; 17) Iwate Medical School, Morioka; 18) Hirosaki University, Hirosaki; 19) Hachinohe Red-Cross Hospital, Hachinohe; 20) Hachinohe City Hospital, Hachinohe; 21) Chiba Cardiovascular Center, Ichihara; 22) Chiba University, Chiba; 23) Funabashi Municipal Medical Center, Funabashi; 24) Tokyo Medical and Dental University Chiba Hospital, Chiba; 25) Tokyo University, Tokyo; 26) Shinshu University, Matsumoto; 27) Yamanashi University, Kofu; 28) Nagoya University, Nagoya; 29) Anjo Kosei Hospital, Anjo; 30) Fujita Health University, Toyoake; 31) Osaka University, Suita; 32) Tenri Hospital, Tenri; 33) Osaka Municipal University, Osaka; 34) National Cardiovascular Center, Suita; 35) Kawasaki Medical School, Kurashiki; 36) Kurashiki Central Hospital, Kurashiki; 37) Okayama University, Okayama; 38) Okayama Medical Laboratory, Kurashiki; 39) Yamaguchi University, Ube; 40) Tokuyama Central Hospital, Shunan; 41) Yamaguchi Prefectural Medical Center, Hofu; 42) Saiseikai Yamaguchi Hospital, Yamaguchi; 43) Kochi Medical School, Nangoku; and 44) Ryukyu University Hospital, Naha.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Appendix 1

Estimation of standard error of slope b by the reduced major axis regression

Assuming a dataset consisting of n points of data pair (x and y), the reduced major axis regression is expressed as follows:

where , represents the means of x and y. The slope b is derived as follows:

The mathematical method to derive standard error (SE) of b, SE(b), is not known and commonly approximated by SE of slope b’, SE(b’), by the ordinary least-square method by the following formula (references 2, 4).

where s represents the standard deviation of data points around the ordinary least-square regression line. s is derived as follows with Y representing a predicted y for a given x, or , and r representing the correlation coefficient.

Using the last formula, approximated SE(b) can be expressed as follows.

Therefore, CV of slope b, or CV(b), can be expressed as follows:

References

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Received: 2012-6-29

Accepted: 2013-1-8

Published Online: 2013-02-23

Published in Print: 2013-07-01

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https://doi.org/10.1515/cclm-2012-0422

Keywords for this article

harmonization; immunoassays; multicenter study; standardization

The Asian project for collaborative derivation of reference intervals: (2) results of non-standardized analytes and transference of reference intervals to the participating laboratories on the basis of cross-comparison of test results

Article

Abstract

Conflict of interest statement

Appendix 1

Estimation of standard error of slope b by the reduced major axis regression

References

Supplementary Material

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