Ann Lab Med 2020; 40(3): 201-208
Clinical Application of Overlapping Confidence Intervals for Monitoring Changes in Serial Clinical Chemistry Test Results
Jooyoung Cho, M.D., Ph.D.1., Dong Min Seo, B.S.2, and Young Uh, M.D., Ph.D.1,2
Departments of 1Laboratory Medicine and 2Medical Information, Yonsei University Wonju College of Medicine, Wonju, Korea
Corresponding author: Young Uh, M.D., Ph.D.
Department of Laboratory Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju 26426, Korea
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Received: April 26, 2019; Revised: August 1, 2019; Accepted: November 22, 2019; Published online: May 1, 2020.
© Korean Society for Laboratory Medicine. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: Interpretation of changes in serial laboratory results is necessary for both clinicians and laboratories; however, setting decision limits is not easy. Although the reference change value (RCV) has been widely used for auto-verification, it has limitations in clinical settings. We introduce the concept of overlapping confidence intervals (CIs) to determine whether the changes are statistically significant in clinical chemistry laboratory test results.
Methods: In total, 1,202,096 paired results for 33 analytes routinely tested in our clinical chemistry laboratory were analyzed. The distributions of delta% absolute values and cut-off values for certain percentiles were calculated. The CIs for each analyte were set based on biological variation, and data were analyzed at various confidence levels. Additionally, we analyzed the data using RCVs and compared their clinical utility.
Results: Most analytes had low indexes of individuality with large inter-individual variability. The 97.5th percentile cut-offs for each analyte were much larger than conventional RCVs. The percentages of results exceeding RCV95% and RCV99% corresponded to those with no overlap at the 83.4% and 93.2% confidence levels, respectively.
Conclusions: The use of overlapping CIs in serial clinical chemistry test results can overcome the limitations of existing RCVs and replace them, especially for analytes with large intra-individual variation.
Keywords: Biological variation, Confidence interval, Intra-individual variation, Serial clinical chemistry test result, Reference change value

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