Ann Lab Med.  2020 May;40(3):201-208. 10.3343/alm.2020.40.3.201.

Clinical Application of Overlapping Confidence Intervals for Monitoring Changes in Serial Clinical Chemistry Test Results

• Cho J
• Seo DM
• Uh Y

• KMID: 2466012
• DOI: http://doi.org/10.3343/alm.2020.40.3.201

Abstract

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 RCV(95%) and RCV(99%) 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.

Keyword

Biological variation; Confidence interval; Intra-individual variation; Serial clinical chemistry test result; Reference change value

MeSH Terms

Chemistry, Clinical*
Clinical Chemistry Tests*
Confidence Intervals*
Individuality

Figure

• 

  Fig. 1 An example of our monitoring system for changes in serial laboratory results using the concept of overlapping confidence intervals (CIs). (A) Initial results and (B) follow-up results of the patient. “HL/D/P/I” indicates reference range (high, low)/delta/panic flag and serum index showing a bias >±10% for hemolysis, icteria, or lipemia. “95% CI” indicates the 95% CI of the current result, and “95% CI_O” indicates whether the CIs of the current and previous results overlap. An arrow at “HL/D/P/I” indicates whether the test value has increased or decreased in comparison with the reference interval, and an arrow at “95% CI_O” indicates whether the CIs of the current result have increased or decreased statistically significantly in comparison with the CIs of the previous result.Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; SGOT, serum glutamic oxaloacetic transaminase; SGPT, serum glutamic pyruvic transaminase; γ-GT, gamma-glutamyl transferase; CK, creatine kinase; LDH, lactate dehydrogenase; HDL, high-density lipoprotein; LDL, low-density lipoprotein.

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