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

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 cutoff 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.

Clinical Application of Confidence Interval for Monitoring Changes in Tumor Markers to Determine the Responsiveness to Cancer Treatment

“…As mentioned in our previous study, the chance of non-overlapping 95% CIs is not at a type I error probability of a = 0.05, which instead corresponds to that of 83.4% CIs [21], but at a = 0.0056. In other words, the chance of non-overlapping 83.4%…”

“…Thereafter, in this study, we attempted to utilize our system to monitor serial tumor marker values, including CV A and CV I . Furthermore, we have applied overlapping 95% CIs to monitor changes in two consecutive tumor marker results in our previous publication concerning clinical chemistry items [21]. The coe cients of variation, CV A , CV I , and CV G , for some tumor markers have been added to the Westgard database [22,25].…”

“…We developed a monitoring system using overlapping CIs for interpreting serial tumor marker values. The detailed processes are described in our previous study [21], and Figure 1 is an example of our new system. If the 95% CIs of the previous and current test values do not overlap, then the two results are signi cantly different from each other.…”

Clinical Application of Confidence Interval for Monitoring Changes in Tumor Markers to Determine the Responsiveness to Cancer Treatment

“…To calculate the changes in two consecutive tumor marker test results, pairs of test results were collected from each patient. The statistical methods are described in detail in our previous publication [21]. In brief, the following statistical processes were used.…”

“…In two-sided comparison, the CIs for two certain values may overlap if they are not signi cantly different. In our previous study, we introduced the concept of CI into the interpretation of our clinical chemistry results [21].…”