Validity of a point of care device (Cholestech LDX) to monitor liver enzyme activity (aminotransferase measures) during a clinical trial

Abstract

Background: Serum transaminase activity is a common measure of liver injury used in clinical trials. The use of a point of care device to monitor serum transaminases would allow immediate evaluation of this safety endpoint and may be less expensive than standard laboratory testing.

Purpose: The objective of this study was to compare a point of care transaminase test to a standard laboratory measurement.

Methods: Subjects were healthy adults participating in a clinical trial measuring the effects of therapeutic doses of acetaminophen on serum transaminase activity. For this study, serum transaminase activity was determined every 3days for 14days. At each measurement, a sample was sent to the clinical laboratory for measurement and also analyzed using a point of care device (Cholestech LDX, Hayward CA). The results were compared using a Bland-Altman plot to identify bias and we also measured the agreement between the techniques for categorizing samples as "low", "normal" or "elevated".

Results: One hundred thirty three samples from 35 subjects were compared. The 95% confidence interval for the limits of agreement between the LDX and the clinical laboratory was -8.46 to 27.09IU/L. Agreement for classification as low, normal or elevated was moderate between the two methods (Kappa=0.37).

Conclusion: The point of care device provided moderate agreement with the laboratory transaminase measurement. However, use of the device would have resulted in misclassification of approximately 1/3 of samples. We do not recommend this point of care device for the measurement of serum transaminases in clinical trials.

Figure 1

Scatterplot of ALT values determined by the clinical laboratory and LDX device. The dashed line shows the line of perfect agreement and the solid line shows the line of best fit for the observed data.

Figure 2

Bland-Altman plot comparing ALT results from LDX and Clinical Laboratory. Shaded area shows the normal range for averaged values.

Figure 3

Bland-Altman plot comparing AST results from LDX and Clinical Laboratory. Shaded area shows the normal range for averaged values.