Background

A1cNow® is a single-use, disposable monitor for the quantitative measurement of %A1c (A1C) in fingerstick or venous whole blood samples. With one drop of blood and just three simple steps, the test can be performed in a physician's office or by the patient at home. Once diluted sample is added to the monitor, there are no further steps, and results are available in about 8 minutes. The monitor performs over 25 internal chemical and electronic quality control checks with each test, including checks for potential hardware or software errors, and potential reagent strip errors. An error code is reported in place of a result if any quality check does not pass.

The A1cNow test is certified by the National Glycohemoglobin Standardization Program (NGSP) and therefore traceable to the DCCT. Further, the test is factory calibrated with a set of blood samples that have been quantitated by an NGSP certified laboratory using an NGSP certified method. Since in-field calibration is neither needed nor possible, the user cannot alter the accuracy of the test. Allowing for the normal variation seen with all laboratory methods, a 7% HbA1c on A1cNow will thus be, on average, the same as a 7% HbA1c on other instruments that are also calibrated to NGSP standards.

Accuracy

Independent Field Study Using A1cNow® (Pacific Northwest)
November 21, 2002

A large health care organization in the Pacific Northwest recently performed a correlation study using A1cNow. The laboratory took 78 EDTA venous samples, performed their routine laboratory testing, A1cNow testing, and sent an aliquot of the sample to the National Glycohemoglobin Standardization Program (NGSP) Secondary Reference Laboratory in Columbia, Missouri. All results were returned to Metrika, and to the health care organization.

Data analysis performed by Metrika showed the following. Bias between A1cNow and the NGSP lab was negligible (0.00%HbA1c), showing accuracy of over 99% for this study. Bias between the health care organization laboratory and A1cNow was small, -0.25%HbA1c, and bias between the health care organization laboratory and the NGSP laboratory was also small, +0.31%HbA1c. Regression statistics are presented in the table below.

Graphic representations of the data are shown, below.

A1cNow vs. NGSP:

A1cNow® Comparison to Quest Diagnostics Clinical Trials Laboratory
December 5, 2002

An in-house clinical study was performed at Metrika on October 14, 2002. The objective of the study was to obtain comparative data between A1cNow and Quest Diagnostics Clinical Trials Laboratory, which uses the BioRad Variant II®. Fingerstick samples were collected for A1cNow and Variant II testing. Venous samples were collected and sent to the National Glycohemoglobin Standardization Program (NGSP) Secondary Reference Laboratory in Columbia, Missouri.

Data analysis performed by Metrika showed the following. Average bias between A1cNow and the NGSP lab was small (+0.1%HbA1c), showing accuracy of approximately 98% for this study. Bias between the Quest laboratory and A1cNow was also small, +0.2%HbA1c, as was the bias between the Quest laboratory and the NGSP laboratory, at -0.1%HbA1c. Means of duplicate pairs were plotted and least-squares linear regression statistics were calculated. Regression statistics are presented in the table below.

Graphic representations of the data are shown below.

A1cNow vs. NGSP

Precision

To evaluate precision, two clinical samples (one approximately 6% A1C and the other approximately 9% A1C) were each tested four times per day over 20 days, yielding 80 results per level. This is the established NGSP precision protocol, as well as the NCCLS precision protocol (EP-5A), and statistical analysis of the data demonstrated percent coefficients of variation (%CVs) of 5.38% for each level.

For reference purposes, the College of American Pathology (CAP) reports %CV's of about 3% to 13% for A1C from proficiency testing by laboratories around the US. CAP data include between-laboratory variability as well as the above factors. Between-laboratory variability, however, is not expected to be significant for A1cNow since it is factory-calibrated and cannot be altered in the field.

Total Error

Total error is a concept that combines both accuracy and precision. Total error is used by the NGSP to describe a test's accuracy, and it is closely related to the probable error for a single laboratory result. An NGSP certified method must provide a result that is within 1% A1C of the "true" result at least 95% of the time.

The NGSP total error protocol requires that 40 samples spanning the test's dynamic range be analyzed by the system that is seeking certification (i.e., A1cNow). These results are then compared to results obtained when the same samples are analyzed by the NGSP (the "true" results). When A1cNow was tested using this protocol, the data showed that A1cNow results were within 0.8% A1C of the established limits. This means that A1cNow performed better than the certification criteria. A bias plot of A1cNow total error is shown below, followed by a graph of A1cNow results compared to the NGSP results.