Clinical Chemistry / LABORATORY EVALUATION OF GLUCOSE METERS

Technical Evaluation of Five Glucose Meters With Data Management Capabilities Jeffrey]. Chance, PhD, Dai J. Li,MD, PhD, Kerrie A. Jones, MS, Karen L. Dyer, MT(ASCP), and James H. Nichols, PhD Key Words: Glucose; Glucose meter; Biosensor; Point-of-care; Diabetes

Abstract Technical performance and data management features are prominent criteria in the selection of an appropriate meter for a point-of-care glucose testing program. We evaluated the technical performance of 5 currently available glucose meters with data management capabilities. The performance of all 5 meters was technically equivalent. Linear regression slopes vs the reference method are in the range of 0.94 to 1.02 and indicate correlation more to plasma values than to whole blood values. The percentage of glucose meter results within ± 15% of the laboratory value was at least 90%; however, the percentage within ± 10% was 75% to 87% for most meters. Within-day and between-day precision ranged from 2% to 5% coefficient of variation. Evaluation of linearity with glucose-spiked venous specimens demonstrated that the linearity of each meter agreed with the manufacturer's stated range in most cases. Meter glucose values tended to bias negative as the hematocrit increased, an effect that may be more pronounced at higher glucose concentrations. No volume effects were noted between 5pL and 40 pL. The results suggest that all meters tested will likely satisfy technical performance criteria in a hospital setting and that selection of a system for point-of-care glucose testing will be influenced by the institution's data management requirements.

Near-patient glucose testing by nurses and other medical personnel is an important component in managing the care of the diabetic patient. By providing faster turnaround times, the clinician can respond rapidly to changes in the patient's glucose levels, resulting in optimum insulin regimens and shorter, less expensive hospitalizations.1 Owing to its perceived success, point-of-care glucose testing has been cited as a model for bringing more tests to the bedside2 and has been the subject of several review articles.27 Small portable meters are now used widely for glucose testing and in 1996 had an estimated worldwide market of $425 million.8 The selection of an appropriate meter for routine use in the hospital setting must at a minimum involve an evaluation of the technical performance of the meter. In addition to the clinical requirement for accurate test results, the meter also should have features that facilitate the manipulation and communication of results and assist meeting regulatory and institutional requirements for quality control and documentation. In response, commercial vendors have developed glucose monitoring systems with a wide variety of data management capabilities. In this article, the Advantage (Boehringer-Mannheim, Indianapolis, IN), HemoCue Glucose (HemoCue, Mission Viejo, CA), One Touch II Hospital (Lifescan, Milpitas, CA), Precision G (Medisense, Bedford, MA), and SureStep Pro (Lifescan) whole blood glucose monitoring systems were evaluated for technical performance and data management capabilities. Correlation with laboratory methods, linearity, effect of hematocrit, effect of volume, and precision were studied.

Materials and Methods All meters, test strips, and quality control materials were supplied to the hospital by the manufacturers for this evaluation. One meter from each manufacturer was evaluated. HemoCue supplied Boehringer Mannheim Glucose BG controls for use © American Society of Clinical Pathologists

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with its meter because HemoCue does not manufacture specific controls. Test strips were the latest strip version being marketed at the time of manuscript submission: the original cuvettes for the HemoCue and test strips for the One Touch II and SureStep; the Advantage H strip with Food and Drug Administration-approved code key modification as of December 1997 ("optimized" Advantage H); and the Precision G2b test strip. Reagents were stored as recommended. Arterial specimens were drawn in lithium heparin syringes and analyzed within 30 minutes of phlebotomy to minimize loss of blood gases and effects of glycolysis. Venous specimens were collected in lithium heparin tubes (Vacutainer, Becton Dickinson, Rutherford, NJ). Meter accuracy was determined by comparison with laboratory reference methods. In the initial study, arterial samples (n = 102) were analyzed on the Nova Stat Profile 5 (glucose oxidase, Nova, Waltham, MA) simultaneously with all 5 meters. The plasma was then immediately separated and analyzed within 30 minutes on the Boehringer-Mannheim Hitachi 747 (hexokinase, Boehringer-Mannheim). A subsequent study was conducted to evaluate the performance of new test strips being introduced for 2 of the meters. Arterial patient samples (n = 120) were analyzed on the Chiron 865 (glucose oxidase, Chiron, Emeryville, CA) simultaneously with the Advantage meter (optimized Advantage H strip) and the Precision G meter (new Precision G2b strip). The plasma was then separated and analyzed as described in the preceding text. The Nova Stat Profile 5 and the Chiron 865 are blood gas-electrolyte analyzers that accept a whole blood specimen but produce results comparable to plasma concentrations, as the sample is not hemolyzed during analysis. The data reported in this article for the Precision G meter reflect a 70-data point subset from the Precision G2b study (n = 120), corresponding to readings in which analysis occurred within 20 minutes of phlebotomy, to avoid interference from "microdot" formation. Meters were evaluated for intra-assay (within-day) and interassay (between-day) precision. The low (approximately 2.8 mmol/L [50 mg/dL]), medium (approximately 5-7.2 mmol/L [90-130 mg/dL]), and high (approximately 16.7-18.3 mmol/L [300-330 mg/dL]) control solutions for each meter were run 20 times in succession on the respective meter to establish intra-assay precision using controls. No medium level control was available for the One Touch Hospital II, however. Intra-assay precision using actual patient specimens was then evaluated using a low glucose and a high glucose arterial specimen, each run 10 times on all 5 meters. Here, only 10 sequential readings were performed on each meter to provide a fair estimate of the precision, free from undue interference from declining glucose concentration due to time-dependent glycolysis. Interassay precision was determined from 20 or more analyses of each 548

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control level during a minimum of 10 days (each control level run twice per day). Linearity was evaluated by using multiple venous spiked specimens. A venous sample was collected and held for 48 hours to allow the glucose concentration to approach zero. An aliquot was spiked to a glucose level of 38.9 mmol/L (700 mg/dL) and then diluted with unspiked blood. All solutions were analyzed in duplicate within 30 minutes of dilution. Aliquots were centrifuged and the plasma analyzed on the Hitachi 747 to confirm the clinical laboratory concentration. Hematocrit effects were determined by using venous specimens. After being held for 48 hours, 1 aliquot of a venous specimen was spiked to a glucose level of 2.8 mmol/L (50 mg/dL), and a second aliquot was spiked to a level of 16.7 mmol/L (300 mg/dL). Each aliquot was then centrifuged, and the RBCs, intermediate leukocyte layer, and a small amount of plasma were separated from the remaining plasma in each tube. The RBC mixture was mixed to produce a solution at approximately 80% (0.80) hematocrit, which was then combined with the plasma to prepare samples at 70%, 56.25%, 42.5%, 28.75%, and 15% hematocrit (0.70, 0.56, 0.42, 0.29, 0.15, respectively). These solutions were analyzed in duplicate on the meters and also with both laboratory reference methods. For the Precision G and Advantage meters, hematocrit effects also were evaluated by determining the hematocrit of the patient correlation samples. Hematocrit was verified by spun microhematocrit. Volume effects were evaluated by testing 5 to 40 uL of a patient sample on the meters with the exception of the HemoCue, which accepts only a fixed 5-LtL volume. In all cases, patient samples, linearity and hematocrit solutions, and controls were mixed thoroughly before analysis. All studies, including all glucose meter readings, were performed by 3 trained operators from our institution. Data management capabilities were obtained from the manufacturer's literature.

Results Data for the technical performance of the meters are listed in ITable II. Intra-assay (within-day) precision was less than 5% (coefficient of variation [CV]) in most cases for control solutions. There was no consistent trend for increasing or decreasing imprecision as a function of glucose concentration. The One Touch Hospital II exhibited the best precision with CV percentages in the range of 1.1 to 2.5. The intra-assay precision using patient (whole blood) samples was less than or equal to a CV of 5% in all cases and was not substantially different from that using the control solutions. The interassay (between-day) precision evaluated during a minimum period of 10 days was also less than 5% (CV) in most cases.

© American Society of Clinical Pathologists

Clinical Chemistry / ORIGINAL ARTICLE •Table II Technical Performance* Parameter Precision (coefficient of variation, %) Intra-assay control Intra-assay patient Interassay control Correlation Nova/Chiron Hitachi 747 Correlation coefficient Nova/Chiron Hitachi 747 Sy/x (mmol/L) Nova/Chiron Hitachi 747 Percentage of laboratory agreement Percentage within ±15% Nova/Chiron Hitachi 747 Percentage within ±10% Nova/Chiron Hitachi 747 Linearity (mmol/L) Manufacturer range

Advantage

HemoCue

One Touch I I

SureStep Pro

Precision G

2.1-4.6

2.7-2.9 1.4-4.5 WB 1.4-4.0 0.7-2.8 2.2-6.8 WB

1.1-2.5

3.4-3.6

3.4-5.2

1.8-1.9 1.9-3.6

3.0-5.0 3.1-4.3

3.6-4.4 3.5-5.5

0.97x-0.05 0.98x + 0.07

0.99X-0.33 0.96x + 0.19

1.02X-0.32 0.98x + 0.27

0.98X-0.30 0.94x + 0.26

0.94x + 0.41 0.96x + 0.39

0.986 0.985

0.981 0.988

0.990 0.991

0.992 0.993

0.974 0.974

0.677 0.694

0.676 0.526

0.506 0.477

0.430 0.391

0.816 0.826

95.0 95.8

85.3 93.1

91.2 93.1

91.2 97.1

94.3 94.3

77.5 86.7

63.7 81.4

86.3 86.3

75.5 93.1

77.1 77.1

0.6-33.3

0-22.2

0-36.6

0-27.8

1.1-33.3

1.9-2.3 2.1-3.3

WB = whole blood control from HemoCue. * For names and locations of manufacturers, see the introductory section. To convert mmol/L to mg/dL, divide by 0.05551

The accuracy of each meter was evaluated by comparison of the meter results with laboratory reference methods. The raw data and the least squares linear regression line for the Nova Stat Profile 5 or Chiron 865 correlation (dashed line) and the Hitachi 747 correlation (solid line) are plotted in •Figure II. In general, all 5 meters correlated extremely well with both reference methods for the glucose concentration range of the patient samples. The regression lines are only very slightly offset from the theoretical 1:1 line, and the cluster of the data is generally tight. The linear regression equations show good correlation with the reference methods for all 5 meters, with little bias. The correlation coefficients (r) are in the range of 0.974 to 0.993, and the standard errors of the estimate (Sy/x) are in the range of 0.391 to 0.826 mmol/L (7-15 mg/dL). The percentage of glucose meter results that were within ±15% and ±10% of the reference method (percentage of laboratory agreement) also are given in Table 1. Linearity of each meter was evaluated by using spiked glucose specimens in a wider (mainly higher) concentration range than that seen in the patient samples IFigure 21. We used the polynomial regression method to evaluate linearity.9 The Advantage meter was found to be linear to 33.3 mmol/L (600 mg/dL), the SureStep to 27.8 mmol/L (500 mg/dL), and the HemoCue to 22.2 mmol/L (400 mg/dL), using the Hitachi 747 as the reference method. These ranges are in agreement with those specified by the manufacturer (Table 1). The One Touch II and the Precision G became nonlinear at high © American Society of Clinical Pathologists

glucose concentrations (lower than the manufacturer-stated range). The One Touch II was linear up to 27.8 mmol/L (500 mg/dL), and the Precision G was linear up to 22.2 mmol/L (400 mg/dL). However, the result for the Precision G meter may be an unavoidable artifact of the protocol—the specimen was held for 48 hours to allow the glucose concentration to approach zero, whereas according to the manufacturer, the test strip should be used only with fresh specimens. With the 0 mmol/L solution, some of the meters reported a result (approximately 0 for HemoCue, One Touch II, and SureStep), while others indicated "