White Paper: Dario Blood Glucose Monitoring System - Performance Evaluation Date: Feb 10, 2014 LabStyle Innovation
TABLE OF CONTENTS 1. PURPOSE... 3 2. SCOPE... 3 3. REFERENCE... 4 4. DEFINITIONS... 4 5. STRUCTURE AND ORGANIZATION OF STUDY... 5 6. OVERVIEW OF EVALUATION... 5 7. RESULT ANALYSIS OF EVALUATION... 6 8. CONCLUSIONS... 9 2
1. PURPOSE This Performance Evaluation study was conducted to evaluate the accuracy of blood glucose level results obtained from fingertip using Labstyle Innovations Dario Blood Glucose Monitoring System (BGMS) compared to reference equipment (YSI 2300 STATPLUS) and to evaluate the ease of use of the Dario BGMS. The performance evaluation was conducted following an independent study performed by Institut für Diabetes-Technologie Forschungs- und Entwicklungsgesellschaft mbh an der Universität Ulm in January 2014. The study showed excellent correlation between SMBG results obtained by OEM based technology and the results obtained by the reference YSI (gold standard). The results where within the acceptance criteria of EN ISO15197:2013 for system accuracy. 2. SCOPE 2.1 Device The device used in this study was the Dario Blood Glucose Monitoring System (BGMS). The device comprises of the following components: Dario Test Strip Dario Lancing Device Dario Blood Glucose Meter (Dongle) Smart Mobile Device Software 2.2 Intended Use Dario Blood Glucose Monitoring System (BGMS) is indicated for the quantitative measurement of glucose in fresh capillary whole blood samples drawn from the fingertips. The system is intended to be used by a single patient and should not be shared. The Dario BGMS is intended for self-testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid in monitoring the effectiveness of diabetes control. The Dario BGMS is not to be used for the diagnosis of or screening of diabetes or for neonatal use. 3
Dario Blood Glucose meter (BGM) must be used with Dario blood glucose test strip, Dario control solutions, Dario lancing device, Dario lancets, and Dario application software 2.3 Test Principle The test is based on electrochemical biosensor technology and the principle of capillary action. The electrical current generated by the reaction of glucose with the reagent of the strip is measured by the meter and is displayed on an ios-based smart mobile device (e.g., iphone, ipod, ipad) as the corresponding blood glucose level. The strength of the current produced by the reaction depends on the amount of glucose in the blood sample. 2.4 Technical Background Dario technology is based on OEM GOD strip technology which was recently evaluated by an independent laboratory. The OEM BGMS accuracy study was performed by Institut für Diabetes-Technologie Forschungs- und Entwicklungsgesellschaft mbh an der Universität Ulm in January 2014. The study results confirmed that the system meets the accuracy requirements of the ISO 15197:2013. Three test strip lots were tested demonstrating accuracy of 95.5%, 98%, and 97%. These results meet the system accuracy requirements of the ISO 15197:2013 and reinforces the notion that the Dario strip technology complies with the same requirements. 3. REFERENCE 1. EN ISO 15197:2013 In vitro diagnostic test systems Requirements for blood-glucose monitoring systems for self-testing in managing diabetes mellitus, Clause 8. User performance evaluation 8.3 User evaluation / 8.4 Evaluation of instructions for use. 2. BS EN 13612:2002 Performance evaluation of in vitro diagnostic medical devices. 4. DEFINITIONS Reference value: YSI (mg/dl) X 1.06 plasma conversion value: 4
The capillary whole blood results obtained by the YSI were multiplied by 1.06 since the YSI is calibrated for venous blood as determined by the below chart 1 : 5. STRUCTURE AND ORGANIZATION OF STUDY The study was conducted in internal laboratory. The following individuals were involved in the performance of this study: Operators - Mr. SH Ha (Medical Technologist, SD Biosensor, Inc.) - Mr. MK Kin (QC, SD Biosensor, Inc.) - Ms. YS Ahn (Nurse, YONSEI Medical Clinic) Study condition: Overall studies by SMBG meter were followed in accordance with Dario BGM system User Instruction Guide, i.e. same intended use condition. 6. OVERVIEW OF EVALUATION The study was conducted over a day period, Sept. 25 th, 2013. A total of 87 subjects were recruited. Fresh capillary blood was obtained from each subject. A range of glucose concentration was tested 28-458 mg/dl. Capillary blood samples were modified - raised or lowered to achieve the required distribution. Methods for adjusting the glucose concentration are described in IST 15197:2013(E) 6.1.2. The samples were tested by using 3 Dario Blood Glucose Meters from different lots and Dario Test Strip (three different test strip lots: Lot No.: SPS1013001, SPS1013002, SPS1013003) and by YSI. 1 Davidson & Parker: Clinical Diabetes Mellitus: A Problem Oriented Approach.2000, p.461 5
7. RESULT ANALYSIS OF EVALUATION The results and accuracy tables are represented in accordance with ISO 15197:2013 Standard for system accuracy comparing the results obtained with Dario BGMS to YSI. Investigator presented regression equations with confidence intervals and plots showing all data points according to ISO 15197:2013. Sample distribution: Glucose Concentration (mg/dl) Percentage of the sample <50 5% 50-80 8% 7% 81-120 20% 121-200 30% 201-300 15% 301-400 5% 5% 401> 5% Evaluation results Individual results of the blood-glucose monitoring system were plotted as the dependent variable and the average of the duplicate reference value (= YSI values * 1.06) as the independent variable. Identical scales and intervals were used for the x- and y-axes. Slope and y-intercept were calculated by regression analysis procedure (EXCEL/TOOL/DATA ANALYSIS/ Regression Analysis). Dario (SPS1013001 Dario(SPS1013002) Dario(SPS1013003) Slope 1.0021 1.0029 1.0012 Y-Intercept 1.2465-0.3243 1.6083 R 0.9972 0.9968 0.9969 6
Figure 1: Consensus Error Grid (mg/dl) Dario SPS 1013001 Figure 2: Consensus Error Grid (mg/dl) Dario SPS 1013002 7
Figure 3: Consensus Error Grid (mg/dl) Dario SPS 1013003 System Accuracy according to ISO15197:2013 Reference: YSI (YSI value * 1.06) Dario BGMS Test Results SPS 1013001 System accuracy results: Dario BGM system (SPS 1013001) concentrations <100 mg/dl concentrations 100 mg/dl Within ± 5 Within ± 10 Within ± 15 Within ± 5 % Within ± 10 % Within ± 15 % mg/dl mg/dl mg/dl 60/72 83% 94/128 73% 122/128 95% 128/128 Dario BGMS Test Results SPS 1013002 System accuracy results: Dario BGM system (SPS 1013002) concentrations <100 mg/dl concentrations 100 mg/dl Within ± 5 Within ± 10 Within ± 15 Within ± 5 % Within ± 10 % Within ± 15 % mg/dl mg/dl mg/dl 62/72 86% 71/72 99% 90/128 70% 121/128 95% 127/128 99% Dario BGMS Test Results SPS 1013003 8
System accuracy results: Dario BGM system (SPS 1013003) concentrations <100 mg/dl concentrations 100 mg/dl Within ± 5 Within ± 10 Within ± 15 Within ± 5 % Within ± 10 % Within ± 15 % mg/dl mg/dl mg/dl 61/72 85% 93/128 73% 119/128 93% 125/128 98% 8. CONCLUSIONS The Performance Evaluation was performed according to the ISO 15197:2013, 6.3 System accuracy. According to the result analysis of this evaluation, the Dario BGMS showed excellent correlation coefficient (R= 0.997, 0.997, 0.997) with YSI reference method (venous plasma - calibrated). The results fell within the acceptance criteria of ISO15197:2013 for system accuracy requirements: Ninety-five percent (95%) of the measured glucose values shall fall within either ±15mg/dL of the average measured values of the reference measurement procedure at glucose concentrations < 100mg/dL or within ±15% at glucose concentrations 100 mg/dl. - 99% of individual glucose measured values shall fall within zones A and B of the Consensus Error Grid(CEG) for type 1 diabetes. Additionally, of individual glucose measured values were within zones A of the Consensus Error Grid(CEG) for type 1 diabetes. The results of this Performance Evaluation study together with the results of the independent study performed in Germany support the conclusion that the Dario BGMS meets the accuracy requirements of EN ISO15197:2013. 9