Accuracy Evaluation of Three Systems for Self-monitoring of Blood Glucose With Three Different Test Strip Lots Following ISO 15197

Abstract

The standard ISO (International Organization for Standardization) 151971 is widely accepted for the accuracy assessment of systems for self-monitoring of blood glucose (SMBG). In the European Union, manufacturers have to provide evidence of conformity with ISO 15197 to obtain the Conformite Europeene (CE) mark for their meter. However, application of the CE mark is a 1-time procedure before the market approval; regular and independent accuracy evaluations of market-released test strip lots of a SMBG system are not mandatory. In fact, studies have repeatedly shown that individual test strip lots of available systems do not comply with ISO 15197 accuracy criteria.2-5 In this study, 3 CE-marked SMBG systems (CareSens N, CareSens N POP, alphacheck professional) with 3 different test strip lots each were procured by the manufacturer (i-SENS, Inc, Korea) to assess compliance to accuracy criteria stipulated in ISO 15197:2003. In addition, more stringent criteria of its revision, ISO 15197:2013,6 were applied. The study was performed at the Institut fur Diabetes-Technologie Forschungs- und Entwicklungsgesellschaft mbH an der Universitat Ulm, Ulm, Germany in compliance with the German Medical Devices Act. The study protocol was approved by the Ethics Committee and the Federal Institute for Drugs and Medical Devices. Each system was tested on 100 capillary blood samples from different subjects (≥18 years, diabetes type 1 or type 2 or no diabetes) following procedures described in ISO 15197:2003. Comparison measurements were performed on capillary plasma with a glucose oxidase laboratory method (YSI 2300 STAT Plus™ glucose analyser, YSI Incorporated, Yellow Springs, OH, USA). To confirm trueness and precision of the comparison method, regular internal and external quality control measures were performed. Each of the tested systems fulfilled with all 3 tested lots accuracy criteria of ISO 15197:2003 with 99.5% to 100% of measurement results within ±15 mg/dl of the comparison measurement at glucose concentrations <75 mg/dl and within ±20% at glucose concentrations ≥75 mg/dl (Table 1). Applying the tighter criteria of the revision ISO 15197:2013, the systems showed 98% to 100% of measurement results within ±15 mg/dl of the comparison measurement at glucose concentrations <100 mg/dl and within ±15% at glucose concentrations ≥100 mg/dl. Consensus error grid analysis as required by ISO 15197:2013 showed for each system 100% of measurement results within zones A and B. The relative bias according to Bland and Altman, that is, average across all differences between SMBG results and comparison method measurement results divided by their mean, ranged from 1.3% to 2.3% for CareSens N, from −0.7% to 1.6% for CareSens N POP and from −0.3% to 0.9% for alphacheck professional. Table 1. System Accuracy Results (Number and Percentage) Within Limits of ISO 15197:2003 and ISO 15197:2013. All 3 systems fulfilled with all 3 investigated test strip lots accuracy requirements of the international standard ISO 15197:2003 and its revision ISO 15197:2013, for which mandatory compliance is recommended after a 36-month transition period. In bias analysis for all 3 systems minimal lot-to-lot variability was observed. Regular and independent evaluations after the market approval of a SMBG system is helpful to ensure constant measurement quality and adherence of market-released test strips to accuracy requirements stipulated in ISO 15197.