System Accuracy Assessment of a Blood Glucose Meter With Wireless Internet Access Associated With Unusual Hypoglycemia Patterns in Clinical Trials

Abstract

Background: In recent randomized clinical trials, an unusual reporting pattern of glycemic data and hypoglycemic events potentially related to an internet enabled blood glucose meter (MyGlucoHealth, BGM) was observed. Therefore, this clinical study was conducted to evaluate the system accuracy of the BGM in accordance with the ISO15197:2015 guidelines with additional data collection. Methods: To investigate system accuracy, 10 of 3088 devices and 6 of 23 strip lots, used in the trials, were selected by a randomization procedure and a standard repeatability assessment. YSI 2300 STAT Plus was used as the standard reference method. The samples were distributed as per the ISO15197:2015 recommendations with 20 additional samples in the hypoglycemic range. Each sample was tested with 6 devices and 6 strip lots with double determinations. Results: Overall, 121 subjects with blood glucose values 26-423 mg/dL were analyzed, resulting in 1452 data points. In all, 186/1452 readings (12.8%) did not meet the ISO acceptance criteria. Data evaluated according to the FDA guidelines showed that 336/1452 (23.1%) readings did not meet the acceptance criteria. A clear bias toward elevated values was observed for BG <100 mg/dL (MARD: 11.0%). Conclusions: The results show that the BGM, although approved according to standard regulatory guidelines, did not meet the level of analytical accuracy required for clinical treatment decisions according to ISO 15197:2015 and FDA requirements. In general, caution should be exercised before selection of BGMs for patients and in clinical trials.

Laboratory Evaluation of Linearity, Repeatability, and Hematocrit Interference With an Internet-Enabled Blood Glucose Meter

“…The results of the clinical study are reported in the same issue of this journal. 8 Since, the devices and test strips were stored at different trial sites, quality assurance for storage cannot be controlled. However, the similarity of results observed across the devices and strips, originating from different geographical locations, vote against the notion that this factor has driven the results.…”

“…7 Therefore, it was necessary to evaluate the accuracy of the devices and strip lots used by patients in the trials using standard laboratory tests and in a clinical study (reported in the same issue of this journal). 8…”

“…7 Therefore, it was necessary to evaluate the accuracy of the devices and strip lots used by patients in the trials using standard laboratory tests and in a clinical study (reported in the same issue of this journal). 8 Three laboratory tests were selected to determine imprecision, measurement bias and the influence of hematocrit when using the suspected BGMs for BG monitoring. These tests were performed in accordance with principles from the ISO 15197:2015 1 and FDA guidelines.…”

Postmarket Surveillance of Blood Glucose Monitor Systems Is Needed for Safety of Subjects and Accurate Determination of Effectiveness in Clinical Trials of Diabetes Drugs and Devices

“…First, Pfützner and colleagues concluded that the tested BGMs did not meet the minimum accuracy criteria specified for this study. 3 Second, Demircik and colleagues concluded that the BGMs met repeatability requirements, but their studies also demonstrated a significant positive measurement bias in the low range (below mg/dL). 4 In addition, in their studies the product failed the ISO15197:2015 criteria for hematocrit interference.…”

“…The articles in this issue of JDST by first authors Philis-Tsimikas, Pfützner, and Demircik 1,3,4 demonstrated a potential safety risk to subjects volunteering for clinical trials, who used a BGMS that the three sets of authors found to be inaccurate according to the protocols that they used. While none of the three protocols was exactly the same as what is specified in the ISO and FDA standards, the three studies showed similar results and suggest that this BGMS would not perform according to these standards, if a formal postmarket test or a surveillance test were to be performed on them with methods specified by FDA or ISO.…”