A Proposal for the Clinical Characterization of Continuous Glucose Monitoring Trend Arrow Accuracy.

The assessment and characterization of trend accuracy, that is, the ability of a continuous glucose monitoring (CGM) system to correctly indicate the direction and rate of change (RoC) of glucose levels, has received comparatively little attention in the overall evaluation of CGM performance. As such, only few approaches that examine the trend accuracy have been put forward. In this article, we review existing approaches and propose the clinical trend concurrence analysis (CTCA) which is an adaptation of the conventional trend concurrence analysis. The CTCA is intended to directly evaluate the trend arrows displayed by the CGM systems by characterizing their agreement to suitably categorized comparator RoCs. Here, we call on manufactures of CGM systems to provide the displayed trend arrows for retrospective analysis. The CTCA classifies any deviations between the CGM trend and comparator RoC according to their risk for an adverse clinical event arising from a possibly erroneous treatment decision. For that, the existing rate error grid analysis and a specific set of trend arrow-based insulin dosing recommendations were used. The results of the CTCA are presented in an accessible graphical display and exemplified on data from three CGM systems. With this article, we hope to increase the awareness for the importance and challenges of assessing the accuracy of trend information displayed by CGM systems.

A Critical Discussion of Alert Evaluations in the Context of Continuous Glucose Monitoring System Performance.

Many continuous glucose monitoring (CGM) systems provide functionality which alerts users of potentially unwanted glycemic conditions. These alerts can include glucose threshold alerts to call the user's attention to hypoglycemia or hyperglycemia, predictive alerts warning about impeding hypoglycemia or hyperglycemia, and rate-of-change alerts. A recent review identified 129 articles about CGM performance studies, of which approximately 25% contained alert evaluations. In some studies, real alerts were assessed; however, most of these studies retrospectively determined the timing of CGM alerts because not all CGM systems record alerts which necessitates manual documentation. In contrast to assessment of real alerts, retrospective determination allows assessment of a variety of alert settings for all three types of glycemic condition alerts. Based on the literature and the Clinical and Laboratory Standards Institute's POCT05 guideline, two common approaches to threshold alert evaluation were identified, one value-based and one episode-based approach. In this review, a critical discussion of the two approaches, including a post hoc analysis of clinical study data, indicates that the episode-based approach should be preferred over the value-based approach. For predictive alerts, fewer results were found in the literature, and retrospective determination of CGM alert timing is complicated by the prediction algorithms being proprietary information. Rate-of-change alert evaluations were not reported in the identified literature, and POCT05 does not contain recommendations for assessment. A possible approach is discussed including post hoc analysis of clinical study data. To conclude, CGM systems should record alerts, and the episode-based approach to alert evaluation should be preferred.

Effect of Arterialization on Venous Blood Glucose Concentrations and Implications for Observed Continuous Glucose Monitoring Accuracy.

Background: Heating of the arm and/or hand ("arterialization") is sometimes used in continuous glucose monitoring (CGM) performance studies with the reported aim of reducing differences between venous and capillary glucose concentrations. In this study, the effect of heating on venous glucose concentrations and CGM accuracy was investigated. Methods: A heating pad set to 50°C (122°F) was used with 20 participants to heat either the dominant or nondominant arm and hand. Venous and capillary samples were obtained every 15 min on both arms throughout each of three 6-h glucose challenges. CGM sensors were worn on each upper arm for each of the three visits. Results: Heating of the arm led to a median increase in venous glucose concentrations of +1.4%. No similar effect on capillary concentrations was observed. As a result, the median capillary to venous difference decreased from +5.9% in the nonheated arm to +4.2% in the heated arm. CGM accuracy observed in this study was affected by the selection of heated venous, nonheated venous, or capillary glucose concentrations as comparator data. The heating effect was more pronounced with rapidly decreasing glucose concentrations. Temperatures on the skin did not exceed 40°C (104°F). No adverse events or protocol deviations were associated with the use of the heating pad. Conclusions: Heating of the arm led to a small increase in venous glucose concentrations, but venous concentrations did not reach the level of capillary glucose concentrations. CGM accuracy observed in this study varied depending on the selected comparator data. This study was registered at the German Clinical Trials Register (DRKS00031197).

Characteristics of Nocturnal Hypoglycaemic Events and Their Impact on Glycaemia.

BACKGROUND: Nocturnal hypoglycaemia is a burden for people with diabetes, particularly when treated with multiple daily injections (MDI) therapy. However, the characteristics of nocturnal hypoglycaemic events in this patient group are only poorly described in the literature. METHOD: Continuous glucose monitoring (CGM) data from 185 study participants with type 1 diabetes using MDI therapy were collected under everyday conditions for up to 13 weeks. Hypoglycaemic events were identified as episodes of consecutive CGM readings <70 mg/dl or <54 mg/dl for at least 15 minutes. Subsequently, the time <54 mg/dl (TB54), time below range (TBR), time in range (TIR), time above range (TAR), glucose coefficient of variation (CV), and incidence of hypoglycaemic events were calculated for diurnal and nocturnal periods. Furthermore, the effect of nocturnal hypoglycaemic events on glucose levels the following day was assessed. RESULTS: The incidence of hypoglycaemic events <70 mg/dl was significantly lower during the night compared to the day, with 0.8 and 3.8 events per week, respectively, while the TBR, TB54, and incidence of events with CGM readings <54 mg/dl was not significantly different. Nocturnal hypoglycaemic events <70 mg/dl were significantly longer (60 vs 35 minutes) and enveloped by less rapidly changing glucose levels. On days following nights containing hypoglycaemic events, there was a decrease in TAR, mean CGM glucose level and morning glucose levels and an increase in TB54, TBR, and CV. CONCLUSIONS: The results showed that nocturnal hypoglycaemic events are a common occurrence in persons with type 1 diabetes using MDI with significant differences between the characteristics of nocturnal and diurnal events.

Performance of a Novel Continuous Glucose Monitoring Device in People With Diabetes.

BACKGROUND: In this multicenter study, performance of a novel continuous glucose monitoring (CGM) system was evaluated. METHODS: Adult participants with diabetes were included in the study. They each wore three sensors of the CGM system on the upper arms for up to 14 days. During four in-clinic visits, frequent comparison measurements with capillary blood glucose (BG) samples were performed. The primary endpoint was the 20/20 agreement rate (AR): the percentage of CGM readings within ±20 mg/dL (at BG values <100 mg/dL) or ±20% (at BG values ≥100 mg/dL) of the comparator. Further evaluations included mean absolute relative difference (MARD) and 20/20 AR in different BG ranges and across the wear time. RESULTS: Data from 48 participants and 139 sensors were analyzed. During in-clinic sessions the 20/20 AR was 90.5% and the MARD was 9.2%. For BG ranges <70, 70-180, and >180 mg/dL, 20/20 AR was 94.3%, 89.0%, and 92.5%, respectively. At the beginning, middle, and end of sensor wear time, 20/20 AR was 92.8%, 91.5%, and 85.9%, respectively. The 14-day survival probability was 82.4%. Pain and bleeding after sensor insertion were within the expected range. Based on the study outcome, the use of the device is regarded as safe. CONCLUSIONS: The system showed a good performance compared to capillary BG measurements. This level of accuracy could be shown over the entire measurement range, especially in the low glycemic range, and the whole wear time of the sensors. The results of this study are supporting a non-adjunctive use of the device.

Comparator Data Characteristics and Testing Procedures for the Clinical Performance Evaluation of Continuous Glucose Monitoring Systems.

Comparing the performance of different continuous glucose monitoring (CGM) systems is challenging due to the lack of comprehensive guidelines for clinical study design. In particular, the absence of concise requirements for the distribution of comparator (reference) blood glucose (BG) concentrations and their rate of change (RoC) that are used to evaluate CGM performance, impairs comparability. For this article, several experts in the field of CGM performance testing have collaborated to propose characteristics of the distribution of comparator measurements that should be collected during CGM performance testing. Specifically, it is proposed that at least 7.5% of comparator BG concentrations are <70 mg/dL (3.9 mmol/L) and >300 mg/dL (16.7 mmol/L), respectively, and that at least 7.5% of BG-RoC combinations indicate fast BG changes with impending hypo- or hyperglycemia, respectively. These proposed characteristics of the comparator data can facilitate the harmonization of testing conditions across different studies and CGM systems and ensure that the most relevant scenarios representing real-life situations are established during performance testing. In addition, a study protocol and testing procedure for the manipulation of glucose levels are suggested that enable the collection of comparator data with these characteristics. This work is an important step toward establishing a future standard for the performance evaluation of CGM systems.