Continuous Glucose Deviation Interval and Variability Analysis (CG-DIVA): A Novel Approach for the Statistical Accuracy Assessment of Continuous Glucose Monitoring Systems

Abstract

Background: The accuracy of continuous glucose monitoring (CGM) systems is crucial for the management of glucose levels in individuals with diabetes mellitus. However, the discussion of CGM accuracy is challenged by an abundance of parameters and assessment methods. The aim of this article is to introduce the Continuous Glucose Deviation Interval and Variability Analysis (CG-DIVA), a new approach for a comprehensive characterization of CGM point accuracy which is based on the U.S. Food and Drug Administration requirements for “integrated” CGM systems. Methods: The statistical concept of tolerance intervals and data from two approved CGM systems was used to illustrate the CG-DIVA. Results: The CG-DIVA characterizes the expected range of deviations of the CGM system from a comparison method in different glucose concentration ranges and the variability of accuracy within and between sensors. The results of the CG-DIVA are visualized in an intuitive and straightforward graphical presentation. Compared with conventional accuracy characterizations, the CG-DIVA infers the expected accuracy of a CGM system and highlights important differences between CGM systems. Furthermore, it provides information on the incidence of large errors which are of particular clinical relevance. A software implementation of the CG-DIVA is freely available ( https://github.com/IfDTUlm/CGM_Performance_Assessment ). Conclusions: We argue that the CG-DIVA can simplify the discussion and comparison of CGM accuracy and could replace the high number of conventional approaches. Future adaptations of the approach could thus become a putative standard for the accuracy characterization of CGM systems and serve as the basis for the definition of future CGM performance requirements.

Comparison of Point Accuracy Between Two Widely Used Continuous Glucose Monitoring Systems

“…Assessment of point accuracy was performed using results obtained from the Dexcom G7 sensor and FreeStyle Libre 3 sensor and compared with laboratory reference values (YSI) 12 and continuous glucose deviation interval and variability analysis (CG-DIVA) 13 were conducted as a post hoc analysis. The statistical analysis procedures used in this study adhered to Good Clinical Practices/International Conference on Harmonization Guidelines.…”

Clinical Performance Evaluation of Continuous Glucose Monitoring Systems: A Scoping Review and Recommendations for Reporting

“…90,96,123,127,131,138,140,155,158,160 However, this cannot be recommended as the CGM value distribution is dependent on CGM accuracy and thus impairs the comparison of testing procedures among studies. 168 The most common choice for the glucose ranges were the established time in range (TIR) bins <70 mg/dL (<3.9 mmol/L), 70 to 180 mg/dL (3.9-10.0 mmol/L), and >180 mg/dL (>10 mmol/L), used in 62.0% of studies that reported a distribution. The remaining studies used various bins, thus making comparisons of different studies very difficult.…”

“…Numerous articles have already discussed the various parameters and approaches that can be used to characterize point accuracy. 5,12,168,[169][170][171] Most of the approaches describe analytical accuracy, and we refer to those articles for detailed discussions of various approaches. This review identified the following nine approaches, the prevalence of which is summarized in Figure 9: • • Mean and/or median absolute relative difference (ARD) (94.6%) between CGM and comparator measurements.…”

Rethinking the safety and efficacy assessment of (Hybrid) Closed Loop systems: Should we promote the need for a minimum of exercise data within the regulatory approval?

“…5,6 Furthermore, the IFCC convened a group of experts that laid out guidelines for study designs that advocate meal and insulin challenges to induce the necessary glucose fluctuations. 6 However, this guideline does not include specifics on testing CGM devices during physical activity and exercise, which is urgently needed when it comes to using CGM within a (hybrid) closed-loop (HCL) system.…”

“…The International Federation for Clinical Chemistry Working (IFCC) Group on CGM established an International Organization for Standardization (ISO) standard, advocating for standardised testing procedures to achieve a minimum of 7.5% of comparator readings in four critical glucose zones, named the Dynamic Glucose Region plot 5,6 . Furthermore, the IFCC convened a group of experts that laid out guidelines for study designs that advocate meal and insulin challenges to induce the necessary glucose fluctuations 6 . However, this guideline does not include specifics on testing CGM devices during physical activity and exercise, which is urgently needed when it comes to using CGM within a (hybrid) closed‐loop (HCL) system.…”