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.

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).

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

The use of different approaches for design and results presentation of studies for the clinical performance evaluation of continuous glucose monitoring (CGM) systems has long been recognized as a major challenge in comparing their results. However, a comprehensive characterization of the variability in study designs is currently unavailable. This article presents a scoping review of clinical CGM performance evaluations published between 2002 and 2022. Specifically, this review quantifies the prevalence of numerous options associated with various aspects of study design, including subject population, comparator (reference) method selection, testing procedures, and statistical accuracy evaluation. We found that there is a large variability in nearly all of those aspects and, in particular, in the characteristics of the comparator measurements. Furthermore, these characteristics as well as other crucial aspects of study design are often not reported in sufficient detail to allow an informed interpretation of study results. We therefore provide recommendations for reporting the general study design, CGM system use, comparator measurement approach, testing procedures, and data analysis/statistical performance evaluation. Additionally, this review aims to serve as a foundation for the development of a standardized CGM performance evaluation procedure, thereby supporting the goals and objectives of the Working Group on CGM established by the Scientific Division of the International Federation of Clinical Chemistry and Laboratory Medicine.

Direct-to-consumer testing - benefits for consumers, people with disease and public health.

Direct-to-consumer (DTC) tests can be defined as any in-vitro diagnostic (IVD) test or, more broadly, any medical test using an IVD or medical device, that is marketed directly to consumers without involvement of a health care provider (HCP). Examples are pregnancy tests, alcohol breath tests, blood pressure measurements (medical device), coagulation tests (INR), self-monitoring of blood glucose, continuous glucose monitoring (medical device), HIV tests, HPV tests, SARS-CoV-2 antigen tests, or genetic tests. DTC tests fulfil various customer needs such as making rapid decisions (e.g. glucose monitoring for insulin dosing, SARS-CoV-2 antigen test, hormone test identifying fertile days, alcohol test), monitoring chronic conditions between consultations (e.g. diabetes, lipidaemia, hypertension), saving time and reducing consultations (e.g. INR, SARS-CoV-2 antigen test, blood pressure monitoring), screening for disease when no symptoms are present (e.g. occult blood, cholesterol, triglycerides, SARS-CoV2 antigen test), or maintaining privacy (e.g. pregnancy test, HIV test, HPV test, certain genetic tests). Further, DTC tests can reduce cost and expand access to care in countries with limited resources and can support healthcare systems in extraordinary circumstances such as a pandemic. Valid concerns about DTC testing need to be described, addressed and resolved with the help of authorities and regulators in collaboration with HCP and should not detract from the advantages DTC tests can provide. HCP should play a more prominent role in educating the public through mass media and social media on the proper use of DTC tests and help to pinpoint problem areas.

Drug Interference in Self-Monitoring of Blood Glucose and the Impact on Patient Safety: We Can Only Guard Against What We Are Looking for.

Self-monitoring of blood glucose is a key aspect of diabetes management. Depending on the technology used, however, various substances can jeopardize the reliability of the measurements and precipitate complications with potentially life-threatening consequences when blood glucose was deemed well-controlled. As such, it is important for all involved to be aware of those factors. Officially suggested procedures for testing and alternatives have each their own advantages and limitations, and interferences may be found beyond the substances to be tested provided by the various pertinent institutions. This article reviews these pros and cons and illustrates how interference testing beyond established standards contributes to patient safety. Once identified, interfering substances are included in product labeling and health care professionals and users need to be trained to be aware of these risks.

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

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.

Patch Pumps: What are the advantages for people with diabetes?

AIM: Patch pumps, i.e. insulin pumps without tubing, are an attractive alternative to conventional insulin pumps for people with type 1 diabetes and type 2 diabetes on insulin therapy. In this review, potential patient-relevant advantages and disadvantages of patch pumps are summarized and respective studies on patient-reported outcomes (PROs) are assessed. METHODS: Relevant studies were identified through a systematic PubMed search. Reference lists in respective articles and Google Scholar were also checked for additional references. Articles in English published before June 30, 2021, were included; no other criteria on publication dates were set. RESULTS: A total of 12 studies were included. The results of this analysis provide evidence that patch pumps improve quality of life, reduce diabetes-related distress, increase patient satisfaction, and are preferred by patients compared to conventional insulin pumps and multiple daily injection therapy (MDI). However, several methodological limitations of the studies identified constrain the significance of this analysis. CONCLUSIONS: Despite the limited number of studies evaluating the benefits of patch pumps on PROs, there is increasing evidence that people with diabetes prefer patch pumps. Although there are numerous PROs for patch pumps, it is surprising that this aspect has been relatively understudied. More systematic evaluation studies of the benefits of patch pumps on PROs are needed.

Self-Monitoring of Blood Glucose as an Integral Part in the Management of People with Type 2 Diabetes Mellitus.

For decades, self-monitoring of blood glucose (SMBG) has been considered a cornerstone of adequate diabetes management. Structured SMBG can follow different monitoring patterns, and it results in improved glycemic control, reduced hypoglycemia, and a better quality of life of people with diabetes. The technology, usability, and accuracy of SMBG systems have advanced markedly since their introduction a few decades ago. Current SMBG systems are small and easy to use, require small (capillary) blood sample volumes, and provide measurement results within seconds. In addition, devices are increasingly equipped with features such as connectivity to other devices and/or digital diaries and diabetes management tools. Although measurement quality can come close to or equal that of the glucose monitoring systems used by healthcare professionals, several available SMBG systems still do not meet internationally accepted accuracy standards, such as the International Organization for Standardization 15197 standard. Reports from China, India, and Brazil based on local experience suggest that in addition of the accuracy issues of SMBG systems, other obstacles also need to be overcome to optimize SMBG usage. Nonetheless, adequate usage of SMBG data is of high relevance for the management of people with type 2 diabetes mellitus.

Real-world data from Europe and Africa suggest that accuracy of systems for self-monitoring of blood glucose is frequently impaired by low hematocrit.

AIMS: Certain systems for self-monitoring of blood glucose (SMBG) demonstrate inaccuracy at low and high hematocrit (HCT). Manufacturers define HCT ranges for accurate performance. Our objective was to assess the frequency of HCT values that can lead to clinically relevant errors. METHODS: In this cross-sectional study, we collected real-world data representing over 360,000 outpatients from the Netherlands (NL), the Czech Republic (CZ), and South Africa (ZA). These were subsequently stratified by sex and age and compared to commonly specified HCT range limits, reference intervals, and data from 1780 healthy Czech subjects. RESULTS: HCT values were comparably distributed in NL and CZ. Outpatients had a higher dispersion of values than healthy subjects. Low HCT values in Europe were common in age groups with a high prevalence of diabetes. All ZA age groups showed a higher prevalence of low HCT than in Europe. CONCLUSIONS: Real-world data indicate that SMBG systems specified to perform only within the frequently used 30-55% HCT range would leave 3% of outpatients in Europe and 18% in South Africa at risk of false SMBG results, with individual age strata being substantially higher. This could affect their diabetes management. Adequate SMBG systems should thus be chosen.

Standardization process of continuous glucose monitoring: Traceability and performance.

People with diabetes are required to regularly check their glucose to make therapy decisions. So far, systems for self-monitoring of blood glucose were used, but nowadays minimally invasive continuous glucose monitoring (CGM) systems are increasingly more often employed, sometimes to partially replace self-monitoring of blood glucose. Most CGM systems on the market measure glucose concentrations continuously in the interstitial fluid of the subcutaneous fatty tissue. However, CGM has a principle limitation. Collecting interstitial fluid frequently in sufficiently large volumes over short time periods is not easy. As a consequence, no internationally accepted reference measurement procedure is currently available for glucose in interstitial fluid which is a prerequisite to achieve an optimal metrological traceability. Recent studies indicate that the analytical performance of minimally invasive CGM systems differs not only between manufacturers but also between individual sensors of the same system, sometimes even in the same subject. Because manufacturers don't provide detailed information about the traceability chain and the measurement uncertainty of their systems glucose values obtained with CGM can currently not be adequately traced to higher-order standards or methods. Therefore, the Working Group on Continuous Glucose Monitoring aims at establishing a traceability chain for minimally invasive CGM systems, as well as procedures and metrics for the assessment of their analytical performance.

Intermittent Use of Continuous Glucose Monitoring: Expanding the Clinical Value of CGM.

In addition to the continuous use, the intermittent use of continuous glucose monitoring (CGM) is an application of CGM, expanding the typical medical use cases. There are a variety of reasons and occasions that speak in favor of using CGM only for a limited time. To date, these circumstances have not been sufficiently discussed. In this article, we define discontinuous or intermittent CGM use, provide reasons for using it, and expand on the benefits and possibilities of using CGM on a temporary basis. We aim to draw attention to this important topic in the discussion of CGM use and give examples for a different method of CGM use. As well, we would like to foster the allocation of CGM to the right patient groups and indications, especially in cases of limited resources. From a global point of view, intermittent CGM use is more likely to occur than continuous use, primarily for economic reasons.

The YSI 2300 Analyzer Replacement Meeting Report.

This is a summary report of the most important aspects discussed during the YSI 2300 Analyzer Replacement Meeting. The aim is to provide the interested reader with an overview of the complex topic and propose solutions for the current issue. This solution should not only be adequate for the United States or Europe markets but also for all other countries. The meeting addendum presents three outcomes of the meeting.

Benefits and Limitations of MARD as a Performance Parameter for Continuous Glucose Monitoring in the Interstitial Space.

High-quality performance of medical devices for glucose monitoring is important for a safe and efficient usage of this diagnostic option by patients with diabetes. The mean absolute relative difference (MARD) parameter is used most often to characterize the measurement performance of systems for continuous glucose monitoring (CGM). Calculation of this parameter is relatively easy and comparison of the MARD numbers between different CGM systems appears to be straightforward on the first glance. However, a closer look reveals that a number of complex aspects make interpretation of the MARD numbers provided by the manufacturer for their CGM systems difficult. In this review, these aspects are discussed and considerations are made for a systematic and appropriate evaluation of the MARD in clinical trials. The MARD should not be used as the sole parameter to characterize CGM systems, especially when it comes to nonadjunctive usage of such systems.

12th Roche Diabetes Care Network Meeting: April 11-13, 2019, Copenhagen, Denmark.

A panel of international experts in the field of diabetes and diabetes technology met in Copenhagen, Denmark, for the 12th Roche Diabetes Care Network Meeting. The goal of these meetings is to share current knowledge, facilitate new collaborations, and encourage further research projects that can improve the lives of people with diabetes. Specific areas of interest included use of telemedicine and mobile health technologies, behavior change, patient-centered care, and multifactorial approaches to addressing all metabolic abnormalities associated with diabetes. The 2019 meeting covered a comprehensive scientific program and four keynote lectures.

Proof of Concept Study to Assess the Influence of Oxygen Partial Pressure in Capillary Blood on SMBG Measurements.

BACKGROUND: Measurement results provided by blood glucose monitoring systems (BGMS) can be affected by various influencing factors. For some BGMS using glucose oxidase (GOx)-based test strips, one of these factors is the oxygen partial pressure (pO2) of the applied blood sample. Because assessing the potential influence of pO2 when measuring capillary blood samples is not straight-forward, we performed a proof of concept study. METHOD: Influence of pO2 was investigated for two GOx-based BGMS (BGMS A and B). Measurement results of the GOx-based BGMS were compared with measurement results from a pO2-independent BGMS (BGMS C). A total of 119 samples from 60 subjects were measured, twice with BGMS C, then 6 times each with BGMS A and BGMS B or vice versa, and again twice with BGMS C. Immediately afterward, pO2 was determined. Linear regression analysis based on relative differences between results from BGMS A or BGMS B and results from BGMS C was performed to estimate the degree of pO2 influence. RESULTS: The relative bias between the lowest and highest pO2 values differed by 14.3% for BGMS A, indicating a pO2 influence that might be clinically relevant, and by 9.7% for BGMS B, indicating that pO2 influence may be too small to be reliably detected because of the BGMS' imprecision. CONCLUSIONS: This proof of concept study showed that with the procedures used, a potentially clinically relevant influence of pO2 in capillary blood samples on GOx-based BGMS could be detected. Further larger-scale studies are needed to verify this influence.

Predicting the early risk of chronic kidney disease in patients with diabetes using real-world data.

Diagnostic procedures, therapeutic recommendations, and medical risk stratifications are based on dedicated, strictly controlled clinical trials. However, a plethora of real-world medical data exists, whereupon the increase in data volume comes at the expense of completeness, uniformity, and control. Here, a case-by-case comparison shows that the predictive power of our real world data-based model for diabetes-related chronic kidney disease outperforms published algorithms, which were derived from clinical study data.

11th Annual Symposium on Self-Monitoring of Blood Glucose: April 12-14, 2018, Oslo, Norway.

A panel of international experts in the field of diabetes and diabetes technology met in Oslo, Norway, for the 11th Annual Symposium on Self-Monitoring of Blood Glucose. The goal of these meetings is to share current knowledge, facilitate new collaborations, and encourage further research projects that can improve the lives of people with diabetes. The 2018 meeting comprised a comprehensive scientific program and four keynote lectures.

10th Annual Symposium on Self-Monitoring of Blood Glucose, April 27-29, 2017, Warsaw, Poland.

International experts in the field of diabetes and diabetes technology met in Warsaw, Poland, for the 10th Annual Symposium on Self-Monitoring of Blood Glucose. The goal of these meetings is to establish a global network of experts to facilitate new collaborations and research projects that can improve the lives of people with diabetes. The 2017 meeting comprised a comprehensive scientific program, parallel interactive workshops, and four keynote lectures.

Analysis of the Accuracy and Performance of a Continuous Glucose Monitoring Sensor Prototype: An In-Silico Study Using the UVA/PADOVA Type 1 Diabetes Simulator.

BACKGROUND: Computer simulation has been shown over the past decade to be a powerful tool to study the impact of medical devices characteristics on clinical outcomes. Specifically, in type 1 diabetes (T1D), computer simulation platforms have all but replaced preclinical studies and are commonly used to study the impact of measurement errors on glycemia. METHOD: We use complex mathematical models to represent the characteristics of 3 continuous glucose monitoring systems using previously acquired data. Leveraging these models within the framework of the UVa/Padova T1D simulator, we study the impact of CGM errors in 6 simulation scenarios designed to generate a wide variety of glycemic conditions. Assessment of the simulated accuracy of each different CGM systems is performed using mean absolute relative deviation (MARD) and precision absolute relative deviation (PARD). We also quantify the capacity of each system to detect hypoglycemic events. RESULTS: The simulated Roche CGM sensor prototype (RCGM) outperformed the 2 alternate systems (CGM-1 & CGM-2) in accuracy (MARD = 8% vs 11.4% vs 18%) and precision (PARD = 6.4% vs 9.4% vs 14.1%). These results held for all studied glucose and rate of change ranges. Moreover, it detected more than 90% of hypoglycemia, with a mean time lag less than 4 minutes (CGM-1: 86%/15 min, CGM-2: 57%/24 min). CONCLUSION: The RCGM system model led to strong performances in these simulation studies, with higher accuracy and precision than alternate systems. Its characteristics placed it firmly as a strong candidate for CGM based therapy, and should be confirmed in large clinical studies.