Avoiding errors in measurement
BY CRAIG FOREBACK, PHD
Point-of-care (POC) glucose devices have been used widely in critical and acute care facilities since the late 1980s. Few choices were available for customers back then, and central labs had little interest in being part of the selection or evaluation process.
By the mid 1990s, with the addition of blood gasses and coagulation, there were still fewer than 10 tests on a typical point-of-care testing (POCT) menu. However, the scope of bedside glucose testing expanded in test volume and location.
A survey conducted in 2004 found nearly 100% of the 493 acute care hospitals interviewed were performing glucose at the point of care using portable meters.
A recent publication from Massachusetts General Hospital1 describes POCT in a large urban academic environment. POCT is performed in nearly all inpatient units and in a variety of outpatient settings. Approximately 600,000 POC tests per year are performed by physicians and nurses in the institution. This volume of testing represents 13.1% of the volume of billable tests performed by the central core laboratory (4.73 million tests in chemistry and hematology). A total of 50.9% of the POC test volume is bedside glucose testing. The choice of testing has also expanded.
The sidebar in no way contains a complete list of all glucose meters available to users, especially when one considers the proliferation of consumer meters. Readers need to be aware that consumer meters intended only for self-monitoring find their way into critical and acute care environments. A study by Teodorcsyk, recently published in the Journal of Diabetes Science and Technology,2 evaluated a number of devices used for glucose monitoring.
There is not an abundance of distinguishing factors among the various devices noted in the sidebar. Most are compact, easy to use, have adequate quality control (QC), and can easily transfer patient and QC data to a laboratory information system (LIS) or hospital information system (HIS).
FEATURES TO CONSIDER
Connectivity is an important issue. Nova Biomedical offers multiple wireless options for its StatStrip system, including a wireless tote option. The wireless tote offers real-time, two-way communication as long as the meter is connected in the tote. Abbott’s FreeStyle Precision Pro system allows for real-time, dual-band wireless communication between the handheld meter at the patient bedside and an HIS, giving clinical staff immediate access to patient test results throughout their facility. The dual-band wireless technology enables the flexibility of wireless access within a hospital’s Wi-Fi-enabled network when properly configured. The system is designed so that clinical operators need not interrupt their workflow to conduct routine docking or attach a data cable to download patient results. Roche offers meter-level wireless. Meter-based wireless (wireless radio located within the meter) has the advantage of having the wireless communications contained in the meter so there is no docking or returning the meter to a tote for the communications to work. The results are stored in real time, which facilitates the Healthcare Common Procedure Coding System (HCP) making decisions immediately.
Among the meters on the market:
Abbott Diabetes Care: Precision Xceed Pro Blood Glucose and Beta-Ketone Monitoring
Hemocue: [removed]Glucose 201 and 201 DM[/removed]
Medtronic Diabetes: iPro2 Professional CGM
Nova Biomedical: StatStrip Hospital Glucose Monitoring System
Some vendors report there is no interference from hematocrit, but even those that have restrictions based on hematocrit have several acceptable ranges.
The ECRI Institute, a nonprofit organization that researches optimal approaches to improving healthcare safety and quality, in January, issued a Health Devices Alert document to its members, stressing the need for hospitals to properly evaluate blood glucose meter (BGM) accuracy. Below is an excerpt.
“Since BGMs are not labeled for use with critically ill patients, it is up to healthcare providers to evaluate the device’s performance for this patient population. This evaluation may include correlating BGM results with laboratory results for patients in critical care settings. Documentation of the study should be retained to demonstrate that the facility has performed its due diligence. Also, guidelines should be in place to limit the use of BGMs to avoid known problems and limitations defined in the product’s labeling.”
The majority of meters on the market today meet or exceed the International Organization for Standardization (ISO) 15197 2003 performance guidelines for glucose testing. However, that standard has been re-evaluated in light of the fact that between 2004 and 2008, nearly 13,000 serious adverse events with glucose meters that met the ISO 15197 expectations were reported to the FDA Manufacturer and User Facility Device Experience surveillance database.
In a paper published by Lyon and Lyon,3 the suggestion is made that the 2003 guidelines for assessing glucose meter performance are too wide. Additionally, a single standard is applied to all categories of patients where glucose monitors are used to assess a patient’s glucose status. The performance goals used to evaluate patients need to be sufficiently narrow to enable consistent
The ISO 15197 standard, the international standard that specifies accuracy requirements of blood glucose monitoring, was created in 2003. That standard may be adequate for ambulatory patients, but it is not appropriate to use those same standards in critically ill patients. Monitoring of blood glucose with an accurate device is an integral component of effective diabetes management or general glucose homeostasis within a hospital population.
The technology employed in blood glucose monitoring systems has made great advances in the last 5 years, and the standard is now considered not only out-of-date for today’s level of technology, but also not stringent enough for current hospital demands.
CRITERIA FOR TESTING PATIENTS WITH SPECIAL NEEDS
A paper by Diaw4 points out the challenges of glucose measurements in the neonatal intensive care setting. Such whole blood measurements are challenged by a wide variation in hematocrit and a high frequency of glucose concentrations at the lower end of the test range. Although validated for adults, new POCT devices need to be specifically evaluated on newborn infants before adopting their routine use in neonatology.
Tendl et al5 have also pointed out the special needs of the neonatal population. They emphasize the importance of reducing the risk of hypoglycemia in the neonatal intensive care unit (NICU). Newborns are usually able to establish their own glucose regulation. However, infants with very low birth weight, or infants who are smaller or larger for their gestational age, and infants of insulin-dependent diabetic mothers or discordant twins, may be at risk of acquiring neonatal hypoglycemia. It is one of the most frequently reported complications in neonates.
A value of 45 mg/dL (2.5 mmol/L) is commonly used as a decision point for therapeutic intervention. POCT for glucose measurements is ideal because of the small sample required for the measurement and the immediate availability of results. The ISO requirement states that 95% of individual glucose results shall fall within +/- 15 mg/dL for values below 75 mg/dL. Thus, a value of 45 could be reported anywhere between 30 and 60, and be considered acceptable using the ISO standard.
Further complicating the picture is that the meters, once approved, may not be subjected to follow-up testing. This does not imply that modern meters have such poor imprecision, but it does point out that the standards need to be changed. The Tendl paper referenced here evaluated the new Nova Biomedical StatStrip, and found it correlated very well with the routine reference method used in the central laboratory across a wide concentration range (13 to 389 mg/dL), and it was not affected by the level of hematocrit.
Other recent publications have shown that both hospital and consumer meters can meet acceptable performance standards even when presented with challenging specimens. Examples include the Hemocue DMRT Hemocue,6 the Contour TS (Bayer),7 and the One Touch Verio (Life Scan).8
Other clinical settings where potential sources for error can occur are in critical and acute care medical facilities, especially in postsurgical patients where tight glycemic control (TGC) is implemented. The performance of the devices does not always allow such applications.6
Van Herp and Mesotten9 have suggested that devices for measuring plasma glucose should be tested under realistic conditions, and be tested in a population of the intended use (eg, gestational diabetes, TGC in the intensive care unit, etc). The authors suggest method evaluations consider
computing total error using the Westgard equation (% total error = % average bias + 1.96* coefficient of variation). Another known technique to approach total error was developed by Bland and Altman.10 In this graphical method, the differences of the paired measurements are plotted against the average of the two values. Next, the limits of agreement (ie, mean difference ± 1.96* standard deviation) show the 95%
STUDIES EVALUATING GLUCOSE MONITORING SYSTEMS
Recent publications have pointed out that the majority of studies on clinical and analytical validation of POC glucose devices have not addressed several important issues.11 The majority of POC glucose devices have not been fully evaluated according to Clinical and Laboratory Standards Institute (CLSI) and STARD (Standards for Reporting of Diagnostic Accuracy, University of Amsterdam; Netherlands) criteria.12 Wide variations exist among the different platforms, even within the same manufacturer.13 Many of the studies do not take into account the influence of exogenous and endogenous preanalytical factors.14 (See Table 1). The overall implementation of POC glucose testing, and the assigned responsibility of the devices within an institution, are often poorly defined.
[ table1 ]
Substances or Conditions That May Contribute to Total Analytical Error in Consumer and Hospital Glucose Meters
Numerous studies have been published reporting the performance of blood glucose monitoring systems. The results of these studies are often conflicting. Correct evaluation is, however, complex, and the apparent contradiction of results creates confusion. One recent article15 provides an overview of frequently made errors in the evaluation of devices and develops an easy-to-use checklist to verify the quality of such studies. This checklist was used with 20 representative studies selected from the literature between 2007 and 2012. The process revealed that limitations on the designs and methods of studies assessing the performance of blood glucose systems are common.
The use of the accuracy checklist showed that 40% of the studies showed clear nonconcordance with ISO 15197. The use of the interference checklist showed that only half of publications were in good agreement with the quality checks. The author concluded that many evaluations are performed poorly, and often present questionable conclusions due to the fact that few publications adhere to international guidelines. Others have also assessed the quality of glucose monitor studies and came to similar conclusions.
In the article by Mahoney and Ellison,13 52 reports were reviewed, none of which conformed to all 38 STARD and CLSI recommendations. Future studies evaluating glucose monitoring systems should be carefully designed and should follow published recommendations to assess the quality of glucose measuring devices.
CHANGING THE LANDSCAPE
New guidelines for the acceptable performance of POC glucose testing are in the final stages of review by several organizations, including the College of American Pathologists (CAP), CLSI, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), the ISO, and the FDA.
In fact, two have recently been published this year.16 Ron Newby, Nova Biomedical, Waltham, Mass, has reviewed CLSI POCT 12-A3 and points out that the standards have been tightened and it better defines how a product should be evaluated and implemented. Newby goes on to recommend that a potential user should independently evaluate any blood glucose monitor using the CLSI standard, including interference studies. The customer should also include patient samples from the patient populations on whom testing is going to be performed.
It will also be interesting to see how the FDA responds. The agency has used the same minimum accuracy standards that are included in the 2003 ISO 15197 guidelines before it will allow a device to be marketed. Is it likely the FDA will adopt the tighter guidelines in its approval process?
Most of the manufacturers already meet the narrower precision guidelines. The new guidelines, along with improved evaluation protocols prior to implementation of new meters, will likely improve the quality of bedside glucose testing and patient safety in hospitals and clinics throughout the United States. The report cited earlier in reference2 evaluated the meters included in the study according to current and proposed ISO 15197 standards. This article would be a good starting point for anyone considering the adoption of a glucose monitoring device.
1. Lee-Lewandrowski E, Gregory K, Lewandrowski K. Point of care testing in a large urban academic medical center: Evolving test menu and clinical applications. Clin Chim Acta. 2010;411(21-22):1799-1805.
2. Teodorczyk M, Nandagopalan S, Maguire P, Stegmann J. System accuracy of blood glucose monitoring devices according to the current and proposed ISO 15197 standards. J Diabetes Sci Technol. 2013;7(3):795-797.
3. Lyon ME, Lyon AW. Analysis of the performance of the CONTOUR® TS blood glucose monitoring system: When regulatory performance criteria are met, should we have confidence to use a medical device with all patients? J Diabetes Sci Technol. 2011;5(1):206-208.
4. Stadelmann Diaw C, Piol N, Urfer J, Werner D, Roth-Kleiner M. Prospective evaluation of three point of care devices for glycemia measurement in a neonatal intensive care unit. Clin Chim Acta. 2013;425C:104-108. [Epub ahead of print]
5. Tendl KA, Christoph J, Bohn A, Herkner KR, Pollak A, Prusa AR. Two site evaluation of the performance of a new generation point-of-care glucose meter for use in a neonatal intensive care unit. Clin Chem Lab Med. 2013;51(9):1747-1754.
6. Kos S, van Meerkerk A, van der Linden J, Stiphout T, Wulkan R. Validation of a new generation POCT glucose device with emphasis on aspects important for glycemic control in the hospital care. Clin Chem Lab Med. 2012;50(9):1573-1580.
7. Frank J, Wallace JF, Pardo S, Parkes JL. Performance of the CONTOUR® TS Blood Glucose Monitoring System. J Diabetes Sci Technol. 2011;5(1):198-205.
8. Teodorczyk M, Cardosi M, Setford S. Hematocrit compensation in electrochemical blood glucose monitoring systems. J Diabetes Sci Technol. 2012;6(3):648-655.
9. Van Herpe T, Mesotten D. Blood glucose measurements in critically ill patients. J Diabetes Sci Technol. 2012;6(1):22-28.
10. Bland JM, Altman DG. Statistical methods of assessing agreement between two methods of clinical measurement. Lancet. 1986;1(8476):307-10.
11. Scott MG, Bruns DE, Boyd JC, Sacks DB. Tight glucose control in the intensive care unit: are glucose meters up to the task? Clin Chem. 2009;55(1):18-20.
12. Sacks DB. Tight glucose control in critically ill patients: should glucose meters be used? Clin Chem. 2009;55(8):1580-1583.
13. Mahoney J, Ellison J. Assessing the quality of glucose monitor studies: a critical evaluation of published reports. Clin Chem. 2007;53(6):1122-1128.
14. Sacks DB, Arnold M, Bakris GL, et al. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem. 2011;57(6):e1-e47.
15. Thorpe GH. Assessing the quality of publications evaluating the accuracy of blood glucose monitoring systems. Diabetes Technol Ther. 2013;15(3):253-259.
16. Clinical and Laboratory Standards Institute. Point of care blood glucose testing in acute and chronic care facilities; approved guideline—Third Edition. Wayne, PAP: Clinical and Laboratory Standards Insistute. 2013. CLSI document POCT 12-A3.
-Lyon ME, DuBois JA, Fick GH, Lyon AW. Estimates of total analytical error in consumer and hospital glucose meters contributed by Hematocrit, Maltose, and Ascorbate. J Diabetes Sci Technol. 2010;4(6):1479-1494.
-Hellman R. Glucose meter inaccuracy and the impact on the care of patients. Diabetes Metab Res Rev. 2012;28(3):207-209.
-Fink KS, Christensen DB, Ellsworth A. Effect of high altitude on blood glucose meter performance. Diabetes Technol Ther. 2002;4(5):627-635.
Craig Foreback, PhD, is a contributing writer for CLP. For more information, contact Editor Judy O’Rourke, [email protected].