COMMENTARY

Timely Hospital Glucose Measurement: HereToday, Gone Tomorrow?

David C. Klonoff, MD, FACP, FRCP (Edin), Fellow AIMBE; Robert A. Vigersky, MD;James H. Nichols, PhD; and Mark J. Rice, MD

From the Diabetes ResearchInstitute, Mills-PeninsulaHealth Services, San Mateo,CA (D.C.K.); Walter ReedNational Military MedicalCenter, Bethesda, MD(R.A.V.); Vanderbilt UniversitySchool of Medicine, Nashville,TN (J.H.N.); and University ofFlorida College of Medicine,Gainesville (M.J.R.).

B lood glucose meters (BGMs), first intro-duced in the US market in the 1970s,have revolutionized the care of patients

with diabetes. Improved glucose control, ena-bled by frequent measurement, has greatlyreduced long-term cardiovascular, renal, andophthalmic complications. Although thesedevices were originally designed for andapproved by the Food and Drug Administra-tion (FDA) for “OTC self-monitoring by lay-persons,”1 they have ubiquitously migratedinto the hospital environment in which theyhave become the mainstay for inpatientglucose testing. Approximately 500 millionof these tests are performed per year in UShospitals.

The increase in hospital point-of-care(POC) testing is the result of 4 major phenom-ena: (1) the move toward tight glycemic control(TGC); (2) the emergence of rapid, easy-to-use,and inexpensive BGMs that require a smallfinger-stickederived sample of whole blood;(3) the progressive improvement in the accu-racy of these devices; and (4) the increasedprevalence of patients with diabetes.

Point-of-care BGMs for hospitalized criti-cally ill patients are now at risk because ofnew enforcement policies proposed by theCenters for Medicare & Medicaid Services(CMS) prohibiting the off-label use of thesedevices. As the CMS attempts to protect pa-tients from this technology, which has notbeen appropriately tested to FDA standards,such enforcement will eliminate this importanttool and no adequate replacement technologycurrently exists. The result will be a CMS-mandated significant decline in the quality ofcare for diabetes patients in the United States.Here, we describe why POC BGMs are used incritically ill patients, how they have been regu-lated, how they are about to be regulated, andwhat can be done to safely transition frominadequate documentation to proper docu-mentation of the performance of this tool.

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Standards of Care for TGCIn 2001, Van den Berghe et al2 reported thatTGC targeting a blood glucose level of 80 to110 mg/dL (to convert to mmol/L, multiplyby 0.0259) using intensive insulin therapysignificantly decreased mortality and mor-bidity in critically ill surgical patients. Thisreport led to increased adoption of POCBGMs in hospitals. Tight glycemic controlwas applied in various settings, including theintensive care unit (ICU), operating rooms,and emergency departments as well as generalcare wards. The enthusiasm for TGC wastempered by the NICE-SUGAR study3 andsubsequent studies of TGC that mostly failedto prove that TGC is beneficial.4 Professionalorganizations and governmental bodies havepromulgated guidelines that, in general, re-commend higher glucose targets than thoseof Van de Berghe et al to avoid hypoglycemiaand also to mitigate the deleterious effects ofhyperglycemia.5-8 Achieving target rangegoals in critical care settings requires hourlyor even more frequent glucose monitoring.The method for testing glucose levels is notedin some of the guidelines. The National HealthService of the United Kingdom recommendscapillary finger-stick blood sampling in theperioperative period,9 the American HeartAssociation specifies that samples can befinger-stickederived capillary blood,7 andthe Canadian Diabetes Association states thatbedside monitoring can be done if the hospitalhas an adequate proficiency testing program.6

However, the American Diabetes Associationand the Society for Critical Care Medicine,while not proscribing POC BGMs, note thatusing them may be problematic because of(1) clinical conditions such as impaired perfu-sion due to hypotension and peripheraledema that interfere with accurate samplingof capillary blood and (2) technical limitationsof the meters that affect accuracy, such ashypoxia in glucose oxidaseebased meters,

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anemia, and certain medications such asacetaminophen.5,8

Regulatory BackgroundThe CMS regulates all laboratory testing(except research) on humans in the UnitedStates through regulations established by theClinical and Laboratory Improvement Amend-ments (CLIA) of 1988.10 The CLIA sets mini-mum quality regulations for laboratory testingregardless of whether a test is conducted in aformal, central laboratory or at the patient’sbedside for POC.10 The BGMs currently inuse for most hospitalized patients are catego-rized as “waived” under the CLIA. In theabsence of accrediting agency or institutionalrequirements, facilities using CLIA-waived de-vices have minimal quality requirements. Theyneed only pay a biennial certificate fee, followthe manufacturer’s instructions for use, andagree to unannounced inspections.

The FDA issued a draft guidance for POCBGMs on January 7, 2014.1 This document pre-sents future requirements for the clearance ofPOC BGMs for professional use, such as in hos-pitals. The FDA proposes to raise the classifica-tion of future cleared hospital-use glucosemeters to the CLIA “moderate complexity.”Hos-pitals performing CLIA moderate complexitytests must currently (1) document operatortraining and annual competency, (2) verifymethod performance, (3) confirm the calibra-tion and method correlation to central labora-tory glucose every 6 months, (4) perform dailyquality control, and (5) subscribe to a profi-ciency testing program. In addition, operatorsmust have a high school diploma or higher edu-cation level documented in their employee re-cords. Hospitals performing CLIA moderatecomplexity glucose testing must be inspectedevery 2 years during which the inspector mustaudit the educational documentation of a groupof operators. Practically, changing the CLIAcomplexity of glucose meters will increase theregulatory burden for hospitals because most fa-cilities have hundreds or thousands of operatorsperforming testing.

No POC BGM has ever been cleared by theFDA for critically ill patients.11 Therefore, thesedevices are being used “off-label” in the ICU,operating room, recovery room, and emergencydepartment. The FDA has also recentlyinstructed manufacturers to change their

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labeling of existing hospital glucose meters toinclude a statement that critically ill patientsshould not be tested with a BGM because resultsmay be inaccurate. The off-label use of glucosemeters is subject to CLIA “high complexity” reg-ulations. The CLIA high complexity testing haseven higher documentation standards thandoes CLIA moderate complexity testing andessentially prevents anyone without an associatedegree in laboratory science or medical technol-ogy from performing testing. Many hospital staffmembers who currently perform POC bloodglucose monitoring will be prohibited fromthis activity if the FDA labeling policies areenforced. The off-label use of a glucose meterwill create 2 separate sets of requirements forhospitals to manage: one for “approved” useand the other for off-label use, which will chal-lenge hospitals with managing 2 sets of differentregulations.

The CMS recently became aware that POCBGMs are being used in hospitals off-label andis ready to enforce the prohibition of their off-label use, according to 2 recent letters from theNew York State Department of Health.12,13 Un-like drugs, cleared devices cannot be used off-label for a different clinical application. Theoff-label use of laboratory devices is forbiddenby the CLIA unless the laboratory establishesits own performance specifications for use inthat facility’s intended patient population toensure accurate results. Yet, if a CLIA auditidentifies off-label use of POC BGMs withoutappropriate evidence of compliance for CLIAhigh complexity testing, the hospital will becited. A cited hospital is at risk of losing itsCLIA certificate, that is, its license to performtesting, as well as having to pay fines for notcomplying with the CLIA high complexity re-quirements. After any citations are issued, it ispossible that many US hospitals will eliminatePOC BGM testing from critically ill settings.One of the unintended consequences may bethe discontinuation of intensive insulintherapy, which requires frequent glucose mea-surements. Unfortunately, this announcedenforcement would then adversely affect themanagement of diabetes in critically ill set-tings. A survey of hospitals about how theyare planning to respond to this situation couldprovide predictive information, but it wouldbe difficult to identify the decision maker ineach hospital and get him/her to enumerate

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how he/she would or would not comply withthe CMS.

Currently, there is a standoff between hos-pital laboratories, industry, and the CMS. TheFDA has invited POC BGM manufacturers tosubmit additional data demonstrating the accu-racy of hospital-cleared POC BGMs for criticallyill patients for these products to get a CLIAwaiver and be used by any hospital staff person,but no company has publicly announced that itis ready to submit such data. Most hospitalshave already conducted correlation data usingtypical patient samples from the hospital wards,but it is not clear which specific types of criti-cally ill patients and how many of them mustbe tested.

POC BGM Devices and Their AlternativesThe alternatives to POC BGM testing are allslower, more difficult to work with, moreexpensive, and/or riskier for the patient thanPOC BGMs.14,15 Without POC BGMs, clini-cians will be left measuring glucose using a cen-tral laboratory device (CLD), blood gas analyzer(BGA), or 1 of 3 nonstrip POC instruments(HemoCue [HemoCue America], iStat [AbbottPoint of Care], or epoc [Epocal]; Table).

CLDs and BGAs. Central laboratory devicesrequire a whole blood specimen (usually >1mL) to be spun for analysis. They are subjectto many types of preanalytical errors, includingincorrect sampling.17 The turnaround time(TAT) can be well over 1 hour.18 The intenselabor required for CLD testing includes blooddrawing, specimen transport, laboratory pro-cessing, sample analysis, and result reporting.

TABLE. Characteristics of BGM Devices Currently Used i

Parameter POC BGM

Analysis time 5 sApproximate TATb Up to 2 minSample type Cap, Ven, Art, Alt siteApproximate sample volume (mL) 0.3-1.2Total cost ($)16 0.75c

CLIA complexity Not clearedAvailable at POC Yes

aAlt ¼ alternate; Art ¼ arterial; BGM ¼ blood glucose monitor; CAmendments; POC ¼ point-of-care; Ven ¼ venous.bTAT is the total time required to complete the test and includes testdevice analysis time only.cApproximate published cost for disposable only. All other costs not

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Under ideal circumstances, the fastest timepossible is usually approximately 25 mi-nutes.16 Blood gas analyzers are much likeCLDs, with a similar accuracy profile. The TATis dependent on location. Blood gas analyzersare usually placed in selected strategic loca-tions (eg, the operating room or the ICU),require frequent maintenance, and are expen-sive when measuring only glucose. Centrallaboratory devices and BGAs are both CLIAmoderate complexity tests, demanding highlytrained personnel, with laboratory technolo-gists running the CLDs and oftentimes regis-tered nurses running the BGAs.

POC Nonstrip Devices (HemoCue, iStat, andepoc). Three POC devices, using inserted car-tridges, are available in the United States: Hemo-Cue, i-Stat, and epoc. There are few accuracystudies for these devices19-23 and little data inthe critical hypoglycemic range (<70 mg/dL)reported for any of them. The TAT is limited tospecimen drawing and device analysis, which issubstantial for HemoCue and i-Stat and less forthe epoc system compared with that for modernPOC BGM devices. The analysis time differenceof a few minutes can be a drawback for a busynurse. The cost of these 3 POC systems is muchhigher than the cost of POC BGM testing. In ourexperience, from a human factors standpoint,these 3 devices are more difficult to use thanPOC BGM devices, which is not surprisingconsidering the many years of design glucosemonitoring devices have undergone for easy useby lay people. Because the data suggest that theyare no more accurate than the newer strip-basedmeters, there would have to be substantial

n Critically Ill Settingsa

CLD BGA HemoCue i-Stat epoc

4 min 60 s 40-240 s 130-200 s 30 sCan be >1 h 3-10 min 3-6 min 3-5 min Up to 3 minCap, Ven, Art Cap, Ven, Art, heel-stick Cap, Ven, Art Ven only Cap, Ven, Art

200 100 5 65 922.01 0.88 1.50c 5.00c 16.00c

Moderate Moderate Waived Waived ModerateNo No Yes Yes Yes

ap ¼ capillary; CLD ¼ central laboratory device; CLIA ¼ Clinical and Laboratory Improvement

ordering, blood draw, transport to the laboratory, analysis time, and result returning. Analysis time is

included.

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improvements in human factors and costs tojustify the limitation of testing to these POCdevices in critically ill patients.

RecommendationsA 5-year moratorium by the CMS is needed todelay (1) enforcement of the FDA requirementfor manufacturers to change their labeling indi-cating “test not validated in critically ill popula-tions” and (2) elevation of glucose meters toCLIA moderate complexity devices. This mora-torium will allow the diabetes community toprepare for converting to new testing methodsif adequate performance data cannot becollected. For themoratorium period to be effec-tive, all the stakeholders in POC blood glucosemonitoring must find ways to make currenttechnology work, or else they must find replace-ments for current technology. Clinicians can usethis moratorium period (1) to identify the typesof acutely ill patients on whom to use or not usePOC BGMs, (2) to develop a consensus defini-tion of “critically ill” because it is these patientswho are going to be affected by the CMS’announced impending enforcement of the off-label, high complexity status of BGMs, (3) toconduct modeling and empiric studies aboutwhich outcomes are associated with usingPOC BGMs of various levels of accuracycompared with using alternative methods, and(4) to develop new workflow processes if POCBGMs may no longer be available in these pop-ulations. The FDA can use this period to workwith industry to encourage the submission ofperformance data in cleared-hospital BGMsfrom selected types of critically ill patients sothat these products can be CLIA-waived for atleast some of these patients. Industry can usethis period to develop next-generation productsthat will be more accurate than the current onesand more likely to become CLIA-waived. Inno-vation will be needed in light of the 2014 draftguidance for POC BGMs presenting the strictestlevels of accuracy ever proposed by the FDA forany type of BGMs.

ConclusionThe POC BGMs were never cleared for criticallyill patients, but they have become the standardof care. The CMS regulators are now studyingwhether to cite hospitals for using this tool incritically ill patients unless their performance isvalidated extensively in this population, and

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such validation does not appear to be forth-coming in the near future. This tool might beremoved from critically ill patients with nogood alternatives. Because of the high cost,poorly studied accuracy, and long analysistime required for the current POC alternatives,this suddenly contemplated regulatory policytoward POC BGMs would have highly negativeunintended consequences. Immediate enforce-ment of such a policy at this time would setback hospital diabetes care by decades. A mora-torium would allow time for clinicians and in-dustry to adjust to the necessary stricterstandards that will govern POC BGMs and affectthe practice of medicine for these types of pa-tients in the future.

ACKNOWLEDGMENTSKatrina S. Thollaug and Rebecca CoreyAstrom provided editorial assistance.

Potential Competing Interests: Dr Klonoff is a consultantfor Google, Roche, and Sanofi. Dr Vigersky has aninvestigator-initiated grant from DexCom. Dr Nichols is aconsultant for Abbott, Instrumentation Laboratories, Roche,and Siemens. Dr Rice has served on several Roche Diabetesadvisory board meetings.

Correspondence: Address to David C. Klonoff, MD, FACP,FRCP (Edin), Fellow AIMBE, Mills-Peninsula Health Services,100 South San Mateo Dr, Rm 5147, San Mateo, CA 94401(dklonoff@diabetestechnology.org).

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