ASVCP Guidelines: Quality Assurance for Portable Blood ... · thick film technology, where the film is composed of several layers, each with a specific function. For example in photometric

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ASVCPGuidelines:

QualityAssuranceforPortableBloodGlucoseMeter(Glucometer)UseinVeterinaryMedicine

Version1.0(September2015)

KarenL.Gerber1,KathleenP.Freeman2

1 CollegeofPublicHealth,MedicalandVeterinarySciences,JamesCookUniversity,Townsville,Queensland,Australia.2IDEXX Laboratories, Ltd, Wetherby, West Yorkshire, UK

DevelopedbytheAmericanSocietyforVeterinaryClinicalPathology(ASVCP)Quality

AssuranceandLaboratoryStandards(QALS)Committee

Suggestedcitation:“Ifcitingthisdocument,thefollowingformatissuggested:AmericanSocietyforVeterinaryClinicalPathology(ASVCP).QualityAssuranceforPortableBloodGlucoseMeter(Glucometer)UseinVeterinaryMedicine.Version1.2015.Availableat:http://www.asvcp.org/pubs/index.cfmAccessed[Date].”

ASVCPQALSPBGMQAguidelines Version1.0 September2015

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TableofContentsTableofContents.....................................................................................................................2

1.0Abbreviations.....................................................................................................................3

2.0Introduction........................................................................................................................4

3.0Scope..................................................................................................................................4

4.0PBGMmethods&technologyoverview.............................................................................5

5.0Considerationsforglucosemetertesting...........................................................................6

5.1Minimizingpre-analyticalerror......................................................................................6

5.1.1Operatorproficiency...............................................................................................6

5.1.2Timingofsamplecollection.....................................................................................6

5.1.3Specimencollectionandhandling...........................................................................6

5.1.4Samplematrix..........................................................................................................8

5.2Minimizinganalyticalerror.............................................................................................8

5.2.1Standardizationofglucosereporting(plasmaequivalentvalue)............................9

5.2.2SourcesofPBGMinaccuracy.................................................................................11

5.1 Minimizingpost-analyticalerror..............................................................................14

5.3.1Unitsofmeasurement...........................................................................................14

5.3.2Records..................................................................................................................15

6.0SpecificqualitymanagementrecommendationsforPBGM............................................15

6.1Allowable(desirable)totalerror(TEa).........................................................................15

6.2ControlmaterialandcontrolruleselectionspecificforPBGM....................................16

6.3Externalqualityassessment(EQA)...............................................................................16

6.3.1Participationinanexternalqualityassuranceprogram........................................17

6.3.2ComparabilityTestingwithaReferenceLaboratory.............................................17

6.4Multipleglucosemetersatonesite.............................................................................18

6.4.1PBGMHarmonization............................................................................................19

6.5Non-StatisticalQualityAssuranceProcedures.............................................................20

6.6RecommendationsforPetOwners..............................................................................21

7.0InstrumentProcurement..................................................................................................21

8.0Summary..........................................................................................................................21

9.0Acknowledgements..........................................................................................................21


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1.0AbbreviationsASVCP AmericanSocietyofVeterinaryClinicalPathologyCLSI ClinicalLaboratoryStandardsInstitution(formerlytheNationalCommittee

forClinicalLaboratoryStandards,orNCCLS)CV Coefficientofvariation(expressedinunitsof%)EQA ExternalQualityAssuranceGDH GlucosedehydrogenaseenzymeGDH-PQQ GlucosedehydrogenasepyrroloquinolineenzymeGO GlucoseoxidaseenzymeHCT HematocritMCV Meancell(corpuscular)volumePBGM Portablebloodglucosemeter(glucometer)Ped ProbabilityoferrordetectionPfr ProbabilityoffalserejectionPOCT Pointofcaretest(ortesting)QA QualityAssuranceQALS QualityAssuranceandLaboratoryStandardsQC QualityControlRBC RedbloodcellsSD StandarddeviationTEa Allowable(desirable)totalerror


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2.0IntroductionPortablebloodglucosemeters(PBGM,a.k.a.glucometers)areaconvenient,cost

effective,andquickmeanstoassesspatientbloodglucoseconcentration.Theycanproviderapidresultsinpatientswithclinicalsignssuggestiveofhypoglycemiaandassistcriticalshorttermtherapeuticstrategies.Theycanbeusedasascreeningtooltoidentifypotentialdiabetesmellituswhichcanthenbeconfirmedbylaboratoryglucoseanalysis.Theyarealsoconvenientwhenmultipleglucosemeasurementsareneededwithinashorttimeinterval(e.g.,toconstructglucosecurves),canbehelpfulwhenmonitoringcriticallyillpatientstopre-empthypoglycemicincidents,andcanbeusedaspartofapre-operativebloodscreen.

PBGMofferafasterturnaroundtimeandrequireasmallersamplevolumecomparedtoreferencelaboratorychemistryanalyzers.ThenumberofcommerciallyavailablePBGMisconstantlyincreasing,makingitchallengingtodeterminewhethercertainmetersmayhavebenefitsoverothersforveterinarytesting.Thechallengeinselectionofanappropriateglucosemeterfromaqualityperspectiveiscompoundedbythevarietyofanalyticalmethodsusedtoquantifyglucoseconcentrationsanddisparatestatisticalanalysisinmanypublishedstudies.

TheFDAhasproduceddraftguidelinestoindustrysettingstricterpre-manufacturerrequirementsforPBGMsintendedforusebyprofessionalsinhospital(medical)settingscomparedtothoseintendedforusebylaypersonsinahomesettingwiththeaimtoimprovetheaccuracyofPBGMsusedfortightglycemiccontrolbymedicalprofessionals.1

ThisdocumentpresentsgeneralinformationaboutPBGM.SpecificbrandsofglucometersarementionedinthisdocumentwhentestswithinformationpertinenttoaccuracyofresultsandQAandQChavebeenstudied.Thisdoesnotrepresentanendorsementorcriticismofthebrandsmentioned,butprovidesinformationthatmaybeusefultoclinicalpathologistswhoseadviceissoughtbyveterinarians,veterinarytechniciansornurses,orotherrelevantoperatorsconsideringusingPBGMs.

3.0Scope

Thepurposeofthisguidelineistoprovideclinicalpathologistsandlaboratorianswithbackgroundknowledge&specificrecommendationsforQA/QCtoimprovethequalityofresultsobtainedwhenusingPBGMs.StrengthsandweaknessesofdifferentanalyticalmethodsusedbyPBGMarepresentedtohelpclinicalpathologistsunderstandtheeffectsofmethodologyonresultsandtoassistthemwithanalysisofthescientificandmarketingliterature.Causesofpre-analytical,analyticalandpost-analyticalerrorarepresentedtohelpclinicalpathologistsadvisecliniciansandveterinarytechniciansornurses,orotherrelevantoperatorsonhowtominimizetheeffectofthesefactorsontheaccuracyoftheirPBGMresults.OneofthecurrentbiggestanalyticalcontributorstotheproductionoferroneousglucoseresultsistheinbuiltcalculationformulaeinmanyPBGMmodelswhichconvertawholebloodglucoseresultandreportacalculatedplasmaequivalentresult.PriorknowledgeoftheimpactofthisfunctionalaspectoftheirdesignisrequiredtohelpclinicalpathologistswhointerpretglucoseresultssubmittedbyveterinariansforcomparativepurposesaspartofQA/QCoftheirPBGMsoransweringqueriesregardingthedifferenceinresultsbetweenPBGMsandlaboratorychemistryanalyzers.ClinicalpathologistscanalsoeducateveterinariansontheimplicationsofacalculatedplasmaequivalentresultsothattheycaninterveneandcorrectresultswherepossibleorselectanotherbrandofPBGM.ClinicalpathologistsshouldtakenoteoftheknownvariationinperformanceofPBGMsat


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extremesofglucoseconcentration(hypo-&hyperglycemia)duetothewidevarietyofmethodologyemployedintheseinstrumentssotheycandisseminatetheinformationtoveterinarians,veterinarytechniciansornursesorotherrelevantoperatorstopreventtheselimitationsleadingtoincorrectclinicaldecisionsandtreatment.InstructionsaregivenforhowtouseexternalqualityassessmentprogramsorcomparabilitystudieswithalocalreferencelaboratoryforongoingQA.Step-by-stepprocedurestocharacterizetheperformanceofindividualPBGMandtoharmonizemultiplePBGMinlargerpractices/institutionsarealsopresentedsoclinicalpathologistscanassistveterinariansinimplementingthesemeasuresascomponentsoftheirqualityplanningandmanagement.Theserecommendationsarenotintendedtobeall-inclusive;rather,theyrepresentaminimumstandardforPBGMmanagementinveterinaryclinicalsettings.

4.0PBGMmethods&technologyoverview

PBGMarebiosensorsthatdetectglucoseviaenzymaticactivity(interactionbetweenglucoseandanenzyme,withresultingconsumptionorproductionofaphysicalorchemicalproductthatissubsequentlymeasured).EnzymesusedinPBGMvaryandincludehexokinase,glucoseoxidase,orglucosedehydrogenase.Broadly,PBGMaredividedintooptical(lightdetecting)andelectrochemical(electriccurrentdetecting)systems.Table1liststhevariousPBGManalyticalmethods,whereavarietyofenzymesmaybecombinedwitheitheropticalorelectrochemicaldetectionmethods.

Eachbatchofglucosemeterteststripshasacodedescribingtheperformanceofthebatchandthecalibratingrelationshipbetweenthephotometricorelectrochemicalsignalandtheconcentrationoftheglucose.2

Itisbeyondthescopeofthisdocumenttodiscussallthesystemsbutafewparticularlyimportantpointsarementionedbelowbecauseoftheireffectontheoutcomeofglucoseresults,whicharediscussedinlatersections.Mostmodernglucosestripsutilizethickfilmtechnology,wherethefilmiscomposedofseverallayers,eachwithaspecificfunction.Forexampleinphotometricsystemsaspreaderlayerisnecessary,whereaselectrochemicalstripsusecapillaryfillsystems.InsomephotometricsystemstheRBCsaretrappedinthefirstsemipermeablemembrane/separationlayer,preventingthemfromenteringthematrix,andanalysisisperformedontheresultantplasma.2Thismaybeimportantsincetheresultsfromthistypeofsystemaremorecomparablewithserumorplasmaglucoseresultsfrombiochemistryanalyzers,thanthosethatmeasureglucoseinwholeblood.Inelectromechanicalsystems,coulometryprovidesmoreaccurateresultsfromasmallersamplesizeandislessaffectedbytemperatureandpatienthematocritbecauseitevaluatesthetotalchargegeneratedinsteadofsteadystatecurrentusedinamperometry.3Thisisimportantinenvironmentsthatmayhaveextremesoftemperatureorinveterinarypatientsthatmayhavehematocritsthatdifferfromthatofadulthumans(hematocritrangetypically40-50%)forwhichmostPBGMaredesigned.

Newermultilayerslidesystemscontainextrapadstoconcurrentlymeasuretwodifferentanalytes,suchasglucoseandhemoglobin.ThisisadvantageousbecausethehemoglobinmeasurementcanbeusedtocalculatethehematocritandmakeadjustmentsforpatientsthathaveahematocritoutsideofthenormalhumanrangeforwhichmostPBGMsaredesigned.ExceptionsincludeanimalswithirondeficiencyandcamelidswherethecalculationofHCTisnotequaltothreetimestheHgbconcentration.InthelattercircumstancesthesePBGMsthatmeasurebothglucoseandhemoglobinmightleadto


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inaccuracies.Therelationshipbetweenglucoseandhematocritisdiscussedinmoredetailinsection5.2.1and5.2.2.

5.0Considerationsforglucosemetertesting

Considerationsforglucosemetertestingincludeknowledgeofsourcesofpre-analytical,analyticalandpost-analyticalerrorsandstrategiestominimizetheseduringroutinetesting.

5.1Minimizingpre-analyticalerrorSourcesofpre-analyticalerrorthatshouldbeconsideredincludeoperatorproficiency,timingofsamplecollection,specimencollectionandhandling,andsamplematrix.

5.1.1OperatorproficiencyOperatorproficiencyshouldbeaddressedbyadequatestafftraining,bothinitially&ongoing,ensuringthatastandardizedoperatingprocedure(protocol)iswrittenandsubsequentlymaintained.FurtherdetailregardingoperatorproficiencyisavailableinASVCPGuidelines:QualityAssuranceforPoint-of-CareTestinginVeterinaryMedicine,Chemistry,Section2.4.4

5.1.2TimingofsamplecollectionHypertriglyceridemiainapost-prandialsamplecancausepseudohypoglycemia(falselylowglucoseconcentration)withsomemethods.5Refertosection5.2.2.3forexplanation.Repeatsamplingforcomparativepurposesshouldbeperformedatthesametimeofdayrelativetofastingorfeeding.Diagnosisofdiabetesmellitusrequiresevaluationoffastingbloodglucose(minimumfast8hours).6

5.1.3Specimencollectionandhandling

5.1.3.1PreparationofpatientskinsurfaceIfisopropylalcoholisusedtocleantheskinsurfacepriortoblood

sampling,itshouldbeallowedtodrypriortocollectionofthespecimeninordertoavoidcontaminationthatmaycauseinterferencewithresults.7

5.1.3.2SamplevolumeOperatorsshouldensurethatPBGMteststripsareadequatelyfilled,

withinsufficientsamplebeingofmoreconcern.(Overfillinghasnotbeenassociatedwithinaccuracyofglucoseresults.8SomeoftheolderPBGMfailtodetectunder-fillingofteststrips.Thiscanleadtoerroneousresults,asthemeasuringprocesswillstartregardlessofsamplevolume.8,9,10InsufficientsamplevolumeisunlikelytooccurinthenewgenerationofPBGM,becausethesizeofadropfromaroutinebloodsamplecollection(22to24gneedle)issufficienttofillthePBGManalyzer.8


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5.1.3.3Samplecollectiontubeadditives(anticoagulants&/orpreservatives)

Internationalqualitystandards(ISO&CCLS)11,12andthisguidelinerecommendthatmanufacturers’instructionsforpropersampletubeuseshouldbefollowed.Afewveterinary(dogs&cats)studiesconcludedthatglucoseresultsfrombloodcollectedintoplain(noanticoagulant),EDTAorlithium-heparinweresimilar8,10,13Incontrast,fluorideanticoagulatedbloodofcats10anddogs8,usingonemeterbrand,the#“SureStep”(GOmethodology)consistentlyunderestimatedtheglucoseconcentration.FluorideisnotaroutinelyusedanticoagulantinveterinarypracticeintheUnitedStatesbutitiscommonlyusedinEurope,Africa,andAustralia.Inthelattercountries,itistheanticoagulantofchoicetoinhibitglycolysisinsamplessubmittedforglucosetestingbychemistryanalyzersifthereisananticipateddelaybetweensampleacquisitionandhandlingsuchthattheplasmawillnotbetestedwithin60minutesofcollection.14Incountrieswherefluorideoxalateisroutinelyusedtosubmitglucosesamplestolaboratories,cliniciansshouldbeawareofitslimitationsforglucosetestingbyPBGMstoavoidthispotentialsourceoferror.8,10

AnavianstudyidentifiednosignificantdifferenceinglucoseresultsbetweenbloodtakenintomicrotainertubeswithnoanticoagulantorheparinbutglucoseconcentrationwassignificantlylowerifbloodwascollectedintomicrotainertubeswithEDTA.15

5.1.3.4SiteofCollection–capillary,venous,andarterialsamples

PBGMarepredominantlydesignedforusewithfreshwholebloodobtainedfromcapillaries.Somemodelsaredesignedforusewithcapillary,venousandarterialblood.Glucoseresultsbetweencapillary,venousandarterialsamplesvary,andthisvariationispartlymeterandmethodspecific.Prandialstatus,pO2andtissueperfusionareadditionalvariableswhichmayinfluencecomparativeresults.

Inafastingstate,capillarybloodglucoseis5mg/dL(0.27mmol/L)higherthanvenousblood,asglucoseisabsorbedbythetissuesasanenergysourceatthecapillarylevel.16,17Inthepostprandialstate(1hourinhumans)capillarybloodglucosemaybe20-25%orgreaterthanvenouslevels.5,18,19,20,21Additionally,thehemoglobinconcentrationincapillarybloodisslightlyhigherthanvenousblood,22andthismightcontributetoadditionalvariationifsamplesfromdifferentsitesarecompared.Finally,thepartialpressureofoxygen(pO2)ishigherincapillarybloodcomparedtovenousblood.Theimpactofthepartialpressureofoxygen(pO2)onglucoseresultsismethoddependent.Inmetersmeasuringglucosebyanelectrochemicalmethod(whichutilizeGOinatwo-stepreaction),capillarybloodglucoseresultscanbelowerthanvenousbloodinhumans23andcats.24,25However,inmetersemployingphotometricdetection,thepO2doesnotinfluencetheresultandcapillarybloodresultsareslightlyhigherthanthoseobtainedinvenousblood.25

Veterinaryliteraturecomparingcapillaryandvenoussamplesisscarce.Somestudiesidentifieddifferences,butconcludedtheywerenot


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clinicallysignificant.24,25AlimitationofthesestudieswastheexclusionofsampleswithHCTsoutsidereferenceintervals.25

Thewiderbloodglucoserangetoleratedinveterinarypatientscouldaccountfortheacceptanceofthelevelofdifferencebetweensamplesitesfoundunacceptableinhumanmedicine.Bearingthisinmind,itisprudenttominimizethenumberofvariableswhenperformingserialglucosetestsbyconsistentlyusingthesamesamplingtechnique,site,andmethodoftesting.

5.1.4Samplematrix

Eachspecieshasauniquesamplematrix,whichincludesbloodviscosity,rheologyetc.(Figure1)26,27,28,29,30,31,32whichmayleadtoinaccurateglucoseresultsmeasuredonglucosemetersdesignedforsamplesfrommaturehumanpatients.Theerrorwilldependonthematrixpropertyandthespecificmethodologyoftheglucosemeter.Whenthesematrix-basedfactorsarepresent,resultsshouldbeinterpretedwithcautionandpreferablyfollowedwithconfirmationatareferencelaboratory.

Animportantmatrix-relatedvariableisthedistributionofglucosebetweenRBCsandplasma.Inhumans,glucoseisdistributedequallywithinRBCsandplasma.Incontrast,dogshavebeenreportedtohave12.5%ofglucoseinRBCsand87.5%inplasmaandcatshave7%ofglucoseinRBCs.30Rabbitshave15%ofglucoseboundinRBCs.33AvianRBCsdonothaveprotein-mediateduptakeofglucoselikemammals,thustheratioofplasmatoRBCglucosemaybemuchhigherwithagreaterconcentrationdifference.34APBGMmarketedforveterinaryspecies,whichclaimedtoaccountforthedifferenceinspeciesRBCglucosebindingcapacityusingproprietaryalgorithmsperformedfavorablyinsometestingaspects.35,36However,thisclaimwasnotsupportedbypublishedstudiesordataonspecificspeciesvalidationorspecies-specificalgorithms.36

PBGMsalsounderreportbloodglucoseinavianspecies15,34,37eventhosewithapsittacine-specific(proprietary)glucometercorrectionalgorithm(althoughthebiasismuchlessthanconcurrentlytestedhumanPBGMs).Thiscouldbeduetothesamplematrixdifference,i.e.presenceofnucleiinavianRBCswhichpotentiallyreducethecurrentflowneededforaccurateelectrochemicalglucosemeasurement34,37althoughthisremainstobeproven.37OtherpotentialexplanationsincludedthehighernormalavianHCTandglucoseconcentrationcomparedtohumans,althoughbothwherewithinthePBGMspublishedranges.34FinallythecorrectionfactorinPBGMstoaccommodateforthedifferencebetweenwholebloodandplasmaisdesignedforhumansandnotavianspecies,whichcouldaccountforthenegativebiascomparedtochemistryanalyzers.34

5.2MinimizinganalyticalerrorPossiblesourcesofanalyticalerrorthatshouldbeconsideredincludestandardizationofglucoseresultreportingandknowledgeofpossiblesourcesofandcontributionstoanalyticalinaccuracy.


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5.2.1Standardizationofglucosereporting(plasmaequivalentvalue)PBGMsvaryintheirmethodofglucosedetectionaswellastheactual

samplequantitytheyreport.Meterseitherdetectglucoseconcentrationinmolarityorglucoseactivityinmolality.Thereportedglucosequantitymaybewholeblood,serum,plasmaorcalculatedplasmaactivity.

Privatediagnosticoruniversitylaboratoriesutilizinglargebiochemistryanalyzersmeasureandreportserumorplasmaglucoseasaconcentration;themajorityofPBGMmeasureglucoseinwholeblood.PBGMmayreportwholebloodglucose,plasmaglucoseor“plasmaequivalent”(calculated)glucose.WhatanindividualPBGMmeasuresandreportscanbeobtainedfromtheuser’smanualorotherliteratureprovidedbythePBGMmanufacturer.

Wholebloodandserum/plasmaglucoseresultsarenotinterchangeable;directcomparisonposesariskofmisinterpretation.Plasmaglucoseconcentrationisroughly10to15%higherthanwholebloodglucose,requiringdifferentreferenceintervalsandclinicaldecisionlimits38asillustratedinastudyinvolvingcattleandsheep.39Thesevaluesdifferbecauseglucosecontentismeasuredintheaqueous(water)componentofasample.Theamountofglucoseperunitwatermass(glucoseconcentration)isthesamethroughoutabloodsample.However,theamountofwaterinRBCs(77%)islessthanthatinplasma(93%).ThisexplainswhythewatercontentofwholebloodvarieswithitsHCT.Therefore,theamountofglucoseinwholeblood(plasma+RBCs)islessthananequivalentvolumeofplasmaorserum(noRBCs).

SomePBGMfirstremovetheRBCcomponentthroughafilterandthentheresultantplasmaistestedforglucosecontent.Theseactualplasmaglucosevaluesmayagreewellwithserumorplasmaglucosedeterminationsmeasuredwithchemistryanalyzersasthewatercontentpervolumeofsampletestedissimilar.

ReportingglucoseconcentrationsasplasmaequivalentvalueshasbeenrecommendedbytheInternationalFederationofClinicalChemistry(IFCC)inanattempttostandardizeandfacilitatecomparisonofglucoseresultsbetweendiagnosticlaboratories(measuringserumorplasma)andPBGM(measuringglucoseinwholeblood).40

TheproblemariseswhenthePBGMreadstheglucoseconcentrationinwholebloodandeitherreportstheconcentrationinwholebloodoraplasmaequivalentvalue(calculatedvalue),duetodifferencesinsamplewatercontentasexplainedabove.

Therearetwoconversionequationswhichattempttoadjustforthedifferentwatercontentinthevarioustypesofsamples:

EquationA

𝐺𝑙𝑢𝑐𝑜𝑠𝑒!"#$%# = 𝐺𝑙𝑢𝑐𝑜𝑠𝑒!!!"# !"##$ ×1.11

Inthisequation,plasmaandwholebloodglucosemustbeexpressedinthesameunits,eitherasmg/dLormmol/L.Thefactorof1.11inequation


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AisbasedonasinglePCVorHCTof40to50%.41,42Theequationisthereforeonlyaccurateifthepatient’sPCVisinthisrange.

EquationB43,44

𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂 = 𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒘𝒉𝒐𝒍𝒆 𝒃𝒍𝒐𝒐𝒅

𝟏.𝟎 − (𝟎.𝟎𝟎𝟐𝟒 ×𝑯𝒄𝒕%)

Inthisequation,plasmaandwholebloodglucosemustbeexpressed

asmg/dLandtheequationincludesanassessmentofthepatient’sPCV/HCT.Figure245demonstratestheoutcomeofapplicationofequationAandBtodetermineplasmaequivalentglucoseresult.Whenthehematocritisoutsideofthenormalhumanreference,of40to50%,(onwhichthefactorof1.11isbased),EquationAproduceserroneouscalculatedplasmaglucoseconcentrationsbutEquationB,whichincorporatesthepatient’sactualhematocrit,ismoreaccurate.Figure2alsodemonstratesthatameasuredwholebloodglucosevalueisclosestinconcentrationtoameasuredorcalculatedplasmaglucosevalueinanemicsamplesbecausetherearefewerRBCsandthereislessofadifferenceinthewatercontentbetweenthetwosampletypes.Asexpected,whenthepatientHCTiswithinthe40-50%,PBGMresultsaresimilarforbothequations.

DuetothevarietyofPBGMmethodologieswithrespecttowhattheymeasure(wholebloodorserum/plasma)andreport(wholeblood,serum/plasmaorcalculatedplasmaequivalent)variousscenariosexist:1. Inmetersthatmeasureglucoseinwholebloodandreportvaluesin

wholeblood,theoperatorcanconvertthewholebloodglucoseresulttoaplasmaequivalentresultbyselectingEquationBinallcircumstancesorEquationAifthepatient’sHCTiswithintherangeof40to50%.Inthesecircumstancestheoperatorwouldhavetodeterminethepatient’shematocritbymeansofanothertest,acalculatedvaluefromanautomatedanalyser(HCT)oraspunPCVusingamicrohematocritcentrifuge(assumingotherQA/QChavebeenachieved).Eithermethodisacceptableaslongasitwasstandardizedwithinthesamepatientifperformingserialtesting.

2. ThefewmetersthatcanconcurrentlymeasureglucoseandthepatientHCTreportanaccurateplasmaequivalentglucosevalue43,44exceptinirondeficientanimalsandcamelids,asmentionedinsection4.0.EquationBisusedbythesemeters,andthepatient’sactualhematocritdeterminesthefactorwithwhichwholebloodismultipliedtoconvertittoaplasmaequivalentvalue.InthesemeterstheresultsareaccuratethroughouttheentirerangeofpossibleHCTconcentrationsinhealthanddisease.

3. ThemajorityofcurrentmetersthatprovideresultsinplasmaequivalentglucoseconcentrationdonotmeasureHCTanduseequationA.InallpatientswithaHCT/PCVoutsidetherangeof40to50%,eitherdueto


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diseasesuchasanemiaorpolycythemiaordifferenceinthe“normal”referenceintervalthiscanleadtoerroneousresults.

ThesituationisfurthercomplicatedinthatwholebloodglucoseconcentrationsintestedsamplesarenotonlyinfluencedbytheHCT/PCV,buttheeffectoftheHCT/PCVinturnisinfluencedbytheactualglucoseconcentration.ThismeansthattheeffectagivenHCThasonwatercontentofasampleandthustheglucosecontentofwholebloodsampleisdifferentinhypoglycemic,normoglycemicandhyperglycemicpatients.Thesecomplexdependenciesaresystem(metertype&itsmethod)dependent,31,46,47theexplanationofwhichisbeyondthescopeofthisdocument.

Therefore,withmetersthatmeasureglucoseconcentrationinwholebloodandreportacalculatedplasmaequivalentglucoseconcentration,asrecommendedbytheIFCC,usersshouldtakenoteoftheequationusedtodeterminethisresult.IfthePBGMcannotdeterminetheHCTconcurrently,theoperatorshouldevaluatethepatient’sHCT/PCVindependently.IftheHCT/PCVisoutsideof40-50%thenmetersusingequationAmaybeinaccurate.

IfoperatorswishtocompareresultsfromaPBGMthatmeasuresandreportstheglucoseconcentrationinwholebloodtoachemistryanalyserresulttheyshouldalsoconverttheresulttoaplasmaequivalentconcentrationusingequationBandthepatient’sactualhematocrit.

5.2.2SourcesofPBGMinaccuracy

Sourcesofinaccuracyincludevariationduetoinstrumentuse,theenvironment,andvariablesrelatedtophysiologyofthepatientandconcurrentdisease.Thefollowingsectionshighlightfactorsaffectingglucometerresultsandstrategiestominimizeoreliminatepossibleerrororvariation.

5.2.2.1Instrumentuse

• TeststripbatchChecktheexpirydateofstripspriortoeachuse.Out-dated

reagentstripsandincorrectstripstorage,suchasopenvialsorexposuretodirectlightwillaffectglucosemeterperformance.48

Striplot-to-lotvariationshouldbeminimizedbyenteringorscanningthekeycodeifoneisrequired(someareautomaticoninsertionofthestrip)andrunningQCmaterialeachtimeanewlotofstripsisopened.Lot-to-lotvariationmaybeamajorfactorinresultaccuracy,affectingprecisionandbias.9,49,50,51,52,53• Operationalprocedure

Thecorrectspeciescodeshouldbeenteredinaveterinary-specificPBGM.Failuretodothiscanleadtoerror.Forexample,whereinsertionofadogcodeforcatsamplesproducedglucoselevels1-4mmol/Lhigherthanthetruevalue.35

Sufficienttimeshouldbegivenfortemperatureequilibrationoftheinstrumentandteststrips,otherwisethetemperatureestimatedbythemeterwillbeincorrect.Temperatureestimationis


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usedinacorrectioncalculation(temperaturecompensationalgorithm)toaccommodateforthetemperaturedependenceofthemeasurementmethodology.54Thistypeofsystemfailurecanhappenwhenstripsarestoredinthefridgeandtheambientenvironmenttemperatureishigher.49

Inmetersthatmeasureglucoseandhemoglobinsimultaneously,thestripscontainextralayersanditisimportanttocoverthewholestrip.Inaddition,theproceduremayhavetobetimedifresultsarecalculatedataparticulartimeinterval.2• Controlmaterial

Ifhighandlowconcentrationcontrolsareused,careshouldbetakennottoreverseliquidcontrollevels,bycheckingthelabelscarefullyeverytimetheyarerun.Controlmaterialsshouldbestoredandhandledaccordingtomanufacturer’srecommendations.

5.2.2.2Environment

Metersmustnotbeoperatedunderenvironmentalconditionsoutsidethosesetbythemanufacturer.48,54Extremesinhumidity(>85%),temperature(>40ºC)andaltitude(seebloodoxygenpressurebelow)maycontributetoproductionoferroneousresults.

5.2.2.3Physiological&Disease

Theconcentrationsatwhichsubstancesinterferewithperformanceareinstrumentspecific(meter&method)andcanbefoundinproductlabelling/insertsormanuals.Iflevelsmightbeexceededorifresultsdonotfitwithotherclinicaldataforthepatient,itisrecommendthatglucoseresultsshouldbeconfirmedbyreferencelaboratorymethods.Someofthesevariablesarehighlightedbelow.• Glucoseconcentration

PBGMsperformdifferentlyatextremesofbloodglucoseconcentration(hypoglycemiaandhyperglycemia)inhumans55,56,57andanimals.8,10,13,25,28,35,58,59,60,61Itmaybeeasiertoclinicallycompensateforameterthatconsistentlyunderoroverestimatesglucoseinaspecificrangethanameterwherethedirectionoferrorrelativetoareferencemethodisunpredictable.InconsistentunderoroverestimationofglucoseresultswasidentifiedinaPBGMmarketedforveterinaryapplicationinastudyindogs36andanotherstudyinalpacas.60• Hematocrit

IncreasedHCTcandecreasetheglucosemeasurement;conversely,adecreasedHCTcanincreaseglucosemeasurements(inhumanmedicine).26,46,47,49,62,63,64,65Thisinverserelationshipismorepronouncedinthehyperglycemicrangeinhumans.66

HCTaffectstheaccuracyofmanyglucosemetersforseveralreasons.Itseffectonmeterswithinbuiltconversionfactorshasbeendiscussedinsection5.2.1.Anotherreasonmaybeanincreased


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diffusionrateofplasmatothereagentpadwithreducednumbersoferythrocytes.26,46,47,62,63,Studies49,51,63,67haveindicatedthatthiserrorcanoccurevenifthemanufacturerstatesthatHCThasnoeffectintheinstrument’sHCTmeasurementrange.InmeterswhereRBCsarelysedpriortomeasuringtheglucoseconcentration,HCTappearstohavelessofaneffect.65

Newertechnology,usingawholebloodglucosebiosensorhasalowersensitivitytotheeffectsofHCTbasedonanimpregnatedporouscarbonelectrodethatexcludeserythrocytes.Thistechnologythusallowstestingofcapillary,venous,arterialorneonatebloodinhumansoverawiderange(20-70%)ofHCT.68MorerecentlydynamicelectrochemistrywhichinvolvescomplexPBGMmathematicalalgorithmsbasedondifferencesinkineticsofelectrochemicalreactionsofglucoseandpotentialinterferingsubstances,havebecomeavailablethatcancorrectforsomeinterferingsubstancesandvariationinHCT.69

Similartoreportsinhumans,HCTcanaffecttheaccuracyofglucosereadingsinanimals.8,10,59,60,70,71InafewveterinarystudieswhichdidnotfindanassociationbetweenglucoseandHCT13,28oneindicatedthattheirstudyhadlimitations(lowsamplenumberwithabnormalPCV)andrequiredfurtherinvestigation.28Ultimately,cliniciansshouldinterpretglucoseconcentrationsinanemicorhemoconcentratedcats,10dogs,8horses,71rabbits59andalpacas60withcaution.• Lipemia/hyperlipidemia

Lipemiamayinterferewithsomemethodologies.Ifthemetermeasuresglucosemolality,variationsinwatercontentofthesamplewillinfluencemeasurements,asproteinsandlipidsdisplacewater.InotherPBGMmethodselevatedcholesterolortriglyceridesmayinterferewiththewaylightisreflectedproducingerroneousresults72.Endocrinopathiesorparentalnutritionmayresultinartifactuallylowerglucoseresults.FalsehighglucosereadingscanoccurwithGDH-PQQmethodologywhentriglyceride>5000mg/dL(56.5mmol/L)73or>265mg/dL(3mmol/L).74• Bilirubin

StudiestestingtheeffectofbilirubinonplasmaglucosemeasurementbyPBGMarelimitedandsomeresultsarediscordantwiththesamemethodology,(Table2).Whereinterferencewasdetectedglucoseresultscouldbeupto21%inaccurateandthiscouldchangeclinicaldecisions.75• Bloodoxygenpressure

TheeffectofpO2onglucosemeasurementbyPBGMsdependsonthemethodofmeasurement54,62,76,77,78,79.AlowpO2duetohighaltitude,hypoxia,oryoungagecancausefalselyelevatedglucose,inmeterswithGOmethodologyinhumans.54,62,76,77AhighpO2e.g.oxygentherapy,mechanicalventilationcancauseafalsedecreaseinglucosewithGOmethodology.62,77,78,79Thisoccurs


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inmetersutilizingGOmethodologybecauseoxygenactsasacompetingelectronacceptor.TheGDHmethoddoesnotappeartobeaffectedbyhigh/lowbloodoxygenpressure.77• BloodpH

BloodpHmayaffectactivityoftheenzymesusedtomeasurebloodglucose.AcidosismayfalselydecreaseglucosereadingsandalkalosismayfalselyincreaseglucosereadingsinglucosemetersusingGOmethods.26,80ThiscouldbeduetoinsufficientbufferingcapacityoftheteststripinthesecircumstancestomaintainpHinarangeneededforoptimalenzymeactivity.80

Aswithothervariables,thereareinconsistentresultsacrossstudies.SomestudiesshowlittleeffectonglucoseresultsofbloodpHintherange6.80to7.55inmeterswithGOmethodology.62Incontrast,othershavefoundsignificantchangesinglucoseatpH<6.95and>7.85.26Severeketoacidosisorotheracid-basedisorderscombinedwithanabnormalityinHCT80ormarkedhyperglycemia81mayresultinmisleadingglucoseresults(particularlywithinstrumentsusingGOmethods).Glucoseresultsshouldbeinterpretedwithcautioninpatientswithpotentialketoacidoticdiabetes.80

5.2.2.4.Administereddrugsortreatments

PBGMmanufacturer’sinstructionsshouldbeconsultedforinformationconcerningsubstanceswhichmaybeusedinmedicationsthatcouldinterferewithindividualmeters.

Drugsorothertherapeuticcompoundsmayfalselyincreaseordecreasethemeasuredglucoseconcentration,73,82,83,84includingcommonlyusedantimicrobials(e.g.tetracycline85),anti-inflammatorydrugs(e.g.aspirinandacetaminophen),potassiumbromideandhemoglobinsubstitutes.Interferencedependsonthetypeofenzyme(GOorGDH)andthemethodofdetection(photometricvs.electrochemical)inPBGMs.Potentialexplanationsfortheseeffectsincludeconsumptionofintermediateproductsinphotometricsystemsordirectoxidationinelectrochemicalsystemswithsomecommonlyuseddrugsorsupplementslikeacetaminophenorascorbicacid.Substanceslikemannitolmayinterferedirectlywithmeasurement.ForlistsofotherpotentialinterferentsrefertotheFDAwebsite72ortextbooks(e.g.Tietz).85

5.1 Minimizingpost-analyticalerrorPost-analyticalerrormayoccurwithinadvertentchangeinunitsof

measurementand/orinkeepingofrecordsrelatedtoPBGMtesting.

5.3.1UnitsofmeasurementOperatorsshouldcheckwhichunitthemeterdisplaysbecause

inadvertentchangeintheunitsofmeasurementcouldleadtomisinterpretationofresultsandinappropriatemedicaldecisions.Onetypeof


15

unitdisplayshouldbeused,eithermmol/Lormg/dL.(Conversionfactor:Glucosemmol/Lx18.018=mg/dL;Glucosemg/dLx0.0555=mmol/L).

5.3.2Records

Accuraterecordsmustbekeptforallaspectsofglucosetesting,aswithotherPOCT.4OneextraitemspecifictoPBGMistorecordbatterychangedates.

6.0SpecificqualitymanagementrecommendationsforPBGM

6.1Allowable(desirable)totalerror(TEa)

PerformancetestingshouldbedoneonPBGMtoensurethatrepeatedresultsfromthesamepatientfallwithintheallowabletotalerror(TEa)of10%forvaluesbelowthereferenceintervalor20%forvalueswithinandabovethereferenceinterval.86

Suchassessmentshouldbeperformedineachofthethreediagnosticallyrelevantglucoseranges;hypoglycemia,normoglycemiaandhyperglycemia.57,87ThisisnecessarybecauseoftheoverwhelmingevidenceintheliteraturethatPBGMperformancevariesacrosstheglycemicrangeinhuman56,57andveterinary8,10,13,25,58,59,88studies.

Thisassessmentisevenmoreimportantinveterinarymedicinewherethereiscurrentlynoconsensusregardingtherange(hypo-,normo-orhyperglycemia)withinwhichmoreerroroccursorwhetherthePBGMunder-orover-estimatetheglucoseconcentrationinthatrange.8,10,13,89,90Arecentstudywhichevaluatedperformanceinallthreeglycemicranges(Table3)inrabbitsusingahumanandveterinaryPBGMfoundthattheTEaguidelinerecommendedbytheACVCPwasexceededinallcategorieswiththeveterinarymeterexceptfortheeuglycemicrangeonthefelinesetting.Thespecifichumanmeterusedinthatstudyperformedbetter,withTEawithintheASVCPguidelineexceptforthehypoglycemiccategory.59ThesameveterinarymeterhadalowerbiasthanahumanPBGMinastudywithferrets,butonlyeuglycemicandrarehypoglycemicsampleswereassessed.91Additionally,theveterinaryPBGMoverestimatedglucoseandhypoglycemicpatientsmightnotbeidentified.91Thesefindingsemphasisetheimportanceofperformanceevaluationinallthreeglycemicrangesinthetargetspecies.59

GlucometerscurrentlybeingmarketedwithFDAapprovalaredesignedtohave95%oftheresultsfallwithin+/-20%forglucoseresults>75mg/dL(4.16mmol/L)andwithin+/-15%forglucoseresults<75mg/dL(4.16mmol/L).11Possiblerevisionsofstandardsandrecommendationsbyvariousorganizationsindicatethatrequirementsmaychangetorequire99%ofresultstofallwithin+/-15%,regardlessoftheleveloftheglucoseresult.Thismeansthatnewerglucometersmayhavedifferentperformancespecificationscomparedtooldermetersandthatorganizationsusingglucometersshouldbeawaretoinquireaboutthisaspectwhenevaluatingglucometers.92

Morestrictqualityspecifications(lowerTEa)maydecreasethelikelihoodofinsulindoseerrorsbasedonmonitoringofbloodglucoselevelsusingPBGMs.InastudyusingmathematicalmodelsforhumanglucoseresultswithPBGMwith5%and


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10%TEa,dosageerrorsoccurredin8-23%and16-45%ofcases,respectively,dependingontheinsulindosagerulesusedandtherangeofbloodglucose.Largeerrorsofinsulindose(two-steporgreater)occurred>5%ofthetimewhentheCVand/orbiasexceeded10-15%.Toprovidetheintendedinsulindosage95%ofthetimerequiredthatboththebiasandtheCVoftheglucosemeterbe<1%or<2%,dependingonmeanglucoseconcentrationsandtherulesforinsulindosing.MostPBGMarenotabletomeetthesequalityrequirements.Theauthorsofthisstudyconcludedthattheeffectsofsuchdosageerrorsonbloodglucoseandonpatientoutcomesrequiresfurtherstudy.93Totheauthor’sknowledge,nostudiesofthistypehavebeenconductedforveterinaryspecies.

6.2ControlmaterialandcontrolruleselectionspecificforPBGM

Customizationofqualitycontrol(QC)protocolsforindividualPBGMisrecommended.4PBGMmanufacturersmayprovide1to3controlmaterial“levels”(glucoseconcentrations).Thisisincontrasttotherecommendationforotherbiochemistryanalytes,whereanalternatesourceofcontrolmaterialsotherthantheinstrumentmanufacturerisrecommended.94Thisexceptionisduetothecommutabilityofvariouscontrolmaterials applicabletoPBGMandthevariationinmethodologyemployedinPBGMs.Ifnotsuppliedbythemanufacturer,thencontrolmateriallevelscanbepurchasedfromsuppliersofin-clinicchemistryinstrumentsoranyotherindependentreputablesuppliers.

EstablishingtheminimumnumberofcontrolmaterialsandcontrolrulestailoredspecificallytoaparticularPBGMcanbeachievedthroughtheprocessofQCvalidation,whichrequiresaninstrumentperformancestudy(assessmentofprecisionandbiasfortheparticularPBGM).Detailontheseproceduresalongwithinformationregardingtherecommended13scontrolrulewhichispreferredforin-clinicusebecauseofitssimplicitycanbefoundintheASVCPGuidelinesforAllowableTotalError86andASVCPGuidelines:QualityAssuranceforPoint-of-CareTestinginVeterinaryMedicine.4

ThePOCTguidelinecontainsatableadaptedfromarecentpublication(Rishniw,etal.)95thatmaybeusedtodecidewhetherPBGMperformanceissuitableforstatisticalQCusingthe13srule.4

TherecommendationforoptimalQCistoanalyzequalitycontrolmaterialsoncedailyorwheneverpatientsamplesarerun(ifnotrundaily).InadditiontothegeneralrecommendationsforwhenQCshouldbeperformedlistedinthePOCTSection2,QCinglucosemetersshouldalsobeperformed:

a.Afterchangingthemeterbattery.b.Whenanewvial/packet/lotofteststripsisopened.c.Ifthemeterhaspotentiallybeendamaged.

6.3Externalqualityassessment(EQA)

ThismaybeachievedbyparticipationinanEQAprogramorcomparability

testingbyperiodiccomparisontoareferrallaboratory.RefertoASVCPqualityassuranceguidelines:externalqualityassessmentandcomparabilitytestingforreferenceandin-cliniclaboratories.94


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6.3.1ParticipationinanexternalqualityassuranceprogramExternalQAprogramsapplywithsingleormultiplePBGMs.• ThesampleprovidedbytheexternalQAprogramcanbeusedfortesting

onaninhousechemistryanalyzerand/orjusttheglucosemetertobetested.

• Itiscrucialtoindicateinthesamplesubmissionthattheinstrumentisaglucosemeterandwhichmethodthemeteruses.Ifthesubmitterfailstodothisthecomparativeresultswillbemeaningless.

• Resultsareconsideredacceptableiftheyfallwithin±TEafromthepeergroupmean.AlthoughotherrecommendationsbyASVCPguidelinesindicatethat±2or3SDor±TEamaybeusedascriteriaforEQAperformance,forglucometers±TEaispreferredduetotherelativelystrictrecommendedqualityrequirementof10%forvaluesbelowthereferenceintervalor20%forvalueswithinandabovethereferenceinterval.86

CurrentExternalQAprogramsspecificforPBGMinclude:• TheNorwegiancentre**forexternalqualityassuranceinprimarycare

(Norsksenterforkvalitetssikringavlaboratorieanalyzerutenforsykehus-**NOKLUS).50,52,96

• Eurotrol***,whoofferwholebloodglucosequalitycontrolsamplesandawebsitewhereanunlimitednumberofPBGMscanbeincluded.97EurotroloperatefromtheNetherlandsinEuropeandMassachusettsintheUS.

ExternalQAprogramsspecificforPBGMsintheUSarecurrentlylimitedinhumanmedicinebecausetheyarepresentontheCLIA(regulatelaboratorytesting)listof“waived”tests.6.3.2ComparabilityTestingwithaReferenceLaboratory

QAmaybeobtainedbycomparingglucosemeterresultstoresultsobtainedbyachemistryanalyzerinareferencelaboratoryorabenchtopbiochemistryanalyzerusedinthein-cliniclaboratory(aslongasthelatterisalsopartofarobustQAprogramtoensureitisavalidreferencemethod).Ideally,theenzymeusedbythereferencemethodandthatinthePBGMarethesame.Comparisonisachievedbysplitsampleanalysis99followingCLSIguidelines.1001. Splitthesample,runonewholebloodsampleinhouseonthePBGMand

processtheothersampletosubmitittoareferraldiagnosticlaboratoryorin-cliniclaboratorytorunonachemistryanalyzer.

2. Promptseparationoftheserumorplasmafromthelattersampleisimportantbecausetheglucoseconcentrationcandecreaseby5-7%perhouror0.33-1.33mmol/L/hour(6-24mg/dL/hour)whiletheplasma/serumisincontactwiththeerythrocytesthatmetabolizeglucosebyglycolysis.101,102,103Plasmashouldbeseparatedwithin5minutesofcollection12andserumat25degreesCelsiusshouldbeseparatedfromtheclotwithin2hoursindogsandwithin4hoursinhorsesandalpacas.104Glucoseconcentrationinaviansamplesisstableupto4hours

jc227604

Sticky Note

Insert reference 98


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aftercollectioninheparinbecausetheirRBCsdonotrelyonglycolysisforenergy.34,105

3. ComparethePBGMresultswiththechemistryanalyserglucoseresult.IfthePBGMreads&reportswholebloodglucosethenconvertittocalculatedplasmaglucoseusingEquationB(seesection1.4.2.1)toenablecomparisontothechemistryanalyzerresult.IfthemetermethodologyseparatesandmeasuresplasmaandreportsplasmaglucoseorifthemeterreadswholebloodglucoseandsampleHCTsimultaneouslyandthenreportscalculatedplasmaglucosebyinternaluseofequationBthendirectcomparisonwiththeserumchemistryanalyzerispossible.However,ifthemetermeasureswholebloodglucoseandconvertsitinternallyusingEquationA(seesection5.2.1)theoperatormustbeawareofthelimitationsandpotentialerrorassociatedwiththistypeofPBGMwhenthepatientshaematocritfallsoutsidethe40–50%range.

4. IfthePBGMglucoseresultfallswithinthelaboratorychemistryanalyzerglucoseresult±TEarecommendedbyASVCPthenglucosemeterperformanceissatisfactory(Table4).

5. IfthePBGMglucoseresultfallsoutsidethelaboratorychemistryanalyzerglucoseresult±TEa(Table4),recommendedbyASVCP,thentheoperatorshouldre-evaluateglucosemeterperformancebycheckingallpotentialsourcesoferrorincludingpre-analytical(e.g.samplepreparation),analytical(checkmethodologyofPBGMandchemistryanalyzerarecomparable)andpost–analyticalerror.ItisparticularlyimportanttocheckthepatientHCTandmethodofresultreporting,e.g.wholeblood,plasmaorcalculatedplasmaequivalent(seeitem5.2.1)106Ifnosucherrorscanbeidentifiedandthechemistryanalyserisperformingasexpected,thenthePBGMshouldnotbeuseduntilresultsofrepeatevaluationarewithinacceptableperformance.ThismayrequireconsultationwiththetechnicalservicerepresentativeofthePBGMmanufacturer.

6.4Multipleglucosemetersatonesite

Eachmetershouldbeclearlymarkedforeasyidentification.AllresultsfromanypatientshouldberecordedinsuchawaythattheyaretraceabletoaspecificPBGMandoperator.

AllPBGMresultsshouldbereportedinthesameformat,preferablyplasmaorplasmaequivalent.Ifconversionsfromwholebloodarerequired,thesamemethodforconversionshouldbeused(seesection5.2.1).

Ideallyifmorethanonereadingismadeforapatient,thesamePBGMshouldbeused.However,ifthisisnotpossibletheoperatorshouldbeabletocompareresultsbetweenmeterswithreasonableconfidence.ThisispossibleifallthePBGMsareinvolvedinregular(minimumquarterly)EQAprogramorcomparabilitytestingwithareferrallaboratoryorinhouseanalyzer(aslongasthelatterisalsopartofarobustQAprogramtoensureitisavalidreferencemethod).IfthismethodisfollowedallthePBGM’smusthaveresultsequivalenttotheEQAmeanorchemistryinstrumentmean+/-TEaforthatglucoseconcentrationrangerecommendedby


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ASVCP.Amorerobustprograminvolvesin-clinicharmonization,whichcanbeachievedfollowingtheguidelinesprovidedbelow.

6.4.1PBGMHarmonizationThein-clinicharmonizationprocedureideallyshouldbeperformedfor

existinginstrumentsandtheneachtimeanewbatchofmeterstripsisusedtocalibratethemeters(forapplicablemodels)oranewinstrumentispurchased.Table5providesapracticalexampleusingthestepsoutlinedbelowtoachieveharmonizationofmultiplePBGMstoaprimarymeter.

1.ExecuteaninstrumentperformanceevaluationforeachPBGM.RefertotheASVCPTEaguidelinedocumentforinstructions.86ThisinvolvesestablishingtheCV,meanandthebiasofeachPBGMcomparedtomanufacturesmeanusingall3levelsofcontrolmaterial.

2.ChoosetheprimaryPBGMpreferablyastheonewithleastbiastomanufacturers’meanorlessfavorablythefirstpurchasedPBGM.

3.DetermineifthebiasofthecomparativemetersrelativetotheprimaryPBGMareacceptableforinclusioninaPBGMharmonizationprogram.ThisisachievedbyestablishingthemaximumallowablebiasofthecomparativemeterrelativetotheprimaryPBGM.

a. Thebiasfortheprimaryglucometerisconsideredtobezerosinceitisthestandardbywhichthecomparativeglucometersarejudged.

b. EstablishtheCVforeachofthecomparativePBGMsandtheprimaryPBGM.

c. Calculatethecombinedinherentimpressionusingthefollowingequation√(CV2primaryglucometer+CV2comparativeglucometer).

d. Derivethemaxcomparativeinstrumentbias.TEa=bias+2CV,thereforeBias=TEa–2(combinedinherentimprecision)

e. Calculatedbiascomparedtotheprimaryglucometer=[Resultprimaryglucometer-Resultcomparativeglucometer/Resultprimaryglucometer]x100

f. Ifthecalculatedbiascomparedtotheprimaryglucometeris<themaximumbiasforthecomparativeglucometer,thentheperformanceisACCEPTABLErelativetotheprimaryPBGM.

g. IfthecalculatedbiascomparedtotheprimaryglucometerisNOT<themaximumbiasforthecomparativeglucometer,thentheperformanceisUNACCEPTABLErelativetotheprimaryPBGM.

4.IfthebiasofthecomparativePBGMisacceptablerelativetotheprimarymeterthencontinuedperformanceevaluationsofthePBGMsintheharmonizationshouldbecarriedoutasfollows:


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a. TheprimaryPBGMshouldbeevaluatedquarterlybymeansofparticipationinanEQAprogramorcomparisontoareferrallaboratoryorinhousechemistryanalyzer.Intheseinstances,performanceoftheprimaryPBGMisconsideredacceptableifthemeanofthePBGMiswithinthemeanoftheEQAgroupmeanorchemistryanalyserresult±TEasetbytheASVCPforthatconcentrationofglucose.Thistestshouldbeperformedwithsamplescontainingglucosewithinallthreeglucoseconcentrationranges(hypo/normo&hyperglycemia).

b. Thecomparativeglucometerscanthenbecomparedtotheprimaryglucometerasthestandardforongoingperformanceevaluations.Theprimaryglucometermeanresultforeachcontrolmaterialorpatientsampleusedforcomparativetestwillbeusedasthe‘bestestimate’ofthetrueresultforallglucometerswithintheorganization.

c. Allcomparativeglucometersshouldhavearesultthatfallswithinmeanprimaryglucometer±TEaforthematerialorpatientsamplethatistested.

d. Iftheglucoseresultofthecomparativemeterdoesnotfallwithinthemeanoftheprimarymeter±TEasetforthatglucoseconcentrationrangethenperformanceisconsideredunacceptable.Potentialcausesforunacceptableperformancecouldincludeoperatorerror,recordingerror,differentstriplotsetc.Furtherinvestigationshouldincludere-evaluationofPBGMperformancetoestablishCV,SDandbias.IfanyofthelaterresultschangetotheextentthattheTEasetbytheASVCPcannotbeachievedforall3glucoseconcentrationlevelsthenthemanufacturershouldbecontactedforassistanceorthePBGMshouldbereplaced.

5.AnnualperformanceevaluationoftheprimaryPBGMshouldensurethattheprecisionremainsthesame(orveryclosetothesame)astheinstrumentages.Shouldtherebeanyquestionregardingashiftinthebiasorchangeinprecisionwiththeprimaryinstrument,itshouldnolongerbeusedasabasisfortheongoingassessmentoftheotherglucometerswithintheorganization.Anewprimaryglucometershouldbechosenandallcomparativeglucometersre-evaluatedbasedonthenewprimaryglucometer.

6.ThisapproachtoharmonizationaimstomaintainthetotalanalyticalerrorwithintheASVCPguidelinestoimprovepatientcarefromatestingperspective.

6.5Non-StatisticalQualityAssuranceProcedures

Allcriterialistedinitem2.6.5ofSection2–QualityAssuranceGuidelinesforVeterinaryPoint-of-CareChemistryTestingarerelevant,butmedicalreviewcriteriadeserveparticularattentionwithPBGM.4

Staffshouldbetrainedtoreportanddocumentglucoseconcentrationsthatrequiretheimmediateattentionofaveterinarianinatimelymanner.Repeatcriteria


21

shouldbeinplacetodeterminewhetherfurtheraction(repeattestingorverificationbysendingouttoareferencelaboratoryorconfirmedbyanin-clinicbiochemistryanalyzer)isneeded.

6.6RecommendationsforPetOwners

OwnersusingPBGMforhomemonitoringofdiabeticpetsshouldreceive

traininginthecollectionofsamples,runningtests,handlingandstorageofteststrips,aswellasuseofoneormorecontrolmaterials.Theyshouldbeinstructedhowtocleanandstoretheglucometerbetweenevaluations.ThePBGMperformanceshouldbeevaluatedpriortoitsuseforhomemonitoringandperiodicparticipationinEQAandcomparativetestingwithareferencelaboratoryorin-cliniclaboratorybiochemistryanalyzerisrecommendedtohelpensureongoingproductionofreliableandaccurateresults.

7.0InstrumentProcurement

IfmultiplePBGMareneededatonehospitalortestingsite,thenideallytheorganizationshouldpurchasemultipleunitsofthesameinstrument.Ifthisisnotpossible,purchasingPBGMusingthesameanalyticalmethodologyandthathavebeencalibratedbythemanufacturertothesameanalyticalmethodisrecommended.Appendix1providescriteriaforconsideringwithinstrumentprocurementandtabulatessomesystemfunctionadvantagesinaquickreviewformat.8.0Summary

PBGMarevaluablePOCTinstruments.AbasicknowledgeofthevarietyofmethodsemployedinthesedevicesandtheirassociatedlimitationsmayassistclinicalpathologistsadvisingcliniciansonhowtogaugethedegreeofconfidencetheycanplaceinthetheirPBGMresults.Minimizingvariableslistedunderconsiderationsforglucosemetertestinginthisdocumentincludingpre-analytic,analyticandpostanalyticalerrorswillreducetheoccurrenceofinaccurateresults.ClinicalpathologistsshouldencourageandassistveterinarianstoestablishandmaintainaqualitymanagementprogramforallPBGMsinanorganizationbyapplyingtheASVCPrecommendations.TheyincludecustomizingQCforeachinstrumentbyQCvalidation,utilizingcontrolmaterials,harmonizationofinstrumentswhenmultipleinstrumentsarepresentatonelocationorwithinasystemofclinics,andparticipatingincomparabilitytestingwiththeirlocallaboratoryorexternalqualityassessmenttoensuretheaccuracyofresultsproducedbyPBGMsandprovideahighqualityofpatientcare.

9.0Acknowledgements

TheauthorswouldliketothankDr.BenteFlatland1,Dr.TracyStokol2andDr.MelindaCamus3fortheirthoroughreviewofthismanuscriptandcontributionstoitscontent.

1DepartmentofBiomedicalandDiagnosticSciences,CollegeofVeterinaryMedicine,UniversityofTennessee,Knoxville,TN,USA;2DepartmentofPopulationMedicineand


22

DiagnosticSciences,CollegeofVeterinaryMedicineCornellUniversity,Ithaca,NY,USA.3DepartmentofPathology,UniversityofGeorgiaCollegeofVeterinaryMedicine,Athens,GA,USA

Footnotes

#SureStepportablebloodglucosemonitor(marketedunderthenameGlucoTouchinEurope),LifeScanInc,Milpitas,Calif.* HemoCueB-glucosesystem(HemoCueAB,Angelhom,Sweden)&(HemoCueAmerica,Brea,CA,USA)Accessed30April,2014.**NOKLUS,Bergen,Norway.http://www.noklus.no/English.aspx.Email:[email protected]***Eurotrol,Inc.Burlington,Massachusetts,USA&EurotrolB.V.,Ede,Netherlands.https://www.eurotrol.com/index.php/products/diabetes-care/glucotrol-wbAccessed5December2013

Disclaimer

ThislistisforinformationalpurposesonlyanddoesnotconstitutealegalcontractorendorsementbetweenASVCPandanypersonorentityunlessotherwisespecified.TheASVCPdoesnotendorseanyparticularvendorormanufacturer.”

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32

11.0Appendix1

Criteria Preference

Technology&Methodology Enzyme&transducertype

Multiplemetersinanorganizationshouldbethesameproductorifnotpossible,usethesamemethodology

Specimentype Venouswholeblood,venousplasma/serum,capillaryblood

Measurementrange Widerange.Establishperformanceovertheentireglycemicrange(hypo/normo/hyperglycemic).

Hematocrit/packedcellvolumerange

TherangeofHCT/PCVwithinwhichglucosemeasurementisaccuratemaybebroaderinmetersdesignedforusebyprofessionalsthanthoseintendedforhomeuse.

Reportedresult Plasma–equivalentcalculatedresultorplasmacalibratedpreferred.

Reportedunit Fixedtooneunitmmol/lormg/dlispreferred

Numberandrangeofqualitycontrolmaterials(QCM)

3QCMarepreferredforperformanceevaluation.NumberofQCMandcontrolrulesideallyshouldbebasedonQCValidationusingperformancedatafromtheperformancevaluationstudy.


33

PropertiestoLookForWhenChoosingaGlucometer

Systemfunctionadvantages

• Systemsthatautomaticallycalibrateanddonotrequireuserinvolvement• Automaticstartandtimingofmeasurement• Ifinsufficientsampleisappliedthemetershouldfailtostartreading,flashawarning

lightoraudiblewarningmessage• Preventuseofincorrectlyinsertedorpreviouslyusedordamagedstrips• Listoflimitationsandinterferences(levels)andmeasurestakentoavoidthem• Training-Instructionmanualsandeducationchartsandmaterials

Valuablemanufacturer’sservices- Technicalsupport- Training- EnrolmentintoEQAschemesforglucosemeasurement

(humanschemesareacceptable)Abilitytoreserveasinglebatchofteststripsforlongtermuse

SystemFunctionAdvantages


34

12.0Tables

Table1.Analyticalanddetectionmethodsusedbyportablebloodglucosemeters

AnalyticalMethodEnzyme(reactswithglucose)

DetectionMethodTransucer(measuresglucose)

HexokinaseGlucoseOxidase(GO)GlucoseDehydrogenase(DHD)

Type SpecificMethod

OpticalSpectrophotometryPhotometry

ElectromechanicalPotentiometryAmperometryCoulometry

Table2Bilirubinconcentrationsatwhichinterferenceresultingininaccuracywasdetectedonportablebloodglucosemeterswithdifferentmethodologies

Method Glucoseoxidase GlucosedehydrogenaseNointerference

Upto1.4mg/dL78 26.5mg/dL74

Interference 17.5mg/dL75 20mg/dL73


35

Table3Exampleofperformanceevaluationusingtotalallowableerror(TE)recommendationsoftheAmericanSocietyofVeterinaryClinicalPathologyforhumanandveterinaryportablebloodglucosemeters(PBGM)inrabbits.59Totalerrorrecommendationsforthestudywere<±10%forresultsbelowtheestablishedreferenceintervaland<±20%forresultswithinoraboveestablishedreferenceinterval.Inthisstudy,theveterinaryPBGMyieldedunsatisfactoryperformanceforrabbitsusingthecanineandfelinesettingformostofthetestedglycemicstateswhereasthehumanPBGMperformedbetterthantheveterinaryinstrument

ASVCPTEaguideline HumanPBGM VeterinaryPBGMCaninesetting

VeterinaryPBGMFelinesetting

Hypoglycemia<10% TE=15.0%exceeded

TE=31.6%exceeded

TE=18.9%exceeded

Euglycemia<20% TE=10.7%acceptable

TE=24.8%exceeded

TE=7.3%acceptable

Hyperglycemia<20% TE=10.9%acceptable

TE=36.4%exceeded

TE=23.2%exceeded

Table4Comparabilitytesting:Examplesofacceptable&unacceptableresultsforPGBMascomparedtoareferencelaboratorychemistryanalyzer(goldstandard)

Referencelaboratorychemistryanalyzerresult

Totalallowableerror

TEarangeofvaluesforchemistryanalyzerresult

Portablebloodglucosemeter(PBGM)result

AcceptabilityofPBGMresultcomparedtoreferencelaboratoryresult

5.27mmol/L(95mg/dL)

20%5.27±20%

4.2-6.3mmol/L(76-114mg/dL)

5.55mmol/L(100mg/dL)

Acceptable

4.99mmol/L(90mg/dL)

20%

4.99±20%4-5.98mmol/L(72-108mg/dL)

3.88mmol/L(70mg/dL)

Unacceptable

2.89mmol/L(52mg/dL)

10%2.89±10%

2.6-3.18mmol/L(46.8-57.2mg/dL)

2.77mmol/L(50mg/dL)

Acceptable


36

Table5.Exampleofharmonizationevaluationofmultipleportablebloodglucosemetersusedinasingleorganization.Theprimarymeterwasusedasthereferencetowhichthetwocomparativeglucometers(1and2)werecompared.

Manufacturervalues

HypoglycemicTargetmean=2.2mmol/L(40mg/dL)

NormoglycemicTargetmean=5.9mmol/L(106mg/dL)

HyperglycemicTargetmean=19.1mmol/L(345mg/dL)

PBGM DatafrominitialperformanceevaluationSD(CV)Primary 0.06mmol/L

(2.9%)0.2mmol/L

(3.4%)0.7mmol/L

(3.7%)

Glucometer1 0.07mmol/L(3.2%)

0.4mmol/L(6.8%)

1.0 mmol/L(5.2%)

Glucometer2 0.07mmol/L(3.2%)

0.35mmol/L(5.9%)

1.2mmol/L(6.3%)

Combinedinherentimprecisionforeachglucometerandtheprimaryglucometer=√(CV2primaryglucometer+CV2

comparativeglucometer).Glucometer1

√(2.92+3.22)=√18.65=4.3%

√(3.42+6.82)=√57.80=7.6%

√(3.72+5.22)=√40.73=6.4%

Glucometer2 √2.92+3.22=√18.65=4.3%

√3.42+5.92=√46.37=6.8%

√3.72+6.32=√53.38=7.3%

MaximumbiasforeachcomparativeglucometerMaxBias=TEa–2*(combinedinherentimprecision)

Glucometer1 MaxBias=10-2(4.3)=10–8.6=1.4%

MaxBias=20–2(7.6)=20–15.2=4.8%

MaxBias=20–2(6.4)=20–12.8=7.2%

Glucometer2 MaxBias=10-2(4.3)=10–8.6=1.4%

MaxBias=20–2(6.8)=20–13.6=6.4%

MaxBias=20–2(7.3)=20–14.6=5.4%

EQAsamples Hypoglycemiarange

Normoglycemiarange

Hyperglycemiarange

PrimaryMeter

2.50mmol/L 6.1mmol/L 21mmol/L

Glucometer1 2.53mmol/L 6.4mmol/L 20mmol/L


37

CalculatedBiasofGlucometer1relativetoPrimarymeter

=(2.5-2.53/2.5)x100=0.03/2.5x100=1.20%

=(6.1-6.4/6.1)x100=0.3/6.1x100=4.9%

=(21-20/21)x100=1/21x100=4.8%

PerformanceofGlucometer1relativetoPrimarymeter

Thecalculatedbiasof1.20%is<maxbiasof1.4%forthehypoglycemicrange

=AcceptablePerformance

Thecalculatedbiasof4.9%is>maxbiasof4.8%forthenormoglycemicrange

=Unacceptableperformance

Thecalculatedbiasof4.8%is<maxbiasof7.2%forthehyperglycemicrange

=AcceptablePerformance


38

13.0FiguresFigure1SampleMatrixpropertieswhichmayaffectPBGMaccuracy

Patientage–neonatelower[glucose]comparedtoadults26,27

HCT26,27

RBCcount26,27

MCV26,27

Color–e.g.pigmentlikebilirubin,hemoglobin(hemolysis)26,27

Rouleaux–equinesamples28

Microclots26,29

Inflammation–increasedfibrinogen26,29

ProportionofglucoseboundinRBCversusplasma(speciesdifference)30,33,34

Plasmawatercontent–variationduetodisease31orspecies34(IfPBGMisdesignedaroundthehumanplasmawaterfractionmeanof0.95.32)


39

Figure245ComparisonofapplicationofEquationsAandBinFigure2tocalculateandreportplasmaglucoseequivalentresultsinportablebloodglucosemeters(PBGM)thatmeasurewholebloodglucose

Example:Wholebloodglucose=3.33mmol/L

EquationA𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂 = 𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒘𝒉𝒐𝒍𝒆 𝒃𝒍𝒐𝒐𝒅 ×𝟏.𝟏𝟏

HCT 15% 40% 60%𝐺𝑙𝑢𝑐𝑜𝑠𝑒!"#$%#

= 3.33×1.11

𝐺𝑙𝑢𝑐𝑜𝑠𝑒!"#$%#= 3.33×1.11

𝐺𝑙𝑢𝑐𝑜𝑠𝑒!"#$%#= 3.33×1.11

=3.69mmol/L =3.69mmol/L =3.69mmol/L

EquationB

𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂 = 𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒘𝒉𝒐𝒍𝒆 𝒃𝒍𝒐𝒐𝒅

𝟏.𝟎 − (𝟎.𝟎𝟎𝟐𝟒 ×𝑯𝒄𝒕%)

Whentheplasmaequivalentglucoseconcentrationiscalculatedfromawholebloodglucoseresult,thenthehighertheHCTofthepatientsamplethesmallerthedenominatorwillbethusgivingagreaterrelativecalculatedplasmaequivalentglucoseresultcomparedasamplewithalowerHCT.

HCT 15% 40% 60%

𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂

= 𝟑.𝟑𝟑𝒎𝒎𝒐𝒍/𝑳

𝟏.𝟎 − (𝟎.𝟎𝟎𝟐𝟒 ×𝟏𝟓%)



𝟏.𝟎 − (𝟎.𝟎𝟎𝟐𝟒 ×𝟒𝟎%)



𝟏.𝟎 − (𝟎.𝟎𝟎𝟐𝟒 ×𝟔𝟎%)𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂

= 𝟑.𝟑𝟑𝒎𝒎𝒐𝒍/𝑳𝟏.𝟎 − (𝟎.𝟎𝟑𝟔)


= 𝟑.𝟑𝟑𝒎𝒎𝒐𝒍/𝑳𝟏.𝟎 − (𝟎.𝟎𝟗𝟔)


= 𝟑.𝟑𝟑𝒎𝒎𝒐𝒍/𝑳𝟏.𝟎 − (𝟎.𝟏𝟒𝟒)



𝟎.𝟗𝟔𝟒



𝟎.𝟗𝟎𝟒



𝟎.𝟖𝟓𝟔𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂 = 𝟑.𝟒𝟓 𝒎𝒎𝒐𝒍/𝑳

𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂 = 𝟑.𝟔𝟖 𝒎𝒎𝒐𝒍/𝑳

𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂 = 𝟑.𝟖𝟗 𝒎𝒎𝒐𝒍/𝑳

WholebloodglucoseonaPBGM=3.33mmol/L(60mg/dl)

Calculatedplasmaglucose

reportedbyPBGM

EquationA EquationB HCT3.69mmol/L(62mg/dl) 3.45mmol/L(62mg/dl) 15%

3.69mmol/L(62mg/dl) 3.68mmol/L(66mg/dl) 40%

3.69mmol/L(62mg/dl) 3.89mmol/L(70mg/dl) 60%


40

14.0PBGMGuidelineComplianceChecklist

CompliancewithASVCPguidelinesisvoluntary.Purposeofthischecklististofacilitateguidelineimplementationandpracticalapplication.

(ThenumbersinthefirstcolumncorrespondtotheitemnumbersinthePBGMGuideline.)

GuidelineRecommendation Compliant? AuditorComment(s)4.0PBGMoperatorsareknowledgeableregardingtheoperation,principleofmeasurement,andpotentialerrorsassociatedwiththemethodologyusedontheinstrument.

☐ Yes☐No

5.1.1PBGMoperatorshavereceivedadequateinitialandongoingtraining,whichisdocumented.

☐ Yes☐No

5.1.2,5.1.3PBGMoperatorsunderstandpatientpreparationrequirementsforthedesiredapplicationofthetest.

☐ Yes☐No

5.1.3PBGMoperatorsareawareofthesamplecollectionvacutainerandvolumerequirementsneededfortheinstrument.

☐ Yes☐No

5.1.3PBGMoperatorsunderstandtheimportanceofstandardizationofthesampletypeandcollectionsitetominimizevariationduetothesepre-analyticalvariables.

☐ Yes☐No

5.1.4OperatorsofPBGMareawareofthepotentialoferroneousresultsduetodifferentanimalsamplerheologicalpropertiesifmetershavenotbeenvalidatedforveterinaryuse.

☐ Yes☐No


41

5.2.1OperatorsofPBGMknowandunderstandtheimportanceofthesampletypethePBGMreportsi.e.wholeblood,plasmaorcalculatedplasmaequivalent.

☐ Yes☐No

5.2.1OperatorsofPBGMsknowwhenandhowtoapplyglucosemeterconversionequations.

☐ Yes☐No

5.2.2.1Teststripsarestoredaccordingtomanufacturer’srecommendationsandareindate.

☐ Yes☐No

5.2.2.1Keycodeorotherinstructionsregardingbatchesofteststripsarefollowed.

☐ Yes☐No

5.2.2.1Correctspeciescodesareused,ifapplicable.

☐ Yes☐No

5.2.2.1Manufacturer’srecommendationsfortemperatureequilibrationofteststripsarefollowed.

☐ Yes☐No

5.2.2.1Manufacturer’sinstructionsfortimingofreactions(ifapplicable)arefollowed.

☐ Yes☐No

5.2.2.2Manufacturer’sinstructionsregardingenvironmentaltemperature,humidityandaltitudearefollowed.

☐ Yes☐No

5.2.2.3OperatorsofPBGMsareawarethattheperformance(accuracy)ofPBGMsmayvaryatdifferentglucoseconcentrations.

☐ Yes☐No

5.2.2.3OperatorsofPBGMsknowwhetherHCTisconcurrentlymeasured,whethertheinstrumentisHCTindependent,orifthisneedstobedoneasaseparateprocedure.OperatorsunderstandtheeffectofrangesofHCTonglucometerresultsandactionsthatshouldbetaken.

☐ Yes☐No


42

5.2.2.3,5.2.2.4Proceduresareinplacetoindicatepossibletestinterferencefromsubstancessuchaslipids,bilirubin,changesinpO2orpH,drugs,ifknownandapplicableattimeoftesting.

☐ Yes☐No

5.3.1PBGMoperatorsshouldbeawareofunitsinwhichtheglucoseresultisreportedtoavoidpossibleinadvertentchangeandmisinterpretationofresultsinadifferentunit.

☐ Yes☐No

5.3.2Recordsregardinginstrumentperformance,maintenance,batterychangedatesandQCarepresentandmaintained.

☐ Yes☐No

6.1ASVCP-recommendedguidelinesforTotalAllowableError(TEa)areusedtoevaluationinstrumentperformanceathypo/normo&hyperglycemicrangespriortoclinicaluse.

☐ Yes☐No

6.2Choiceofqualitycontrolmaterialsandruleshasbeentailoredforthespecificinstrument.

☐ Yes☐No

6.2PeriodicQCisperformedandfrequencyjustified.

☐ Yes☐No

6.2QCisperformedanddocumentedfollowingbatterychange,newlot/vial/batchofteststrips,instrumentdamage(e.g.dropped),orifthereisanyconcernregardingresultaccuracy.

☐ Yes☐No

6.3ThelaboratoryparticipatesinanExternalQualityAssuranceprogramforallPBGMsordoescomparativetestingwithareferencelaboratory.

☐ Yes☐No


43

6.3.EQAorcomparativetestingperformanceisdocumentedalongwithappropriateactionsifaproblemisidentified.

☐ Yes☐No

6.4IfmultiplePBGMsareused,theseshouldbeofthesametype(manufacturer)orusethesamemethodology.

☐ Yes☐No

6.4IfmultiplePBGMsareusedatonesite,thePBGMidentificationisrecordedwiththepatientresultandserialevaluationsconductedwiththesamePBGM(ifpossible).

☐ Yes☐No

6.4.IfmultiplePBGMsareusedatonesite,theyshouldallbeincludedinEQAorcomparativetestingorharmonizedtoensurecomparableresults.

☐ Yes☐No

6.5Appropriatenon-statisticalQC/QAproceduresareusedanddocumented,suchasrepeattesting,criticalmedicaldecisionlimitnotification,and/orverificationtesting.

☐ Yes☐No

6.6PetownersoperatingPBGMsfortheirdiabeticpetsshouldbetrainedtooperatePBGMsfordailyuseandapplicationofqualitycontrolmeasures.

☐ Yes☐No

6.6PerformanceofPBGMsusedbypetownersshouldevaluatedpriortohomeuseandperiodicallyinanEQAorcomparativetestprogram.

☐ Yes☐No