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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].”
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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
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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
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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
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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
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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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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.
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PropertiestoLookForWhenChoosingaGlucometer
Systemfunctionadvantages
• Systemsthatautomaticallycalibrateanddonotrequireuserinvolvement• Automaticstartandtimingofmeasurement• Ifinsufficientsampleisappliedthemetershouldfailtostartreading,flashawarning
lightoraudiblewarningmessage• Preventuseofincorrectlyinsertedorpreviouslyusedordamagedstrips• Listoflimitationsandinterferences(levels)andmeasurestakentoavoidthem• Training-Instructionmanualsandeducationchartsandmaterials
Valuablemanufacturer’sservices- Technicalsupport- Training- EnrolmentintoEQAschemesforglucosemeasurement
(humanschemesareacceptable)Abilitytoreserveasinglebatchofteststripsforlongtermuse
SystemFunctionAdvantages
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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
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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
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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
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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
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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)
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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%)
𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂
= 𝟑.𝟑𝟑𝒎𝒎𝒐𝒍/𝑳
𝟏.𝟎 − (𝟎.𝟎𝟎𝟐𝟒 ×𝟒𝟎%)
𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂
= 𝟑.𝟑𝟑𝒎𝒎𝒐𝒍/𝑳
𝟏.𝟎 − (𝟎.𝟎𝟎𝟐𝟒 ×𝟔𝟎%)𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂
= 𝟑.𝟑𝟑𝒎𝒎𝒐𝒍/𝑳𝟏.𝟎 − (𝟎.𝟎𝟑𝟔)
𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂
= 𝟑.𝟑𝟑𝒎𝒎𝒐𝒍/𝑳𝟏.𝟎 − (𝟎.𝟎𝟗𝟔)
𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂
= 𝟑.𝟑𝟑𝒎𝒎𝒐𝒍/𝑳𝟏.𝟎 − (𝟎.𝟏𝟒𝟒)
𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂
= 𝟑.𝟑𝟑𝒎𝒎𝒐𝒍/𝑳
𝟎.𝟗𝟔𝟒
𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂
= 𝟑.𝟑𝟑𝒎𝒎𝒐𝒍/𝑳
𝟎.𝟗𝟎𝟒
𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂
= 𝟑.𝟑𝟑𝒎𝒎𝒐𝒍/𝑳
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%
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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
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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
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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
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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