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    ROCCurvesAnalysis

    Introduction

    Receiveroperatingcharacteristic(ROC)curvesareusedinmedicinetodetermineacutoffvaluefora

    clinicaltest. Forexample,thecutoffvalueof4.0ng/mlwasdeterminedfortheprostatespecificantigen

    (PSA)testforprostatecancer. Atestvaluebelow4.0isconsideredtobenormalandabove4.0tobe

    abnormal. ClearlytherewillbepatientswithPSAvaluesbelow4.0thatareabnormal(falsenegative)and

    thoseabove4.0thatarenormal(falsepositive). ThegoalofanROCcurveanalysisistodeterminethe

    cutoffvalue.

    Assumethattherearetwogroupsofmenandbyusingagoldstandardtechniqueonegroupisknownto

    benormal(negative),nothaveprostatecancer,andtheotherisknowntohaveprostatecancer(positive).

    Abloodmeasurementofprostatespecificantigenismadeinallmenandusedtotestforthedisease.

    Thetestwillfindsome,butnotall,abnormalstohavethedisease. Theratiooftheabnormalsfoundby

    thetesttothetotalnumberofabnormalsknowntohavethediseaseisthetruepositiverate(alsoknown

    assensitivity). Thetestwillfindsome,butnotall,normalstonothavethedisease. Theratioofthe

    normalsfoundbythetesttothetotalnumberofnormals(knownfromthegoldstandardtechnique)is

    thetruenegativerate(alsoknownasspecificity). ThehopeisthattheROCcurveanalysisofthePSAtest

    willfindacutoffvaluethatwill,insomeway,minimizethenumberoffalsepositivesandfalsenegatives.

    Minimizingthefalsepositivesandfalsenegativesisthesameasmaximizingthesensitivityandspecificity.

    For

    the

    PSA

    test

    abnormal

    values

    are

    large

    (>

    4)

    and

    normal

    values

    are

    small

    (

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    1 - Specificity

    0.0 0.2 0.4 0.6 0.8 1.0

    Sensitivity

    0.0

    0.2

    0.4

    0.6

    0.8

    1.0

    Albumin, A = 0.72

    Figure1:AnexampleROCcurve.

    AnimportantmeasureoftheaccuracyoftheclinicaltestistheareaundertheROCcurve. Ifthisareais

    equalto1.0thentheROCcurveconsistsoftwostraightlines,oneverticalfrom0,0to0,1andthenext

    horizontalfrom0,1to1,1. Thistestis100%accuratebecauseboththesensitivityandspecificityare1.0

    sotherearenofalsepositivesandnofalsenegatives. Ontheotherhandatestthatcannotdiscriminate

    betweennormalandabnormalcorrespondstoanROCcurvethatisthediagonallinefrom0,0to1,1. The

    ROCareaforthislineis0.5. ROCcurveareasaretypicallybetween0.5and1.0likeshowninFigure1.

    TwoormoretestscanbecomparedbystatisticallycomparingtheROCareasforeachtest. Thetestsmay

    becorrelatedbecausetheyoccurredfrommultiplemeasurementsonthesameindividual. Ortheymay

    beuncorrelatedbecausetheyresultedfrommeasurementsondifferentindividuals. TheROCCurves

    AnalysisModulereferstothisasPairedandUnpaired,respectively,andcananalyzeeithersituation.

    Thetestmeasurementsmaycontainmissingvaluesandtwomethodsareprovidedtohandlemissing

    valueswhencomparingROCareaspairwisedeletionandcasewisedeletion. Thisisdescribedindetail

    later.

    Givenavaluefortheprobabilitythatthepatienthasthedisease(pretestprobability)theprobabilitythat

    thepatienthasthedisease,giventhevalueofthetestmeasurement,canbecomputed. Also,givena

    valueforthefalsepositive/falsenegativecostratio(forthescreeningexampleabove,thefalsenegative

    costwould

    be

    greater

    than

    the

    false

    positive

    cost),

    an

    optimal

    test

    value

    cutoff

    can

    be

    computed.

    The

    presentprogramallowsentryofthepretestprobabilityandthefalsepositive/falsenegativecostratio.

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    DataEntry

    Datacan

    be

    entered

    in

    two

    formats

    in

    SigmaPlot

    Indexed

    and

    Grouped.

    IndexedDataFormat

    ThisistheformatfoundinstatisticsprogramssuchasSYSTATandSigmaStat. Indexedisthe

    terminologyusedinSigmaStat. Ithasonecolumnthatindexesanothercolumn(orothercolumns). Itis

    alsotheformatoftheoutputoflogisticregressionwhereROCcurvesareusedtodeterminetheabilityof

    differentlogisticmodelstodiscriminatenegativefrompositivetestresults(normalsfromabnormals).

    Eachdatasetconsistsofapairofcolumnsaclassificationvariableandatestvariable. Theclassification

    variablehasabinarystatethatiseithernegative(normal)orpositive(abnormal).Manyprogramsusea

    valueof1forpositiveand0fornegative. Theclassificationvariableisrequiredtobelocatedincolumn1

    oftheworksheet. Thetestvariableisacontinuousnumericvariableandcontainsthetestresults. A

    singletest

    variable

    will

    be

    located

    in

    column

    2.

    Multiple

    test

    variables

    will

    be

    located

    in

    multiple

    columns

    startingincolumn2. Thereisnobuiltinlimitforthenumberoftestvariables. Thereisonlyone

    classificationvariableformultipletestvariablesanditislocatedincolumn1. Thetestvariablecolumns

    mustbeleftjustifiedandcontiguous. Thereforenoemptycolumnstotheleftoforwithinthedataare

    allowed.

    Thefollowingexampleshowsafewrowsofdatafortwodatasets. Thefirstcolumnistheclassification

    variable. ItcontainsacolumntitleThyroidFunctionwhichistheclassificationvariablename. Italso

    containsthetwoclassificationstatesHypothyroidandEuthyroid(normalthyroidfunction).

    HypothyroidandEuthyroidaretheabnormalandnormalclassificationstates,respectively. T4andT5are

    thenamesofdifferentbloodteststhatwillbeusedintheROCanalysistodiscriminatebetweennormal

    andabnormalandthencomparedtodeterminewhichisthebettertest. Theclassificationvariablemust

    be

    in

    column

    1

    and

    the

    two

    test

    variables

    in

    the

    two

    columns

    adjacent

    to

    it

    Theclassificationvariablenamewillbeobtainedfromthecolumn1columntitleifitexists. Thetest

    nameswillbeobtainedfromthecolumntitlesofthetestvariablecolumnsiftheyexist. Theclassification

    statenameswillbeobtainedfromtheentriesinthecellsofcolumn1. Ifnocolumntitleshavebeen

    enteredforthetestvariablesthendefaultnamesforthetests,Test1,Test2,etc.,willbeusedand

    displayedinthegraphsandreports. Thetestvariablenamesshouldbeuniquebuttheprogramwill

    subscriptanyidenticalnamesthatarenot.

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    Figure2:

    Indexed

    data

    format

    for

    two

    tests.

    The

    test

    names

    are

    T4

    and

    T5,

    the

    classificationstatesareEuthyroidandHypothyroidandtheClassificationvariable

    nameisThyroidFunction. Theindexcolumnisalwayscolumn1anddata

    columnsmustbeleftadjusted.

    Theremustbetwoormorenonmissingdatapointsforeachtestforeachclassificationstate.Missing

    valuesarehandledautomaticallybytheanalysis. Fordatacolumns,missingvaluesareeverythingbut

    numericvalues(blankcells,theSigmaPlotdoubledashmissingvaluesymbol,+inf,inf, NaN,etc.).

    MissingvaluesareignoredforallcomputationsexceptthePairedareacomparison(seetheMissingValue

    Methodsection)wheretheyarehandledusingoneoftwopossiblealgorithms.

    GroupedData

    Format

    Thegroupeddataformatconsistsofpairsofdatacolumnsonepairforeachtest. Onecolumninadata

    pairconsistsofthenegative(normal)datavaluesandtheothercolumnforpositive(abnormal)values.

    So,forexample,iftwotestsaretobecompared,theworksheetwillcontainfourcolumnsofdatathe

    firsttwocolumnsforthefirsttestandthethirdandfourthcolumnforthesecondtest.

    Aspecificcolumntitleformatisusedtoidentifythetestassociatedwiththedatacolumnpairandthe

    classificationstateswithineachpair. Theuserisencouragedtousethisformatsinceitclearlyidentifies

    thedatainthedataworksheetandwillannotateallthegraphsandreportsgenerated. Itisnotnecessary

    tousecolumntitlesastheprogramwillidentifycolumnpairsstartingincolumn1withthegeneratedtest

    namesTest1,Test2,etc.,andwillarbitrarilyassign1and0classificationstatenamestothefirst

    andsecond

    columns,

    respectively,

    but

    this

    is

    clearly

    not

    the

    best

    way

    to

    organize

    the

    data.

    Since

    the

    test

    namesandclassificationstatesarenumericalitisalsomoredifficulttointerprettheresults.

    ColumnTitleConventionforGroupedData

    ThiscolumntitleconventionisasimplewaytoidentifyworksheetdatafortheGroupeddataformat. The

    followingexampleshowsafewrowsfortwodatasets. ThefirsttwocolumnscontainthedatafortheT4

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    test. ThefirstcolumnT4 EuthyroidisthecolumnwiththenormaldatafortestT4. Thecolumntitle

    consistsofthetestnamefollowedbyaminussignfollowedbytheclassificationstate. Spacesoneither

    sideoftheminussignareignored. ThesecondcolumnT4 Hypothyroidisthecolumnwiththe

    abnormaldatafortestT4. Thethirdandfourthcolumntitlesarethesameasthefirsttwoexceptthe

    secondtestnameT5isused.

    Figure3. Groupeddataformatfortwotests. ThisisthesamedataasinFigure

    1. TherearetwotestsT4andT5. Eachtestconsistsofapairofdatacolumns. In

    thiscaseT4isincolumns1and2andT5incolumns3and4. TheTestState

    columntitleformatisusedtoidentifythetwotestsandthenormal(Euthyroid)

    andabnormal(Hypothyroid)states.

    Thetestnamesinbothcolumnsofacolumnpairmustbethesame. Alsotheremustbeexactlytwo

    classificationstatesinthecolumntitles.

    Likethe

    Indexed

    format,

    missing

    values

    in

    the

    worksheet

    cells

    are

    ignored

    except

    for

    special

    handling

    whencomparingROCareas(seetheMissingValueMethodsection).

    ProgramOptions

    SelectingROCCurvesfromtheSigmaPlotToolboxmenuopensthedialog

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    TestandclassificationstatenamesfromtheindexeddatashowninFigure2oftheDataEntrysectionare

    displayedinthisdialog.

    DataSelectionOptions

    DataFormat(AutomaticDetermination)

    Inmostcasetheprogramwillidentifythedataformatfromtheinformationinthedataworksheet. Inthe

    dialogabovetheformatwasidentifiedasIndexed. Youmayselectfromthetwoformats Indexedand

    Grouped.

    AvailableDataSetsSelectedDataSets

    SelectoneormoreoftheavailabledatasetsbyclickingonthemintheAvailableDataSetswindowand

    thenclickingontheAddbutton. Ifdesired,youmaythenselectatestnameintheSelectedDataSets

    windowandclickRemovetodeselectthetest.

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    DataType

    IftwoormoredatasetsareselectedthentheDataTypeoptionforcorrelatedtestsismadeavailable

    YoumayselecteitherPaired,forcorrelatedtests,orUnpaired. IfPairedisselectedtheROCareasand

    areacomparisonsaredeterminedusingtheDeLong,DelongandClarkePearsonmethod(2). IfUnpairedis

    selectedtheareasarecomputedusingtheHanleyandMcNeilmethod(3)

    andtheareasarecompared

    usingaZtest.

    MissingValueMethod

    IfmissingvaluesexistthentwooptionsareavailableforthepairwisecomparisonofROCareasPairwise

    DeletionandCasewiseDeletion. Thisoptionisnotavailableifnomissingvaluesexist.

    Pairwisedeletiononlydeletesrowscontainingmissingvaluesfortheparticularpairbeinganalyzednot

    foranentirerowofdata. Fewerdatavaluesaredeletedusingthismethod. Therearesituationswhen

    pairwisedeletionwillfailbutthisistheoptiontousewhenitispossible. Casewisedeletiondeletesall

    cellsinanyrowofdatacontainingamissingvalue.Muchmoredatamaybedeletedusingthisoption. To

    betterunderstandthedifference,considerasimpleexampleoftwodatacolumnsofequallengthoneof

    whichhasnomissingvaluesandtheotherhasonemissingvalue.WhenROCareasarebeingcompared,

    certaincomputationsonthesetwocolumnswillbedonepairwisethefirstcolumnwithitself,thefirst

    columnwiththesecondcolumnandthesecondcolumnwithitself.Whenthecolumnwithoutamissingvalueisbeingcomparedwithitselfnorowdeletionsoccurforpairwisedeletion. Forcasewisedeletion,

    however,therowthatcontainsthemissingvaluewillbedeletedfrombothdatasets. So,forcasewise

    deletion,thecomputationinvolvingthecolumnwithoutamissingvaluewithitselfwillbedonewithone

    rowdeleted(therowcorrespondingtothemissingvalueintheotherdataset). Theprogramdetermines

    whenpairwisedeletionisnotvalidandinformstheuserwhenthisisthecase.

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    PositiveStateOptions ClassificationStateandDirection

    ThetwoclassificationstatesarereferredtoasNegative(normal)orPositive(abnormal). TheROC

    analysissoftwaremustbeinformedwhichstateisPositiveandwhetherthetestmeasurementvalues

    forthepositivestateareHigh,meaninghigherthanthoseofthenegativestate,orLow,meaning

    lowerthanthoseofthenegativestate.

    AcceptednormalvaluesforthePSA(prostatespecificantigen)testarelessthan4ng/mlandabnormal

    valuesarehigherthanthis. Thusifthetwoclassificationstatesnamesarepositiveandnegativethen

    thePositivestateispositiveandthePositiveDirectionisHigh. Inthiscaseyouwouldselecttheradio

    buttonnexttopositiveandHigh.

    Ontheotherhand,fortheT4(thyroxine)testforhypothyroidismtheT4valuesarelowerintheabnormal

    statethanforthenormalstate. InthiscasetheabnormalPositiveStateisHypothyroidandthePositive

    DirectionisLow. SoyouwouldselecttheradiobuttonnexttoHypothyroidandLow.

    Whathappensifyouselecttheincorrectoption? Sensitivity(specificity)isdefinedintermsofthepositive

    (negative)state. Soifthepositivestateisincorrectlyselectedthensensitivityandspecificitywillbe

    incorrectlydefined(switched)andtheROCcurvewillhavetheXandYaxesswitched. Thiswillresultinan

    ROCcurvethatappearsbelowthediagonalunityline. Itwillhaveanarealessthan0.5. Theprogramwill

    detectthisandgiveyoutheoptions

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    ItispossiblethatthereissomethingwrongwiththedatasoyoucanAborttheanalysisandcorrectthe

    problem.MorelikelyyouhaveselectedtheincorrectpositivestateordirectionsoyoucanRetrythe

    analysiswithcorrectselections. Inrareoccasionsformultipletestssometestswillhaveareasgreater

    than0.5andoneormorewillhaveareaslessthan0.5. InthiscaseyoucanIgnorethiswarningand

    continuewiththeanalysis.

    ReportOptions

    ConfidenceIntervals

    ConfidenceintervalsarecomputedforstatisticsinboththeSensitivity&SpecificityandAreaComparison

    reports. Youcangenerate90,95and99%confidenceintervals.

    CreateSensitivityandSpecificityReport

    Cutoffvaluesarecreatedbetweeneachtestdatavalueinthe(sorted)dataset. Iftherearealarge

    numberof

    data

    points

    and

    several

    tests

    then

    there

    will

    be

    alarge

    number

    of

    cutoff

    values

    and

    the

    Sensitivity&SpecificityReportcanbeverylong. Thecheckbox

    allowsyoutoturnoffthisreport. Ifyouturnoffthisreportthenallreportoptionsinthedialogbelowthis

    arenotrequiredandaredisabled.

    Fractions/Percents

    Youmaydisplaysensitivities,specificitiesandprobabilitiesineitherfractionorpercentformat. Selecting

    Percentsalso

    requires

    the

    pre

    test

    probability

    to

    be

    entered

    as

    apercent.

    CreatePostTestResults

    Selectingthisoptionallowsentryofthepretestprobability. Italsoenablesthepossibleentryofthe

    falsepositive/falsenegativecostratio. Givenapretestprobabilitytheprogramwillcreateposttest

    probabilities,boththepositivepredictivevalue(PV+=probabilityofdiseasegivenapositivetestresult)

    andthenegativepredictivevalue(PV =probabilityofnodiseasegivenanegativetestresult),foreach

    cutoffvalue. Ifthecostratiooptionisselectedthentheoptimalcutoffvaluewillbecomputed. Allof

    theseresultsaredisplayedforeachtestintheSensitivity&Specificityreport.

    ROCGraph

    Options

    AllofthegraphoptionsinthedialogapplytotheROCgraph. Theyallowyoutoaddadiagonallinetothe

    graph,addgridlines,addsymbolsforsensitivityandspecificityateachcutoffpointandchangetheROC

    plotlinesfromsolidtodifferentlinestyles.

    AnalysisResults

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    Introduction

    TypicalresultsoftheROCanalysisareshowninthefollowingexamplefromtheNotebookManager.

    ThefirstsectionentitledOvarianCancercontainstheworksheetcontainingtherawdata. Theprogram

    createdthenextthreesectionsthatcontaintwographsandtworeports. Thecontentsofthetwographs

    ROCCurves

    DotHistogram

    andthetworeports

    Sensitivity&Specificity

    ROCAreas

    aredescribedinthenextsections.

    ROCCurvesGraph

    TheROCcurvesgraphforthreedatasetsisshowninFigure4. Thesegraphsarederivedfromnumerical

    resultsintheworksheetentitledGraphData. Thegraphtitleisobtainedfromthesectionname

    containingtherawdata. ThelegendshowsthetestnamesandtheROCareasforeachcurve. The

    diagonallineandgridsoptionswereselectedforthisgraph.

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    Ovarian Cancer ROC Curves

    1 - Specificity

    0.0 0.2 0.4 0.6 0.8 1.0

    Sensitivity

    0.0

    0.2

    0.4

    0.6

    0.8

    1.0

    US, A = 0.85

    CT, A = 0.93

    MR, A = 0.99

    Figure4. TheROCcurvesgraphforthreetests.

    Ofcoursethisgraphcanbeeditedinanywayyouwish. Youmightwanttochangethestartingcolorof

    thecolorschemeusedforthelinecolors. YoucandothisbydoubleclickingononeoftheROCplotlines

    andthenrightclickingontheLineColorlistboxasshownnext.

    DotHistogramGraph

    DothistogramsforthedataassociatedwiththeROCcurvesinFigure4areshowninFigure5below.

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    Ovarian Cancer Data

    US-normal

    US-abnormal

    CT-norm

    al

    CT-abnormal

    MR-norm

    al

    MR-abno

    rmal

    TestValue

    0

    2

    4

    6

    8

    10

    12

    14

    Cutoff < 7.13

    Sens = 0.78

    Spec = 0.85

    Cutoff < 7.14

    Sens = 0.84

    Spec = 0.97

    Cutoff < 8.34

    Sens = 0.94

    Spec = 0.97

    Figure5: Dothistogrampairsforeachtest. Thehorizontallinesandthetables

    belowthegraphshowtheoptimalcutoffvaluesdeterminedfromthepretest

    probabilityandcostratio.

    Thegraphtitleisobtainedfromthetitleofthesectioncontainingtherawdata. Thexaxisticklabelsare

    obtainedfromthetestnamesandtheclassificationstatenames. Theticklabelswillrotateiftheyaretoo

    longto

    fit

    horizontally.

    The

    symbol

    layout

    design

    allows

    for

    symbols

    to

    touch

    horizontally

    and

    nest

    vertically.

    Ifvaluesforpretestprobabilityandfalsepositive/falsenegativecostratioareenteredthentheoptimal

    cutoffvaluesforeachtestarecomputedandrepresentedasahorizontallineacrossthetwodot

    histogramsforeachtest. Thenumericvaluesfortheoptimalcutoffparametersareshownastables

    belowthexaxis.

    Sensitivity&SpecificityReport

    Thesensitivity&Specificityreportcontainsresultsforalltestswithadditionaltestsresultsplacedin

    reportrows

    below

    those

    of

    prior

    tests.

    The

    results

    for

    each

    test

    can

    be

    separated

    into

    three

    parts:

    1)

    optimalcutoffvalue,2)sensitivityandspecificityversuscutoffvaluesand3)likelihoodratiosandpost

    testprobabilities.

    Ifvaluesforbothpretestprobabilityandcostratiohavebeenenteredthentheoptimalcutoffis

    calculated. AslopeofthetangenttotheROCcurvemisdefinedintermsofthetwoenteredvalues(P=

    pretestprobability)(1)

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    1false positive c os t Pm

    false negative cos t P

    =

    (1)

    Theoptimalcutoffvalueiscomputedfromsensitivityandspecificityusingtheslopembyfindingthe

    cutoffthatmaximizesthefunction(1)

    ( )1Sensitivity m Specificity (2)

    TheresultsofthiscomputationintheSensitivity&SpecificityreportareshowninTable1.

    Table1: OptimalcutoffresultsintheSensitivity&Specificityreport.

    Forthisdataset,theoptimalcutoffis7.125forapretestprobabilityof0.5andcostratioof1.0.

    Sensitivities,specificitiesandtheirconfidenceintervalsarelistedasafunctionofcutoffvalueinthe

    secondpartofthereport. AportionoftheseresultsisshowninTable2. Theseresultscanbeexpressed

    asfractionsorpercentsbyusingtheFractions/Percentsoption.

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    Table2: SensitivityandspecificityresultsintheSensitivity&Specificityreport.

    ThethirdpartoftheSensitivity&Specificityreportcontainsthelikelihoodratiosandposttest

    probabilities.

    Thepositiveandnegativelikelihoodratiosaredefinedrespectivelyas

    1

    Pr obability of a positive test given the presenceof disease SensitivityLR

    Pr obability of a positivetest given the absenceof disease Specificity+ = =

    (3)

    1Pr obability of a negativetest given the presence of disease SensitivityLR

    Pr obability of a negative test given the absenceof disease Specificity

    = = (4)

    Theposttestprobabilitiesaretheprobabilityofdiseasegivenapositivetest(PV+)andtheprobabilityof

    nodiseasegivenanegativetest(PV). Thesewillbecomputedwhenapretestprobabilityhasbeen

    entered.Using

    P=pre

    test

    probability,

    the

    equations

    used

    for

    these

    probabilities

    are

    ( ) ( )1 1Sensitivity x P

    PVSensitivity x P Specificity x P

    + =+

    (5)

    ( )

    ( ) ( )

    1

    1 1

    Specificity x PPV

    Specificity x P Sensitivity x P

    =

    + (6)

    AportionofthereportshowingthelikelihoodandposttestprobabilitiesresultsisshowninTable3.

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    Table3: Positiveandnegativelikelihoodratios,LR+andLR,andposttest

    probabilities,PV+andPV,intheSensitivity&Specificityreport.

    Thepositivelikelihoodratioisnotdefinedforsomecutoffvaluessincespecificity=1.

    ROCAreas

    Report

    TheROCAreareportconsistsoftwoparts:1)ROCareasandtheirassociatedstatisticsand2)pairwise

    comparisonofROCareas. AnexampleofareportisshowninTable4.

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    Table4: AnexampleROCAreasreport. Fromtoptobottomitshowsthetypeof

    analysisusedtogetherwiththemissingvaluemethod,theROCareasand

    associatedstatisticsandapairwisecomparisonofROCareas.

    Inthis

    case

    there

    are

    three

    correlated

    tests.

    Row

    two

    of

    the

    report

    shows

    that

    aPaired

    Analysis

    was

    performedand,sincethereweremissingvaluesinthedata,PairwiseDeletionofmissingvalueswas

    selectedtocomparetheareas.

    ThefirstsectionofthereportshowstheROCcurveareasforthethreetests. Thisisfollowedbythe

    standarderroroftheareaestimate,the95%confidenceinterval(90%and99%arealsoavailable)andthe

    Pvaluethatdeterminesiftheareavalueissignificantlydifferentfrom0.5. Thesamplesizeandthe

    numberofmissingvaluesforeachclassificationstatearegiven. Thenumberofmissingvaluesreflects

    onlywhatisseeninthedataanddoesnotgivethenumberusedforeachcomputationpairinthe

    pairwisedeletedcomparisonofareas.

    Thesecondsectionshowstheresultsofthepairwisecomparisonofareas. ThemethodofDeLong,

    DeLongandClarkePearson(2)

    isusedtocompareareaswhenthePaireddatatypeoptionisselected.

    Whenthe

    Unpaired

    data

    type

    is

    selected,

    areas

    are

    compared

    using

    aZtest.

    The

    report

    shows

    results

    for

    allpairsofdatasets. Thedifferenceofeachareapairanditsstandarderrorand95%confidenceinterval

    arecomputed. Thisisfollowedbythechisquarestatisticfortheareacomparison(orZstatisticif

    Unpairedisselected)anditsassociatedPvalue.

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    FormattedFullPrecisionDisplay

    Thisreportpresentsthenumericresultsinafoursignificantdigitformatwithfullprecisionavailable.

    Doubleclickonanycell(excepttheconfidenceintervals)todisplaythenumberatfullprecision.

    AdditionalGraphs

    Resultsdatainbothreportscanbeusedtocreateadditionalgraphs. Someexamplesseeninthe

    literatureareshownhere.

    SensitivityandSpecificityvs.Cutoff

    ThedataforthegraphinFigure6isfromtheSensitivity&Specificityreportincolumns1,2and4. Use

    theDataSamplingoptioninGraphProperties,Plots,Datatospecifytherowrangeforthegraph(youcan

    alsodragselecttherowsintheworksheettodothis).

    Cutoff

    0 2 4 6 8 10 12 14

    Sensitivity

    0.0

    0.2

    0.4

    0.6

    0.8

    1.0

    S

    pecificity

    0.0

    0.2

    0.4

    0.6

    0.8

    1.0

    Figure6:Graphofsensitivityandspecificityvs.cutoffforonetestusingdata

    fromcolumns1,2and4oftheSensitivity&Specificityreport.

    LikelihoodRatios

    ThepositiveandnegativelikelihoodratiosforthreedifferentimagingmodalitiesareshowninFigure7

    (thedataisartificial). Thedataisincolumns1,6and7oftheSensitivity&Specificityreport. Thevalues

    associatedwiththeoptimalcutoffareshownassolidsymbols. Thelargestpositivelikelihoodand

    smallestnegativelikelihoodattheoptimalcutoffisassociatedwithmagneticresonanceimaging(MR).

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    Likelihood Ratio of a Positive Test

    Cutoff

    4 5 6 7 8 9 10

    LR

    +

    0

    20

    40

    60

    80

    US

    CT

    MR

    Likelihood Ratio of a Negative Test

    Cutoff

    4 5 6 7 8 9 10

    LR-

    0.0

    0.2

    0.4

    0.6

    0.8

    1.0

    1.2

    US

    CT

    MR

    Figure7: Positiveandnegativelikelihoodratiosgraphedfromdatainthe

    Sensitivity&Specificityreportfromcolumns1,6and7. Theresultsforthree

    testsareshowntogetherwithvaluesassociatedwiththeoptimalcutoff(solid

    symbols).

    OptimalCutoffvs.CostRatio

    Frequentlyitcanbedifficulttodetermineavalueforthefalsepositive/falsenegativecostratio. Soitis

    worthperformingasensitivityanalysis(sensitivityheremeanshowmuchonevariablechangeswith

    changesinasecondvariable)toseewhetherthecutoffvaluechangessignificantlyintherangeofcost

    ratiovaluesofinterest. TheROCCurvesModulewasrunmultipletimesfordifferentcostratiosanda

    graphofoptimalcutoffvs.costratioforthethreeimagingmodalitytestsisshownbelow.

    Cost Ratio

    0.1 1 10

    OptimalCutoff

    4

    6

    8

    10

    12

    14

    US

    CTMR

    Figure8: Optimalcutoffvaluesobtainedfrommultiplerunsoftheprogram.

    Regionsofinsensitivity,orstrongsensitivity,tocostratiocanbeidentified.

    Iftherelativecostofafalsepositiveismuchgreaterthanthatofafalsenegativethenthecostratiois

    greaterthan1. Butletsassumethatwedontknowexactlyhowmuchgreateritisbuthavesomeidea

    thatitshouldbeintherangeof2to5,say. Lookingattheoptimalcutoffforthebestimagingmodality

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    (MR,greenline)wefindthatitdoesntchangeforcostratiosfrom2to20. Sotheoptimalcutoffis

    insensitivetocostratioand,inthiscase,itisnotimportanttoknowaprecisevalueforcostratio.

    PostTestProbabilityvs.PreTestProbability

    Givenvaluesofsensitivityandspecificityassociatedwiththeoptimalcutoffagraphofposttest

    probabilitiesasafunctionofpretestprobabilitycanbecreatedusingequations(5)and(6). Theposttest

    probabilityofdiseasewhenthetestispositive,bluelinesinFigure9,wasobtainedfromequation(5)and

    theposttestprobabilityofdiseasewhenthetestwasnegative,redlines,wasobtainedfrom1.0minus

    equation(6). AtransformwaswritteninSigmaPlotimplementingthesetwoequationsthatgeneratedthe

    posttestprobabilitiesforarangeofpretestprobabilities. Theresultsforthebesttest,MR,andworst

    test,US,areshown. TheMRtestisclearlybettersincetheposttestprobabilityrange,fromnegativetest

    topositivetest,islarger. Thusgivenapositivetestthepatientismorelikelytohavethediseaseusingthe

    MRtestratherthantheUStest. Similarly,givenanegativetestitislesslikelythatthepatienthasthe

    diseaseusingtheMRtest.

    Imaging Modalities

    Pre-Test Probability

    0.0 0.2 0.4 0.6 0.8 1.0

    Post-TestProbability

    0.0

    0.2

    0.4

    0.6

    0.8

    1.0

    US

    MR

    Test Positive

    Test Negative

    Figure9: Posttestprobabilitiesofdiseasegivenpositiveandnegativetest

    results. TheMRtestisbasedonsensitivity=0.94andspecificity=0.97whereas

    theUStestusedsensitivity=0.78andspecificity=0.85.

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