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Understandingsurvivalanalysis:KaplanMeierestimate

IntJAyurvedaRes.2010OctDec1(4):274278.

PMCID:PMC3059453

doi:10.4103/09747788.76794

Understandingsurvivalanalysis:KaplanMeierestimate
ManishKumarGoel,PardeepKhanna,andJugalKishore1
DepartmentofCommunityMedicine,PostGraduateInstituteofMedicalScience,Rohtak,Haryana,India
1
DepartmentofCommunityMedicine,MaulanaAzadMedicalCollege,NewDelhi,India
Addressforcorrespondence:Prof.JugalKishore,DepartmentofCommunityMedicine,MaulanaAzadMedicalCollege,NewDelhi110002,
India.Email:drjugalkishore@gmail.com
Received2010Oct8Accepted2011Jan15.
Copyright:InternationalJournalofAyurvedaResearch
ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionNoncommercialShareAlike3.0Unported,which
permitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.

Abstract
KaplanMeierestimateisoneofthebestoptionstobeusedtomeasurethefractionofsubjectslivingfora
certainamountoftimeaftertreatment.Inclinicaltrialsorcommunitytrials,theeffectofaninterventionis
assessedbymeasuringthenumberofsubjectssurvivedorsavedafterthatinterventionoveraperiodoftime.
Thetimestartingfromadefinedpointtotheoccurrenceofagivenevent,forexampledeathiscalledas
survivaltimeandtheanalysisofgroupdataassurvivalanalysis.Thiscanbeaffectedbysubjectsunderstudy
thatareuncooperativeandrefusedtoberemainedinthestudyorwhensomeofthesubjectsmaynot
experiencetheeventordeathbeforetheendofthestudy,althoughtheywouldhaveexperiencedordiedif
observationcontinued,orwelosetouchwiththemmidwayinthestudy.Welabelthesesituationsas
censoredobservations.TheKaplanMeierestimateisthesimplestwayofcomputingthesurvivalovertimein
spiteofallthesedifficultiesassociatedwithsubjectsorsituations.Thesurvivalcurvecanbecreated
assumingvarioussituations.Itinvolvescomputingofprobabilitiesofoccurrenceofeventatacertainpointof
timeandmultiplyingthesesuccessiveprobabilitiesbyanyearliercomputedprobabilitiestogetthefinal
estimate.Thiscanbecalculatedfortwogroupsofsubjectsandalsotheirstatisticaldifferenceinthesurvivals.
ThiscanbeusedinAyurvedaresearchwhentheyarecomparingtwodrugsandlookingforsurvivalof
subjects.
Keywords:Survivalanalysis,KaplanMeierestimate

INTRODUCTION
Forhumansubjects,tocompareefficacyandsafety,controlledexperimentsareconductedwhicharecalled
asclinicaltrials.[1]Inclinicalorcommunitytrials,theeffectofaninterventionisassessedbymeasuringthe
numberofsubjectssurvivedorsavedafterthatinterventionoveraperiodoftime.Sometimeitisinteresting
tocomparethesurvivalofsubjectsintwoormoreinterventions.Insituationswheresurvivalistheissuethen
thevariableofinterestwouldbethelengthoftimethatelapsesbeforesomeeventtooccur.Inmanyofthe
situationsthislengthoftimeisverylongforexampleincancertherapyinsuchcaseperunitdurationoftime
numberofeventssuchasdeathcanbeassessed.Inothersituations,thedurationforhowlonguntilacancer
relapsesorhowlonguntilaninfectionoccurscanbeassessed.Sometimesitcanevenbeusedforaspecific
outcome,likehowlongittakesforacoupletoconceive.Thetimestartingfromadefinedpointtothe
occurrenceofagiveneventiscalledasthesurvivaltime[2]andtheanalysisofgroupdataasthesurvival
analysis.[3]
Theseanalysesareoftencomplicatedwhensubjectsunderstudyareuncooperativeandrefusedtobe
remainedinthestudyorwhensomeofthesubjectsmaynotexperiencetheeventordeathbeforetheendof
thestudy,althoughtheywouldhaveexperienceordied,orwelosetouchwiththemmidwayinthestudy.
Welabelthesesituationsasrightcensoredobservations.[2]Forthesesubjectswehavepartialinformation.
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Weknowthattheeventoccurred(orwilloccur)sometimeafterthedateoflastfollowup.Wedonotwantto
ignorethesesubjects,becausetheyprovidesomeinformationaboutsurvival.Wewillknowthatthey
survivedbeyondacertainpoint,butwedonotknowtheexactdateofdeath.
Sometimeswehavesubjectsthatbecomeapartofthestudylater,i.e.asignificanttimehaselapsedfromthe
start.Wehaveashorterobservationtimeforthosesubjectsandthesesubjectsmayormaynotexperiencethe
eventinthatshortstipulatedtime.However,wecannotexcludethosesubjectssinceotherwisesamplesizeof
thestudymaybecomesmall.TheKaplanMeierestimateisthesimplestwayofcomputingthesurvivalover
timeinspiteofallthesedifficultiesassociatedwithsubjectsorsituations.
TheKaplanMeiersurvivalcurveisdefinedastheprobabilityofsurvivinginagivenlengthoftimewhile
consideringtimeinmanysmallintervals.[3]Therearethreeassumptionsusedinthisanalysis.Firstly,we
assumethatatanytimepatientswhoarecensoredhavethesamesurvivalprospectsasthosewhocontinueto
befollowed.Secondly,weassumethatthesurvivalprobabilitiesarethesameforsubjectsrecruitedearlyand
lateinthestudy.Thirdly,weassumethattheeventhappensatthetimespecified.Thiscreatesproblemin
someconditionswhentheeventwouldbedetectedataregularexamination.Allweknowisthattheevent
happenedbetweentwoexaminations.Estimatedsurvivalcanbemoreaccuratelycalculatedbycarryingout
followupoftheindividualsfrequentlyatshortertimeintervalsasshortasaccuracyofrecordingpermitsi.e.
foroneday(maximum).TheKaplanMeierestimateisalsocalledasproductlimitestimate.Itinvolves
computingofprobabilitiesofoccurrenceofeventatacertainpointoftime.Wemultiplythesesuccessive
probabilitiesbyanyearliercomputedprobabilitiestogetthefinalestimate.Thesurvivalprobabilityatany
particulartimeiscalculatedbytheformulagivenbelow:

Foreachtimeinterval,survivalprobabilityiscalculatedasthenumberofsubjectssurvivingdividedbythe
numberofpatientsatrisk.Subjectswhohavedied,droppedout,ormoveoutarenotcountedasatriski.e.,
subjectswhoarelostareconsideredcensoredandarenotcountedinthedenominator.Totalprobabilityof
survivaltillthattimeintervaliscalculatedbymultiplyingalltheprobabilitiesofsurvivalatalltimeintervals
precedingthattime(byapplyinglawofmultiplicationofprobabilitytocalculatecumulativeprobability).For
example,theprobabilityofapatientsurvivingtwodaysafterakidneytransplantcanbeconsideredtobe
probabilityofsurvivingtheonedaymultipliedbytheprobabilitysurvivingtheseconddaygiventhatpatient
survivedthefirstday.Thissecondprobabilityiscalledasaconditionalprobability.Althoughtheprobability
calculatedatanygivenintervalisnotveryaccuratebecauseofthesmallnumberofevents,theoverall
probabilityofsurvivingtoeachpointismoreaccurate.Letustakeahypotheticaldataofagroupofpatients
receivingstandardantiretroviraltherapy.Thedatashowsthetimeofsurvival(indays)amongthepatients
enteredinaclinicaltrial(E.g.1)6,12,21,27,32,39,43,43,46F*,89,115F*,139F*,181F*,211F*,
217F*,261,263,270,295F*,311,335F*,346F*,365F*(*meansthesepatientsarestillsurvivingafter
mentioneddaysinthetrial.)
Weknowaboutthetimeoftheevent,i.e.deathineachsubject,afterhe/shehadenteredthetrial,mayitbeat
differenttimes.Therearealsoafewsubjectswhoarestillsurvivingi.e.attheendofthetrial.Eveninthese
conditionswecancalculatetheKaplanMeierestimatesassummarizedinTable1.
ThetimetforwhichthevalueofLi.e.totalprobabilityofsurvivalattheendofaparticulartimeis0.50is
calledasmediansurvivaltime.Theestimatesobtainedareinvariablyexpressedingraphicalform.Thegraph
plottedbetweenestimatedsurvivalprobabilities/estimatedsurvivalpercentages(onYaxis)andtimepastafter
entryintothestudy(onXaxis)consistsofhorizontalandverticallines.[4]Thesurvivalcurveisdrawnasa
stepfunction:theproportionsurvivingremainsunchangedbetweentheevents,eveniftherearesome
intermediatecensoredobservations.Itisincorrecttojointhecalculatedpointsbyslopinglines[Figure1].
Wecancomparecurvesfortwodifferentgroupsofsubjects.Forexample,comparethesurvivalpatternfor
subjectsonastandardtherapywithanewertherapy.Wecanlookforgapsinthesecurvesinahorizontalor
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verticaldirection.Averticalgapmeansthatataspecifictimepoint,onegrouphadagreaterfractionof
subjectssurviving.Ahorizontalgapmeansthatittooklongerforonegrouptoexperienceacertainfraction
ofdeaths.
LetustakeanotherhypotheticaldataforexampleofagroupofpatientsreceivingnewAyurvedictherapyfor
HIVinfection.Thedatashowsthetimeofsurvival(indays)amongthepatientsenteredinaclinicaltrial(as
ine.g.1)9,13,27,38,45F*,49,49,79F*,93,118F*,118F*,126,159F*,211F*,218,229F*,263F*,
298F*,301,333,346F*,353F*,362F*(*meansthesepatientsarestillsurvivingaftermentioneddaysinthe
trial.)
TheKaplanMeierestimatefortheaboveexampleissummarizedinTable2.
Thetwosurvivalcurvescanbecomparedstatisticallybytestingthenullhypothesisi.e.thereisnodifference
regardingsurvivalamongtwointerventions.Thisnullhypothesisisstatisticallytestedbyanothertestknown
aslogranktestandCoxproportionhazardtest.[5]Inlogranktestwecalculatetheexpectednumberof
eventsineachgroupi.e.E1andE2whileO1andO2arethetotalnumberofobservedeventsineachgroup,
respectively[Figure2].Theteststatisticis

Thetotalnumberofexpectedeventsinagroup(e.g.E2)isthesumofexpectednumberofevents,atthetime
ofeacheventinanyofthegroup,takingbothgroupstogether.Atthetimeofeventinanygroupthe
expectednumberofeventsistheproductofriskofeventatthattimewiththetotalnumberofsubjectsalive
atthestartofthetimeofeventinthatverygroup(e.g.atday6,46patientswerealiveatthestartoftheday
andonedied,sotheriskofeventwas1/46=0.021739.As23patientswerealiveatthestartofthedayin
group2,theexpectednumberofeventsatday6ingroup2was230.021739=0.5).Thetotalnumberof
expectedeventsingroup2issumoftheexpectedeventscalculatedatdifferenttime.Thetotalnumberof
expectedeventsintheothergroup(i.e.E1)iscalculatedbysubtractingthetotalnumberofexpectedevents
ingroup2i.e.E2,fromthetotalofobservedeventsinboththegroupsi.e.O1+O2.
ConsideringtheaboveexamplethelogranktestcanbeappliedasshowninTable3.

Computationsofallthevaluesintheabovementionedformulawillgiveteststatisticvalue.Theteststatistic
andthesignificancecanbedrawnbycomparingthecalculatedvaluewiththecriticalvalue(usingchisquare
table)fordegreeoffreedomequaltoone.Theteststatisticvalueislessthanthecriticalvalue(usingchi
squaretable)fordegreeoffreedomequaltoone.Hence,wecansaythatthereisnosignificantdifference
betweenthetwogroupsregardingthesurvival.
Thelogranktestisusedtotestwhetherthedifferencebetweensurvivaltimesbetweentwogroupsis
statisticallydifferentornot,butdonotallowtotesttheeffectoftheotherindependentvariables.Cox
proportionhazardmodelenablesustotesttheeffectofotherindependentvariablesonsurvivaltimesof
differentgroupsofpatients,justlikethemultipleregressionmodel.Hazardisnothingbutthedependent
variableandcanbedefinedasprobabilityofdyingatagiventimeassumingthatthepatientshavesurvived
uptothatgiventime.Hazardratioisalsoanimportanttermanddefinedastheratiooftheriskofhazard
occurringatanygiventimeinonegroupcomparedwithanothergroupatthatverytimei.e.ifH1,H2,H3
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andh1,h2,h3arethehazardsatagiventimesT1,T2,T3ingroupAandB,respectively,then
hazardratioattimesT1,T2,T3areH1/h1,H2/h2,H3/h3,respectively.BothlogranktestandCox
proportionhazardtestassumethatthehazardratioisconstantovertimei.e.intheabovementionedscenario
H1/h1=H2/h2=H3/h3.
Toconclude,KaplanMeiermethodisaclevermethodofstatisticaltreatmentofsurvivaltimeswhichnot
onlymakesproperallowancesforthoseobservationsthatarecensored,butalsomakesuseoftheinformation
fromthesesubjectsuptothetimewhentheyarecensored.SuchsituationsarecommoninAyurvedaresearch
whentwointerventionsareusedandoutcomeassessedassurvivalofpatients.SoKaplanMeiermethodisa
usefulmethodthatmayplayasignificantroleingeneratingevidencebasedinformationonsurvivaltime.

Footnotes
SourceofSupport:Nil
ConflictofInterest:Nonedeclared

REFERENCES
1.ArmitageP,BerryG,MatthewsJN.4thed.Oxford(UK):BlackwellScience2002.Clinical
trials.Statisticalmethodsinmedicalresearchp.591.
2.BerwickV,CheekL,BallJ.Statisticsreview12:Survivalanalysis.CritCare.20048:38994.
[PMCID:PMC1065034][PubMed:15469602]
3.AltmanDG.London(UK):ChapmanandHall1992.AnalysisofSurvivaltimes.In:Practicalstatisticsfor
Medicalresearchpp.36593.
4.IndrayanA,SurmukaddamSB.MeasurementofCommunityHealthandSurvivalanalysis.In:ChowSC,
editor.MedicalBiostatistics.Vol.7.NewYork(US):MarcelDekker2001.pp.23242.
5.MarubiniE,ValsecchiMG.Chichester(UK):JohnWileyandSonsChichester(UK):JohnWileyand
Sons1995.EstimationofSurvivalProbabilities.Analysingsurvivaldatafromclinicaltrialsand
observationalstudiespp.418.

FiguresandTables
Table1

KaplanMeierestimateforpatientsmentionedine.g.1
Figure1

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PlotsofKaplanMeierproductlimitestimatesofsurvivalofagroupofpatients(asine.g.1)receivingARVtherapy

Table2

KaplanMeierestimate(KM)forpatientsmentionedine.g.2
Figure2

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PlotsofKaplanMeierproductlimitestimatesofsurvivalofagroupofpatients(asine.g.1and2)receivingARTandnew
AyurvedictherapyforHIVInfection.

Table3

Logrankstatisticforpatientsmentionedinexamples1and2
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