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Stats Kaplan Meier (June 27, 2000) DearProfessorMean,WhenIreadmymedicaljournals,Ikeeponcomingacrosstermslike"Kaplan-MeierProduct Limitestimate"or"Kaplan-Meiersurvivalcurve."Whatdothesetermsmeanandwhenaretheyused? [Link](andthemost morbid)[Link],wewanttoestimatethe fractionofpatientswhosurviveforatleastonemonth,atleastthreemonths,[Link] knownasasurvivalcurve.

Thetermsurvivalissometimesmisleading,becausewecanuseitforotherlesssevereoutcomeslike howlonguntilacancerrelapse,[Link] forapositiveoutcome,[Link], we'llkeepthingssimplebyassumingthattheoutcomeistimeuntildeath.

Estimatingasurvivalcurveisoftencomplicatedbytheuncooperativewayinwhichresearchsubjects [Link],somesubjectsdecidetoleaveastudypartofthewaythrough. [Link] [Link],[Link] survivedatleastthreeyears,butthenwehadtoterminatethestudy. Short explanation TheKaplan-Meierestimateisasimplewayofcomputingthesurvivalcurveinspiteofallthese [Link] point,[Link] probabilitiesbyanyearliercomputedprobabilities,whichisonereasonthisiscalleda"productlimit estimate."

[Link], withverticalstepsdownwardatthetimeofdeathofeachindividualsubject.

[Link],whatisthesurvival [Link] [Link],onegroup [Link] experienceacertainfractionofdeaths. More details Tocomputeasurvivalcurve,youneedtonotethetimeofoccurrenceofevents(e.g.,failures,deaths)

Itispossiblefortwoormoreeventstooccuratthesametime,inwhichcasethenumberofdistinct [Link]'sinorderfromsmallestto [Link],

Youalsoneedtodefinethestartingpointofthestudy,

ThebasiccomputationsfortheKaplan-Meiersurvivalcurverelyonthecomputationofconditional [Link],theprobability

whichcanbeinterpretedastheprobabilityofyoursurvivingtoaspecifictime,giventhatyousurvived [Link] ataspecifictimeandifyouknowthenumberofpatientsatriskatthatsametime. Amoredifficult(butmoreimportant)probabilityistheunconditionalprobabilityofsurvival,

[Link] betweenthisunconditionalprobabilityandtheconditionalprobability:

Atfirstglance,thisdoesnotseemtohelp,becausetherighthandsideoftheequationstillincludesan [Link]

andwecancontinuealongtheselinestoget

[Link] intentionallyrecruitdeadsubjects,[Link],theunconditionalprobability isequaltothecumulativeproductofconditionalprobabilities. Ateachtimepoint,youshouldcount

Youshouldalsocount

Armedwiththisinformation,[Link] calculatethenumberofpatientsatrisk,

Inotherwords,thenumberatriskatanyspecifictimepointisjustthenumberatriskattheprevious timepoint,minusthenumberofdeaths/[Link] convenience,wedefine

Nextyoucomputetheconditionalprobabilityofsurvival:

Finally,theunconditionalprobabilityofsurvivalissimplythecumulativeproductoftheconditional probabilities:

Example ThefollowingexampleisfromChadhaetal(2000).Theauthorsstudiedasampleof36pediatric [Link] [Link](eitherocclusion, leakage,exit-siteinfection,orperitonitis). [Link] catheterinthisgroupofpatientswerethatthepatientrecovered(n=4),thepatientdied(n=9),orthe catheterwaschangedtoadifferenttypeelectively(n=5).Ifthecatheterwasremovedpriorto complications,thatrepresentedacensoredobservation,becausetheyknewthatthecatheterstayed complicationfreeatleastuntilthetimeofremoval.

Figure3.1Failuresandcensoredobservationsforcatheterstudy.

Thetableaboveliststhedaysatwhichfailuresand/orcensoredobservationsoccurred.

Figure3.2Computationofnumberofpatientsatrisk

TocomputeaKaplan-Meiersurvivalcurve,youfirstneedtocomputethenumberofcathetersatrisk [Link] calculationsappearinthetableshownabove.

Figure3.3Compuationofconditionalprobabilityofsurvival.

[Link] willsurviveataspecifictimepoint,giventhatitsurvived(andwasnotcensored)atanyprevioustime [Link].

Figure3.4Computationofunconditionalsurvivalprobabilities.

Finally,youneedtocomputethecumulativeproduct:theproductofeachconditionalprobabilitywith [Link] [Link].

Figure3.5Graphofunconditionalsurvivalprobabilities(Kaplan-Meiercurve).

[Link]|SURVIVAL |KAPLAN-MEIERfromthemenutogetthisgraph.

Figure3.6SPSSdialogboxforKaplan-Meierprocedure.[Imageisalreadyfullsize]

[Link](eitherfailureorcensoring)goesin [Link],youshouldplacethevariablewhichindicateswhethertheevent [Link] used.

Figure3.7SPSSdialogboxfordefiningevents.[Imageisalreadyfullsize]

ThefigureshownaboveistheSPSSdialogboxwhereyoudistinguishbetweenfailuresandcensoring. Inthisdataset,avalueof1indicatesafailureand0representscensoring.

Figure3.8SPSSdialogboxforKaplan-Meieroptions.[Imageisalreadyfullsize]

[Link] [Link] checked. Reference Tenckhoff Catheters Prove Superior to Cook Catheters in Pediatric Acute Peritoneal Dialysis. ChadaV,WaradyBA,BloweyDL,SimckesAM,AlonUS. AmericanJournalofKidneyDiseases(2000),35(6):1111-1116. Further reading TherearemanybeginninglevelbooksonbiostatisticsthatdiscusstheKaplan-Meiercurve,suchas Woolson'[Link]'sbook.
1. Modelling Survival Data in Medical Research. CollettD. LondonEngland:ChapmanandHall(1994). ISBN:0-412-44890-4. 2. Statistical Methods for the Analysis of Biomedical Data WoolsonRF. NewYorkNY:JohnWiley&Sons,Inc.(1987). ISBN:0-471-80615-3.

HereissomeextramaterialthatIneedtointegrateintotheabovedescription.

[Link],theeventinvolves [Link],becausethestudy endsbeforetheydie,[Link] havepartialinformation,weknowthattheeventoccurred(orwilloccur)sometimeafterthedateof [Link]'twanttoignorethese patients,becausetheyprovidesomeinformationaboutsurvival,butweneedtohandlethem differently. [Link] knowtheexactdateofdeath(orfailure)foreachpatient,[Link] situations,however,[Link] survivedbeyondacertainpoint,butbecausethestudyendedbeforeallthepatientsdied,orbecause welosttouchwithsomeofthepatients,orbecausetheywithdrewfromthestudy,wedonotknowthe [Link],observationsthatyouhaveto accountfordifferentlythanothers. Asimpleexampleofcensoreddatainvolvesfailureofadevice,[Link] studyofcathetersforperitonealdialysis,thesecatheterscanfailduetoocclusion,leakage,or [Link],usuallyeitherbecausethepatientcompleted [Link],thatisconsideredacensored observation. Catheters Day removed priorto failure 1 2 3 4 5 6 7 10 12 13 8 2 1 1 5 2 2 1 1 3 2 1 2 2 1 Catheters failed

Ifyouwantedtoestimatetheprobabilitythatacatheterwillsurviveitsfirstday,that'[Link] were34catheters,2didnotsurvivethefirstday,15failedondays2-13.For17ofthecatheters,we didnotknowwhentheywouldhavefailed,butwedoknowthattheyallsurvivedatleastoneday. Sotheprobabilityofsurvivingthefirstdayis32/34=94%. Buthowwouldweestimatetheprobabilityofsurvivingtwodays?fourdays?tendays? Thisistricky,becausethecensoredobservationsprovideinformationuptothedayofcensoring,but [Link] [Link] [Link] anycathetersthatwerecensoredonpreviousdays. Catheters Day removed priorto failure 1 2 3 4 5 6 7 10 12 13 8 2 1 1 5 2 2 1 1 3 2 1 2 2 1 34 34-8-2=24 24-2-2=20 20-1-1=18 18-1-1=16 16-5-3=8 8-2=6 6-1=5 5-2=3 3-2=1 Catheters failed Catheters atrisk

Wethenneedtocomputetheconditionalprobabilityofsurvivingateachtimepointgiventhatthe [Link] (numberatrisk-numberoffailures)/(numberatrisk) Catheters Day removed priorto failure 1 2 3 4 5 6 7 10 12 13 8 2 1 1 5 2 2 1 1 3 2 1 2 2 1 34 34-8-2=24 24-2-2=20 20-1-1=18 18-1-1=16 16-5-3=8 8-2=6 6-1=5 5-2=3 3-2=1 32/34 =0.94 22/24 =0.92 19/20 =0.95 17/18 =0.94 13/16 =0.81 6/8 =0.75 5/6 =0.83 3/5 =0.60 1/3 =0.33 0/1 =0.00 Catheters failed Catheters atrisk Conditional probability

[Link]-Meier estimateofthesurvivalprobability. Catheters Day removed priorto failure 1 2 3 4 5 6 7 10 12 13 8 2 1 1 5 2 2 1 1 3 2 1 2 2 1 34 34-8-2=24 24-2-2=20 20-1-1=18 18-1-1=16 16-5-3=8 8-2=6 6-1=5 5-2=3 3-2=1 32/34 =0.94 22/24 =0.92 19/20 =0.95 17/18 =0.94 13/16 =0.81 6/8 =0.75 5/6 =0.83 3/5 =0.60 1/3 =0.33 0/1 =0.00 0.94 0.94*0.92 =0.86 0.86*0.95 =0.82 0.82*0.94 =0.77 0.77*0.81 =0.62 0.62*0.75 =0.46 0.46*0.83 =0.38 0.38*0.60 =0.23 0.23*0.33 =0.08 0.08*0.00 =0.00 Catheters failed Catheters atrisk Conditional probability Cumulative product

Hereisagraphofthesesurvivalprobabilities.

Theplothasa"stairstep"pattern,becausewedon'tknowthesurvivalprobabilityatfractionaldays (suchas2.5days)andatsomeintegerdays(suchas9days).Byconvention,weestimatethesurvival probabilityforthesevaluesasequalingthesurvivalprobabilityoftheclosestvaluethatisstillsmaller (the2daysurvivalprobabilityfor2.5days,andthe7daysurvivalprobabilityat9days). Noticethattheestimatedmediansurvivaltime(thetimeatwhich50%ofthecatheterssurvived)issix days. Tenckhoff Catheters Prove Superior to Cook Catheters in Pediatric Acute Peritoneal Dialysis. ChadhaV.AmericanJournalofKidneyDiseases2000:35(6);1111-1116. Category:AskProfessorMean,Category:Survivalanalysis

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