BiostatV:SurvivalAnalysis

Whatdoessurvivaldatamean?
Howdowedescribesurvivaldata?
Howdowecomparesurvivalfortwo
groups?
Howcanwedoaregressionmodelfor
survivaldata?
Howdoesitdifferfromlogisticregression?
 Anexampleofsurvivaldata
DatasetfromDept.ofRadiologyat
Stanfordinlate1950s,HenryKaplan.
Earlyclinicaltrialofextendedradiationin
Hodgkinsdisease.Beforethat,standard
carewaslocalradiation,and5yearsurvival
wasabout20%.Inthisstudy,17people
wererandomizedtoreceiveextended
radiationand12peopletolocalradiation.
Theresults:Survivaltimeindays
Localradiation:150,180+,482+,496,503,
538,558+,716,806,1140,2055+,2141+
Extendedradiation:202+,370+,383+,
391+,418+,425+,447+,542+,583+,593+,
625+,802+,857+,1308+,1357+,2001+
The+denotessomeonewhoenteredthe
studythatlongagoandwasstillaliveatthe
timethedataweresummarized.
 Featuresofsurvivaldata
Weknowtwothings:whetherpersondied,
andhowlongwesawthemalive.
Forsomepeople,wehavecensoreddata.
Thatis,weknowtheysurvivedatleastuntil
acertaintime,liketheendofthestudy,so
deathoccurredonlyafterthattime.
Censoreddataareinformative!Shouldnot
throwawaythatinformation.
 Describingsurvivaldata:you
needmorethanyes/no.
Supposeyoudecidedtolookat5year
survivalrates.Inthelocalradiationtherapy
group,7peoplediedbefore5years,2
peoplesurvivedlongerthan5years,and3
areunknownbecausetheywerestudiedless
than5yearsandwerestillalive.Only1
personinextendedradiationsurvived
longerthan5years;otherswerecensored.
 Lifetableapproach
Wecandescribethesurvivalusingalife
tableapproach.Thislooksatthechanceof
deathinthenexttimeperiod(day,week,
year)giventhatyouwerestillaliveatthe
beginningofthetimeperiod.
Lifetablescangiveyoubothgraphics
(KaplanMeiercurve)andsummary
measures(mediansurvivaltime).
Exampleoflifetable:localrad.
Timeindays Knownalive Cumulative
sincelasttime fractionalive
150 11/12 11/12=0.91
496 8/9 0.92*8/9=0.81
503 7/8 0.81*7/8=0.71
538 6/7 0.71*6/7=0.61
 KaplanMeierplot
Wecanmakeagraphictoshowthis.
Eachtimethereisadeath,thesurvival
curvedrops(stepfunction.)
Eachtimethereisacensoring,the
denominatorinthelifetablechanges,but
theplotstaysthesame.Wemarkcensoring
byhashmarks.
Summarystatisticsfromlifetable
Wecanestimatethemediansurvivaltime
fromlifetables.
Forlocalizedradiation,itisabout716days
(alittlelessthantwoyears),becauseKM
is0.49at716days.
Forextendedradiation,weknowatleast
halfthepeoplesurvivedmorethan583days
butthatisjustalowerbound(censoring).
 Comparingsurvivalcurves
2of9vs1of1.Chancethattheoneperson
whogotextendedtherapywasasurvivor,if
treatmentmadenodifference,was3/10(the
numberofsurvivorsoverall.)Easilycould
bechancealone.(onesidedPvalue.)For
twoyears,4/9vs.5/5.(twosidedP=0.06).
Howcanwedoabetterjobofdescribing
thedata,giventhecensoring?
Howdowecomparetwocurves?
Mostcommontestisalogranktest.Its
kindoflikearanksumtestbutusesthe
censoreddataiftheyareinformative.
Someonewhowascensoredat202days
livedlongerthansomeonewhodiedat150.
Forthisdataset,thelogranktestgivesa
chisq=8.2,1df.(P=0.0043).
 Morethanonepredictor:Cox
proportionalhazardsmodels
Supposewewanttoseehowpredictors
influencesurvivaltime.
TwowaysNOTtodoit:
Linearregression(doesntdistinguishtimetill
deathandtimetillcensoring.
Logisticregression(doesntuseinformation
aboutlengthofsurvivalorcensoringtime).
Mostcommonway:Coxmodels.
 Whatdoproportionalhazards
modelslookat?
Theyassumethereferencegrouphasa
survivalcurvelikeaKaplanMeier,and
theydontspecifyitsexactshape.
Theyassumechangingthecharacteristicsof
thepersondoesnotchangethegeneral
shapeofthiscurve,justitsmagnitude.
Theyestimatetheeffectofthepredictorson
thehazardofdeath.
 Whatisthehazard?
Thehazardofdeathattimetistherateof
dying,relativetohowmanypeoplearestill
aliveatthattime.
Onthelifetable,itsthefractionwhodied
outofthenumberaliveatthattime.
Onacontinuoussurvivalcurve,itsthe
derivativeorslopedividedbytheheightor
currentsurvivingfraction.
 Proportionalhazardsmodel
Theproportionalhazardsassumptionis
thataoneunitchangeinthepredictoris
associatedwiththesamepercentagechange
inthehazard,nomatterwheninstudyor
whattheotherpredictorsaretellingyou.
Forexample,ifhazardofsmokingfor
strokeis3,thensmokingtriplesyourriskof
strokeatallages,bothMandF,andsoon.
Exampleofproportionalhazards
regressionmodel
Populationbasedstudyofpeople65+.
Samplereceivedfullclinicalevaluationby
neurologist,includingthesedomains:
Gaitdisorder
Bradykinesia
Rigidity
Tremor
Parkinsonism:2ormoredomainspresent.
 Survivalanalysis
Samplefollowedforaverageof9.2years.
Therewere460peopleinsample(note;
oversampledolder,sickerpeople.)
Of460,159withparkinsonism,276deaths.
Parkinsonismandmortalitybothassociated
withage,sex,soneedtoadjustforthem.
Ref:Bennettetal.NEJM1996,pp7176.
ResultsofCoxmodel:parameter
estimates
Predictor Estimateof Effecton
log(hazard) hazard
Ageinyears 0.06 1.06

Malesex 0.38 1.47

Parkinsonism 0.59 1.80

 Interpretingresults
Notethat,likelogisticregression,Cox
modelparametersareonlogscale.
Eachyearolderincreaseshazardofdeath
about6%(onaverage,6%ofsurvivorsdie
peryear).
Beingmaleincreasesriskofdeath47%.
Parkinsonismincreasesriskofdeath80%
ornearlyDOUBLE.
 Inferencesabouttheseresults
WecangetPvalues(all<0.001here).
Theseresultsareveryunlikelytobedueto
chancealone.
Wecanalsogetconfidenceintervals.The
95%CIfortheeffectofparkinsonismon
deathisabout1.5to2.4.
WecanalsolookatKaplanMeier.Butthat
picturedoesnottakeaccountofageorsex.
 Someadditionalnotes:
Survivalanalysistellsyoumoredetails
aboutoutcomeofclinicaltrialsorabout
influenceofriskfactorsthandoeslogistic
regression.
Youcantdoitunlessyouknowtheexact
timeaneventoccurs.
Youneedaprospectivedesign.