PrinciplesofDecisionMaking

CLINICALDECISION
USINGANARTICLEABOUT
TREATMENT
GeorgeG.Lim,MD,FPSGS,FPCS,FPSCRS

KnowingthepaEentstruestateisoGen
unnecessary
Treatmenterrorisalwaysapossibilitywhenthe
diagnosisisuncertain
TheneedfordiagnosEccertaintydependson
thepenaltyforbeingwrong

ProfessorI,DepartmentofSurgery
USTFacultyofMedicine&Surgery

DecisionMakinginMedicine
Themainissueismakingchoices
Diagnosis
o ShouldIrequestforalaboratoryexaminaEonor

treatrightaway?

o BetweentwodiagnosEcalternaEves,whichone

shouldIrequest?

Treatment

DecisionMakingintheOldParadigm
Pathophysiologicunderstanding
Commonsense
Experience
Experts
MedicalEvidence

o ShouldIstarttreatmentorobserverst?
o Betweentwoormoredrugs,whichoneshouldI

prescribe?

DecisionMakingintheNewParadigm
MedicalEvidence
Pathophysiologicunderstanding
Commonsense
Experience
Experts

ThePaDent
A72yearoldfemaleconsultedyouforhypertension
andelevatedcholesterol.Duringyourdiscussionon
cardiacrisks,sheinquiresabouttheneedtotakean
anEcholesteroldrug.
Whatadvisewillyougive?

DecisionMakingintheOldParadigm
Pathophysiology
o Hypercholesterolemiapromotescoronaryarterydiseasethuscholesterol

isariskfactor

Commonsense
o Loweringcholesterolalsolowerstheriskofcoronaryarterydisease

Experience
o IfcholesteroliselevatedbylaboratoryexaminaEon,itcanbeloweredby

drugs

Experts

DecisionMakingintheNewParadigm
Formulatetheproblemintoananswerable
quesEon
ConductasystemaEcmedicalliteraturesearch
CriEcallyappraisethemedicalliterature
Applytheresults
EvaluatetheapplicaEon

o NaEonalCholesterolEducaEonProgram:screenalladultpaEentsand

intervenewhennecessary

TheEBMPracDDoner
EBMPracEEoner
o AmongelderlypaEentswhohaveelevated

cholesterol,willanEcholesteroldrugsbe
benecial?

Thesearch
o MEDLINE
o Randomizedtrialofcholesterolloweringin4444

paEentswithcoronaryheartdisease:the
ScandinavianSimvastaEnSurvivalStudy

CaseControlStudies
Advantages
o Quickandcheap
o Onlyfeasiblemethodforveryraredisordersor

thosewithlonglagbetweenexposureandoutcome
o FewersubjectsneededthancrosssecEonalstudies

CaseControlStudies
Disadvantages
o Relianceonrecallorrecordstodetermineexposure

status

o Confounders
o SelecEonofcontrolgroupsisdicult
o PotenEalbias:recall,selecEon

CrossSecDonalSurvey
Advantages

CohortStudy
Advantages

o Cheapandsimple

o Ethicallysafe

o Ethicallysafe

o Subjectscanbematched

Disadvantages
o EstablishesassociaEonatmost,notcausality
o RecallbiassuscepEbility
o Confoundersmaybeunequallydistributed

o CanestablishEminganddirecEonalityofevents
o Eligibilitycriteriaandoutcomeassessmentscanbe

standardized

o AdministraEvelyeasierandcheaperthanRCT

o Neymanbias
o Groupsizesmaybeunequal

CohortStudy
Disadvantages
o ThecontrolsmaybediculttoidenEfy
o Exposuremaybelinkedtoahiddenconfounder
o Blindingisdicult
o RandomizaEonnotpresent
o Forraredisease,largesamplesizesorlongfollowup

necessary

CrossoverDesign
Disadvantages
o AllsubjectsreceiveplacebooralternaEvetreatment

atsomepoint
o Washoutperiodlengthyorunknown
o Cannotbeusedfortreatmentswithpermanent
eects

CrossoverDesign
Advantages
o Allsubjectsserveasowncontrolsanderrorvariance

isreducedthusreducingsamplesizeneeded

o Allsubjectsreceivetreatment(atleastsomeofthe

Eme)

o StaEsEcaltestsassumingrandomizaEoncanbeused
o Blindingcanbemaintained

RandomizedControlledTrial
Advantages
o UnbiaseddistribuEonofconfounders
o Blindingmorelikely
o RandomizaEonfacilitatesstaEsEcalanalysis

Disadvantages
o Expensive:Emeandmoney
o Volunteerbias
o EthicallyproblemaEcatEmes

RandomizedControlledTrial
ProvidetheBESTevidenceofeecEveness
Individualsarerandomlyassigned
(randomizaEon)toeitherofthegroups
RandomizaEontriestomakethegroups
SIMILAR
TheyareobservedFORWARDinEmeandtheir
outcomescompared
Theoutcomecanbethecureofadisease,relief
ofsymptoms,orimprovementinqualityoflife

Relevance
IstheobjecEveofthearEclecomparing
intervenEonssimilartoyourclinicaldilemma?
o PopulaEonofthestudy(P)shouldbesimilartothe

characterisEcofyourpaEent

o IntervenEon/comparaEveintervenEon/exposure(I)

shouldincludethetherapeuEcintervenEonyou
wanttotest
o Outcomeofthestudy(O)oneoftheoutcomes
measuredshouldbethegoalyouandyourpaEent
wishtoworkfor

Relevance
IstheobjecEveofthearEclecomparing
intervenEonssimilartoyourclinicaldilemma?
o YES

TheobjecEveofthestudyistocompare
SimvastaEn,ananEcholesteroldrugwith
placebo

AretheResultsValid?
WastheassignmentofpaEentstotreatments
randomized?
o YES

TheEtle,abstractandthemethodologysecEon
statedthatthestudywasadoubleblind
randomizedcontrolledtrial

EBMonTherapy
Validity
o IsthearEclelikelytobetrue?

Importance
o Howlargeisthesizeoftheeect?

Applicability
o WillthendingsworkinmypaEent?

AretheResultsValid?
WereallpaEentswhoenteredthetrialproperly
accountedforandagributedatitsconclusion?
o Wasfollowupcomplete?
o WerepaEentsanalyzedinthegroupstowhichthey

wererandomized?

Dropouts
Control
DropoutRate
A.1%

AretheResultsValid?

Treatment
DropoutRate

Control
DeathRate

Treatment
DeathRate

1%

20%

10%

B.1%

1%

2%

1%

C.10%

10%

50%

10%

D.10%

10%

10%

5%

E.1%

10%

5%

5%

WereallpaEentswhoenteredthetrialproperly
accountedforandagributedatitsconclusion?
o YES

4,444paEentswererandomizedandanalyzed
accordingtointenEontotreatprinciple.
IntheTableforthemainanalysis,thesumof
paEentsineachgrouptotaled4,444,thenumber
whowererandomized

IntenDontoTreatPrinciple
Subjects Treatment

IntenDontoTreatPrinciple

FailureA

Subjects Treatment

FailureA

FailureB

1000
(0)

6months

100/1000=
10%

1000
(0)

6months

100/1000=
10%

100/1000=
10%

1000
(100)

1year

45/900=
5%

1000
(100)

1year

45/900=
5%

135/1000=
13.5%

AretheResultsValid?

AretheResultsValid?

WerepaEents,healthworkersandstudy
personnelblindtotreatment?

Werethegroupssimilaratthestartof
treatment?

o YES

Thestudywasadoubleblindcontrolledtrial

o YES

Table1oftheresultssecEonshowednomajor
dierenceinthebaselinecharacterisEcs
betweenthetwogroups

AretheResultsValid?

WhataretheResults?

AsidefromexperimentalintervenEon,werethe
groupstreatedequally?
o YES

TherewerenoplannedcointervenEonforthe
twogroups

Ifyouweighed80kgaGertheChristmas
holidays,and60kgaGerasummerdiet,what
wouldbethewaysofexpressingyourweight
loss?
o Ilost20kg(absoluteweightreducEon)
o Iamnow75%ofwhatIusedtoweigh(relaEve

weight)

o Ilost25%ofmyweight(relaEveweightreducEon)

WhataretheResults?
Measures

WhataretheResults?

Formula

Figures

RiskinControl(Rc)

DeathControl/NControl

256/2222=11.5%

RiskinTreatment(Rt)

DeathTreatment/
NTreatment

182/2222=8.2%

AbsoluteRiskReducEon
(ARR)

RcRt

11.58.2%=3.3%or
0.03

RelaEveRisk(RR)

Rt/Rc

0.082/0.115=0.71

RelaEveRiskReducEon
(RRR)

1RR

10.71=0.29or29%

NumberNeededtoTreat
(NNT)

1/ARR

1/0.03=33.3

WhataretheResults?
HowprecisewastheesEmateofthetreatment
eect?
o RRofdeathintheSimvastaEngroup=0.71
o 95%CI0.580.85,p=0.0003

Measures
RiskinControl(Rc)
RiskinTreatment(Rt)
AbsoluteRiskReducEon
(ARR)

Figures
256/2222=11.5%
182/2222=8.2%
11.58.2%=3.3%or
0.03

Deathispreventedin3%of
paEentstakingthedrug

0.082/0.115=0.71

Theriskofdeathisnow71%
ofwhatitusedtobe

RelaEveRiskReducEon
(RRR)

10.71=0.29

29%reducEonindeath
whentakingdrugcompared
totakingplacebo

NumberNeededtoTreat
(NNT)

1/0.03=33.3

Youwillhavetotreat33
paEentstoprevent1death

RelaEveRisk(RR)

Cantheresultshelpmeincaringfor
mypaDent?
CantheresultsbeappliedtomypaEentcare?
o YES

SubjectsincludedinthisstudywerepaEentswith
anginaorMIandelevatedcholesterol

Cantheresultshelpmeincaringfor
mypaDent?
Wereallclinicallyimportantoutcomes
considered?
o YES

Cantheresultshelpmeincaringfor
mypaDent?
Arethelikelytreatmentbenetsworththe
potenEalharmandcost?
o 33paEentstoprevent1death(orsave1life)

Themainoutcomesconsideredwerenewonset
ofMI,coronarydeath,andoverallcauseofdeath

Cantheresultshelpmeincaringfor
mypaDent?
AreyourpaEentsvaluesandpreferences
saEsedbytheregimenanditsconsequences?
o DoyourpaEentandyouhaveaclearassessmentof

theirvaluesandpreferences?

o Aretheymetbythisregimenanditsconsequences?

o 40mgtabat@P25.00

At365days=P18,250
For33paEents=P602,250
For5years=P3M
o 72yearoldpaEent

Whatadvicewillyougive
your72yearoldpaDent?
A72yearoldfemaleconsultedyouforhypertension
andelevatedcholesterol.Duringyourdiscussionon
cardiacrisks,sheinquiresabouttheneedtotakean
anEcholesteroldrug.
Whatadvisewillyougive?
Iwouldrathernotgiveanan1cholesteroldrug.The
benetistoosmallforthecostitwilltake.

Whatadvicewillyougive
your72yearoldpaDent?
A72yearoldfemaleconsultedyouforhypertension
andelevatedcholesterol.Duringyourdiscussionon
cardiacrisks,sheinquiresabouttheneedtotakean
anEcholesteroldrug.
Whatadvisewillyougive?
Iwillprescribeanan1cholesteroldrug.Mypa1ent
canaordthecostevenifthebenetisnotlarge.

KeepASKING
KeepSEARCHING
KeepLEARNING

Thankyou.