Applied Epidem

APPLIED EPIDEMIOLOGY
Prepared by
Antonio E. Chan, M.D.
Learningobjectives
1. Define epidemiology and outline its scope
2. Differentiate epidemiology from clinical
epidemiology
3. Describe approaches to establishing
normality
4. Describe criteria and measures of disease
occurrence commonly used in
epidemiology
5. Enumerate some routinely available data
use in epidemiology
Learningobjectives
6. Understanddiagnostictestinrelationto
disease
7. Describethemaintypesof
epidemiologicalstudies
8. Enumeratetheadvantagesand
disadvantagesofobservationalstudies
comparedwithexperimentalstudies
9. Explaincauseofdisease
10. Outlinethestepsnecessarytoestablish
thecauseofdisease

Learningobjectives
11. Appreciate the differing approaches used
in epidemiology to compare the
occurrence of disease
12. Outlinetheroleofepidemiologyin
describingthenaturalhistoryofadisease
andprognosis
13. Understandtheroleofepidemiologyinthe
preventionandcontrolofdiseasethrough
identificationofthecausesofdisease
14. Relatethedifferentstagesofthe
developmentofadiseasetothephasesof
prevention
WhatisEpidemiology?
The study of the distribution and
determinants of health-related states
or events in specified populations, and
the application of this study to control
of health problems
AIMSOFEPIDEMIOLOGY
Tounderstandthecourseofthe
disease(naturalhistoryofthedisease)
Toidentifythecausesorriskfactors
Toprovideeffectivemeasuresof
treatmentandprevention
Uses of epidemiology
Genetic factors

1. Causation

Environmental factors
(including lifestyle)

2. Natural history

3. Description of health status
of population

Proportion with ill health,
change over time,
change with age, etc
Good health
Ill health
Good health
Subclinical
changes
Clinical
disease
Death
Recovery
Good health
ILL
health
Time
Uses of epidemiology

4. Evaluation of
intervention

Good health

Ill health
Treatment
Medical care
Health promotion
Preventive measures
Public health services
APPLIEDEPIDEMIOLOGY
Clinicalepidemiology
Communicablediseaseepidemiology
Environmentalandoccupational
epidemiology
Molecularepidemiology
CLINICALEPIDEMIOLOGY
Definition
istheapplicationofepidemiologicalprinciplesand
methodstothepracticeofclinicalmedicine
isthescienceofmakingpredictionsaboutindividual
patientsbycountingclinicaleventsinsimilar
patients,usingscientificmethodsforstudiesof
groupsofpatientstoensurethatthepredictionsare
accurate
CLINICAL EPIDEMIOLOGY
Purpose:
todevelopandapplymethodsofclinical
observationsthatwillleadtovalid
conclusionsbyavoidingbeingmisledby
systematicerrorandchance
tomakegooddecisionsinthecareofpatients
TheRelationshipBetween
EPIDEMIOLOGY+ CLINICALMEDICINE
Populations
Individuals
Studies/Assessments
Prevention
Evaluation
Planning
Diagnosis
Treatment
Curing
Caring
ClinicalQuestion
IssueQuestion
Abnormality Isthepatientsickorwell?
Diagnosis Howaccuratearetestsusedtodiagnosedisease?
Frequency Howoftendoesadiseaseoccur?
Risk Whatfactorsareassociatedwithanincreasedriskofdisease?
Prognosis Whataretheconsequencesofhavingadisease?
Treatment Howdoestreatmentchangethecourseofdisease?
Prevention Doesaninterventiononwellpeoplekeepdiseasefromarising?
Doesearlydetectionandtreatmentimprovethecourseof
disease?
Cause Whatconditionsleadtodisease?Whatarethepathogenetic
mechanismsofdisease
Cost Howmuchwillcareforanillnesscost?
Sourcesofdatausefulfor
epidemiologystudies
Data on vital events birth and death
Morbidity or disease statistics
Data on physiologic and or pathologic
condition
Statistics on health resources and services
Statistics pertaining to the environment
Demographic data
Socio-cultural data
MeasuringHealthandDisease
Clinicalquestion:Isthepatientsickorwell?
Healthisdefinedasastateofcomplete
physical,mental,andsocialwell-being
andnotmerelytheabsenceofdiseaseor
infirmity.
Epidemiologistsdefinitionofhealthstates
diseasepresentordiseaseabsent
Diagnostictests
qualitativediagnostictest
quantitativediagnostictest
Normal(Gaussian)distributionmethod
Percentilemethod
Therapeuticmethod
Predictivevaluemethod
Diagnostic criteria are usually based on
symptoms, signs and test results

1. Hepatitis presence of antibodies in the blood
2. Asbestosis - symptoms and signs of specific changes
in lung function,
- radiographic demonstration of fibrosis of
the lung tissue or pleural thickening and
- history of exposure to asbestos fibers.
Major Manifestations Minor Manifestations
CarditisClinical:
Polyarthritisfever
Choreaathralgia(jointpains)
Erythemamarginatumpreviousrheumaticfeveror
Subcutaneousnodulesrheumaticheartdisease
Laboratory:
Acutephasereactants:
AbnormalESR,CRP,
leukocytosis
ProlongedP-Rinterval

TheJonesCriteria(revised)forGuidanceinthe
DiagnosisofAcuteRheumaticFever
Ahighprobabilityofrheumaticfeverisindicatedbythepresenceoftwomajor
oronemajorandtwominor,manifestations,ifsupportedbyevidenceofa
precedingGroupAstreptococcalinfection
MAJORSIGNS MINORSIGNS
Weightloss>10%Persistentcough>1month
Fever>1month Generalpruriticdermatitis
Chronicdiarrhea>1monthRecurrentherpeszoster
Generallymphadenopathy
Chronicherpessimplex
Oralcandidiasis
WHOCASE-DEFINITIONFORAIDS
ThepresenceofdisseminatedKaposissarcomaor
cryptococcalmeningitis
or
Twomajorsignsinassociationwithatleastoneminorsign
Diagnosticcriteriamustbeclearlystated,easytouse
andeasytomeasureinastandardmannerundera
widevarietyofcircumstancesbydifferentpeople
Diagnosticcriteriamaychangequiterapidlyas
knowledgeortechniquesimprove.
Definitionsusedinclinicalpracticearelessrigidly
specifiedandclinicaljudgmentismoreimportantin
diagnosis
The development of criteria to establish
the presence of disease requires
definition of normality and abnormality

Difficult to define what is normal

No clear distinction between normal and
abnormal
Approachesinestablishingnormality
Problem(misclassification)
Clinicalmeasurements
nominalasymptomatic
ordinalcut-offpoint
intervalorratio
Clinicalmeasurementshaveskeweddistributions
Percentilemethod(sameprevalencerates)
Levelatwhichtreatmentdoesmoregoodthanharm-Cost
Inspecificagegroupsformenandwomenatwhichtreatmentmakes
economicaswellasmedicalsense
Criteriachangefromtimetotime
Approachesinestablishingnormality
Normal Abnormal
commonorusualbeingunusual
well beingsick
notbeingtreatablebeingtreatable
Measuresofdiseasefrequency
Clinicalquestion:Howoftendoesadiseaseoccur?
Prevalenceofadiseaseisthenumberofcasesin
adefinedpopulationataspecifiedpointintime
Pointprevalence
Periodprevalence
Incidenceisthenumberofnewcasesarisingina
givenperiodinaspecifiedpopulation

Measuringdiseasefrequency
Theprevalencerate(P)foradiseaseiscalculatedas
follows:
Numberofpeoplewiththediseaseorcondition
P=-----------------------------------------------------------------(xfactor)
Numberofpeopleinthepopulationatriskatthe
specifiedtime
Incidencerate(I)
Numberofpeoplewhogeta
diseaseinaspecifiedperiod
I=----------------------------------------------------X(factor)
Sumofthelengthoftimeduringwhich
eachpersoninthepopulationisatrisk
Incidencerate
Thenumeratoristhenumberofnewevents
thatoccurinadefinedtimeperiod
Thedenominatoristhepopulationatriskof
experiencingtheeventduringthisperiod
Themostaccuratewayofcalculating
incidencerateistocalculatetheperson-
timeincidencerate(Incidencedensity)
Cumulativeincidencerateorrisk(CI)
Numberofpeoplewhogeta
diseaseduringaspecifiedperiod
CI=----------------------------------------------------X(factor)
Numberofpeoplefreeofthediseasein
thepopulationatriskatthebeginningof
theperiod
Factorsinfluencingobservedprevalencerate
Increasedby:Decreasedby:
LongerdurationofthediseaseShorterdurationofdisease
ProlongationoflifeofpatientHighcase-fatalityratefromdisease
withoutcure
IncreaseinnewcaseDecreaseinnewcases
(increaseinincidence)(decreaseinincidence)
In-migrationofcasesIn-migrationofhealthypeople
Out-migrationofhealthypeopleOut-migrationofcases
In-migrationofsusceptiblepeopleImprovedcurerateofcases
Improveddiagnosticfacilities
(betterreporting)
Prevalencestudiesdonotusuallyprovide
strongevidenceofcausality
Itishelpfulinassessingtheneedforhealth
careandtheplanningofhealthservices
Prevalenceratesareoftenusedtomeasure
theoccurrenceofconditionsforwhichthe
onsetofdiseasemaybegradual
Cumulativeincidencerate
Unlikeincidencerate,itmeasuresthedenominatoronlyatthe
beginningofastudy
Thisratehasasimplicitythatmakesitsuitableforthe
communicationofhealthinformationtodecisionmakers
Easytointerpretandprovideausefulsummarymeasure
Itisusefulapproximationofincidenceratewhentherateis
loworwhenthestudyperiodisshort
274
CI=------------x1000=2.3per1000
118,539
Example
Relationshipbetweencigarettesmokingandincidencerate
Strokeinacohortof118,539women
Neversmoked 70395,59417.7
Ex-smoker65232,71227.9
Smoker139280,14149.6
Total274908,44730.2
Person-yearsStrokeincidencerate
SmokingNo.ofcasesofobservation(per100,000
Categoryofstroke(over8years)person-years)
Case-fatalityrate
ameasureoftheseverityofadisease
No.ofdeathsfromadisease
inaspecifiedperiod
Casefatalityrate=------------------------------------------X100
(CFR)No.ofdiagnosedcasesofthe
diseaseinthesameperiod
USEOFAVAILABLEINFORMATION
(Mortality)
Numberofdeathsinaspecifiedperiod
Crudemortalityrate=---------------------------------------------------------XF
(CMR)Averagetotalpopulationduringthatperiod
Thismortalitycanbemadespecificastoage,sexorcause
Notappropriatetouseforcomparisonbecausedeathvaries
accordingage,sex,race,socio-economicclassandotherfactors
Comparisonofmortalityratesbetweengroupsofdiverseage
structureareusuallybasedonage-standardizedrates
Standardizationofrates
(Adjustmentofrates)
1.Directadjustmentofrates
Thisrequirestheselectionofsomepopulation,calledastandard
population,towhichtheage-specificratesforeachpopulation
canbeapplied.
2.Indirectadjustmentofrates
Standardizationisbasedonage-specificratesratherthanage
composition
Thepopulationwhoseratesformthebasisforcomparisonis
referredtoasthestandardpopulation
Thelargerofthetwopopulationsisusuallychosenasstandard
becauseitsratestendtobemorestable
(Adjustmentofrates)
Ifdevelopedandanundevelopedcountryarecompared,the
developedcountrywouldprobablybetakenasthestandard
Acommonwayofcarryingoutindirectage-adjustmentisto
relatethetotalexpecteddeathsthusobtainedtoobserved
deathsthroughaformulaknownastheStandardizedMortality
Ratio(SMR)
Totalobserveddeathsinapopulation
SMR=-------------------------------------------------------
Totalexpecteddeathsinthatpopulation
(Adjustmentofrates)
Interpretation:
Ifthismortalityratioisgreaterthan1,itmeansthatmoredeaths
areobservedinthesmallerorcomparisonpopulationthan
wouldbeexpectedonthebasisofratesinthelarger
(standard)population
Iftheratioislessthan1,fewerdeathsareobservedthan
expected
Example:Directmethod
Comparisonofdeathratesintwopopulationsbyage
AnnualAnnual
Age-specificNumberCrude
AgePopulationDeathrateofDeathrate
(years)NumberProportion(per1000)Deaths(per1000)
(1)(2) (3) (4)(5)(6)
PopulationA<151,500 0.30 2 3
15442,0000.40612
451,5000.302030
45
Allages5,0001.0045---------=9.0
5,000
PopulationB<152,0000.4024
15442,5000.50615
455000.102010
29
Allages5,0001.0029--------=5.8
5,000
ComputationofExpectedNumberofDeathsbyDirectMethod
Example1:IdenticalAge-specificRates
PopulationAPopulationB
Age-specificAge-specific
AgeStandardPopulationDeathRateExpectedDeathRateExpected
(years)(AandBCombined)per1000Deathsper1000Deaths
(1)(2)(3)=(2)x(1)(4)(5)=(4)x(1)
<153,500 2 72 7
15444,500627627
452,00020402040
Allages10,0007474
Conclusion:ThereistrulynodifferencebetweenAandBinriskofdeath
ComputationofExpectedNumberofDeathsbyDirectMethod
Example2:DifferentAge-specificRates
PopulationAPopulationB
Age-specificAge-specific
AgeStandardPopulationDeathRateExpectedDeathRateExpected
(years)(AandBCombined)per1000Deathsper1000Deaths
<153,500 2 7 27
15444,5006271045
452,00020402040
Allages10,0007492
7492
----------=7.4----------=9.2
10,00010,000
Conclusion:ThereisdifferencebetweenAandBinriskofdeath
ExampleofIndirectMethod
DeathsbyAgeandPhotofluorogramReading(Whites)for
Three-and-a-HalfYearObservationPeriod,
MuscogeeCounty,Georgia,1946
NegativeforCardiovascularDiseaseSuspectforCardiovascular
Age-specificDisease
Agein1946NumberofdeathratesNumberof
(years)Population Deathsper100 PopulationDeaths
153413,681350.25231
35548,8381021.15245
55andover2,2531496.616514
-----------------------------
Allages24,77228611220
Crudedeathrateper1001.1517.9
PercentageDistributionbyAgeofNegativesandSuspects,
MuscogeeCounty,Georgia
1534 13,681 55.2 23 20.5
35548,838 35.7 24 21.4
55andover2,253 9.1 65 58.0
Allages24,772100.0112 99.9
NegativeforSuspectfor
CardiovascularDiseaseCardiovascularDisease
AgePercentagePercentage
(years)NumberofPopulationNumberofPopulation
CalculationofStandardizedMortalityRatiofor
SuspectsComparedwithNegatives,
MuscogeeCounty,Georgia
(1) (2)(3)=(1)x(2) (4)
153423 0.25 .1 1
3554 24 1.15 .3 5
55andover 65 6.61 4.3 14
Allages4.720
DeathRatesper100ExpectedDeathsObserved
forPersonsNegativeamongSuspectsDeaths
AgeNumberofforCardiovascularAccordingtoRatesamong
(years)SuspectsDiseaseforNegativesSuspects
Observeddeaths20
SMR=--------------------------=---------=4.25
Expecteddeaths4.7
No.ofdeathsinayearofchildrenless
than1yearofage
Infantmortalityrate=------------------------------------------------------XF
No.oflivebirthsinthesameyear
Ameasureofoverallhealthstatusforagivenpopulation
Itisbasedontheassumptionthatitisparticularlysensitiveto
socio-economicchangesandtohealthcareintervention
Othermeasuresofmortalityinearlychildhoodare:
1.Fetaldeathrate
2.Stillbirthorlatefetaldeathrate
3.Perinatalmortalityrate
4.Neonatalmortalityrate
5.Postneonatalmortalityrate
Mortality

Child mortality rate
is based on deaths of children aged 1 4 years and is important
because accidental injuries, malnutrition and infectious diseases
are common in this age group

Maternal pregnancy-related
deaths in a year
Maternal mortality rate = -------------------------------------
Total births in the same year

Life expectancy
is the average number of years an individual of a
given age is expected to live if current mortality rates continue
Mortality
LifeExpectancy(years)atselectedages
forfourcountries
Age Mauritius Bulgaria USA Japan
Birth65.068.371.675.8
45years25.327.330.432.9
65years11.712.615.016.2
DIAGNOSIS
Clinicalquestion:Howaccuratearetestsusedtodiagnosedisease?
Diagnostictesttheobjectiveistodiagnoseanytreatable
diseasepresent
Characteristicsofadiagnostictest
Reliablegivesthesamemeasurementwhenrepeatedmorethanonce
Valid-measureswhatitintendstomeasure
Accuratecorrectlydeterminesthosewithdiseaseandthosewithout
Easytousecanbeperformedbyotherpeoplewithoutdifficulty
Notexpensiveaffordable
Safeandacceptable
Goldstandard
asounderindicationoftruthorastandardof
accuracy
-anewdiagnostictestiscompared
-elusive(notavailable)
-expensiveandriskybiopsy,surgicalexploration,
autopsy
-sometimessimplethroatswabculture
DIAGNOSIS
80 90 100 110 120 130 140 150 160 170
Normal Group Abnormal Group
B l o o d L e v e l ( mg / 100 ml )
Cut-offpoints
DIAGNOSIS
Validityofadiagnostictest
a=no.oftruepositives,b=no.offalsepositives
c=no.offalsenegatives,d=no.oftruenegatives
Sensitivity=probabilityofapositivetestin
peoplewiththedisease
=a/(a+c)
Specificity=probabilityofanegativetestin
peoplewithoutthedisease
Positivepredictivevalue=probabilityofthepersonhaving
thediseasewhenthetest
ispositive
=a/(a+b)
Negativepredictivevalue=probabilityofthepersonnot
havingthediseasewhenthe
testisnegative
=d/(c+d)
DISEASE
Clinicalquestion:Howaccurateareteststodiagnosedisease?
Useofmultiplediagnostictests
useofimperfectdiagnostictests,withlessthan
100%sensitivityandspecificity,asingletest
frequentlyresultsinaprobabilityofdiseasethatis
neitherveryhighorverylow.
DISEASE
Paralleltests(allatonce)
-usedwhenrapidassessmentisnecessaryasinhospitalizedor
emergencypatients,orforambulatorypatientswhocannot
returneasilyforevaluationbecausetheyhavecomefroma
longdistance
- Paralleltestsgenerallyincreasethesensitivityand,therefore,
thenegativepredictivevalueforagivendiseaseprevalence
abovethoseofeachindividualtest.Ontheotherhand,
specificityandpositivepredictivevaluearelowered
- Paralleltestingisusefulwhentheclinicianisfacedwiththe
needforaverysensitivetestbuthasavailableonlytwoor
morerelativelyinsensitiveones.
DISEASE
Serialtesting(consecutively,basedonprevioustest
result)
-usedwhenrapidassessmentisnotrequired
-usedwhensomeofthetestsareexpensiveorrisky
-maximizesspecificityandpositivepredictivevalue
butlowerssensitivityandthenegativepredictive
value.
-theprocessismoreefficientifthetestwiththe
highestspecificityisusedfirst.
EffectofSequenceisSerialTesting:AThenBversusBThenA
Prevalence of Disease
Number of patients tested 1000
Number of patients with disease 200 (20% prevalence)
Sensitivity and Specificity of the Tests
Test Sensitivity Specificity
A 80 90
B 90 80
Sequence of Testing
Begin with Test A Begin with Test B
Disease Disease
+ - + -
A + 160 80 240 B + 180 160 340
- 40 720 760 - 20 640 660
200 800 1000 200 800 1000

240 Patients Retested with B 340 Patients Retested with A
Disease Disease
+ - + -
B + 144 16 160 A + 144 16 160
- 16 64 80 - 46 144 180
160 80 240 180 160 340
DISEASE
Statementsaboutvaliditytest
Sensitivityandspecificityareinverselyrelated.
Asensitivetestcanpickupmostcasesofthediseasebutit
willerroneouslylabelaspositivemanypersonswhodonot
havethedisease.
Ahighlyspecifictestwillcorrectlylabelasnegativethose
whodonothavethediseasebutitwillmissmanycases.
Trade-OffbetweenSensitivityandSpecificitywhenDiagnosingDiabetes
BloodSugarLevel
2hrafterEating Sensitivity Specificity
(mg/100mL) (%) (%)
7098.6 8.8
80 97.1 25.5
90 94.3 47.6
100 88.6 69.8
110 85.7 84.1
120 71.4 92.5
130 64.3 96.9
140 57.1 99.4
15050.0 99.6
16047.1 99.8
17042.9 100.0
180 38.6 100.0
19034.3 100.0
20027.1 100.0
DISEASE
Averysensitivetestgivesalowpositivepredictivevaluesince
itproducesmanyfalsepositive.Conversely,averyspecific
testgivesahighpositivepredictivevalue.
Sensitivityandspecificityareunaffectedbytheprevalenceof
thediseaseorcondition.Sincesensitivitydependsonlyon
thosewiththediseaseorconditionandspecificityonlyon
thosewithoutthediseaseorcondition.
Thepositivepredictivevalueofatestincreaseswiththe
prevalenceofthedisease.
DISEASE
Usesofsensitivetests
Asensitivetestshouldbechosenwhenthereisanimportant
penaltyformissingadisease(dangerousbuttreatable
condition)
Asensitivetestismosthelpfultotheclinicianwhenthetest
resultisnegative(toruleoutdisease)
Usesofspecifictests
Highlyspecifictestsareneededwhenfalse-positiveresults
canharmthepatientphysically,emotionally,orfinancially.
Aspecifictestismosthelpfulwhenthetestresultispositive
(toconfirmorruleinthedisease
DISEASE
Problems:
Lackofinformationonnegativetests
Lackofinformationontestresultsinthe
nondiseased
Lackofobjectivestandardsfordisease
Consequencesofimperfectstandards
Ifanewtestiscomparedwithanold(butinaccurate)standard
test,thenewtestmayseemworseevenwhenitisactually
better
DISEASE
Reliabilityandvalidity
Measurementerror
InstrumentThemeansofmakingthemeasurement
ObserverThepersonmakingthemeasurement
Biologicvariation
WithinindividualsChangesinpeoplewithtimeandsituation
AmongindividualsBiologicdifferencesfrompersontoperson
DISEASE
Typesofepidemiologicalstudy
Type of study Alternative name Unit of study
Observational studies
Descriptive studies
Analytical studies
Ecological Correlational Population
Cross-sectional Prevalence Individuals
Case-control Case-reference Individuals
Cohort Follow-up Individuals

Experimental studies Interventional studies
Randomized controlled trials Clinical trials Patients
Field trials Healthy people
Community trials Community intervention Communities
studies
(Descriptivestudies)
Casereports
-detailedpresentationsofasinglecaseorahandfulofcases
-meansofdescribingrareclinicalevents
-describeunusualmanifestationsofdisease
-elucidatethemechanismsofdiseaseandtreatment
-placeissuesbeforemedicalcommunityandoftentrigger
moredecisivestudies
-susceptibletobias
(Descriptivestudies)
Case-series
-asimpledescriptiveaccountofinterestingcharacteristics
observedinagroupofpatients
-studylargergroupofpatients(e.g.10ormore)withparticular
disease
-describetheclinicalmanifestationsofdiseaseandtreatments
inagroupofpatientsassembledatonepointintime
-absenceofacomparisongroup,notconclusive
-hypothesis-generating
-selectionbias
(Observationalstudies)
Ecologicalstudies
-aggregateriskstudies
-unitsofanalysisarepopulationsorgroupsofpeoplerather
thanindividuals
-relyondatacollectedforotherpurposes;dataondifferent
exposuresandonsocioeconomicfactorsmaynotbeavailable
-ecologicalfallacy(bias)
-usefulinraisinghypothesis
Cross-sectionalStudy(PrevalenceStudy)
Observationalstudies
Cross-sectional(Prevalencestudy)
(ObservationalStudies)
Cross-sectionalstudies(Prevalencestudies)
-measuretheprevalenceofdisease
-measurementsofexposureandeffectaremadeat
thesametime
-usefulforinvestigatingexposuresthatarefixed
characteristicsofindividuals,suchasethnicity,
socio-economicstatusandbloodgroup,orchronic
diseasesorstableconditions
-Insuddenoutbreaksofdiseaseitisthemost
convenientfirststepinaninvestigationintothe
cause
-Raredisease,conditionsofshortdurationor
diseaseswithhighcasefatalityareoftennot
detected
-short-termandthereforelesscostly
-providenodirectestimateofrisk
-pronetobiasfromselectivesurvival
-estimatesofprevalencemaybebiasedbythe
exclusionofcasesinwhichdeathorrecoveryare
rapid
Case-controlstudies
-longitudinalstudies(lookingbackwardfromthe
diseasetoapossiblecause)
-usenew(incident)cases
-usedtoinvestigatecause(etiology)ofdisease,esp.
rarediseases
-usedoddsratio
Case-controlstudies
-relativelyefficient,requiringsmallersample
thancohortstudy
-completedfasterandmoreeconomical
-earliestpracticalobservationalstrategyfor
determininganassociation
-antecedent-consequenceuncertainty
TablearrangementandformulaforOddsratio(OR)
DiseaseNodiseaseTotal
RiskfactorpresentABA+B
RiskfactorabsentCDC+D
TotalA+CB+D
[A/(A+C)]/[C/(A+C)]A/CAD
OR=-------------------------------=-------=-------
[B/(B+D)]/[D/(B+D)]B/DBC
(Observational studies)
Oddsratiomeasureofthestrengthassociation
InterpretationofOddsratio
TheoddsofhavingthediseaseinquestionareOR
timesgreateramongthoseexposedthanthosewithno
exposure
ThelargerthevalueofOR,thestrongertheassociation
betweenthediseaseinquestionandexposuretothe
riskfactor
WhenthevalueofORiscloseto1,thediseaseandthe
exposuretotheriskfactorareunrelated
(Observationalstudy)
InterpretationofOddsratio
ValueofORlessthan1indicatesanegative
association(i.e.,protectiveeffect)betweentherisk
factorandthedisease
Forraredisease(e.g.,mostchronicdiseaseswith
diseaseprevalenceoflessthan10%),OR
approximatesRR
Exampleofcase-controlstudy
Associationbetweenrecentmeatconsumptionand
enteritisnecroticansinPapuaNewGuinea
Exposure
(recentmeatingestion)
YesNoTotal
DiseaseYes501161
(enteritisnecroticans)No164157
Total6652118
Exampleofcase-controlstudy
[A/(A+C)]/[C/(A+C)]A/CAD
OR=--------------------------------=--------=-----
[B/(B+D)]/[D/(B+D)]B/DBD
50X41
OR=-------------=11.6
11X16
Thecaseswere11.6timesmorelikelythanthe
controlstohaverecentlyingestedmeat
Cohort studies
PastPresentFuture
CohortFollow-up
assembled
Historical
cohort
CohortFollow-up
assembled
Concurrent
cohort
Cohortstudies
-longitudinalstudies(forward)
-providethebestinformationaboutthe
causationofdisease
-mostdirectmeasurementoftheriskof
developingdisease
-providethepossibilityofestimatingthe
attributablerisks
-userelativerisk
Cohortstudies
-mostcloselyresembleexperimentalstudies
-Long-term,notalwaysfeasible
-Samplesizerequiredforthestudyextremely
large
-Attritionismostseriousproblem
Tablearrangementandformulaforrelativerisk(RR)
Disease No Disease Total

Risk factor present A B A + B

Risk factor absent C D C + D

Total A + C B + D
A/(A+B)
RR=-----------------
C/(C+D)
Interpretationofrelativerisk(RR)
Thedisease(orotherhealthrelatedoutcome)isRR
timesmorelikelytooccuramongthoseexposedthan
amongthosewithnoexposure
ThelargerthevalueofRR,thestrongertheassociation
betweenthediseaseinquestionandexposuretothe
riskfactor
Interpretationofrelativerisk(RR)
ValueofRRcloseto1indicatesthatthe
diseaseandexposuretotheriskfactorare
unrelated
ValueofRRlessthan1indicatesanegative
associationbetweentheriskfactorandthe
disease(i.e.,protectiveratherthan
detrimental)
Exampleofcohortstudy
Problem:
Acountyschoolsystemprovideslunchto10,000
schoolchildren.Duringthefirstweekofschool,2,500
ofthesechildrenatechickensaladlatershowntobe
contaminatedwithsalmonella.Theentirepopulation
of10,000studentswassubsequentlyfollowedforone
monthtodeterminewhetherexposuretosalmonella
increasedtheriskofdiarrhea.
Exampleofcohortstudy
DiarrheaNoDiarrhea
Exposure(D+)(D-)Totals
E+302,4702,500
E-607,4407,500
Totals909,91010,000
A/(A+B)30/2,500
RR=---------------=-----------------=1.5
C/(C+D)60/7,500
1.5timesgreaterthaninchildrenwithnosuchexposure
Advantagesanddisadvantagesofdifferentobservational
studydesigns
Probabilityof:
selectionbiasNAmediumhighlow
recallbiasNAhighhighlow
losstofollow-upNANAlowhigh
confoundinghighmediummediumlow
Timerequiredlowmediummediumhigh
Costlowmediummediumhigh
EcologicalCross-Case-Cohort
sectionalcontrol
Applicationsofdifferentobservationalstudydesigns
Investigationofraredisease++++-+++++-
Investigationofrarecause++--+++++
Testingmultipleeffectof+++-+++++
cause
Studyofmultipleexposure+++++++++++
anddeterminants
Measurementsoftime++-++++++
relationship
Directmeasurementof--++++++
incidence
Investigationoflong--+++-
latentperiods
EcologicalCross-Case-Cohort
sectionalcontrol
(Experimentalstudies)
Randomizedcontrolledtrials(RCTs)
- Goldstandardorreferenceinmedicine
- Providethegreatestjustificationfor
concludingcausality
- Subjecttotheleastnumberofproblemsor
biases
- Beststudydesigntoestablishtheefficacyof
atreatmentoraprocedure
Randomizedcontrolledtrials(RCTs)
-Expensiveandtime-consuming
-Difficulttoobtainapprovaltoperform
properlydesignedclinicaltrials
Relativeabilityofdifferenttypesofstudytoprove
causation
TypeofstudyAbilitytoprovecausation
RandomizedcontrolledtrialsStrong
CohortstudiesModerate
Case-controlstudiesModerate
Cross-sectionalstudiesWeak
EcologicalstudiesWeak
BiasinClinicalObservation
Selectionbiasoccurswhencomparisonsare
madebetweengroupsofpatientsthatdifferin
determinantsofoutcomeotherthantheoneunder
study
Measurementbiasoccurswhenthemethodsof
measurementaredissimilaramonggroupsof
patients
Confoundingbiasoccurswhentwofactorsare
associated(traveltogether)andtheeffectofone
isconfusedwithordistortedbytheeffectofthe
other
MethodsofControllingSelectionBias
PhaseofStudy
MethodDescriptionDesignAnalysis
Randomization Assignpatientstogroupsinawaythat+
giveseachpatientequalchanceof
fallingintooneortheothergroup
Restriction Limittherangeofcharacteristicsof+
ofpatientsinthestudy
Matching Foreachpatientinonegroupselectone+
ormorepatientswiththesame
characteristics(exceptfortheone
understudy)foracomparisongroup
StratificationComparerateswithinsubgroups(strata)+
withotherwisesimilarprobabilityofthe
outcome
MethodsforControllingSelectionBias
PhaseofStudy
MethodDescriptionDesignAnalysis
Adjustment
SimpleMathematicallyadjustcruderatesforone+
orfewcharacteristicssothatequalweight
isgiventostrataofsimilarrisk
MultipleAdjustfordifferenceinlargenumberoffactors+
relatedtooutcome,usingmathematical
modellingtechniques
Bestcase/Describehowdifferenttheresultscouldbe+
Worsecaseunderthemostextremeorsimplyveryunlikely)
conditionsofselectionbias
Cause
Clinicalquestion:Whatconditionsleadtodisease?
Whatarethepathogeneticmechanismsofdisease?
Webstersdefinition
somethingthatbringsaboutaneffectora
result
Medicine:etiologypathogenesis
mechanismsorriskfactors
Importance:prevention,diagnosisand
treatmentofdisease
Cause
ConceptsofCause
Singlecausation(Kochspostulates)
aparticulardiseasehasonecauseanda
particularcauseresultsinonedisease
1. Theorganismmustbepresentineverycaseofthedisease
2. Theorganismmustbeisolatedandgrowninpureculture
3. Theorganismmustcauseaspecificdiseasewhen
inoculatedintoananimalsand
4. Theorganismmustthenberecoveredfromtheanimaland
identified
Cause
Multiplecausation(Webofcausation)
Effectsneverdependonsingleisolatedcauses,but
ratherdevelopastheresultofchainsofcausation
inwhicheachlinkitselfistheresultofacomplex
genealogyofantecedents.
Manyfactorsacttogethertocausedisease
Cause
ConceptofCause
Acausemustprecedeadisease
Acauseistermedsufficientwhenitinevitably
producesorinitiatesadisease
Acauseistermednecessaryifadisease
cannotdevelopinitsabsence
Cause
Asufficientcauseisnotusuallyasinglefactor,but
oftencomprisesseveralcomponents
Itisnotnecessarytoidentifyallthecomponentsofa
sufficientcausebeforeeffectivepreventioncantake
place
Eachsufficientcausehasanecessarycauseasa
component
Acausalfactoronitsownisoftenneithernecessary
norsufficient
Cause
Cause
Conceptofcause
Proximityofcausetoeffect
Diseaseisalsodeterminedbylessspecific,moreremote
causesorriskfactors,suchaspeoplesbehavioror
characteristicsoftheirenvironment.
Thesefactorsmaybeevenmoreimportantcausesof
diseasethanarepathogeneticmechanisms
Ifthepathogeneticmechanismisnotclear,knowledgeof
riskfactorsmaystillleadtoveryeffectivetreatmentsand
prevention
SUSCEPTIBLEHOSTINFECTIONTUBERCULOSIS
Exposureto
Mycobacterium
TissueInvasionandReaction
Crowding
Malnutrition
Vaccination
Genetic
RiskFactorsforMechanismsof
TuberculosisPathogenesisTuberculosis
DistantfromOutcomeProximaltoOutcome
Causesoftuberculosis
Cause
Conceptofcause
Interplayofmultiplecauses
Synergismthejointeffectisgreaterthanthesum
oftheeffectsoftheindividualcauses
Antagonismthejointeffectislesser
EffectModificationaspecialtypeofinteraction
Asubstantialimpactonapatientshealthbychanging
onlyoneorasmallnumberofthecauses
Causeasariskfactor
Riskreferstotheprobabilityofsomeuntowardevent
Riskindicatesthelikelihoodthatpeoplewhoare
exposedtocertainfactors(riskfactors)will
subsequentlydevelopaparticulardisease
Riskfactorreferstocondition,physicalcharacteristic,
orbehaviorthatincreasestheprobability(i.e.,risk)
thatacurrentlyhealthyindividualwilldevelopa
particulardisease.
Causeasariskfactor
Whatarethepathogeneticmechanismofdisease?
Exposuretoriskfactorcanoccuratasinglepointin
timeoroveraperiodoftime
everexposed
currentdose
largestdosetaken
totalcumulativedose
yearsofexposure
yearssincefirstcontact
Causeasariskfactor
Recognizingrisk
Largerisksassociatedwitheffectsthatoccurrapidly
afterexposureareeasyforanyonetorecognize
Mostmorbidityandmortalityarecausedbychronic
diseases.Therelationshipbetweenexposureand
diseasearefarlessobviouslatencyperiod
Comparingdiseaseoccurrenceamong
exposedandunexposed
Absolutecomparison
Riskdifference,alsocalledattributablerisk(exposed),excess
riskorabsoluterisk
Attibutablefraction(exposed)oretiologicalfraction(exposed)
Populationattributableriskorattributablefraction(population)
Relativecomparison
Riskratio
Standardizedmortalityratio
Relationshipbetweencigarettesmokingandincidencerateof
strokeinacohortof118,539women
Neversmoked70395,59417.7
Ex-smoker65232,71227.9
Smoker139280,14149.6
Total274908,44730.2
Smoking Person-y ears Stroke incidence rate
category No. of cases of observation (per 100,000
of stroke (over 8 years) person-years)
exposedandunexposed
Riskdifference
isthedifferenceinratesofoccurrencebetween
exposedandunexposedgroups
usefulmeasureoftheextentofthepublichealth
problemcausedbytheexposure
Example:
49.617.7=31.9per100,000person-years
exposedandunexposed
Attributablefraction(exposed)
istheproportionofthediseaseinthespecificpopulationthat
wouldbeeliminatedintheabsenceofexposure
determinedbydividingtheriskdifferencebytherateof
occurrenceamongtheexposedpopulation
Example:
[(49.617.7)/49.6]x100=64%
Interpretation:Onewouldexpecttoachievea64%reduction
intheriskofstrokeamongthewomensmokersifsmoking
werestopped,ontheassumptionthatsmokingisbothcausal
andpreventable
exposedandunexposed
Populationattributablerisk[attributablefraction(population)]
isameasureoftheexcessrateofdiseaseinatotalstudypopulationwhich
isattributabletoanexposure
usefulfordeterminingtherelativeimportanceofexposuresfortheentire
populationandistheproportionbywhichtheincidencerateofthe
outcomeintheentirepopulationwouldbereducedifexposurewere
eliminated.
p
u p
p
I
I I
AF

=
30.2 17.7
= ------------------ = 0.414 o r 41.4%
30.2
exposedandunexposed
Riskratioorrelativerisk
theratiooftheriskofoccurrenceofadiseaseamongexposed
peopletothatamongtheunexposed
betterindicatorofthestrengthofanassociationthantherisk
difference
usedinassessingthelikelihoodthatanassociationrepresents
acausalrelationship
Example:
RR=49.6/17.7=2.8
Causeasariskfactor
Clinical question: What conditions lead to disease ?
What are the pathogenetic mechanisms of disease ?
Usesofriskfactor
1. predicttheoccurrenceofdisease
2. markerofdiseaseoutcome
3. improvethepositivepredictivevalueofa
diagnostictest
4. preventdisease
Cause
Establishingcause
Inclinicalmedicine,itisnotpossibleto
provecausalrelationshipbeyondanydoubt.
Itisonlypossibletoincreaseones
convictionofacauseandeffectrelationship,
bymeansofempiricevidence,causeis
established.
Cause
Establishingcause
Factorsthatareconsideredcausesatone
timearesometimesfoundtobeindirectly
relatedtodiseaselater,whenmore
evidencesareavailable
Cause
Establishingcause
Twofactorsthesuspectedcauseandtheeffect
obviouslymustappeartobeassociatediftheyare
tobeconsideredascauseandeffect
However,notallassociationsarecausal
Twofactorsmaybeassociatedbutnotcausal
duetothepresenceofselectionandmeasurement
biases,chanceandconfounder
Temporal Doesthecauseprecedetheeffect?(essential)
Plausibility Istheassociationconsistentwithotherknowledge?
(mechanismofaction;evidencefromexperimentalanimals)
Consistency Havesimilarresultsbeenshowninotherstudies?
Strength Whatisthestrengthoftheassociationbetweenthecauseand
theeffect?(relativerisk)
Dose-response Isincreasedexposuretothepossiblecauseassociated
relationship withincreasedeffect?
Reversibility Doestheremovalofapossiblecauseleadtoreductionof
diseaserisk?
Studydesign Istheevidencebasedonastrongstudydesign?
JudgingtheevidenceHowmanylinesofevidenceleadtotheconclusion?
Naturalhistoryofadiseaseandprognosis
Clinicalquestion:Whataretheconsequencesofhavingadisease?
Prognosis
isapredictionofthefuturecourseofdisease
followingitsonset
Naturalhistoryofdisease
referstothestagesofadisease
a.Natural
b.Clinicalcourse
Natural history of disease and prognosis
Clinical question: What are the consequences of having a disease ?
Prognosticfactors
areconditionsthatareassociatedwithagiven
outcomeofthedisease
RiskfactorsPrognosticfactors
eventsbeingcountedisavarietyofconsequences
theonsetofdiseaseofdiseasearecounted
predictlowprobabilitydescriberelativelyfrequent
eventsevents
Clinicalquestion:Whataretheconsequenceofhavingadisease?
Multipleprognosticfactorsandpredictionrules

Acombinationoffactorsmaygiveamoreprecise
prognosisthaneachofthesamefactorstakenone
atatime
Clinicalpredictionrulesestimatetheprobabilityof
outcomesaccordingtoasetofpatient
characteristics
OutcomesofDisease(theFiveDs)
Death Abadoutcomeifuntimely
Disease Asetofsymptoms,physicalsigns,andlaboratory
abnormalities
Discomfort Symptomssuchaspain,nausea,dyspnea,itching,
andtinnitis
Disability Impairedabilitytogoaboutusualactivitiesathoe,
work,orrecreation
Dissatisfaction Emotionalreactiontodiseaseanditscare,suchas
sadnessoranger
Clinical question: What are the consequences of having a disease ?
Descriptionsofprognosisshouldincludethefull
rangeofmanifestationsthatwouldbeconsidered
importanttopatients
Cohortsinprognosticstudiesareobservedstarting
fromapointintime,,calledzerotime.
Thispointshouldbespecifiedclearlyandbethe
samewell-definedlocationalongthecourseof
disease(e.g.onsetofsymptoms,timeofdiagnosis
orbeginningoftreatment)foreachpatient
Naturalhistoryofdiseaseandprognosis
Clinicalquestion:Whataretheconsequenceofhavingadisease?
RatesCommonlyUsedtoDescribePrognosis
RateDefinition
5-yearsurvival Percentofpatientssurviving5yearsfrom
somepointinthecourseoftheirdisease
Casefatality Percentofpatientswithadiseasewhodie
ofit
Disease-specificmortalityNumberofpeopleper10,000population
dyingofaspecificdisease
Response Percentofpatientsshowingsome
evidenceofimprovementfollowingan
intervention
Remission Percentofpatientsenteringaphasein
whichdiseaseisnolongerdetectable
Recurrence Percentofpatientswhohavereturnof
diseaseafteradisease-freeinterval
Naturalhistoryofdiseaseandprognosis
Clinicalquestion:Whataretheconsequencesofhavingadisease?
Survivalanalysis(Kaplan-Meiranalysis)
awayofestimatingthesurvivalofacohortovertime
Lifetableanalysis
Treatment
Clinicalquestion:Howdoestreatmentchangethe
courseofdisease?
Usuallytheeffectsoftreatmentaremuchless
obviousandmostinterventionsrequireresearchto
establishtheirvalue
Specificinterventionsmustdomoregoodthan
harmamongpatientswhousethem(efficacious
andeffective)
Themostdesirablemethodformeasuringefficacy
andeffectivenessisthatoftherandomized
controlledtrial
Treatment
courseofdisease?
Interventionstudies
Clinicaltrials
Controlledtrials
Uncontrolledtrials
Concurrentcontrol
Treatment
courseofdisease?
Typesofclinicaltrial(accordingtopurpose)
Prophylactictrials,e.g.immunization,contraception
Therapeutictrials(drugtreatment,surgicalprocedures
Safetytrials(side-effectsofdrug)
Effectivenesstrials(theoretical,use,andextendeduse
effectivenessofcontraceptivemethods)
Riskfactortrials(provingetiologyofdisease)
Efficiencytrials
Treatment
courseofdisease?
PhasesofClinicalTrials
PhaseIClinicalTrials
experimentalanimalsusedtoestablishthatthenew
agentiseffectiveandsuitableforhumanuse
1
st
phaseinhumanspharmacologicandtoxicologic
studies
Phase2ClinicalTrials
assesstheeffectivenessofthedrugordevice
determinetheappropriatedose
investigateitssafety
Treatment
courseofdisease?
Phase3ClinicalTrials(Classicalphase)
performedonpatientswithconsent
carriedoutmostlyonhospitalin-patients
assesstheeffectiveness,safetyandcontinueduse
ofthedrug/device
Phase4ClinicalTrials
atrialinnormalfieldorprogramsetting
reassesseffectiveness,safety,acceptabilityand
continueduseofthedrugs
Prevention
Clinicalquestion:Doesaninterventiononwellpeoplekeep
diseasefromarising?Doesearlydetectionandtreatment
improvethecourseofdisease?
Prevention(Webstersdefinition)theactof
keepingfromhappening
Inclinicalmedicine,thedefinitionisrestricted;
dependingonwheninthecourseofdisease
interventionsaremade
Prevention
ASYMPTOMATIC
NODISEASEDISEASECLINICALCOURSE
Onset
Clinical
Diagnosis
PrimarySecondaryTertiary
RemoveriskEarlydetectionReduce
factorsandtreatmentcomplications
Levelsofprevention
Prevention
Clinicalquestion:Doesaninterventiononwellpeoplekeepthe
LevelofpreventionPhaseofdiseaseTarget
Primary SpecificcausalfactorTotalpopulation,
selectedgroups
andhealthy
individuals
SecondaryEarlystageofdiseasePatients
TertiaryLatestageofdiseasePatients
(treatment,rehabilitation)
Prevention
Primaryprevention
Immunization(communicablediseases)
Folicacidadministrationtopreventneuraltubedefects
Counselingpatientstoadopthealthylifestyles
Chlorinationandfluoridationofthewatersupply
Lawsmandatingseatbeltuseinautomobileand
helmetsformotorcycleuse
Useofearplugsordustmasksincertainoccupational
setting
Prevention
Secondaryprevention
Papsmear
Screeningtest
identificationofanunrecognizeddiseaseor
riskfactorbyhistorytaking,physical
examination,laboratorytestorotherprocedure
thatcanbeappliedrapidly

Criteriaforinstitutingascreeningprogram
Disease Serious
Highprevalenceofpreclinicalstage
Naturalhistoryunderstood
Longperiodbetweenfirstsignsandovertdisease
DiagnostictestSensitiveandspecific
Simpleandcheap
Safeandacceptable
Reliable
Diagnosisand Facilitiesareadequate
TreatmentEffective,acceptable,andsafetreatmentavailable
Prevention
Tertiaryprevention
Limitationofdisability
Rehabilitation
Thegoalhereisnottopreventdeathbutto
maximizetheamountofhigh-qualitytimea
patienthasleft.
Prevention
HealthmaintenanceorPeriodichealthexamination
Proceduresareperformedonpatientswithout
specificcomplaints,toidentifyandmodifyrisk
factorstoavoidtheonsetortofinddiseaseearly
initscoursesothatbyinterveningpatientsremain
well
CriteriaforDecidingWhetheraMedicalCondition
ShouldBeIncludedinPeriodicHealthExamination
1. Howgreatistheburdenofsufferingcausedbythecondition
intermsof:
DeathDiscomfort
DiseaseDissatisfaction
DisabilityDestitution
2. Howgoodisthescreeningtest,ifoneistobeperformed,in
termsof:
SensitivityCost
SpecificitySafety
SimplicityAcceptability
3.a.Forprimaryprevention,howeffectiveistheintervention?
or
b.Forsecondaryprevention,iftheconditionisfound,how
effectiveistheensuingtreatmentintermsof:
Efficacy
Patientcompliance
Earlytreatmentbeingmoreeffectivethanlatertreatment
Prevention
Clinicalquestion:Doesaninterventiononwellpeoplekeepthe
HealthmaintenanceorPeriodichealthexamination
Howmuchharmforhowmuchgood?
Beforeundertakingahealthpromotionprocedure
onapatient,especiallyiftheprocedureis
controversialamongexpertgroups,theclinician
shoulddiscussboththepros(probabilityofand
hopedforhealthbenefits)andcons(probabilityof
unintendedeffects)oftheprocedurewiththe
patient.
Thank You
Thespectrumofillnessfromcommunicabledisease
INAPPARENT MILD SEVERE DEATH
INFECTION DISEASE DISEASE

No signs or Clinical illness with signs and symptoms
symptoms
Origin
Over2,000yearsago,Hippocrates
environmentalfactorscaninfluence
theoccurrenceofdisease
Intheearly19
th
century,the
distributionofdiseaseinspecific
humanpopulationgroupswas
measured
JohnSnowsepidemiologicalstudieson
theriskfactorofCholerainLondon
Deaths from Cholera in districts of London
Supplied by two water companies,
8 July to 26 August 1854
WaterSupplyPopulationNo.ofdeathsCholeradeath
Company 1851 fromcholerarateper1000
population
________________________________________________________
Southwark 167,654 844 5.0
Lambeth 19,133 18 0.9

ACHIEVEMENTSINEPIDEMIOLOGY
EradicationofSmallpox
IdentificationofmethylmercuryMinamata
Disease
IdentificationoffactorscausingRheumaticfever
andRheumaticheartdisease
Iodinedeficiencydisease
AIDS,SARS
PROGNOSIS
Survivalcurve
1. Actuarialorlifetableanalysis
(Cutler-Ederermethod)
1. Kaplan-Meiercurve
PatientDateofTransplantDatelosttoFollow-upDateofKidneyFailureMonthsinStudy
1111-197948-19782
2118-1978 23
31291978 23
44419784241978<1
54191978 20
65101978 19
7514197882819783
8521197811219785
96619781115197817
10 6171978 18
11 6211978 18
12 722197811719783
13 9271978 15
14 105197812019793
15 10221978 14
16 11151978 13
17 1261978 12
18 12121978 12
19 211979 10
20 2161979 10
21 481979 8
22 4111979 8
23 4181979 8
24 62619798 419791
25 731979 5
26 7121979 5
27 71819798119794
28 8231979 4
29 10161979 2
30 12121979 <1
31 12241979 <1
DataforActuarial(LifeTable)AnalysisofRejection(Deaths)ofKidneys
A. Arrangementofsurvivaldata
MonthssinceAliveatbeginningRejectionduringWithdrawnaliveor
Entryintostudyofintervalintervallosttofollow-up
n
i
d
i
W
i
0upto23132
2upto42632
4upto62113
6upto91703
9upto121402
12upto151204
15upto18811
18upto21604
21upto24202
B.ActuarialCalculation
MonthssinceProbabilityofProbabilityofCumulativeProbability
entryintostudyrejectionordeathkidneyretentionofkidneyretention
q
i
=d
i
/[n
i
(w/2)]p
i
=1q
i
s
i
=p
i
p
i-1
p
i-2
.p
1
0upto23/[31(2/2)]=.10.90.90
2upto43/[26(2/2)]=.12.88.79
4upto61/[21(3/2)]=.05.95.75
6upto90/[17(3/2)]=01.00.75
9upto120/[14(2/2)]=01.00.75
12upto150/[12(4/2)]=01.00.75
15upto181/[8(1/2)]=.13.87.65
18upto210/[6(4/2)]=01.00.65
21upto240/[2(2/2)]=01.00.65
Calculationforconfidencebandforactuarialcurve
Intervalq
i
n
i
d
i
w
i
s
i
020.1031320.0037
240.1226320.0055
460.0521130.0027
69017030
912014020
1215012040
15180.138110.0200
182106040
212402020
( )
(
(

i i i
i
i
w d n
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Southwark 167,654 844 5.0

Lambeth 19,133 18 0.9

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