Applied Epidem

7/31/2019 Applied Epidem

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APPLIED EPIDEMIOLOGY

Prepared by

Antonio E. Chan, M.D.


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1. Define epidemiology and outline its scope

2. Differentiate epidemiology from clinicalepidemiology

3. Describe approaches to establishingnormality

4. Describe criteria and measures of disease

occurrence commonly used inepidemiology

5. Enumerate some routinely available datause in epidemiology


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Learningobjectives

6. Understanddiagnostictestinrelationtodisease

7. Describethemaintypesofepidemiologicalstudies

8. Enumeratetheadvantagesanddisadvantagesofobservationalstudiescomparedwithexperimentalstudies

9. Explaincauseofdisease

10. Outlinethestepsnecessarytoestablishthecauseofdisease


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Learningobjectives

11. Appreciate the differing approaches usedin epidemiology to compare theoccurrence of disease

12. Outlinetheroleofepidemiologyindescribingthenaturalhistoryofadiseaseandprognosis

13. Understandtheroleofepidemiologyinthe

preventionandcontrolofdiseasethroughidentificationofthecausesofdisease

14. Relatethedifferentstagesofthedevelopmentofadiseasetothephasesofprevention


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WhatisEpidemiology?

The study of the distribution and

determinants of health-related states

or events in specified populations, and

the application of this study to controlof health problems


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Tounderstandthecourseofthe

disease(naturalhistoryofthedisease) Toidentifythecausesorriskfactors

Toprovideeffectivemeasuresof

treatmentandprevention


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Uses of epidemiologyGenetic factors

1. Causation

Environmental factors(including lifestyle)

2. Natural history

3. Description of health statusof population

Proportion with ill health,change over time,

change with age, etc

Good health Ill health

Good health Subclinicalchanges

Clinicaldisease

Death

Recovery

Good health

ILLhealth

Time


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Uses of epidemiology

4. Evaluation ofintervention Good health Ill health

TreatmentMedical care

Health promotionPreventive measuresPublic health services


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APPLIEDEPIDEMIOLOGY

Clinicalepidemiology

Communicablediseaseepidemiology

Environmentalandoccupationalepidemiology

Molecularepidemiology


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CLINICALEPIDEMIOLOGY

Definition

istheapplicationofepidemiologicalprinciplesand

methodstothepracticeofclinicalmedicine

isthescienceofmakingpredictionsaboutindividual

patientsbycountingclinicaleventsinsimilar

patients,usingscientificmethodsforstudiesofgroupsofpatientstoensurethatthepredictionsare

accurate


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CLINICAL EPIDEMIOLOGY

Purpose:

todevelopandapplymethodsofclinicalobservationsthatwillleadtovalid

conclusionsbyavoidingbeingmisledby

systematicerrorandchance

tomakegooddecisionsinthecareofpatients


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TheRelationshipBetween

EPIDEMIOLOGY+ CLINICALMEDICINE

Populations Individuals

Studies/Assessments

Prevention

EvaluationPlanning

Diagnosis

Treatment

Curing

Caring


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ClinicalQuestion

IssueQuestion

Abnormality Isthepatientsickorwell?

Diagnosis Howaccuratearetestsusedtodiagnosedisease?

Frequency Howoftendoesadiseaseoccur?

Risk Whatfactorsareassociatedwithanincreasedriskofdisease?Prognosis Whataretheconsequencesofhavingadisease?

Treatment Howdoestreatmentchangethecourseofdisease?

Prevention Doesaninterventiononwellpeoplekeepdiseasefromarising?

Doesearlydetectionandtreatmentimprovethecourseof

disease?

Cause Whatconditionsleadtodisease?Whatarethepathogenetic

mechanismsofdisease

Cost Howmuchwillcareforanillnesscost?


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Sourcesofdatausefulfor

epidemiologystudies

Data on vital events birth and death

Morbidity or disease statistics

Data on physiologic and or pathologiccondition

Statistics on health resources and services

Statistics pertaining to the environment Demographic data

Socio-cultural data


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MeasuringHealthandDiseaseClinicalquestion:Isthepatientsickorwell?

Healthisdefinedasastateofcomplete

physical,mental,andsocialwell-being

andnotmerelytheabsenceofdiseaseorinfirmity.

Epidemiologistsdefinitionofhealthstates diseasepresentordiseaseabsent


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MeasuringHealthandDiseaseClinicalquestion:Isthepatientsickorwell?

Diagnostictests

qualitativediagnostictest

quantitativediagnostictestNormal(Gaussian)distributionmethod

Percentilemethod

TherapeuticmethodPredictivevaluemethod


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MeasuringHealthandDisease

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.


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Major Manifestations Minor ManifestationsCarditisClinical:

PolyarthritisfeverChoreaathralgia(jointpains)

Erythemamarginatumpreviousrheumaticfeveror

Subcutaneousnodulesrheumaticheartdisease

Laboratory:

Acutephasereactants:

AbnormalESR,CRP,

leukocytosis

ProlongedP-Rinterval

TheJonesCriteria(revised)forGuidanceinthe

DiagnosisofAcuteRheumaticFever

Ahighprobabilityofrheumaticfeverisindicatedbythepresenceoftwomajor

oronemajorandtwominor,manifestations,ifsupportedbyevidenceofa

precedingGroupAstreptococcalinfection


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MAJORSIGNS MINORSIGNS

Weightloss>10%Persistentcough>1month

Fever>1month GeneralpruriticdermatitisChronicdiarrhea>1monthRecurrentherpeszoster

Generallymphadenopathy

Chronicherpessimplex

Oralcandidiasis

WHOCASE-DEFINITIONFORAIDS

ThepresenceofdisseminatedKaposissarcomaor

cryptococcalmeningitis

or

Twomajorsignsinassociationwithatleastoneminorsign


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Diagnosticcriteriamustbeclearlystated,easytouseandeasytomeasureinastandardmannerunderawidevarietyofcircumstancesbydifferentpeople

Diagnosticcriteriamaychangequiterapidlyasknowledgeortechniquesimprove.

Definitionsusedinclinicalpracticearelessrigidlyspecifiedandclinicaljudgmentismoreimportantindiagnosis


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The development of criteria to establishthe presence of disease requires

definition of normality and abnormality

Difficult to define what is normal

No clear distinction between normal andabnormal


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ApproachesinestablishingnormalityClinicalquestion:Isthepatientsickorwell?

Problem(misclassification)

Clinicalmeasurements

nominalasymptomatic

ordinalcut-offpointintervalorratio

Clinicalmeasurementshaveskeweddistributions

Percentilemethod(sameprevalencerates)


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Levelatwhichtreatmentdoesmoregoodthanharm-Cost

Inspecificagegroupsformenandwomenatwhichtreatmentmakes

economicaswellasmedicalsense

Criteriachangefromtimetotime


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ApproachesinestablishingnormalityClinicalquestion:Isthepatientsickorwell?

Normal Abnormal

commonorusualbeingunusual

well beingsick

notbeingtreatablebeingtreatable


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MeasuresofdiseasefrequencyClinicalquestion:Howoftendoesadiseaseoccur?

Prevalenceofadiseaseisthenumberofcasesinadefinedpopulationataspecifiedpointintime

Pointprevalence

Periodprevalence

Incidenceisthenumberofnewcasesarisingina

givenperiodinaspecifiedpopulation


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MeasuringdiseasefrequencyClinicalquestion:Howoftendoesadiseaseoccur?

Theprevalencerate(P)foradiseaseiscalculatedas

follows:

Numberofpeoplewiththediseaseorcondition

P=-----------------------------------------------------------------(xfactor)

Numberofpeopleinthepopulationatriskatthe

specifiedtime


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Incidencerate(I)

Numberofpeoplewhogeta

diseaseinaspecifiedperiodI=----------------------------------------------------X(factor)

Sumofthelengthoftimeduringwhich

eachpersoninthepopulationisatrisk


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Incidencerate

Thenumeratoristhenumberofnewevents

thatoccurinadefinedtimeperiod Thedenominatoristhepopulationatriskof

experiencingtheeventduringthisperiod

Themostaccuratewayofcalculating

incidencerateistocalculatetheperson-

timeincidencerate(Incidencedensity)


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Cumulativeincidencerateorrisk(CI)

Numberofpeoplewhogetadiseaseduringaspecifiedperiod

CI=----------------------------------------------------X(factor)

Numberofpeoplefreeofthediseasein

thepopulationatriskatthebeginningoftheperiod


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Factorsinfluencingobservedprevalencerate

Increasedby:Decreasedby:

LongerdurationofthediseaseShorterdurationofdisease

ProlongationoflifeofpatientHighcase-fatalityratefromdisease

withoutcure

IncreaseinnewcaseDecreaseinnewcases

(increaseinincidence)(decreaseinincidence)

In-migrationofcasesIn-migrationofhealthypeople

Out-migrationofhealthypeopleOut-migrationofcases

In-migrationofsusceptiblepeopleImprovedcurerateofcases

Improveddiagnosticfacilities

(betterreporting)


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Prevalencestudiesdonotusuallyprovidestrongevidenceofcausality

Itishelpfulinassessingtheneedforhealthcareandtheplanningofhealthservices

Prevalenceratesareoftenusedtomeasuretheoccurrenceofconditionsforwhichtheonsetofdiseasemaybegradual


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Cumulativeincidencerate

Unlikeincidencerate,itmeasuresthedenominatoronlyatthe

beginningofastudy

Thisratehasasimplicitythatmakesitsuitableforthe

communicationofhealthinformationtodecisionmakers

Easytointerpretandprovideausefulsummarymeasure

Itisusefulapproximationofincidenceratewhentherateis

loworwhenthestudyperiodisshort

E l


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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)


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Measuringdiseasefrequency

Clinicalquestion:Howoftendoesadiseaseoccur?

Case-fatalityrate

ameasureoftheseverityofadisease

No.ofdeathsfromadiseaseinaspecifiedperiod

Casefatalityrate=------------------------------------------X100

(CFR)No.ofdiagnosedcasesofthe

diseaseinthesameperiod


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USEOFAVAILABLEINFORMATION

(Mortality)

Numberofdeathsinaspecifiedperiod

Crudemortalityrate=---------------------------------------------------------XF

(CMR)Averagetotalpopulationduringthatperiod

Thismortalitycanbemadespecificastoage,sexorcause

Notappropriatetouseforcomparisonbecausedeathvaries

accordingage,sex,race,socio-economicclassandotherfactors

Comparisonofmortalityratesbetweengroupsofdiverseage

structureareusuallybasedonage-standardizedrates


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Standardizationofrates

(Adjustmentofrates)

1.Directadjustmentofrates

Thisrequirestheselectionofsomepopulation,calledastandardpopulation,towhichtheage-specificratesforeachpopulation

canbeapplied.

2.Indirectadjustmentofrates

Standardizationisbasedonage-specificratesratherthanagecomposition

Thepopulationwhoseratesformthebasisforcomparisonis

referredtoasthestandardpopulation

Thelargerofthetwopopulationsisusuallychosenasstandard

becauseitsratestendtobemorestable


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(Adjustmentofrates)

Ifdevelopedandanundevelopedcountryarecompared,the

developedcountrywouldprobablybetakenasthestandard

Acommonwayofcarryingoutindirectage-adjustmentistorelatethetotalexpecteddeathsthusobtainedtoobserved

deathsthroughaformulaknownastheStandardizedMortality

Ratio(SMR)

Totalobserveddeathsinapopulation SMR=-------------------------------------------------------

Totalexpecteddeathsinthatpopulation


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(Adjustmentofrates)

Interpretation:

Ifthismortalityratioisgreaterthan1,itmeansthatmoredeaths

areobservedinthesmallerorcomparisonpopulationthanwouldbeexpectedonthebasisofratesinthelarger

(standard)population

Iftheratioislessthan1,fewerdeathsareobservedthan

expected


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Example:Directmethod

Comparisonofdeathratesintwopopulationsbyage

AnnualAnnualAge-specificNumberCrude

AgePopulationDeathrateofDeathrate

(years)NumberProportion(per1000)Deaths(per1000)

(1)(2) (3) (4)(5)(6)PopulationA


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ComputationofExpectedNumberofDeathsbyDirectMethod

Example1:IdenticalAge-specificRates

PopulationAPopulationBAge-specificAge-specific

AgeStandardPopulationDeathRateExpectedDeathRateExpected

(years)(AandBCombined)per1000Deathsper1000Deaths

(1)(2)(3)=(2)x(1)(4)(5)=(4)x(1)


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ComputationofExpectedNumberofDeathsbyDirectMethodExample2:DifferentAge-specificRates

PopulationAPopulationBAge-specificAge-specific

AgeStandardPopulationDeathRateExpectedDeathRateExpected

(years)(AandBCombined)per1000Deathsper1000Deaths


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p

DeathsbyAgeandPhotofluorogramReading(Whites)for

Three-and-a-HalfYearObservationPeriod,

MuscogeeCounty,Georgia,1946

NegativeforCardiovascularDiseaseSuspectforCardiovascularAge-specificDiseaseAgein1946NumberofdeathratesNumberof

(years)Population Deathsper100 PopulationDeaths

153413,681350.25231

35548,8381021.15245

55andover2,2531496.616514

-----------------------------

Allages24,77228611220

Crudedeathrateper1001.1517.9


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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


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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


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No.ofdeathsinayearofchildrenlessthan1yearofage

Infantmortalityrate=------------------------------------------------------XF

No.oflivebirthsinthesameyear

Ameasureofoverallhealthstatusforagivenpopulation

Itisbasedontheassumptionthatitisparticularlysensitiveto

socio-economicchangesandtohealthcareintervention

Othermeasuresofmortalityinearlychildhoodare:

1.Fetaldeathrate 2.Stillbirthorlatefetaldeathrate

3.Perinatalmortalityrate

4.Neonatalmortalityrate

5.Postneonatalmortalityrate

Mortality


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Child mortality rate

is based on deaths of children aged 1 4 years and is importantbecause accidental injuries, malnutrition and infectious diseases

are common in this age group

Maternal pregnancy-relateddeaths in a year

Maternal mortality rate = -------------------------------------

Total births in the same year

Life expectancyis the average number of years an individual of agiven age is expected to live if current mortality rates continue

Mortality


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LifeExpectancy(years)atselectedages

forfourcountries

Age Mauritius Bulgaria USA Japan

Birth65.068.371.675.8

45years25.327.330.432.9

65years11.712.615.016.2


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DIAGNOSISClinicalquestion:Howaccuratearetestsusedtodiagnosedisease?

Diagnostictesttheobjectiveistodiagnoseanytreatable

diseasepresent

Characteristicsofadiagnostictest

Reliablegivesthesamemeasurementwhenrepeatedmorethanonce

Valid-measureswhatitintendstomeasure

AccuratecorrectlydeterminesthosewithdiseaseandthosewithoutEasytousecanbeperformedbyotherpeoplewithoutdifficulty

Notexpensiveaffordable

Safeandacceptable


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Goldstandard

asounderindicationoftruthorastandardof

accuracy

-anewdiagnostictestiscompared

-elusive(notavailable)

-expensiveandriskybiopsy,surgicalexploration,

autopsy-sometimessimplethroatswabculture



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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


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V lidit f di ti t t


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Validityofadiagnostictest

a=no.oftruepositives,b=no.offalsepositives

c=no.offalsenegatives,d=no.oftruenegativesSensitivity=probabilityofapositivetestin

peoplewiththedisease

=a/(a+c)

Specificity=probabilityofanegativetestinpeoplewithoutthedisease

Positivepredictivevalue=probabilityofthepersonhaving

thediseasewhenthetest

ispositive

=a/(a+b)Negativepredictivevalue=probabilityofthepersonnot

havingthediseasewhenthe

testisnegative

=d/(c+d)


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DISEASEClinicalquestion:Howaccurateareteststodiagnosedisease?

Paralleltests(allatonce)-usedwhenrapidassessmentisnecessaryasinhospitalizedoremergencypatients,orforambulatorypatientswhocannotreturneasilyforevaluationbecausetheyhavecomefroma

longdistance

- Paralleltestsgenerallyincreasethesensitivityand,therefore,thenegativepredictivevalueforagivendiseaseprevalenceabovethoseofeachindividualtest.Ontheotherhand,

specificityandpositivepredictivevaluearelowered

- Paralleltestingisusefulwhentheclinicianisfacedwiththeneedforaverysensitivetestbuthasavailableonlytwoormorerelativelyinsensitiveones.


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Serialtesting(consecutively,basedonprevioustest

result)

-usedwhenrapidassessmentisnotrequired

-usedwhensomeofthetestsareexpensiveorrisky

-maximizesspecificityandpositivepredictivevalue

butlowerssensitivityandthenegativepredictive

value.

-theprocessismoreefficientifthetestwiththe

highestspecificityisusedfirst.

EffectofSequenceisSerialTesting:AThenBversusBThenA


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q g

Prevalence of DiseaseNumber of patients tested 1000Number of patients with disease 200 (20% prevalence)

Sensitivity and Specificity of the Tests

Test Sensitivity SpecificityA 80 90B 90 80

Sequence of Testing

Begin with Test A Begin with Test BDisease 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 ADisease Disease+ - + -

B + 144 16 160 A + 144 16 160- 16 64 80 - 46 144 180

160 80 240 180 160 340


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DISEASEClinicalquestion:Howaccuratearetestsusedtodiagnosedisease?

Statementsaboutvaliditytest

Sensitivityandspecificityareinverselyrelated.

Asensitivetestcanpickupmostcasesofthediseasebutit

willerroneouslylabelaspositivemanypersonswhodonot

havethedisease.

Ahighlyspecifictestwillcorrectlylabelasnegativethose

whodonothavethediseasebutitwillmissmanycases.


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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 84.1120 71.4 92.5

130 64.3 96.9

140 57.1 99.4

15050.0 99.6

16047.1 99.817042.9 100.0

180 38.6 100.0

19034.3 100.0

20027.1 100.0


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Averysensitivetestgivesalowpositivepredictivevaluesince

itproducesmanyfalsepositive.Conversely,averyspecific

testgivesahighpositivepredictivevalue.

Sensitivityandspecificityareunaffectedbytheprevalenceof

thediseaseorcondition.Sincesensitivitydependsonlyon

thosewiththediseaseorconditionandspecificityonlyon

thosewithoutthediseaseorcondition.

Thepositivepredictivevalueofatestincreaseswiththe

prevalenceofthedisease.


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Usesofsensitivetests

Asensitivetestshouldbechosenwhenthereisanimportantpenaltyformissingadisease(dangerousbuttreatable

condition)

Asensitivetestismosthelpfultotheclinicianwhenthetest

resultisnegative(toruleoutdisease)

Usesofspecifictests

Highlyspecifictestsareneededwhenfalse-positiveresultscanharmthepatientphysically,emotionally,orfinancially.

Aspecifictestismosthelpfulwhenthetestresultispositive

(toconfirmorruleinthedisease


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Problems:

Lackofinformationonnegativetests

Lackofinformationontestresultsinthe

nondiseased

Lackofobjectivestandardsfordisease

Consequencesofimperfectstandards

Ifanewtestiscomparedwithanold(butinaccurate)standardtest,thenewtestmayseemworseevenwhenitisactuallybetter


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Reliabilityandvalidity

Measurementerror

InstrumentThemeansofmakingthemeasurement

ObserverThepersonmakingthemeasurement

Biologicvariation

WithinindividualsChangesinpeoplewithtimeandsituation

AmongindividualsBiologicdifferencesfrompersontoperson


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Typesofepidemiologicalstudy

Type of study Alternative name Unit of study

Observational studies

Descriptive studies

Analytical studies

Ecological Correlational PopulationCross-sectional Prevalence Individuals

Case-control Case-reference Individuals

Cohort Follow-up Individuals

Experimental studies Interventional studiesRandomized controlled trials Clinical trials Patients

Field trials Healthy people

Community trials Community intervention Communities

studies

Types of epidemiological study


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Typesofepidemiologicalstudy(Descriptivestudies)

Casereports

-detailedpresentationsofasinglecaseorahandfulofcases

-meansofdescribingrareclinicalevents

-describeunusualmanifestationsofdisease

-elucidatethemechanismsofdiseaseandtreatment

-placeissuesbeforemedicalcommunityandoftentrigger

moredecisivestudies

-susceptibletobias



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Typesofepidemiologicalstudy(Descriptivestudies)

Case-series

-asimpledescriptiveaccountofinterestingcharacteristics

observedinagroupofpatients

-studylargergroupofpatients(e.g.10ormore)withparticular

disease

-describetheclinicalmanifestationsofdiseaseandtreatments

inagroupofpatientsassembledatonepointintime

-absenceofacomparisongroup,notconclusive

-hypothesis-generating

-selectionbias


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Typesofepidemiologicalstudy(Observationalstudies)

Ecologicalstudies

-aggregateriskstudies

-unitsofanalysisarepopulationsorgroupsofpeoplerather

thanindividuals

-relyondatacollectedforotherpurposes;dataondifferent

exposuresandonsocioeconomicfactorsmaynotbeavailable

-ecologicalfallacy(bias)

-usefulinraisinghypothesis


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Cross-sectionalStudy(PrevalenceStudy)

Typesofepidemiologicalstudy


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Observationalstudies

Cross-sectional(Prevalencestudy)


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Typesofepidemiologicalstudy(ObservationalStudies)

-measuretheprevalenceofdisease

-measurementsofexposureandeffectaremadeatthesametime

-usefulforinvestigatingexposuresthatarefixed

characteristicsofindividuals,suchasethnicity,socio-economicstatusandbloodgroup,orchronic

diseasesorstableconditions


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Cross-sectionalstudies(Prevalencestudies)

-Insuddenoutbreaksofdiseaseitisthemost

convenientfirststepinaninvestigationintothecause

-Raredisease,conditionsofshortdurationor

diseaseswithhighcasefatalityareoftennotdetected

T f id i l i l d


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Cross-sectionalstudies(Prevalencestudies)

-short-termandthereforelesscostly

-providenodirectestimateofrisk

-pronetobiasfromselectivesurvival

-estimatesofprevalencemaybebiasedbytheexclusionofcasesinwhichdeathorrecoveryarerapid

T f id i l i l d


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T f id i l i l d


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Case-controlstudies

-longitudinalstudies(lookingbackwardfromthe

diseasetoapossiblecause)

-usenew(incident)cases

-usedtoinvestigatecause(etiology)ofdisease,esp.

rarediseases

-usedoddsratio


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TablearrangementandformulaforOddsratio(OR)

DiseaseNodiseaseTotal

RiskfactorpresentABA+B

RiskfactorabsentCDC+D

TotalA+CB+D

[A/(A+C)]/[C/(A+C)]A/CADOR=-------------------------------=-------=-------

[B/(B+D)]/[D/(B+D)]B/DBC

T f id i l i l t d


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Typesofepidemiologicalstudy(Observational studies)

Oddsratiomeasureofthestrengthassociation

InterpretationofOddsratio

TheoddsofhavingthediseaseinquestionareOR

timesgreateramongthoseexposedthanthosewithno

exposure

ThelargerthevalueofOR,thestrongertheassociation

betweenthediseaseinquestionandexposuretothe

riskfactor

WhenthevalueofORiscloseto1,thediseaseandthe

exposuretotheriskfactorareunrelated

T f id i l i l t d


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Typesofepidemiologicalstudy(Observationalstudy)

InterpretationofOddsratio

ValueofORlessthan1indicatesanegative

association(i.e.,protectiveeffect)betweentherisk

factorandthedisease

Forraredisease(e.g.,mostchronicdiseaseswith

diseaseprevalenceoflessthan10%),ORapproximatesRR


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Exampleofcase-controlstudy

Associationbetweenrecentmeatconsumptionand

enteritisnecroticansinPapuaNewGuinea

Exposure(recentmeatingestion)

YesNoTotal

DiseaseYes501161

(enteritisnecroticans)No164157

Total6652118


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Exampleofcase-controlstudy

[A/(A+C)]/[C/(A+C)]A/CAD

OR=--------------------------------=--------=-----

[B/(B+D)]/[D/(B+D)]B/DBD

50X41

OR=-------------=11.6

11X16

Thecaseswere11.6timesmorelikelythanthecontrolstohaverecentlyingestedmeat

T pes of epidemiological st d


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Cohort studies


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PastPresentFuture

CohortFollow-up

assembled

Historical

cohort

CohortFollow-upassembled

Concurrent

cohort



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Cohortstudies

-longitudinalstudies(forward)

-providethebestinformationaboutthecausationofdisease

-mostdirectmeasurementoftheriskofdevelopingdisease

-providethepossibilityofestimatingtheattributablerisks

-userelativerisk



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Cohortstudies

-mostcloselyresembleexperimentalstudies

-Long-term,notalwaysfeasible-Samplesizerequiredforthestudyextremely

large

-Attritionismostseriousproblem


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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)



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Interpretationofrelativerisk(RR)

Thedisease(orotherhealthrelatedoutcome)isRR

timesmorelikelytooccuramongthoseexposedthanamongthosewithnoexposure

ThelargerthevalueofRR,thestrongertheassociation

betweenthediseaseinquestionandexposuretothe

riskfactor


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Exampleofcohortstudy

Problem:

Acountyschoolsystemprovideslunchto10,000

schoolchildren.Duringthefirstweekofschool,2,500ofthesechildrenatechickensaladlatershowntobe

contaminatedwithsalmonella.Theentirepopulation

of10,000studentswassubsequentlyfollowedforone

monthtodeterminewhetherexposuretosalmonella

increasedtheriskofdiarrhea.

Example of cohort study


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Exampleofcohortstudy

DiarrheaNoDiarrhea

Exposure(D+)(D-)Totals

E+302,4702,500

E-607,4407,500

Totals909,91010,000

A/(A+B)30/2,500RR=---------------=-----------------=1.5

C/(C+D)60/7,500

1.5timesgreaterthaninchildrenwithnosuchexposure

Advantagesanddisadvantagesofdifferentobservational

study designs


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studydesigns

Probabilityof:

selectionbiasNAmediumhighlow

recallbiasNAhighhighlow

losstofollow-upNANAlowhigh

confoundinghighmediummediumlow

Timerequiredlowmediummediumhigh

Costlowmediummediumhigh

EcologicalCross-Case-Cohort

sectionalcontrol

Applicationsofdifferentobservationalstudydesigns


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Investigationofraredisease++++-+++++-

Investigationofrarecause++--+++++

Testingmultipleeffectof+++-+++++

cause

Studyofmultipleexposure+++++++++++

anddeterminants

Measurementsoftime++-++++++

relationship

Directmeasurementof--++++++

incidence

Investigationoflong--+++-

latentperiods

EcologicalCross-Case-Cohort

sectionalcontrol


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101/164

Typesofepidemiologicalstudy(Experimentalstudies)

Randomizedcontrolledtrials(RCTs)

- Goldstandardorreferenceinmedicine

- Providethegreatestjustificationfor

concludingcausality

- Subjecttotheleastnumberofproblemsor

biases

- Beststudydesigntoestablishtheefficacyofatreatmentoraprocedure


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103/164


104/164

BiasinClinicalObservation

Selectionbiasoccurswhencomparisonsare

madebetweengroupsofpatientsthatdifferin

determinantsofoutcomeotherthantheoneunder

study

Measurementbiasoccurswhenthemethodsof

measurementaredissimilaramonggroupsof

patients

Confoundingbiasoccurswhentwofactorsare

associated(traveltogether)andtheeffectofone

isconfusedwithordistortedbytheeffectofthe

other

MethodsofControllingSelectionBias


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PhaseofStudy

MethodDescriptionDesignAnalysis

Randomization Assignpatientstogroupsinawaythat+

giveseachpatientequalchanceof

fallingintooneortheothergroup

Restriction Limittherangeofcharacteristicsof+ofpatientsinthestudy

Matching Foreachpatientinonegroupselectone+

ormorepatientswiththesame

characteristics(exceptfortheone

understudy)foracomparisongroup

StratificationComparerateswithinsubgroups(strata)+

withotherwisesimilarprobabilityofthe

outcome

MethodsforControllingSelectionBias

Ph f St d


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PhaseofStudy

MethodDescriptionDesignAnalysis

Adjustment

SimpleMathematicallyadjustcruderatesforone+

orfewcharacteristicssothatequalweight

isgiventostrataofsimilarrisk

MultipleAdjustfordifferenceinlargenumberoffactors+

relatedtooutcome,usingmathematical

modellingtechniques

Bestcase/Describehowdifferenttheresultscouldbe+

Worsecaseunderthemostextremeorsimplyveryunlikely)

conditionsofselectionbias

Cause


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Clinicalquestion:Whatconditionsleadtodisease?

Whatarethepathogeneticmechanismsofdisease?

Webstersdefinition

somethingthatbringsaboutaneffectora

result

Medicine:etiologypathogenesis

mechanismsorriskfactors

Importance:prevention,diagnosisand

treatmentofdisease


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Cause


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Multiplecausation(Webofcausation)

Effectsneverdependonsingleisolatedcauses,but

ratherdevelopastheresultofchainsofcausation

inwhicheachlinkitselfistheresultofacomplex

genealogyofantecedents.

Manyfactorsacttogethertocausedisease


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111/164


112/164


113/164

Causesoftuberculosis


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SUSCEPTIBLEHOSTINFECTIONTUBERCULOSIS

Exposureto

Mycobacterium

TissueInvasionandReaction

Crowding

Malnutrition

Vaccination

Genetic

RiskFactorsforMechanismsof

TuberculosisPathogenesisTuberculosis

DistantfromOutcomeProximaltoOutcome


115/164


116/164


117/164


118/164


119/164

Relationshipbetweencigarettesmokingandincidencerateof


120/164

p g g

strokeinacohortof118,539women

Neversmoked70395,59417.7

Ex-smoker65232,71227.9

Smoker139280,14149.6

Total274908,44730.2

Smoking Person-y ears Stroke incidence ratecategory No. of cases of observation (per 100,000

of stroke (over 8 years) person-years)


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Comparingdiseaseoccurrenceamong


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exposedandunexposed

Attributablefraction(exposed)

istheproportionofthediseaseinthespecificpopulationthatwouldbeeliminatedintheabsenceofexposure

determinedbydividingtheriskdifferencebytherateofoccurrenceamongtheexposedpopulation

Example:

[(49.617.7)/49.6]x100=64%

Interpretation:Onewouldexpecttoachievea64%reductionintheriskofstrokeamongthewomensmokersifsmokingwerestopped,ontheassumptionthatsmokingisbothcausalandpreventable

Comparingdiseaseoccurrenceamong


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exposedandunexposed

Populationattributablerisk[attributablefraction(population)]

isameasureoftheexcessrateofdiseaseinatotalstudypopulationwhich

isattributabletoanexposure

usefulfordeterminingtherelativeimportanceofexposuresfortheentire

populationandistheproportionbywhichtheincidencerateofthe

outcomeintheentirepopulationwouldbereducedifexposurewere

eliminated.

p

up

pI

IIAF

30.2 17.7= ------------------ = 0.414 o r 41.4%

30.2


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CauseasariskfactorClinical question: What conditions lead to disease ?


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Clinical question: What conditions lead to disease ?What are the pathogenetic mechanisms of disease ?

Usesofriskfactor

1. predicttheoccurrenceofdisease

2. markerofdiseaseoutcome

3. improvethepositivepredictivevalueofa

diagnostictest

4. preventdisease

CauseClinical question: What conditions lead to disease ?


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Establishingcause

Inclinicalmedicine,itisnotpossibleto

provecausalrelationshipbeyondanydoubt.Itisonlypossibletoincreaseones

convictionofacauseandeffectrelationship,

bymeansofempiricevidence,causeisestablished.

CauseClinical question: What conditions lead to disease ?


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Establishingcause

Factorsthatareconsideredcausesatonetimearesometimesfoundtobeindirectly

relatedtodiseaselater,whenmore

evidencesareavailable


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129/164


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Temporal Doesthecauseprecedetheeffect?(essential)

Plausibility Istheassociationconsistentwithotherknowledge?

(mechanismofaction;evidencefromexperimentalanimals)

Consistency Havesimilarresultsbeenshowninotherstudies?

Strength Whatisthestrengthoftheassociationbetweenthecauseand

theeffect?(relativerisk)Dose-response Isincreasedexposuretothepossiblecauseassociated

relationship withincreasedeffect?

Reversibility Doestheremovalofapossiblecauseleadtoreductionof

diseaserisk?Studydesign Istheevidencebasedonastrongstudydesign?

JudgingtheevidenceHowmanylinesofevidenceleadtotheconclusion?


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Naturalhistoryofadiseaseandprognosis


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Clinicalquestion:Whataretheconsequencesofhavingadisease?

Prognosis

isapredictionofthefuturecourseofdiseasefollowingitsonset

Naturalhistoryofdisease

referstothestagesofadisease

a.Natural

b.Clinicalcourse


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Natural history of disease and prognosis


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Clinical question: What are the consequences of having a disease ?

Prognosticfactors

areconditionsthatareassociatedwithagivenoutcomeofthedisease

RiskfactorsPrognosticfactors

eventsbeingcountedisavarietyofconsequences

theonsetofdiseaseofdiseasearecounted

predictlowprobabilitydescriberelativelyfrequent

eventsevents



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Clinicalquestion:Whataretheconsequenceofhavingadisease?

Multipleprognosticfactorsandpredictionrules

Acombinationoffactorsmaygiveamoreprecise

prognosisthaneachofthesamefactorstakenoneatatime

Clinicalpredictionrulesestimatetheprobabilityof

outcomesaccordingtoasetofpatientcharacteristics


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OutcomesofDisease(theFiveDs)

Death Abadoutcomeifuntimely

Disease Asetofsymptoms,physicalsigns,andlaboratory

abnormalities

Discomfort Symptomssuchaspain,nausea,dyspnea,itching,

andtinnitis

Disability Impairedabilitytogoaboutusualactivitiesathoe,

work,orrecreation

Dissatisfaction Emotionalreactiontodiseaseanditscare,suchas

sadnessoranger



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Clinical question: What are the consequences of having a disease ?

Descriptionsofprognosisshouldincludethefullrangeofmanifestationsthatwouldbeconsideredimportanttopatients

Cohortsinprognosticstudiesareobservedstartingfromapointintime,,calledzerotime.

Thispointshouldbespecifiedclearlyandbethe

samewell-definedlocationalongthecourseofdisease(e.g.onsetofsymptoms,timeofdiagnosisorbeginningoftreatment)foreachpatient

NaturalhistoryofdiseaseandprognosisClinicalquestion:Whataretheconsequenceofhavingadisease?

Rates Commonl Used to Describe Prognosis


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RatesCommonlyUsedtoDescribePrognosis

RateDefinition

5-yearsurvival Percentofpatientssurviving5yearsfrom

somepointinthecourseoftheirdisease

Casefatality Percentofpatientswithadiseasewhodie

ofit

Disease-specificmortalityNumberofpeopleper10,000population

dyingofaspecificdisease

Response Percentofpatientsshowingsome

evidenceofimprovementfollowingan

interventionRemission Percentofpatientsenteringaphasein

whichdiseaseisnolongerdetectable

Recurrence Percentofpatientswhohavereturnof

diseaseafteradisease-freeinterval

NaturalhistoryofdiseaseandprognosisCli i l i Wh h f h i di ?


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Clinicalquestion:Whataretheconsequencesofhavingadisease?

Survivalanalysis(Kaplan-Meiranalysis)

awayofestimatingthesurvivalofacohortovertime

Lifetableanalysis

TreatmentClinical question: How does treatment change the


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Clinicalquestion:Howdoestreatmentchangethe

courseofdisease?

Usuallytheeffectsoftreatmentaremuchlessobviousandmostinterventionsrequireresearchtoestablishtheirvalue

Specificinterventionsmustdomoregoodthanharmamongpatientswhousethem(efficaciousandeffective)

Themostdesirablemethodformeasuringefficacyandeffectivenessisthatoftherandomizedcontrolledtrial

TreatmentClinicalquestion:Howdoestreatmentchangethe

f di ?


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courseofdisease?

Interventionstudies

Clinicaltrials

Controlledtrials

Uncontrolledtrials

Concurrentcontrol


f di ?


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courseofdisease?

Typesofclinicaltrial(accordingtopurpose)

Prophylactictrials,e.g.immunization,contraception

Therapeutictrials(drugtreatment,surgicalprocedures

Safetytrials(side-effectsofdrug)

Effectivenesstrials(theoretical,use,andextendeduse

effectivenessofcontraceptivemethods)

Riskfactortrials(provingetiologyofdisease)

Efficiencytrials


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144/164

q g

courseofdisease?

Phase3ClinicalTrials(Classicalphase)

performedonpatientswithconsent

carriedoutmostlyonhospitalin-patients

assesstheeffectiveness,safetyandcontinueduse

ofthedrug/device

Phase4ClinicalTrials

atrialinnormalfieldorprogramsettingreassesseffectiveness,safety,acceptabilityand

continueduseofthedrugs

PreventionClinicalquestion:Doesaninterventiononwellpeoplekeep

disease from arising? Does early detection and treatment


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diseasefromarising?Doesearlydetectionandtreatment

improvethecourseofdisease?

Prevention(Webstersdefinition)theactof

keepingfromhappening

Inclinicalmedicine,thedefinitionisrestricted;

dependingonwheninthecourseofdisease

interventionsaremade




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ASYMPTOMATIC

NODISEASEDISEASECLINICALCOURSE

Onset

Clinical

Diagnosis

PrimarySecondaryTertiary

RemoveriskEarlydetectionReducefactorsandtreatmentcomplications

Levelsofprevention

PreventionClinicalquestion:Doesaninterventiononwellpeoplekeepthe



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LevelofpreventionPhaseofdiseaseTarget

Primary SpecificcausalfactorTotalpopulation,

selectedgroupsandhealthy

individuals

SecondaryEarlystageofdiseasePatients

TertiaryLatestageofdiseasePatients

(treatment,rehabilitation)


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149/164



Secondaryprevention

Papsmear

Screeningtest

identificationofanunrecognizeddiseaseor

riskfactorbyhistorytaking,physical

examination,laboratorytestorotherprocedurethatcanbeappliedrapidly

Criteriaforinstitutingascreeningprogram


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Disease Serious

Highprevalenceofpreclinicalstage

Naturalhistoryunderstood

Longperiodbetweenfirstsignsandovertdisease

DiagnostictestSensitiveandspecific

Simpleandcheap

Safeandacceptable

Reliable

Diagnosisand Facilitiesareadequate

TreatmentEffective,acceptable,andsafetreatmentavailable




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Tertiaryprevention

Limitationofdisability

Rehabilitation

Thegoalhereisnottopreventdeathbutto

maximizetheamountofhigh-qualitytimea

patienthasleft.




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HealthmaintenanceorPeriodichealthexamination

Proceduresareperformedonpatientswithout

specificcomplaints,toidentifyandmodifyriskfactorstoavoidtheonsetortofinddiseaseearly

initscoursesothatbyinterveningpatientsremain

well

CriteriaforDecidingWhetheraMedicalCondition

ShouldBeIncludedinPeriodicHealthExamination

H t i th b d f ff i d b th diti


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1. Howgreatistheburdenofsufferingcausedbytheconditionintermsof:

DeathDiscomfortDiseaseDissatisfaction

DisabilityDestitution

2. Howgoodisthescreeningtest,ifoneistobeperformed,intermsof:

SensitivityCostSpecificitySafety

SimplicityAcceptability

3.a.Forprimaryprevention,howeffectiveistheintervention?

or

b.Forsecondaryprevention,iftheconditionisfound,how

effectiveistheensuingtreatmentintermsof:Efficacy

Patientcompliance

Earlytreatmentbeingmoreeffectivethanlatertreatment

PreventionClinicalquestion:Doesaninterventiononwellpeoplekeepthe



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HealthmaintenanceorPeriodichealthexamination

Howmuchharmforhowmuchgood?

Beforeundertakingahealthpromotionprocedureonapatient,especiallyiftheprocedureis

controversialamongexpertgroups,theclinician

shoulddiscussboththepros(probabilityofand

hopedforhealthbenefits)andcons(probabilityof

unintendedeffects)oftheprocedurewiththe

patient.


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ThankYou

Thespectrumofillnessfromcommunicabledisease


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INAPPARENT MILD SEVERE DEATH

INFECTION DISEASE DISEASE

No signs or Clinical illness with signs and symptoms

symptoms

Origin


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Over2,000yearsago,Hippocratesenvironmentalfactorscaninfluencetheoccurrenceofdisease

Intheearly19thcentury,thedistributionofdiseaseinspecific

humanpopulationgroupswasmeasured

JohnSnowsepidemiologicalstudieson

the risk factor of Cholera in London


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theriskfactorofCholerainLondon

Deaths from Cholera in districts of LondonSupplied 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


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EradicationofSmallpox

IdentificationofmethylmercuryMinamata

Disease

IdentificationoffactorscausingRheumaticfever

andRheumaticheartdisease

Iodinedeficiencydisease

AIDS,SARS

PROGNOSIS


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Survivalcurve

1. Actuarialorlifetableanalysis

(Cutler-Ederermethod)

1. Kaplan-Meiercurve

PatientDateofTransplantDatelosttoFollow-upDateofKidneyFailureMonthsinStudy

1111-197948-197822118-197823

3129197823

44419784 241978


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6510197819

751419788 2819783

8521197811 219785966197811 15197817

10 617197818

11 621197818

12 722197811 719783

13 927197815

14 10519781 2019793

15 1022197814

16 111519781317 126197812

18 1212197812

19 21197910

20 216197910

21 4819798

22 41119798

23 41819798

24 62619798 41979125 7319795

26 71219795

27 71819798 119794

28 82319794

29 101619792

30 12121979


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MonthssinceAliveatbeginningRejectionduringWithdrawnaliveor

Entryintostudyofintervalintervallosttofollow-up

nidiWi

0upto23132

2upto42632

4upto621136upto91703

9upto121402

12upto151204

15upto18811

18upto21604

21upto24202

B.ActuarialCalculation

MonthssinceProbabilityofProbabilityofCumulativeProbability

entryintostudyrejectionordeathkidneyretentionofkidneyretention

q d / [n ( /2)] p 1 q s pp p p


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qi=di/[ni(w/2)]pi=1qisi=pipi-1pi-2.p1

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

iii

ii

wdn

qs

21


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Intervalqinidi wisi

020.1031320.0037

240.1226320.0055

460.0521130.0027

69017030

912014020

121501204015180.138110.0200

182106040

212402020

iii 2

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