Studi Kohort

Cohort in epidemiology:a group of people who share a common experience or condition

Experimental vs. Cohort In experimental studies, individuals are ASSIGNED to a group and the exposure is FORCED upon them

In a cohort study, the exposure is NATURAL and individuals are NOT ASSIGNED to a group; they are in a group either by their own choosing (smoking vs. not) or by chance (exposure to radiation leak or not)

Cohort definition- People living in a geographical area Members of all worker ever employed in one factory- Cohort of workers from different plants but engage the same industrial process- Member of professional organization

Cohort DefinitionAdvantage of first option, restricting the cohort to a place:Characterization of exposure is more consistent and precisePooling cohort members from multiple facilities increases the study size

Closed vs. Dynamic Closed cohort study subjects are observed continuously from the time joining the study forward. It assumes no subject enter or exit when the study is definedDynamic (open population) allows the member enter or exit from the study. person-time experiences accumulate from a changing of individual

TIMEPopulationPeople WithoutdiseaseExposedNot exposedDiseaseNo diseaseDiseaseNo disease

Groups are classified on the basis of presence or absence of exposureFree of outcome of interest at the start of follow-upSubjects are followed to assess outcome

Types of Cohort StudyRetrospective cohortBoth exposure and outcome have already occurred Prospective cohortExposure may or may not have occurred but the outcome have not

Prospective CohortExposureDiseasex?o?

Retrospective CohortExposureDiseasex?o?

Retrospective cohort vs. Prospective cohort Factors to be considered ScientificDoes available data provide adequate detail information on risk factors?

Logistic

Planning a Cohort StudyIs the study cohort sufficiently large to yield statistically reliable data?Will the cohort have an adequate length of follow-up for studying delayed effects or rare disease?Are exposure data suitable for assessing exposure-response relationship?

Selection of exposed populationIs the exposure common or rare in the population?

Does it allow complete and accurate exposure and follow-up information on all study participants?

Special exposure populationIndustrial-based (Occupational) Living near suspected hazardous environmentBeing present at given event (hiroshima population, veteran of vietnams war)

Groups of people that provide adequate informationHealth insurance, profession, student

Population in specific geographic

Selection of comparison population

Groups being compared should be as similar as possible in terms of Other risk factors of outcome Exposure assessment Outcome assessment

Selection of comparison populationInternal comparisonLevels of exposureSmoking among physicianGeneral population ( SMR analysis)Outcome occurrence in study population is compared to that in general populationSpecial comparisonE.g. Groups are compared based on different taskMultiple comparison

Defining ExposureQuality of exposure assessment determine validity of environmental epidemiology studyYes/no or high/low nonhomogenous within groupOrdinal dose-responseContinuous from relevant time increases sensitivity

Measuring ExposureInterviews, questionnaires, structured diariesMeasurements in external media (macroenvironment) from existing records or conducted for epidemiologic investigationConcentrations in the personal or microenvironmentIndividual dosesBiologic monitoring substance (blood lead) biologic marker (phenol as urinary metabolite of benzene)

Exposure variableIntensity = magnitude of the amount of a substance that potentially can enter the body Duration = length of time during which a given intensity is maintainedCumulative exposure (CE) = I x D

Sources of DataExposureRecordsQuestionnaire, InterviewPhysical examinationDirect measurement OutcomeHospital or clinic recordsDeath certificatePeriodic health examinationQuestionnaire, interview

Follow-up of the CohortUpdate interview, resend questionnaire, update physical exam, exposure measurement, outcomeSketch diagram on how to follow-up the subjectsDevelop a guide on how to search losses of follow-up. It should not be related to exposure or outcome.

Issues in AnalysisBiasLosses to follow-upMisclassification of exposureNondifferential: a similar proportion of inaccuracy occurs in each study groupDifferential

Measure of associationAbsolute measureRisk difference (RD) = Ie - Iue Relative measure Risk ratio Rate ratioIncidence exposedIncidence unexposed

Data analysisPerhitungan RR untuk CI

Outcome (+)Outcome (-)Total

E (exposed)aba + b

NE (unexposed)cdc + d

Totala + cb + dN (a + b + c + d)

CI pada populasi exposed (E) --- a/(a + b)RR=CI pada populasi unexposed (NE) --- c/(c + d)

Data analysisPerhitungan RR untuk IR

Outcome (+)Person-time

E (exposed)aN1

NE (unexposed)cN0

Totala + cT

IR pada populasi exposed (E) --- a/N1RR=IR pada populasi unexposed (NE) --- c/N0

SMR analysisStudy CohortReference population(1)(2)(3)(4)AgeObsP-YRate Exp =SMR =per 1000(2) x (3)(1) : (4)

40-49612002.53250-592723406.114.271.8960-6998375012.446.502.1170-79489752524.381.97

Total17988.152.03

Does HIV infection increase risk of developing TB among drug users?

Various Levels ExposuresExposure levelsPopulation Cases IncidenceRRat Risk

HighN1a1I1RR1MediumN2a2I2RR2LowN3a3I3RR3NoneN0a0I0Ref

Presentation of data: Various exposure levels

Daily number of cigarettes smoked

Person-years at risk

Lung cancer

cases

> 25

25,100

57

15 - 24

38,900

54

1 - 14

38,600

22

none

42,800

3

StrengthsDesign of choice to study rare exposureCan examine multiple outcomes of a single exposureCan elucidate temporal relation between exposure and outcome Minimize bias of exposure assessment Direct measurement of incidence

LimitationsInefficient to study rare diseaseIf prospective, costly and time consumingIf retrospective, requires adequate records prone to losses to follow-up threat validity of the result

Person-time for dynamic population

Persons

Person-weeks

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1 _______________________________________________

5

2. _______x

1

3. ______________________________________________X

5

4. _____________________x

2

5. _______________________________________________

5

6. ___________________22

7. ______________________________________________

5

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

0

1

2

3

4

5 25

Years of f-u

3 cases / 25 p_wks = 12cases/100p_wks

Plant openJan 1,1940Cohort enumerationJan 1, 195019601970T1End of follow-upDec 31, 1984ABCDEFGH

Person-time for fixed cohort

Persons

Person-weekrs

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

1 _______________________________________________

5

2. _______x

1

3. ______________________________________________X

5

4. _____________________x

2

5. _______________________________________________

5

6. _______________________________________________

5

7. ______________________________________________

5

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

0

1

2

3

4

5 28

Weeks

3 cases /28 p_weeks = 11cases/100p_weeks

Macro is ecologic measure and is useful if 1) overall pollutants are of concern than individual pollutants, 2) exposure is widespread in some but not in other geographic or time period Must be validated.Individual: duration of contact as surrogate exposure concentration with implicit that duration correlates with cumulative exposure. But could be poor for individual absorbed dose because of variability of breathing rate, age, sex, medical conditions, etc. Biologic monitoring: U have to know route of exposure, e.g. benzene: inhalation, dermal, oral ingestions