Following the roman soldiers

Cohort studies

FETP India

Competency to be gained from this lecture

Design a cohort study

Key areas

• Study population• Prospective / retrospective cohorts• Measurement of outcome • Measurement of exposure• Experimental design

A cohort of Roman soldiers

Elements that may define a study population for a cohort

• Residence• Demographic characteristics • Cultural background• Socio-economic group • Employment • Sharing a common experience or

condition

Population

Elements defining the study population become the recruitment

criteria • Inclusion criteria• Exclusion criteria

Same as inclusion criteria Just considered in a mirror

Population

Fixed cohorts

• Study participants are included from the beginning to the end of the cohort

• Simple• Common

Population

Dynamic cohorts

• Study participants can come in and out of the cohort

• More complex• Less common

Population

Potential objectives of a cohort study

• Descriptive Estimate incidence

• Analytic Compare the incidence of a disease in

various subgroups:• Exposed • Unexposed

Population

Ill Non-ill Total

Exposed a b a+b

Non-exposed c d c+d

Total a+c b+d a+b+c+d

Presentation of the data of an analytical study in a 2 x 2 table

Population

Ill Non-ill Total

Exposed a b a+b

Non-exposed c d c+d

Total a+c b+d a+b+c+d

Presentation of the data of an analytical cohort study in a 2 x 2

table

Population

The unexposed group in a cohort study

• Unexposed subjects must belong to the same population

• Unexposed subjects must have the same theoretical risk to develop the disease if they are exposed to the risk factor

Population

Prospective cohorts studies

• Recruitment of study participants at the beginning of the observation period

• Initial observation Baseline collection of information about exposure Verification of “non-ill” status

• Follow-up over time to identify persons who develop an illness

• Key issue: Not missing persons who develop the illness Loss to follow-up

Prospective and retrospective cohorts

Retrospective cohorts studies

• Recruitment of study participants at the end of the observation period

• Retrospective assessment Collection of information about exposure Collection of information about illness

• Key issue: Identify ill subjects appropriately-

retrospectively

Prospective and retrospective cohorts

Collecting data about outcome in cohort studies

• Baseline and end of the observation period Cumulated incidence Attack rate

• Regular intervals Incidence rate Incidence density rate

Outcome

Calculation of incidence density:Status of study participants at a

given point in time• At risk

The subject is being observed

• Censored The subject is lost to follow-up The subject had not developed the illness

when he was lost to follow-up

• Illness The subject has developed the illness

(He is not followed-up after)

Outcome

Study participants observed over time in a cohort study

One year Development of illness Censored

Blue lines denote an observation

Each yellow line is a person followed

Outcome

Calculation of incidence density in a cohort study

One year Development of illness Censored

Person-year at risk:41Illness:2Incidence density:4.9 / person -year

Outcome

Calculation of cumulated incidence in a cohort study

Development of illness

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Person included:8Lost to follow-up:4Illness:1Incidence:25%

Duration of the study

Outcome

Outcome assessment in cohort studies:

Summary Single assessment

• Easier• Does not measure

observation time• Subject to bias

because of loss to follow-up

• Does not allow calculation of incidence density

Regular assessment• More difficult• Measures observation

time• Less subject to bias

because of loss to follow-up

• Allows calculation of incidence density

Outcome

Ill Non-ill Total

Exposed a b L1

Non-exposed c d L0

Total a+c b+d L1 + L0

Calculation of the risk for the whole population in a cohort study

R = (a+c)/(L1 + L0)

Outcome

Events Person-time Rate

Exposed a PT1 Rate1

Non-exposed c PT0 Rate0

Total a+c PT Rate

Calculation of the rate for the whole population in a cohort study

Rate = a+c/PT

Outcome

Examining one or multiple exposures

in cohort studies• One exposure • Multiple exposures

Various exposed and unexposed subgroups examined differently in the analysis

Exposure

Collecting good data on exposure

• Objectively Reproducibility of exposure measurement

• Accurately Information reflecting as closely as possible

the effect of exposure

• Precisely Total quality management in exposure

measurement

Exposure

Measuring the dose of exposure

• Dichotomous exposure measurement Exposed / unexposed

• Measurement of the dose of exposure Accurate measurement of the dose of

exposure(e.g., Cumulated number of cigarettes smoked)

Exposure categories Dose / response effect

Exposure

Basic relation between exposure, time and outcome

Exposure

Outcomes(e.g., Disease)

Time

Referent exposure

period(Time during which

exposure occurs)

Time at risk for exposure effects

Understand that dynamic when designing the cohort

Exposure

Considering how the exposure played over time

• Duration of exposure Brief

(e.g., exposure to an atomic bomb) Chronic

(e.g., smoking)

• Induction (“incubation”) period Short

(e.g., infectious diseases) Long

(e.g., chronic diseases)

Exposure

Collecting exposure data over time in cohort studies

• Examining average exposure One measurement Regular measurements

• Examining changes of exposure over time Regular measurements of exposures Sub analyses examining the association

between exposure and outcome in specific windows of time

Exposure

Experimental component in a cohort study

• Intervention at the individual level Clinical trial

e.g., South India BCG trial

• Intervention at the population level Community intervention study

e.g., Mwanza trial, Tanzania

Experimental design

Take-home messages

• Cohorts bring together persons sharing a common experience to follow them over time

• The logistics of cohorts may be prospective or retrospective

• Cohorts allow person-time denominators

• Cohorts allow precise assessment of exposure over time

• Cohorts allow experimental designs