Cohort studyCohort study

Dr K N Prasad MD., DNB

Community Medicine

Aim of Epidemiological studies

1. To determine distribution of disease

2. To examine determinants of a disease

3. To judge whether a given exposure causes or prevents disease

Epidemiological study designs1. Descriptive studies

1. Populations 1. Correlated studies

2. Individuals1. E.g. case-series, case reports, cross-sectional surveys

2. Analytical studies1. Observational studies

1. Case-control studies2. Cohort studies

3. Experimental studies 1. Intervention studies after randomise exposure

1. Clinical trials

Case-control study

Study Population

Cases

Controls

Exposed

Non-exposed

Exposed

Non-exposed

Cohort study / Follow-up study

Study population

Exposed

Non-exposed

Disease +

Disease +

Disease -

Disease -

General considerations

A cohort :A cohort :

A group of persons, identified at one point in time, who march off together into the future under the watchful eye of an investigator.

A cohort study:

A group of persons is defined, certain characteristics about each individual are recorded, and they are then followed up in such a way that new events (such as disease and death) or other changes in their characteristics are detected.

Cohort StudyCohort Study Longitudinal study, Follow-up study,

prospective study

DefinitionDefinition: An analytical epidemiological study in which two or more groups of people according to the extent of exposure (e.g. exposed and unexposed) are compared with respect to outcome or disease incidence

Most reliable for showing an association between a suspected risk factor and subsequent disease

Features of cohort study

1. Cohorts must be free from the disease under study

2. Both the groups should be equally susceptible to disease under study

3. Diagnostic and eligibility criteria of the disease must be defined beforehand

Cohort studyCohort study Exposed and non exposed individuals are

followed over time to determine whether they experience the outcome of interest.

Examples of exposureExamples of exposure : Medication use, Environmental factors,

condition, Procedure

Examples of outcomeExamples of outcome: Disease. Death, etc.

Cohort studies

• Retrospective– Exposure Disease

• Yes ?• No ?

• Prospective– Exposure Disease

• Yes ?• No ?

• Ambidirectional

Timing of cohort studies

• Retrospective: both exposure and disease have occurred at start of study

Exposure------------------------Disease

*Study starts

Timing of cohort studies

• Prospective: exposure has (probably) occurred, disease has not occurred

Exposure----------------------Disease *Study starts

• Ambi-directional: elements of both

Elements of cohort studyElements of cohort study

1. Selection of study subjects( cohorts)

2. Selection of comparison group

3. Obtaining data on exposure

4. Follow up

5. Analysis

Selection of the Exposed Population

Sample of the general population:Geographically area, special age groups, birth

cohorts (Framingham Study)

A group that is easy to identify:Nurses health study

Special population (often occupational epidemiology):Rare and special exposurePermits the evaluation of rare outcomes

Selection of the Comparison Selection of the Comparison PopulationPopulation

Internal Control GroupExposed and non-exposed in the same Study

population (Framingham study, Nurses health study)Minimise the differences between exposed and non-

exposed

External Control GroupChosen in another group, another cohort

(Occupational epidemiology: Asbestosis vs. cotton workers)

The General Population

Selection of comparison groupSelection of comparison group

Internal comparison group: according to the degrees or levels of exposureSmokers, BP, Alcohol, diet etc.

External comparisonSimilar in all respects without any exposure

Comparison with general population ratesOutcomes are compared with the similar

outcome rates in the general population

Sources of exposure information:Sources of exposure information:

Pre-existing records - inexpensive, data recorded before disease occurrence but level of detail may be inadequate.

Records may be missing, / usually don't contain information on confounders

Sources of exposure information:Sources of exposure information:

Questionnaires, interviews: good for information not routinely recorded but

have potential for recall bias

Direct physical exams, tests, environmental monitoring may be needed to ascertain certain exposures.

Follow upFollow upRegular follow up of all participants

Periodic medical examination of each memberReviewing physician and hospital recordsRoutine surveillance of death recordsMailed questionnaires, telephone call, periodic

home visits

Sources of outcome information:Sources of outcome information:

Death certificatesPhysician, hospital, health plan recordsQuestionnaires (verify by records)Medical examinations

Analysis in cohort studyAnalysis in cohort study

1. Incidence of disease among exposed and non exposed

2. Relative risk estimation

3. Attributable risk estimation

Table for analysis cohort studyTable for analysis cohort studyDisease present

Disease absent

Total

Exposure

Present ( cohort)

a b a + b

Exposure absent (comparison)

c d c + d

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

Incidence of disease among exposed = a / a+b

Incidence of disease among non exposed = c / c+d

P value should be <0.05

Relative riskRelative risk

Relative risk is calculated as

Incidence of disease among exposed

Incidence of disease among non exposed

Relative risk (Risk ratio)Relative risk (Risk ratio)

Quantifies magnitude of the association between exposure and disease

Varies from 0 to infinity RR<1: exposure decreases the risk for disease RR=1: no association RR>1: exposure is a risk factor for disease;

increases risk for disease

Example: RR=2.0 can be interpreted as two fold increase in

risk

Attributable risksAttributable risks1. Also known as risk difference

2. It is the difference in incidence rates of disease between exposed group and non exposed group.

3. It suggests the amount of disease that might be eliminated if the risk factor could eliminated or controlled.

Incidence of disease among exposed - incidence of disease among non exposed

------------------------------------------------------- x 100

Incidence of disease among non exposed

ex. AR is 90%. Interpretation-

Bias in Cohort studyBias in Cohort study1. Selection bias - less of a problem than case

control studies

2. Information bias/misclassification

3. Degree of accuracy of classification of exposure, confounders and disease status

4. Loss to follow-up (affects validity)

5. Non response (limits generalisability, not validity)

6. Confounding

Cohort studyCohort studyLimitationsLimitations Loss to follow-up Misclassification of diseaseor exposure status logistically challenging –

especially for prospective design

Hard to study rare diseases Changes over time in

staff/methods Little control over natureand quality of data inretrospective designs

StrengthsStrengths Can establish time order Can obtain incidence rates Can study more than onedisease or outcome Minimizes bias inascertainment of exposurestatus and covariates –especially if collecting dataprospectively Efficient for rare exposures No controls, so no bias incontrol selection

Cohort study• Rare exposure• Examine multiple

effects of a single exposure

• Minimizes bias in the in exposure determination

• Direct measurements of incidence of the disease

• Validity can be affected by losses to follow-up

Case-control study• Quick, inexpensive• Well-suited to the

evaluation of diseases with long latency period

• Rare diseases• Examine multiple

etiologic factors for a single disease

• Selection Bias and recall bias

Key points in Cohort studyKey points in Cohort study

1. Presence or absence of risk factor is determined before outcome occurs

2. Identify cohort (s).

3. Measure exposure and outcome variables

4. Follow for development of outcomes

5. Estimate incidence rates, RR and AR, if possible population AR.

Thought for the dayThought for the day

Motivation is what gets you started.

Habit is what keeps you going.

-Jim Ryun

Thank youThank you

Strengths of Cohort Studies

• Efficient for rare exposures, diseases with long induction and latent period

• Can evaluate multiple effects of an exposure

• If prospective, good information on exposures, less vulnerable to bias, and clear temporal relationship between exposure and disease

Weaknesses of Cohort Studies

• Inefficient for rare outcomes

• If retrospective, poor information on exposure and other key variables, more vulnerable to bias

• If prospective, expensive and time consuming, inefficient for diseases with long induction and latent period

• Keep these strengths and weaknesses in mind for comparison with case-control studies

Cohort study• Example of cohort studies• The association between statin use and prostate cancer risk• All men 45+ years enrolled in GHC for at least 2 years during 1990-2004• Exposure is statin use, which may change over 14 years• Follow 14 years until develop prostate cancer, die, or disenroll from GHC• Each subject will contribute person-time to follow-up Survival analysis

to account for time varying exposure, adjust for other risk factors, & account• for censoring • Prostate cancer• No cancer• Statin user• Nonuser• 14 years• Prostate cancer• No cancer

Prospective vs. retrospective Prospective vs. retrospective Cohort StudiesCohort Studies

• Prospective Cohort Studies– Time consuming, expensive– More valid information on exposure– Measurements on potential confounders

• Retrospective Cohort Studies– Quick, cheap– Appropriate to examine outcome with long latency

periods– Admission to exposure data– Difficult to obtain information of exposure– Risk of confounding

Analysis in Cohort studyAnalysis in Cohort study Exposed and non-exposed individuals are

followed over time to determine whether they

experience the outcome of interest

Examples of exposure:

Environmental factor, condition, procedure

Examples of outcome:

Disease, death, costs