Transcript Study types Cohort and case

Cohort 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 designs
1. Descriptive studies
1. Populations
1. Correlated studies
2. Individuals
1. E.g. case-series, case reports, cross-sectional surveys
2. Analytical studies
1. Observational studies
1. Case-control studies
2. Cohort studies
3. Experimental studies
1. Intervention studies after randomise exposure
1. Clinical trials
Case-control study
Exposed
Cases
Non-exposed
Study Population
Exposed
Controls
Non-exposed
Cohort study / Follow-up study
Disease +
Exposed
Disease Study population
Disease +
Non-exposed
Disease -
General considerations
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 Study
Longitudinal study, Follow-up study, prospective
study
Definition: 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 study
 Exposed and non exposed individuals are
followed over time to determine whether they
experience the outcome of interest.
 Examples of exposure :
 Medication use, Environmental factors,
condition, Procedure
 Examples 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 study
1.
2.
3.
4.
5.
Selection of study subjects( cohorts)
Selection of comparison group
Obtaining data on exposure
Follow up
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 exposure
Permits the evaluation of rare outcomes
Selection of the Comparison
Population
Internal Control Group
Exposed and non-exposed in the same Study
population (Framingham study, Nurses health
study)
Minimise the differences between exposed and nonexposed
External Control Group
Chosen in another group, another cohort
(Occupational epidemiology: Asbestosis vs. cotton
workers)
The General Population
Selection of comparison group
Internal comparison group: according to the
degrees or levels of exposure
Smokers, BP, Alcohol, diet etc.
External comparison
Similar in all respects without any exposure
Comparison with general population rates
Outcomes are compared with the similar
outcome rates in the general population
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:
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 up
Regular follow up of all participants
Periodic medical examination of each member
Reviewing physician and hospital records
Routine surveillance of death records
Mailed questionnaires, telephone call, periodic
home visits
Sources of outcome information:
Death certificates
Physician, hospital, health plan records
Questionnaires (verify by records)
Medical examinations
Analysis in cohort study
1. Incidence of disease among
exposed and non exposed
2. Relative risk estimation
3. Attributable risk estimation
Table for analysis cohort study
Disease
present
a
Exposure
Present
( cohort)
Exposure
c
absent
(comparison)
Total
a+c
Disease
absent
b
Total
d
c+d
b+d
a+b+c+d
a+b
Incidence of disease among exposed = a / a+b
Incidence of disease among non exposed = c / c+d
P value should be <0.05
Relative risk
Relative risk is calculated as
Incidence of disease among exposed
Incidence of disease among non exposed
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 risks
1. 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 study
1. 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 study
Limitations
Strengths
Loss to follow-up
Misclassification of disease
or exposure status
logistically challenging –
especially for prospective
design
Hard to study rare diseases
Changes over time in
staff/methods
Little control over nature
and quality of data in
retrospective designs
Can establish time order
Can obtain incidence rates
Can study more than one
disease or outcome
Minimizes bias in
ascertainment of exposure
status and covariates –
especially if collecting data
prospectively
Efficient for rare exposures
No controls, so no bias in
control selection
Cohort study
Case-control 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
• 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 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 day
Motivation is what gets you started.
Habit is what keeps you going.
-Jim Ryun
Thank 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
Cohort 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 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