06-02-2025

Evidence Based Hierarchy

Systematic review & Meta-Analysis

COHORT STUDY DESIGN
Randomized
control Trial

Presentor : Dr Prasanth Cohort Studies

Case-Control Studies
Moderator :Dr Monisha Cross-Sectional Studies

Case Series/ Case Reports

Content Concepts of Cohort

• The word cohort is derived from the Latin

• Concepts of cohort "cohorts" meaning an enclosure, company,
• Definition of cohort or crowd.
• Features of cohort
• Indications for cohort study • In Roman times,a cohort was a body
• Elements of cohort study of 300-600 infantry.
• Types of cohort study
• Biases
• Advantages and Disadvantages In epidemiological terms the cohort is a group of people with
something in common, usually an exposure or involvement in a
• References
defined population group . (eg:age,occupation,exposure to a
drug or vaccine,pregnancy,insured persons,etc)

Epidemiological Study design Concepts of Cohort

Epidemiological studies • Thus a group of people born on the same day or in the same
period of time (usually a year) form a "birth cohort". All those
Observational Studies Experimental studies born in 2010 form the birth cohort of 2010.

Randomized
• Persons exposed to a common drug, vaccine or infection
Field trial within a defined period constitute an "exposure cohort".
Control trial

Descriptive Analytic Community

trial • A group of males or females married on the same day or in
Individuals
Populations
the same period of time form a "marriage cohort"

Ecological Case-control
Cross-sectional Cohort study
study study

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Definition of cohort study Framework of cohort study

• the basic approach in cohort studies is to work from
Cohort study is another type of analytical study which is usually "cause to effect"
undertaken to obtain additional evidence to refute or support
the existence of an association between suspected cause and
disease.

It is known by variety of names

Prospective study
Longitudinal study In a case control study, In a cohort study, the
Incidence study exposure and disease have exposure has occurred, but
already occurred when the
Forward-looking study But
the disease has not occured
study is initiated.

Features of cohort studies

• The distinguishing features of cohort studies are :
Disease • We begin with a group or
Cohort Total
Yes No cohort (a+b) exposed to a
a. the cohorts are identified prior to the appearance of the particular factor thought to
disease under investigation be related to disease occulter
Exposed a b a+b and group(c+d) not exposed
to that particular factor.
b. the study groups, so defined, are observed over a period of
time to determine the frequency of disease among them Non-exposed c d c+d

The basic design of a simple cohort study is

c. the study proceeds forward from cause to effect shown in table

Indications for cohort study ELEMENTS OF A COHORT STUDY

 There is good evidence of an association between exposure

and disease, from other studies. Selection of study subjects
 Exposure is rare but incidence of disease high among exposed
Obtaining data on exposure
 Attrition of study population can be minimized.
Selection of comparison group
eg:follow-up is easy Elements
of Follow-up
 Sufficient fund is available. Cohort

Analysis

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1.Selection of study subjects 3.Selection of comparison group

The usual procedure is to locate or identify the cohort, which Internal comparison
may be a total population in an area or sample Only one cohort involved in study
Sub classified and internal comparison done
General population eg: smoking, blood pressure,serum cholestrol
* Whole population in an area
* A representative sample  External comparison
More than one cohort in the study for the purpose of
 Special group of population comparison
* Select group - occupation group / professional group e.g. smokers and non smokers

1.Selection of study subjects 3.Selection of comparison group

 Exposure groups Comparison with general population rates
* Person having exposure to some physical, chemical or If no comparison group is available we can compare the
biological agent rates of study cohort with general population.
e.g. X-ray exposure to radiologists
eg: comparison of frequency of lung cancer
among uranium mine worker in general
population of miners resided.

2.Obtaining data on exposure 4.Follow-up

Information should be collected in a manner that allows • To obtain data about outcome to be determined (morbidity or death)
classification of cohort according to whether or not they have
 Mailed questionnaire, telephone calls, personal interviews
been exposed to suspected factor
 Periodic medical examination
 Reviewing records
• From Cohort Members  Surveillance of death records
• Review of Records  Follow up is the most critical part of the study

• Medical examination/ Special tests

Some loss to follow up is inevitable due to death change of address,
• Environmental Survey migration, change of occupation.
* Loss to follow-up is one of the draw-back of the cohort study

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5.Analysis Estimation of risk

Data analyzed in terms of  Attributable Risk - difference in incidence rates
Incidence rate of outcome among exposed and non exposed
 Estimation of risk Incidence of disease among exposed - incidence of
disease among non exposed
• AR= x 100
Incidence of disease among exposed

• AR indicates to what extent the disease under study can be

attritubed to the exposure.

Incidence rate of outcome Estimation of risk

A = Exposed persons who later Population Attributable risk
develop disease or die
Death No death
B = Exposed persons who do not
develop diseases or die Incidence of the disease in total population - Incidence of
Exposed A B
C = Unexposed persons who later disease among non exposed
develop disease or die
Unexposed C D
D = Unexposed persons who do
not develop diseases or die • it provides an estimate of the amount by which the disease
could be reduced in that population if the suspected factor
The total number of exposed persons = A + B
was eliminated or modified.
The total number of unexposed persons = C + D
Incidence of disease(or death) among exposed= A/A+B
Incidence of disease(or death) among non-exposed= C/C+D

Estimation of risk Example

Incidence of lung cancer
LUNG CANCER
among smokers
Smoking Total
Yes No 70/7000= 10 per 1000

YES 70 A 6930 B 7000 Incidence of lung cancer

(A+B) among non smokers
• Estimation of relative risk is important in aetiological enquiries 3/3000=1 per 1000
3000
• It is direct measure of the strength of the association between NO 3 C 2997 D (C+D)
suspected cause and effect. RR= 10/1= 10
73 9927 10000
RR = 1 indicates no association AR= 10-1/10 X 100= 90%
RR > 1 indicates positive association
RR <1 indicates negative association RR= Lung cancer is 10 times more common among
smokers than non-smokers
The larger the RR,the greater the strength of association between
suspected factor and disease. AR= 90% of the cases of lung cancer among smokers
are attributed to their habit of smoking

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Consideration during selection of

Prospective cohort study
Cohort
A prospective cohort study (or "current" cohort study) is one in
* It must be free from disease under study. which the outcome (e.g., disease) has not yet occurred at the
* Insofar as the knowledge permits, both the groups should be time the investigation begins. Most prospective studies begin in
equally susceptible to disease under study. the present and continue into future.

* Both the groups must be comparable in respect of all variable

which influence the occurrence of disease
* Diagnostic and eligibility criteria of the disease must be defined
beforehand.

Consideration during selection of

Examples: Framingham Heart Study
Cohort

• The groups are then followed, under the same identical

conditions, over a period of time to determine the outcome of
exposure (e.g., onset of disease, disability or death) in both the
groups.
• In chronic diseases such as cancer the time required for the
follow-up may be very long

Types of cohort Framingham Heart Study

• Initiated in 1948 to study the relationship of a variety of
factors to the subsequent development of heart disease with
5127 (samples 30 to 62 yrs) at Framingham.
Prospective cohort study • Study subjects were examined every 2 yrs for 20 years.
• Daily Surveillance of hospitalization at Framingham hospital.
Retrospective cohort study
• Study found that Hypertensive, tobacco smoking, elevated
Combination of Retrospective and Prospective cohort study- blood cholesterol are associated to CHD
Ambidirectional study • Increased physical activity associated with decreased risk of
CHD

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Retrospective cohort studies Retrospective cohort studies

A retrospective cohort study (or "historical" cohort study) is one • The most notable retrospective cohort studies to date are
those of occupational exposures, because the recorded
in which the outcomes have all occurred before the start of the information is easily available.
investigation.
Examples
 study of the role of arsenic in human carcinogenesis,
 study of lung cancer in uranium miners,
 study of the mortality experience of groups of physicians in
relation to their probable exposure to radiation.

Retrospective cohort studies Retrospective cohort studies

• The investigator goes back in time, sometimes 10 to 30 years,

to select his study groups from existing records of past • Retrospective cohort studies are generally more economical
employment, medical or other records and traces them and produce results more quickly than prospective cohort
forward through time, from a past date fixed on the records, studies
usually up to the present.

Retrospective cohort studies Example

• This type of study is known by a variety of names:

Retrospective cohort study,

Suppose that we began our study on
"historical" cohort study,
association between smoking habit
prospective study in retrospect and and lung cancer in 2008
non-concurrent prospective study.

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Retrospective cohort studies Potential Biases in Cohort studies

• Now we find that an old roster of elementary school children • a number of potential biases must be either avoided or taken
from 1988 is available in our community, and that they had into account in conducting cohort studies.
been surveyed regarding their smoking habits in 1998.
I. Selection Bias
II. Information Bias
• Using these data resources in 2008, we can begin to
III. Measurement bias
determine who in this population has developed lung cancer
IV. Observer bias
and who has not.
V. Cross over bias
VI. Loss to follow-up bias

Combination of Retrospective and Prospective

Selection Bias
cohort study- Ambidirectional study
• In this type of study, both • Non participation and non response can introduce major biases
the retrospective and
that can complicate the interpretation of the study findings.
prospective elements are
combined.
• The cohort is identified • If participants refuse to join a cohort, might their characteristics
from past records, and is
assessed of date for the differ sufficiently from those who consent to enroll, and might
outcome and the same these differences lead to misguided inferences regarding
cohort is followed up exposures to outcomes
Schematic diagram of concurrent, retrospective,
prospectively into future
and ambidirectional cohort studies
for further assessment of
outcome.

Combination of Retrospective and Prospective

Information Bias
cohort study
• Court-Brown and Doll (1957) applied this approach to study the
effects of radiation. 1.If the quality and extent of information obtained is different for
assembled a
had received large
exposed persons than for the unexposed persons, a significant bias
cohort in 1955 between 1934 ankylosing can be introduced.
doses of radiation
with 13,352 and 1954. spondylitis
therapy
patients
2. If the person who decides whether the disease has developed in
death from each subject also knows whether that subject was exposed, and if
between 1935
leukaemia
Outcome that person is aware of the hypothesis being tested, that person's
or and 1954.
aplastic anaemia
judgment as to whether the disease developed may be biased by
that knowledge.
• A prospective component was added to the study and the cohort
was followed, as established in 1955, to identify deaths occurring
in subsequent years

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Case-control studies based within a defined

Information Bias
cohort
• In recent years, considerable attention has focused on
3. As in any study, if the epidemiologists and statisticians who whether it is possible to take advantage of the benefits of both
are analyzing the data have strong preconceptions, they may case-control and cohort study designs by combining some
unintentionally introduce their biases into their data analyses elements of both into a single study.
and into their interpretation of the study findings.
• The resulting combined study is in effect a hybrid design in
which a case-control study is initiated within a cohort study

Case-control studies based within a defined

cohort
• Measurement bias: • In this type of study, a
population is identified and
This type of bias can occur when there is a difference in followed over time.
determining the outcome of the disease because of disparity • At the time the population
in the methods used by the observer. is identified, baseline data
are obtained from records
or interviews, from blood
• Observer bias: or urine tests, and in other
When the investigator knows about the exposure status of ways.
the subjects being studied. Blinding regarding the exposure • The population is then
status can avoid this type of bias. followed for a period of
years.

Case-control studies based within a defined

cohort
Cross over bias: • A case-control study is then carried out using as cases persons
• Few subjects in the exposed group may shift to the non- in whom the disease developed and using controls a sample of
exposed group and vice-versa
• This type of bias can be minimized by regular follow-up. those in whom the disease did not develop.
• Such cohort-based case-control studies can be divided into
Loss to follow-up bias: two types, largely on the basis of the approach used for
• In spite of best efforts, a certain percentage of losses to follow selecting the controls.
up are inevitable due to death, change of residence, migration,
etc. • These two types of studies are called nested case-control
studies and case-cohort studies.
• However, it is recommended that 95% follow-up should be
achieved if possible. Detailed address of the study subjects
should be taken to avoid loss to follow-up.

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Nested case-control studies Nested case-control studies

• In nested case-control studies the controls are a sample of
individuals who are at risk for the disease at the time each
case of the disease develops.

• A shows the starting point as a defined cohort of individuals. Fig. E shows control #2 being selected at that time and
In this hypothetical example, the cohort is observed over a 5- Fig F shows cases #3 and #4 developing after 4 years,
year period.

Nested case-control studies Nested case-control studies

• B-#1 shows the time sequence in which the cases develop • Fig G shows controls #3 and #4 being selected at that time.
after the start of observations. At the time each case or cases
develop, the same number of controls is selected.

Finally, Fig. H shows the final case (#5) developing after 5

years.

Nested case-control studies Nested case-control studies

• Fig.I shows control #5 being

selected at this point
• The final study populations
used in the nested case-
control study.
• At the end of 5 years, five
• The solid arrows denote the appearance of cases of the disease cases have appeared, and at
• The dotted arrows denote the selection of controls who are the times the cases
disease free but who are at risk of developing the disease in appeared a total of five
question at the time the case develops the disease controls were selected for
Fig. C shows control #1 being selected at that time. study.
Fig. D shows case #2 developing after 2 years,

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Nested case-control studies Case-cohort studies

• In this way, the cases and controls are, in effect, matched on • An advantage of this design is that because controls are not
calendar time and length of follow-up. Because a control is individually matched to each case
selected each time a case develops, a control who is selected
• it is possible to study different diseases (different sets of cases)
early in the study could later develop the disease and become
in the same case-cohort study using the same cohort for
a case in the same study
controls.

Case-cohort studies
• In this design, in contrast to the nested case-control design,
• The second type of cohort-based case-control study is the cases and controls are not matched on calendar time and
case-cohort design length of follow-up; instead, exposure is characterized for the
subcohort.
• In the hypothetical case-cohort study seen here, cases
develop at the same times that were seen in the nested case- • This difference in study design needs to be taken into account
control design just discussed, but the controls are randomly in analyzing the study results.
chosen from the defined cohort with which the study began.
• This subset of the full cohort is called the subcohort.

Case-cohort studies Advantage of Cohort Studies

• Temporality can be established
• Incidence can be calculated.
• Several possible outcome related to exposure can be studied
simultaneously.
• Provide direct estimate of risk.
• Since comparison groups are formed before disease develops
certain forms of bias can be minimized like misclassification
bias.
• Allows the conclusion of cause effect relationship

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Disadvantage of Cohort Studies

• Large population is needed
• Not suitable for rare diseases.
• It is time consuming and expensive
• Certain administrative problems like loss of staff, loss of
funding and extensive record keeping are common.
• Problem of attrition of initial cohort is common
• Study itself may alter people's behavior

References
1.Park.Textbook of preventive and social medicine .27th
ed.Jabalphur:banarsidas bhanot;2023.89-93p

2.David D.celentano.Gordis epidemiology.6th

ed.Elsevier;2018.178-196p

3. Rajvir Bhalwar et.al Textbook of public health and

community medicine.1st ed.Pune:AFMC;2009

4.A.M Kadri et.al IAPSM’s textbook of community medicine

2nd edition.bhotahity:Jaypee brothers medical
publishers;2019. 180-183p

THANK YOU

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