analytical study designs -cohort study -observational study design .

1. ANALYTICAL STUDY DESIGN
COHORT STUDY
DR.NISHANT MISHRA

2. Concept of cohort
• The term “cohort” - a group of people who share a common
characteristic or experience within a defined time period.{age,
occupation, exposure)
E.g.-
o Birth cohort
o Exposure cohort
o Marriage cohort

3. Indication of cohort studies
 When there is good evidence of association between exposure and disease or
the alleged exposure is known.
 When exposure is rare, but the incidence of disease is high among exposed.
 When attrition of study population can be minimized (cooperative, easily
accessible).
 When ample funds are available.
 When the time between exposure and disease is relatively short.

4. Design of cohort study
Population without
the disease
Exposed
disease
No disease
Not
exposed
disease
No disease
Exposure
(cause)
Outcome
(effect)
Direction of inquiry

5. Framework of cohort study
Cohort Disease total
yes no
Exposed to etiologic
factor
a b a+b
Not Exposed to
etiologic factor
c d c+d
Where
a+b = study cohort
c+d = control cohort

6. Types of cohort study
 On the basis of time of occurrence of disease in relation to the time at which
the investigation is initiated and continued:
1. Prospective cohort studies / concurrent cohort/ longitudinal study
2. Retrospective cohort studies / non concurrent cohort / historical cohort study
3. A combination of both retrospective and prospective cohort study
/Ambispective cohort study.

8. • Investigator starts the study with identification of population and the
exposure status.
• Follows them over time for the development of disease.
• Takes relatively long time to complete the study .
• E.g.
1. Framingham heart study
2. Doll and Hill study on smoking and lung cancer.
Prospective cohort study

9. Framingham heart study
 A prospective cohort study
 By USPHS & NHLBI, initiated on 1948 at the town of Framingham .
 To study the relationship of a number of risk factors (e.g. serum cholesterol ,BP,
weight, smoking)to subsequent development of cardiovascular diseases.
 Exposures – BP, Smoking , Bodyweight ,Diabetes ,Exercise etc
 Outcomes –coronary heart disease, stroke, congestive heart failure, peripheral
arterial disease.
 Several hypothesis where tested – different exposures and outcomes.
 The lower and upper limits of study population was set at 30 & 59 yrs.
 The study population was examined every 2 yrs for a period of 20 yrs.

10. total
Study population (of age group 30-59) 10000
Random sample 6507
Respondents 5209
Respondents with clinically relevant CHD 82
Respondents free of CHD 5127
Total repondents that actually underwent 1st examination 4469
The table depicts the number of study participants in Framingham heart study by USPHS

11. 1948
• Start of FRAMINGHAM HEART STUDY
1960
• Cigarette Smoking found to increase risk of Heart Disease
1961
• Cholestrol , BP, and ECG abnormalities found to increase risk of heart
disease.
1965
• First Framingham heart study report on stroke.
1967
• Physical activity found to reduce risk of heart disease: obesity to increase
the risk
1970 • High BP found to increase the risk of stroke.
https://www.framingham.com/heart/timeline.htm
TIMELINE OF MILESTONES FROM THE FRAMINGHAM STUDY

12. In October 1951 DOLL and HILL sent
questionnaire to 59600 british doctors.
• Enquiring about smoking
habits
40701 replies
• Followed up for a period of
4yrs and 5 months
Obtaining notification pf
phisicians’ death from registrar
general,general medical council
and british medical association.
DOLL and HILL prospective study on relation of smoking to
lung cancer.

13. • Investigator uses existing data collected in the past to identify the
population and their exposure status
• Investigator spends a relatively short time to assemble study population
from past data and determine disease status at present time no future follow
up.
• E.g.:-
1) Boston hospital study on electronic fetal monitoring during labour and
outcome measured was neonatal death.
2) Aniline dyes and urinary bladder cancer .
3) Study of role of arsenic in human carcinogenesis
4) Study of lung cancers in uranium miners.
Retrospective cohort study

14. Employees working in dye
industry (n=4622)
Exposure to
aniline dyes
Death due to bladder
tumors
1920 1930 1940 1950
Start of the study
Expected cases of bladder cancer using
national statistics.
Aniline dyes and urinary bladder cancer

15. Combination of retrospective and prospective cohort
studies
 Investigator uses existing data collected in the past to identify the population
and the exposure status− Follow them into the future for the development of
the disease .
 Spends a relatively short time to assemble study population (and the
exposed/not exposed groups) from past data − Will spend additional time
following them into the future for the development of disease .
 E,g:-court brown and doll study on effects of radiation(1957)

16. Court brown and doll study on effects of
radiation(1957)
Pts of ankylosing spondylitis receiving
high dose dose of radiation
n= 13352 Death from
leukemia or
aplastic
anemia
Start of the
stuidy
1934-1954
In 1955 a prospective component was added
to the study and cohort was followed in
subsequrent years

17. Elements of cohort study
1. Selection of study population.
2. Obtaining data on exposure .
3. Selection of comparison groups.
4. Follow-up
5. Analysis

18. 1.Selection of study population.
 General population cohorts or subsets
E,g:- Framingham heart study
 Selected groups
e.g.:-Doll And Hill’s study
 Special exposure cohorts
e.g.:- occupational exposure groups

19. 2. Obtaining data on exposure
 Valid assessment of exposure status of members of cohort
• Identification data
• Exclude individuals having disease at baseline
• Define individuals at risk
• Obtain data on co-variables (other exposure variables)

20. Sources of baseline information
 Existing records
• Hospital records, employment records
 Interviews
• Personal interviews/mailed questionnaires etc.
 Examinations
• Medical and other special examination
 Environment Survey
• E.g. air pollution, exposure to radiation

21. 3.Choice of comparison group
 Internal comparison group
• Unexposed persons in the population
 External comparison group
• When internal comparison group not available.
• Ex: a cohort of radiologists compared with a cohort of
ophthalmologists.
 Comparison with general population
• The mortality experience of exposed is compared with mortality
experience of whole population.

22. 4.Follow-up
 The procedure involves
a) Periodic medical examination of each member of the cohort
b) Reviewing physician and hospital records .Routine surveillance of
death records
c) Mailed questionnaires, telephone calls, periodic home visits-
preferably all three on an annual basis
d) Uniform surveillance in exposed and unexposed groups
e) Complete ascertainment of exposures and outcome/s
f) Standardized diagnosis of outcome events

23. 5.Analysis
 Data can be analyzed in terms of :-
1. Incidence rate
2. Relative risk
cigarette
smoking
Develop lung
cancer
Do not
develop lung
cancer
total
Yes 70(a) 6930(b) 7000(a+b)
No 3 (c) 2997 (d) 3000 (c+d)
An hypothetical example of lung cancer and smoking depicted in a contingency table

24. Incidence rate
 Incidence rate of cancer in exposed(i.e. cigarette smoking ) is
=a/a+b =70/7000
Incidence rate among smokers = 10 per 1000 exposed population.
 Incidence rate of cancer among non exosed = c/c+d
= 3/3000
Incidence rate among non smokers = 1 per 1000 exposed population.

25. Relative risk / risk ratio
 Relative risk (RR) is the ratio of incidence of the disease among
exposed and the incidence among non exposed.
 RR= incidence among exposed
incidence among non exposed
= 10/1 =10
 A relative risk of 10 indicates that the incidence rate of disease is 10
times higher in exposed group as compared to the non- exposed.

26. Interpreting Relative risk
 RR=1
• Incidence in exposed and unexposed is same
• Exposure is not associated with disease
 RR > 1
• Incidence in exposed is higher than unexposed
• Exposure is positively associated with disease
 RR < 1
• Incidence in exposed is lower than unexposed
• Exposure is negatively associated with disease

27. Attributable risk / risk difference
 Expressed in percent.
attributable risk = incidence among exposed – incidence among non exposed
incidence among exposed
= 10-1/10 *100
=90 percent .
 It indicates to what extent the disease under study can be attributed to the
exposure.
*100

28. Population attributable risk
 Population attributable risk = incidence in total population – incidence
among non-exposed
Incidence in the total population 73
Incidence among exposed 70
Incidence among non - exposed 3
Population AR =73-3/73
= 95.8%
IT PROVIDES AN ESTIMATE OF THE AMOUNT BY WHICH THE DISEASE COULD BE
REDUCED IN THAT POPULATION

29. Cardiovascular risk
100,000 patient years
age (30-39) (40-44)age
Relative risk 2.8 2.8
Attributable risk 3.5 20.0
Table .The relative and attributable risks of cardiovascular complications in women taking oral contraception
Cause of death Death rate/1000 RR AR(%)
smokers Non-
smokers
Lung cancer 0.90 0.07 12.86 92.2
CHD 4.87 4.22 1.15 13.3
Risk assessment ,smokers vs non smokers

30. Advantages and disadvantages of cohort study
 Advantages
• Allows calculation of
incidence
• Examine multiple
outcomes for a given
exposure
• Direct estimate of
relative risk
• Dose- response ratio can
also be calculated
Mis- classification of
individuals is minimized.
• Disadvantage
• May have to follow large no. of
subjects for a long time.
• Expensive
• extensive record keeping is
required
• time consuming.
• Not good for rare diseases.
• Study may alter the people’s
behavior .
• Ethical problems.
• Differential loss to follow up
can introduce bias.

31. Case control study Cohort study
1 Proceeds from “effect to cause” Proceeds from “cause to effect”
2 Starts with the disease Starts with people exposed to risk factor or
suspected cause
3 Usually first step in testing of a
hypothesis, but also useful for exploratory
studies.
Reserved for testing of precisely formulated
hypothesis.
4 Yields relatively quick results Long follow up
5 Fewer number of subjects Involves large number of subjects
6 SN Inappropriate when the disease or exposure
under investigation is rare.
7 Relatively inexpensive expensive
8 Cannot yield information about disease
other than that selected for the study
Can yield information about more than one
disease outcome.

32. References
1. Park 25th edition.
2. BCBR by ICMR.
3. https://www.framingham.com/heart/timeline.htm