2. Aim of epidemiological studies
To determine distribution
of disease
To examine determinants
of a disease
To judge whether a given
exposure causes or
prevents disease
4. Observational / Non-experimental
To determine Both Exposure & Disease
have already occurred
whether or not
an association
exists between a measure exposure
disease and a
particular risk
factor. Uses Comparison Group
Retrospective
Effect to Cause Back in time
6. Why case-control design for study of rare
diseases?
Consider some rare disease say some cancer
(leukemia)
• Crude Annual Incidence = 3.4/100000 (< 15
years)
• Cohort Study: A year of observation on a
million children to identify 34 cases
• Sample of 34 cases: Sub-divided in 2 or more
exposure categories
• What about conducting case-control design?
7. Research questions
• Is OC use associated with MI in women?
• Is current IUD use associated with PID?
• Is OC use associated with the risk of breast cancer?
• Is age at first coitus associated with cervical cancer?
8. Selection of cases
Cases may be located from
Select cases after the hospitals, clinics, disease
diagnostic criteria and registries, screenings, etc.
definition of the disease is
clearly established
Incident cases are preferable
to prevalent cases for
reducing
• Conceptual
definition • Recall bias
• Obesity defined as
• Over-representation of cases of
body fat
Case percentage > 33% long duration
definition
• Operational
definition
The most desirable way to obtain
cases is to include all incident cases
• Body Mass Index >
30 in a defined population over a
specified period of time
9. Why controls?
• Controls estimate the exposure rate to be
expected in cases if there were no
association between exposure and disease
10. Selecting Controls
Controls
should
Come from the
same population
Representative
11. Sources of cases and controls
Cases Controls
All cases diagnosed in the Sample of general population
community
All cases diagnosed in a Non-cases in a sample of the
sample of the population population
All cases diagnosed in all Sample of patients in all
hospitals hospitals who do not have the
disease
All cases diagnosed in a Sample of patients in the same
single hospital hospital who do not have the
disease
Any of the above methods Spouses, siblings or associates of
cases
12. Ascertainment of Disease and exposure
status
• Death • Questionnaires
and interviews,
certificates, information from
• Disease a surrogate
External Internal (spouses or
sources: registries, sources: mother of
• Hospital and children),
physicians biological
sampling( e.g.
records etc. antibody)
13. Bias in Case-Control studies
Selection bias
Any trend in the • Unequal chance of getting into study
collection, analysis, Berkson’s bias
interpretation, • Variable rate of hospitalization
publication or review affecting case selection
of data that can lead Neyman fallacy
to conclusions that • Incident case Vs prevalent case
are systematically Detection bias
different from the • Due to closer medical attention,
truth (Last, 2001) detection of endometrial cancer was
more in a group using estrogen
14. Matching
Matching is Matching may be
defined as the of two types:
process of
selecting the
controls so that
they are similar to
the cases in certain Individual
Group matching
characteristics, matching.
such as age, race,
sex, Case selection Select one case
socioeconomic
status, and
Select next hospital
occupation. Calculate proportions
admission that
matches age and
Control selection sex as control
18. Calculating the Odds Ratio
Disease Status
CHD cases No CHD
(Cases) (Controls)
Exposure Smoker 112 176
Status Non- 88 224
smoker
Total 200 400
AD 112 x 224
Odds Ratio = = = 1.62
BC 176 x 88
19. Calculating the Odds Ratio
Disease status
CHD (Cases) No CHD
Exposure (Controls)
status Smoker 112 (a) 176 (b)
Non smoker 88 (c) 224 (d)
200 400
20. Interpreting the Odds Ratio
Those with CHD are 1.62 times more likely to be smokers than those
without CHD
or
Those with CHD are 62% more likely to be smokers than
those without CHD
21. Inference
OR<1 OR=1 OR>1
Odds of exposure Odds of Odds of exposure
Odds exposure are for cases are
for cases are less
comparison equal among greater than the
than the odds of
between cases cases and odds of exposure
exposure for
and controls controls for controls
controls
Exposure
Exposure
Exposure as a reduces Particular
increases
risk factor for disease risk exposure is not a
disease risk
the disease? (Protective risk factor
(Risk factor)
factor)
22. Advantages of Case-Control Studies
• Quick and easy to complete, cost effective
• Most efficient design for rare diseases
• Usually requires a smaller study population
than a cohort study
23. Disadvantages of Case-Control
Studies
Uncertainty of exposure-disease time
relationship
Inability to provide a direct estimate of risk
Not efficient for studying rare exposures
Subject to biases (recall & selection bias)
24.
25. Cohort Studies
At baseline (1st observation point)
Subjects are all disease free
Exposure is used to classify subjects into exposed or
unexposed groups
Subjects are followed to document incidence (2nd observation point)
26. Types of Cohort Study
Prospective cohort study
Retrospective (historical) cohort
study
Combination of Retrospective and
Prospective cohort study.
27. Selection of study subjects
General population
• Whole population in an area
• A representative sample
Special group of population
• Select group
• occupation group / professional group (Dolls study )
• Exposure groups
• Person having exposure to some physical, chemical
or biological agent
• e.g. X-ray exposure to radiologists
28. Obtaining data on exposure
Personal interviews / mailed questionnaire
Reviews of records
• Dose of drug, radiation, type of surgery etc
Medical examination or special test
• Blood pressure, serum cholesterol
Environmental survey
By obtaining the data of exposure we can classify cohorts as
• Exposed and non exposed and
• By degree exposure we can sub classify cohorts
29. Selection of comparison group
Internal comparison
• An internal comparison group consists of unexposed members of the
same cohort.
• An internal comparison group should be used whenever possible,
because its characteristics will be most similar to the exposed
External comparison
• More than one cohort in the study for the purpose of comparison
• e.g. Cohort of radiologist compared with ophthalmologists
Comparison with general population rates
• If no comparison group is available we can compare the rates of study
cohort with general population.
• Cancer rate of uranium miners with cancer in general population
30. Follow-up
To obtain data about outcome to be determined (morbidity
or death)
• Mailed questionnaire, telephone calls, personal interviews
• Periodic medical examination
• Reviewing records
• Surveillance of death records
• Follow up is the most critical part of the study
Some loss to follow up is inevitable due to death change of
address, migration, change of occupation.
Loss to follow-up is one of the draw-back of the cohort study.
34. Relative Risk (RR)
• A ratio that measures the risk of disease among
the exposed to the risk among the unexposed
• RR Numerator: Incidence rate in the exposed
• RR Denominator: Incidence rate in the unexposed
35. Example: Calculating the Relative Risk
Disease Status
CHD cases No CHD
TOTAL
(Cases) (Controls)
Exposure Smoker 112 176 288
Status Non-
88 224 312
smoker
A/(A+B) 112 / 288
Relative Risk = = = 1.38
C/(C+D) 88 / 312
36. Example: Interpreting the Relative Risk
Relative Risk = 1.38
The risk of developing CHD is 1.38 times higher for a smoker
than for a nonsmoker.
or
The risk of developing CHD is 38% higher for a smoker than
for a nonsmoker.
37. Inference
RR<1 RR=1 RR>1
Risk for disease is
Risk comparison Risk of disease is equal Risk for disease is
lower in the exposed
between exposed for exposed and higher in the exposed
than in the
and unexposed unexposed than in the unexposed
unexposed
Exposure reduces
Exposure as a risk disease risk Exposure increases
Particular exposure is
factor for the disease risk
(Protective not a risk factor
disease? (Risk factor)
factor)
38. Attributable Risk
Incidence of disease among exposed –
incidence of disease among non exposed
Incidence of disease among exposed
a/a+b – c/c+d
AR =
a/a+b
40. Smoking Lung cancer Total
YES NO
YES 70 6930 7000
NO 3 2997 3000
73 9927 10000
Find out RR and AR for above data
41. • Incidence of lung cancer among smokers
70/7000 = 10 per 1000
• Incidence of lung cancer among non-smokers
3/3000 = 1 per thousand
RR = 10 / 1 = 10
(lung cancer is 10 times more common among
smokers than non smokers)
AR = 10 – 1 / 10 X 100
= 90 %
(90% of the cases of lung cancer among smokers are
attributed to their habit of smoking)
42. Advantages of Cohort Studies
Temporality: Exposure
precedes outcome Efficient for studying May be used to study
because the cohort is rare exposures multiple outcomes
disease free at baseline
Allows for calculation of
incidence of diseases in
Minimizes recall bias
exposed and unexposed
individuals
43. Disadvantages of Cohort Studies
Loss to follow-up
Tend to be expensive
• When multiple outcomes or
(large sample size) and specific disease incidence is
time consuming (long the outcome of interest, bias
follow-up period) can be a serious problem
Inefficient to study rare
diseases
44. Disadvantages of Cohort Studies (cont.)
• Nonparticipation (selection bias) – it cannot be
assumed that those who chose to participate had
the same prevalence of exposures nor incidence of
disease as those who did not participate
– A difference in prevalence of exposure in
nonparticipants will not bias the results
– A difference in rate of disease among
nonparticipants will bias the results
