Observational Studies

Analytical studies: concerned with

(causal) relationships between risk
factors and disease/health states
Is X linked to Y?

Koh Woon Puay

Associate Professor
Email: ephkwp@nus.edu.sg
Tel: 65164975

Commonest question in Epidemiological evidence

epidemiological research versus complements
Experimental evidence
• Is a factor linked to/associated with the
occurrence or outcome of a disease?
– Is smoking linked to lung cancer?
– Is EBV infection linked to nasopharyngeal
carcinoma?
– Is hormone replacement therapy linked to breast
cancer?

• Association is not equivalent to causality

– Need to be backed up by biological explanation
from experimental data

Types of observational studies Case reports

ƒ Describe rare clinical
• Descriptive studies • Analytical studies events or unusual
manifestations of
– case reports – cross-sectional disease
studies
– case series ƒ Highly detailed, can use
– case-control sophisticated methods
– cross-sectional studies
studies ƒ Unable to estimate
– cohort studies frequency, or the role of
bias or chance

1
 Association between number of TV sets per
10 persons versus cancer incidence per
Case series 100,000
ƒ Study of a larger group of
patients (e.g. 10 or more) with a
particular health condition
ƒ Often used to delineate the
clinical picture of a disease

ƒ Most important limitation:

absence of a comparison group
ƒ Care should be taken against
unwarranted generalizations.

Ecologic (or correlation) studies Used to evaluate (causal) relationships

between risk factor and disease
ƒ Seek to determine the extent to which the risk
factor and disease occurrence are related at Analytical studies
the population level

ƒ Useful in generating hypotheses for further Cross- Case-

Cohort
study, but have several limitations sectional control
studies
studies studies
ƒ Ecologic fallacy: ascribing to members of a
group characteristics that they in fact do not
possess as individuals

The cross-sectional study: Analytical component

The cross-sectional study
Example :
• Our basic hypothesis: Smoking causes heart disease
Population

• Rephrasing
p g the hypothesis
yp for a cross-sectional study:
y
In a general population with smokers and non-
time Descriptive smokers, as well as subjects with or without heart
Point of contact Component disease, is heart disease more common among
smokers?

A population is studied at a
particular “cross-section” in time

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 The cross-sectional study Cross-sectional study: salient features
• Measures frequency of a disease / health state
Smoker Non smoker
• Studies a specific / well-defined population
Heart disease patients A B
• Studies a specified point / period (i.e., cross-section) in
Healthy subjects C D time
• May have both descriptive and analytical components
• At any one time-point, 4 groups of people can be found in a
population. • ‘Risk factor’ (exposure) and ‘Disease’ (outcome) are
measured concurrently
• Prevalence of smokers among heart disease patients
• Descriptive use of a cross-sectional study provides valid
• = A/ (A+B)
results (i.e. what we estimate is the “truth”)
• Prevalence of smokers among healthy subjects = C/ (C/D)
• Analytical use of a cross-sectional study provides clues
• Ratio ([A/(A+B) / C/(C+D)] is the prevalence ratio and regarding a “true” causal association (i.e. suggestive, not
measures association between smoking and heart disease. conclusive evidence)

Cross-sectional studies Prevalence or length bias

Slowly progressing cases are more likely to be sampled
in a cross-sectional survey than those with severe/
ƒ Advantages ƒ Disadvantages faster disease progression
¾ Not good for rare or acute
conditions (e.g.
9 Fairly simple, rapid, prevalence of
Time=0 Time= x years
inexpensive if tagged retinoblastoma or
onto an already prevalence of chicken-
planned
l dd
descriptive
i ti pox))
cross-sectional study
¾ Problem of temporality;
cannot establish cause-
effect relationship
9 Can study a wide (“chicken or egg”)
range of factors (e.g.
blood lead and ¾ ‘Length bias’
diabetes) ¾ Study of “survivors”
and “survival factor”

Prevalence or length bias

Slowly progressing cases are more likely to be sampled in a Basic elements of a cohort study
cross-sectional survey than those with severe/ faster disease
progression

Time= x years
Study Determine Follow-up and compare
Time=0
population exposure outcome between
that is free status at exposed and unexposed
of outcome baseline Which group has more
di
disease or has
h di
disease
at a faster rate?
Free of lung cancer
Smoking Occurrence of
(exposed) lung cancer

Non-smoking Occurrence of
Slowly progressing “surviving” cases observed in a cross-section in time may (not exposed)
represent “healthy” cases and may not be suitable for studying putative risk factors lung cancer

Particularly true if you are studying an older population, or a diseased population

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 Cohort studies Cohort studies

• Longitudinal / prospective Advantages:

• Individuals are grouped on exposure and followed-up

for outcome 9 Describe natural history of disease
9 Calculate cumulative incidence/ incidence
• Well-conducted cohort studies rate
– are least susceptible to bias, relative to other 9 Direct measure of risk
observational study designs
9 Temporal sequence can be distinguished
– provide the highest level of evidence for an
association among observational studies 9 Several outcomes can be studied
9 Least susceptible to bias among
observational studies

Cohort study not feasible when:

Case-control study design used when:
The disease is rare:
•Down’s syndrome: 1 in 2000 live births
•Renal cell cancer: 1 in 15,000
• The disease is very rare
There is a long latent period between exposure and disease :
• There is a long latent
•Radiation exposure and thyroid cancer
period between exposure
•Cancer in children of atomic bomb survivors and disease
•Maternal diethyl silbesterol and vaginal
adenocarcinoma in female children

Free of cancer Occurrence of

Smokers
(exposed) Lung cancer cases
Time Occurrence of
lung cancer
Cohort study
Non-smokers
Without
(not exposed) lung cancer controls
Select Classify Follow-up Without
disease- on for outcome
lung cancer
free exposure
persons
In a case-control study:

Case-control study • Cases and controls come from a “virtual cohort”

Select on • Important to capture all the new cases within the study
Compare outcome period (not just the survivors as in a cross-section study)
exposure (cases /
controls) • Controls should come from the same “population-base” as
the cases and represent the “non-cases” in the population

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Selection bias
Smokers Occurrence of Case-control studies
(exposed) lung cancer cases
Occurrence of ™ Compare frequency of exposure between
lung cancer persons with disease (cases) and persons
without disease (controls)
Non-smokers
(not exposed)
Without lung controls
cancer
™ Selection of all incident cases within a
Free of cancer Without lung specific period of recruitment: clinics,
cancer hospitals registries,
hospitals, registries etc.
etc

Smokers Occurrence of ™ Selection of control: from comparable

(exposed) lung cancer cases population without the disease (e.g.
Occurrence of community, other hospital patients)
lung cancer

Non-smokers ™ Prone to bias (e.g. recall bias or selection

Without lung bias)
(not exposed) cancer
Free of cancer Without lung controls
cancer

Case-control studies
Advantages
Quick, less resource
Quick resource-
intensive
Practically the only
study design possible
for rare diseases
STUDY DESIGNS
COHORT CASE-CONTROL
Start with X; end with Y Start with Y; end with X
Disadvantages
Temporal relationship
more difficult to
establish
Y = f (X)
Prone to bias (e.g. recall
bias or selection bias)
Does not measure “risk”
directly (calculates CROSS-SECTIONAL
“odds”) Start with X and Y
together

References

• Medical
Epidemiology
• Raymond SS. Greenberg et al
• Chapters 8 and 9