South Asian Cardiovascular
Research Methodology Workshop
Basic Epidemiology
Web of Causation;
Exposure and Disease Outcomes
Thomas Songer, PhD
Purpose of Epidemiology
To provide a basis for developing
disease control and prevention
measures for groups at risk. This
translates into developing measures
to prevent or control disease.
Background
Towards this purpose, epidemiology seeks to
describe the frequency of disease and its
distribution
consider person, place, time factors
assess determinants or possible causes of
disease
consider host, agent, environment
Basic Question in Analytic Epidemiology
Are exposure and disease linked?
Exposure
Disease
Basic Questions in Analytic
Epidemiology
Look to link exposure and disease
What is the exposure?
Who are the exposed?
What are the potential health effects?
What approach will you take to study the
relationship between exposure and effect?
Wijngaarden
What qualities should an
exposure variable have to make
it worthwhile to pursue?
RS Bhopal
A good epidemiologic exposure
variable should.
Have an impact on health
Be measureable
Differentiate populations
Generate testable hypotheses
Help to prevent or control disease
RS Bhopal
What qualities should a
disease have to make it
worthwhile to investigate?
Disease investigations should have
some public health significance
The disease is important in terms of
the number of individuals it affects
The disease is important in terms of
the types of populations it affects
The disease is important in terms of its
causal pathway or risk characteristics
Research Questions/Hypotheses
Is there an association between Exposure (E)
& Disease (D)?
Hypothesis: Do persons with exposure have
higher levels of disease than persons without
exposure?
Is the association real, i.e. causal?
Sever
Big Picture
Look for links between exposure & disease
to intervene and prevent disease
Look to identify what may cause disease
Basic definition of cause
exposure that leads to new cases of disease
remove exposure and most cases do not occur
Big Picture
On a population basis
An increase in the level of a causal factor
will be accompanied by an increase in the
incidence of disease (all other things
being equal).
If the causal factor is eliminated or
reduced, the frequency of disease will
decline
Infectious Disease Epidemiology
Investigations/studies are undertaken to
demonstrate a link [relationship or association]
between an agent (or a vector or vehicle carrying
the agent) and disease
Exposure
[ Agent ]
[ Vector/Vehicle ]
Disease
Injury Epidemiology
Studies are undertaken to demonstrate
a link [association] between an agent /
condition and an injury outcome
Exposure
Disease
[ Agent Energy Transfer ]
[ Vehicle carrying the agent automobile ]
[ Condition Risk taking behaviour ]
Chronic Disease Epidemiology
Studies are undertaken to demonstrate
a link [relationship or association]
between a condition/agent and disease
Exposure
Disease
[ Condition e.g. gene, environment ]
Issues to consider
Etiology (cause) of chronic disease is often
difficult to determine
Many exposures cause more than one
outcome
Outcomes may be due to a multiple
exposures or continual exposure over time
Causes may differ by individual
-- Whereas a physician tries to determine
presence of disease and causes in individuals,
epidemiologists focus on populations
-- Unlike microorganisms (like a bacteria)
which can be linked to a given disease (disease
is defined as exposure to that microorganism) few chemical/physical factors have a unique
effect on health - for example exposure to
asbestos - causes lung cancer, but other things
may also cause lung cancer
-- Also, outcomes may be due to a combination
of factors - e.g., genetics + environmental
exposure = disease, so env. exposure is a
component cause
-- Different individuals within population with
the disease may have gotten it through different
causal pathways - one person through env.
exposure another through personal factor, etc.
Causation and Association
Epidemiology does not determine the cause of a disease in a given
individual
Instead, it determines the relationship or association between a given
exposure and frequency of disease in populations
We infer causation based upon the association and several other factors
-- Therefore, an epidemiologic study cannot
predict the exact cause of the disease in every
individual
-- It looks at a population and tries to determine
whether exposure is significantly associated to the
disease on average - uses statistical techniques to
make conclusions about the strength of these
relationships
-- Often these relationships are more
strongly supported/concluded when a
plausible biological mechanism exists for
the effect
-- In general, epidemiologic studies are not
experimental - cant expose humans
deliberately to something that may affect
their health, instead often look at
populations that were inadvertently exposure
to an agent due to job or where they live
(clinical trials is exception)
Association vs. Causation
Association - an identifiable relationship
between an exposure and disease
implies that exposure might cause disease
exposures associated with a difference in disease
risk are often called risk factors
Most often, we design interventions based
upon associations
Association vs. Causation
Causation - implies that there is a
true mechanism that leads from
exposure to disease
Finding an association does not
make it causal
General Models of Causation
Cause: event or condition that plays an
role in producing occurrence of a disease
How do we establish cause in situations
that involve multiple factors/conditions?
For example, there is the view that
most diseases are caused by the
interplay of genetic and
Environmental factors.
General Models of Causation
How do we establish cause?
Exposure
Disease
Additional Factors
Web of Causation
There is no single cause
Causes of disease are interacting
Illustrates the interconnectedness
of possible causes
RS Bhopal
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RS Bhopal
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RS Bhopal
Hills Criteria for Causal Inference
Consistency of findings
Strength of association
Biological gradient (dose-response)
Temporal sequence
Biological plausibility
Coherence with established facts
Specificity of association
Consistency of Findings of Effect
Relationships that are demonstrated in
multiple studies are more likely to be causal
Look for consistent findings
across different populations
in differing circumstances
with different study designs
Strength of Association
Strong associations are less likely to be
caused by chance or bias
A strong association is one in which the
relative risk is
very high, or
very low
Biological Gradient
There is evidence of a dose-response relationship
Changes in exposure are related to a trend in
relative risk
Temporal Sequence
Exposure must precede disease
In diseases with latency periods,
exposures must precede the latent
period
In chronic diseases, often need longterm exposure for disease induction
Plausibility and Coherence
The proposed causal mechanism should be
biologically plausible
Causal mechanism must not contradict what is
known about the natural history and biology of
the disease, but
the relationship may be indirect
data may not be available to directly support the
proposed mechanism
must be prepared to reinterpret existing understanding
of disease in the face of new findings
Specificity of the Association
An exposure leads to a single or
characteristic effect, or affects
people with a specific susceptibility
easier to support causation when
associations are specific, but
this may not always be the case
many exposures cause multiple diseases
Causal Inference: Realities
No single study is sufficient for causal
inference
Causal inference is not a simple process
consider weight of evidence
requires judgment and interpretation
No way to prove causal associations for
most chronic diseases and conditions
Judging Causality
Weigh weaknesses
in data and other
explanations
RS Bhopal
Weigh quality
of science and
results of causal
models
Prevailing Wisdom in
Epidemiology
Most judgments of cause and effect
are tentative, and are open to change
with new evidence
RS Bhopal
Pyramid of Associations
Causal
Non-causal
Confounded
Spurious / artefact
Chance
RS Bhopal
