Concepts of Cause

and causal
inference
Liyan Guo Associate Professor
Epidemiology Department
Room 209, Public Health Building.
Tel: 2203624 (O)
Email: yz220@126.com
Review…

What is the definition

about cause of specific
disease event?

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 DEFINITION
cause of specific disease
event
 A cause of a specific disease event
as an antecedent event, condition,
or characteristic that was
necessary for the occurrence of the
disease at the moment it occurred,
given that other conditions are
fixed.

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 Cause of Disease

 Factors can increase disease

incidence rate of population.
(Lilienfeld AM)

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 What is the sufficient
cause?

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Sufficient cause
 A "sufficient cause," which means
a complete causal mechanism, can
be defined as a set of minimal
conditions and events that
inevitably produce disease.

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 Is the disease caused by
multifactor causation or single
causation?
 If a component cause that is
neither necessary nor sufficient is
blocked, what would happen?

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STRENGTH OF A CAUSE
 Is usually measured by the change
in disease frequency

 May be measured in absolute or

relative terms.

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STRENGTH OF A CAUSE
 Incidence is a measure of risk of
disease.
 Risk can be defined as the
probability of an event (such as
developing a disease) occurring.

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STRENGTH OF A CAUSE
 Absolute risk
 The incidence of a disease in a
population is termed the absolute
risk.

 Relative risk
 The ratio of the risk of disease in
exposed individuals to the risk of
disease in non-exposed individuals.
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Deriving inferences: from
association to causation
 The multi-factorial etiology of
disease
 To judge whether an association is
causal
 No association
 False association
 Association exist: RR or OR is
statistically significant
 Causal association 11
 Bradford-Hill Criteria
(1968)
1. Strength of association
2. Consistency
3. Specificity
4. Temporality
5. Biological gradient (dose
response)
6. Plausibility
7. Coherence
8. Experimental evidence
9. Analogy 12
Strength of association
Strong associations are more likely
to be causal than weak ones
yes
 common source outbreaks

e.g. Salmonella Agona and peanut snacks (OR=87)

but
 not all strong associations are causal

e.g. multiple births and Downs syndrome

 weak associations do not rule out causality

and may have public health importance
e.g. passive smoking and lung cancer (RR 1.4) 13
 Consistency
Repeated observations of association
in different populations under
different circumstances.

yes
 smoking and lung cancer

100 studies over last 30 years demonstrate increased

risk
but
 consistency of results in observational

studies may simply be due to same 14

Oral pre-admission antibiotics and
mortality from meningococcal
disease
Risk Ratio
Study1

Study2

Study3

Study4

Study5

0.01 0.05 0.1 0.25 0.5 1 2 3 4 5

Risk Ratio
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Specificity
One cause leads to one effect,
not multiple effects.

Not very helpful in causality

 main argument of those who do not wish
smoking
to be cause of lung cancer

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Temporality
Exposure must precede disease.

Yes
this is only criterion fundamental
to postulating cause and effect

but

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 Temporality

how about MMR (meales-mumps-rubella)

vaccine and autism?

 strong temporality observed in some cases

 does this mean causation?

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 Biological gradient (dose
response)
Risk of outcome increases with
increasing exposure to the suspected
risk factor
yes
 linear relationship supports causality:

e.g. more cigarettes smoked, greater the risk of lung

cancer
but

 not always causal:

e.g. Downs syndrome and age but not birth rank 19
 Coherence

Interpretation of cause-effect relationship

does not conflict with what is known of
the natural history and biology of disease.

Similar to plausibility

 Absence of coherence cannot be taken as evidence

against causality
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 Plausibility
Consistency with current
biological knowledge about the
disease

Very subjective!
 based on prior beliefs or knowledge:
 John Snow and cholera epidemic in London (Vibrio
cholerae not yet discovered)

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Experimental evidence
Important to get if at all possible

 Koch’s postulates

 Randomised controlled trials

 Does removing exposure or intervention

reverse direction in outcome?
Example of pertussis vaccination

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Henle-Koch's postulates
(1877,1882)

Koch stated that four postulates should be met before

a causal relationship can be accepted between a
particular bacterial parasite (or disease agent) and the
disease in question. These are:
1. The agent must be shown to be present in every
case of the disease by isolation in pure culture.
2. The agent must not be found in cases of other
disease.
3. Once isolated, the agent must be capable of
reproducing the disease in experimental animals.
4. The agent must be recovered from the experimental
disease produced.
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 Analogy

Existence of other cause-effect

relationships analogous to the one
studied supports a causal interpretation.

Weak criterion for causality. Useful for

speculating
how risk factor may operate in different context

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 Study questions

1. Please give the cause of following

diseases:
a Hepatitis A
b Hypertension
c lung cancer

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The cause of Hypertension
 Overweight or obesity
 High-salt diet (high concentration
of sodium)
 excessive drinking……

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 2. Please calculate the RR and AR in table 1.
Table 1–Risk of Lung cancer and CVD(Cases per
100000 Person-Years) According to Smoking Status
Smoking Non-smoking RR AR
(1/100000 (1/100000PY) (1/100000
PY) PY)

Lung
50.12 4.69
cancer

CVD 296.75 170.32

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3. In each of following examples,
which is more likely to be a
causal factor, X or Y? Explain
your selection.
a Persons who eat food X show a
twofold increase in stomach
cancer incidence. Persons who
drive car Y show a twofold
increase in stomach cancer 28
b Persons who eat food X show a twofold
increase in stomach cancer incidence.
Persons who eat food Y show a 3.5-fold
increase in stomach cancer incidence.
c The percentage of stomach cancer cases
who now eat food X is twice as great as
the corresponding percentage of
controls. The percentage of stomach
cancer cases who ate food Y in their
twenties is twice as great as the
corresponding percentage of controls.
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d Food X is shown to be associated
with a twofold increase in risk of
stomach cancer among Hawaiian
Japanese, residents of Helsinki,
Finland, and certain Bantu tribes in
Africa. Food Y is shown to be
associated with a 2.3-fold increase
in risk of stomach cancer in Helsinki
but not in other study population
mentioned.
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