Post on 30-May-2018
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Concepts of Causeand causalinference
Liyan Guo Associate ProfessorEpidemiology Department
Room 209, Public Health Building.Tel: 2203624 (O)
Email: yz220@126.com
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Review
What is the definitionabout cause of specificdisease event?
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A cause of a specific disease eventas an antecedent event, condition,
or characteristic that wasnecessary for the occurrence of thedisease at the moment it occurred,
given that other conditions arefixed.
cause of specific disease
event
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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 minimalconditions and events thatinevitably produce disease.
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Is the disease caused bymultifactor 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 orrelative terms.
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STRENGTH OF A CAUSE Incidence is a measure of risk of
disease.
Risk can be defined as theprobability of an event (such asdeveloping a disease) occurring.
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STRENGTH OF A CAUSE Absolute riskThe incidence of a disease in a
population is termed the absoluterisk.
Relative riskThe ratio of the risk of disease in
exposed individuals to the risk ofdisease in non-exposed individuals.
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Deriving inferences: from
association to causationThe multi-factorial etiology of
diseaseTo judge whether an association is
causal
No association False association Association exist: RR or OR is
statistically significant Causal association
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Bradford-Hill Criteria
(1968)1. Strength of association
2. Consistency
3. Specificity4. Temporality
5. Biological gradient (dose
response)6. Plausibility
7. Coherence
8. Experimental evidence
9. Analogy
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Strength of association
Strong associations are more likelyto be causal than weak ones
yes common source outbreaks
e.g. Salmonella Agona and peanut snacks (OR=87)
but
not all strong associations are causale.g. multiple births and Downs syndrome
weak associations do not rule out causalityand may have public health importance
e.g. passive smoking and lung cancer (RR 1.4)
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ConsistencyRepeated observations of associationin different populations under
different circumstances.
yes smoking and lung cancer
100 studies over last 30 years demonstrate increasedrisk
but consistency of results in observational
studies may simply be due to same
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mortality from meningococcaldisease
Risk Ratio
0.01 0.05 0.1 0.25 0.5 1 2 3 4 5Risk Ratio
Study1
Study2
Study3
Study4
Study5
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SpecificityOne cause leads to one effect,not multiple effects.
Not very helpful in causality
main argument of those who do not wish
smokingto 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 (doseresponse)
Risk of outcome increases withincreasing exposure to the suspected
risk factoryes
linear relationship supports causality:
e.g. more cigarettes smoked, greater the risk of lungcancer
but
not always causal:
e.g. Downs syndrome and age but not birth rank
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Coherence
Interpretation of cause-effect relationshipdoes not conflict with what is known ofthe natural history and biology of disease.
Similar to plausibility
Absence of coherence cannot be taken as evidenceagainst causality
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Plausibility
Consistency with currentbiological knowledge about thedisease
Very subjective! based on prior beliefs or knowledge:
John Snow and cholera epidemic in London (Vibriocholerae not yet discovered)
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Experimental evidence
Important to get if at all possible
Kochs postulates
Randomised controlled trials
Does removing exposure or interventionreverse 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 beforea causal relationship can be accepted between aparticular bacterial parasite (or disease agent) and the
disease in question. These are:
1. The agent must be shown to be present in everycase of the disease by isolation in pure culture.
2. The agent must not be found in cases ofotherdisease.
3. Once isolated, the agent must be capable ofreproducing the disease in experimental animals.
4. The agent must be recovered from the experimentaldisease produced.
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Analogy
Existence of other cause-effect
relationships analogous to the onestudied supports a causal interpretation.
Weak criterion for causality. Useful forspeculating
how risk factor may operate in different context
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Study questions
1. Please give the cause of followingdiseases:
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.
170.32296.75CVD
4.6950.12Lungcancer
AR
(1/100000PY)
RRNon-smoking
(1/100000PY)
Smoking
(1/100000PY)
Table 1Risk of Lung cancer and CVD(Cases per100000 Person-Years) According to Smoking Status
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3. In each of following examples,which is more likely to be a
causal factor, X or Y? Explainyour selection.
a Persons who eat food X show a
twofold increase in stomachcancer incidence. Persons whodrive car Y show a twofold
increase in stomach cancer
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b Persons who eat food X show a twofoldincrease 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 asthe corresponding percentage of
controls. The percentage of stomachcancer cases who ate food Y in theirtwenties is twice as great as thecorresponding percentage of controls.
b Persons who eat food X show a twofoldincrease 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 asthe corresponding percentage of
controls. The percentage of stomachcancer cases who ate food Y in theirtwenties is twice as great as thecorresponding percentage of controls.
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d Food X is shown to be associatedwith a twofold increase in risk ofstomach cancer among Hawaiian
Japanese, residents of Helsinki,Finland, and certain Bantu tribes inAfrica. Food Y is shown to be
associated with a 2.3-fold increasein risk of stomach cancer in Helsinkibut not in other study populationmentioned.