concepts of cause 0416

8/14/2019 Concepts of Cause 0416

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Concepts of Causeand causalinference

Liyan Guo Associate ProfessorEpidemiology Department

Room 209, Public Health Building.Tel: 2203624 (O)

Email: [email protected]


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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.

concepts of cause 0416

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