Concepts Of Cause 0416
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Concepts of Cause and causal inference Liyan Guo Associate Professor Epidemiology Department Room 209, Public Health Building. Tel: 2203624 (O) Email: [email protected]
Review… What is the definition about cause of specific disease event?
2
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.
3
Cause of Disease
Factors can increase disease incidence rate of population. (Lilienfeld AM)
4
What is the sufficient cause?
5
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.
6
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?
7
STRENGTH OF A CAUSE
Is usually measured by the change in disease frequency
May be measured in absolute or relative terms.
8
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.
9
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. 10
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. 2. 3. 4. 5.
Strength of association Consistency Specificity Temporality 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 Risk Ratio
1
2
3 4 5 15
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
16
Temporality Exposure must precede disease. Yes this is only criterion fundamental to postulating cause and effect but
17
Temporality how about MMR (meales-mumps-rubella) vaccine and autism?
strong temporality observed in some cases does this mean causation?
18
Biological gradient (dose response) Risk of outcome increases with increasing exposure to the suspected risk factor yes linear relationship supports causality: cancer
e.g. more cigarettes smoked, greater the risk of lung
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 20
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) 21
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 22
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. 23
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 24
Study questions 1. Please give the cause of following diseases: a Hepatitis A b Hypertension c lung cancer
25
The cause of Hypertension
Overweight or obesity High-salt diet (high concentration of sodium) excessive drinking……
26
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 (1/100000 PY)
Non-smoking (1/100000PY)
Lung cancer
50.12
4.69
CVD
296.75
170.32
RR
AR (1/100000 PY)
27
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. 29
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. 30
Review… What is the definition about cause of specific disease event?
2
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.
3
Cause of Disease
Factors can increase disease incidence rate of population. (Lilienfeld AM)
4
What is the sufficient cause?
5
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.
6
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?
7
STRENGTH OF A CAUSE
Is usually measured by the change in disease frequency
May be measured in absolute or relative terms.
8
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.
9
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. 10
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. 2. 3. 4. 5.
Strength of association Consistency Specificity Temporality 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 Risk Ratio
1
2
3 4 5 15
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
16
Temporality Exposure must precede disease. Yes this is only criterion fundamental to postulating cause and effect but
17
Temporality how about MMR (meales-mumps-rubella) vaccine and autism?
strong temporality observed in some cases does this mean causation?
18
Biological gradient (dose response) Risk of outcome increases with increasing exposure to the suspected risk factor yes linear relationship supports causality: cancer
e.g. more cigarettes smoked, greater the risk of lung
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 20
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) 21
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 22
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. 23
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 24
Study questions 1. Please give the cause of following diseases: a Hepatitis A b Hypertension c lung cancer
25
The cause of Hypertension
Overweight or obesity High-salt diet (high concentration of sodium) excessive drinking……
26
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 (1/100000 PY)
Non-smoking (1/100000PY)
Lung cancer
50.12
4.69
CVD
296.75
170.32
RR
AR (1/100000 PY)
27
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. 29
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. 30
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