S10) Concepts of Causality

Question 1

What are the three aspects of Henle-Koch’s Postulates in terms of causation?

Answer 1

• Necessity
• Specificity
• Sufficiency

Question 2

What does it mean when a cause is necessary?

Answer 2

Necessary – a cause always precedes the disease i.e. disease cannot occur without cause being present

Question 3

What does it mean when a cause is specific?

Answer 3

Specific – the cause is absent in other diseases (no longer considered relevant, including in microbiology)

Question 4

What does it mean when a cause is sufficient?

Answer 4

Sufficient – a cause alone can lead to the disease (once predisposing and precipitating factors are in place)

Question 5

Complete the following table to apply Henle-Koch’s Postulates (1882) to the 21st Century

Answer 5

Question 6

Describe the cause-effect relationship in an epidemiological context

Answer 6

• Disease results from the interplay of host, environment and agent
• A cause is an exposure/factor that increases the probability of disease
• Exposures do not have to be either necessary/sufficient to be important causes

Question 7

Provide four examples of exposures which are neither necessary (i.e. other causes) nor always sufficient (i.e. need other factors) to cause a disease

Answer 7

• Alcohol consumption → liver cirrhosis
• Ionising radiation → leukaemia
• Smoking tobacco → heart disease
• Traffic speed → pedestrian injury

Question 8

Associations may be present in the absence of a true cause-effect relationship.

Explain this in terms of systematic / random variation

Answer 8

• Confounding (“erroneous”) – known, possible, unknown
• Bias (“incorrect”) – selection bias and information bias
• Chance (“luck”) – measured by p value

Question 9

Provide four possible alternative explanations for an observed association between X and Y

Answer 9

• Due to an unknown confounding factor
• Due to a common cause e.g. lung cancer is associated with chronic bronchitis but both are caused by tobacco smoking
• Reverse causality (you think X→Y but Y→X) e.g. bar work is associated with alcoholism amongst staff
• A true causal association (X → Y)

Question 10

How does one evaluate the strength of evidence in favour of a cause-effect relationship using Bradford Hill’s criteria for causality?

Answer 10

• Association features – strength of association, specificity of association, consistency of association
• Exposure/outcome – temporal sequence, dose response, reversibility
• Other evidence – coherence of theory, biological plausibility, analogy

Question 11

Using an example, explain strength of association in the Bradford Hill Criteria

Answer 11

• A causal link is more likely with strong associations
• Strong associtions are unlikely to be explained by undetected confounding/bias
• E.g. heavy smokers have 20 times risk of mortality from laryngeal cancer than non-smokers*

Question 12

Using an example, explain specificity of association in the Bradford Hill Criteria

Answer 12

• A causal link is more likely when an outcome is associated only with a specific factor and vice-versa
• Specificity of association strengthens the case for a causal link
• E.g. Mesothelioma is associated with exposure to asbestos – no other factors are significant causes of mesothelioma*

Question 13

Using an example, explain consistency of association in the Bradford Hill Criteria

Answer 13

• A causal link is more likely if the association is observed in different studies and different sub-groups
• Consistency of association between studies or groups is unlikely to be due to the same confounding or bias
• E.g. Many different studies demonstrated the association between smoking and ischaemic heart disease*

Question 14

Using an example, explain temporal sequence in the Bradford Hill Criteria

Answer 14

• A causal link is more likely if exposure to the putative factor has been shown to precede the outcome
• The corollary is that a causal link cannot exist if the outcome preceded exposure to the putative factor
• E.g. British Doctors Cohort Study showed that tobacco smoking was not only associated with many diseases but preceded them*

Question 15

Using an example, explain dose response in the Bradford Hill Criteria

Answer 15

• A causal link is more likely if different levels of exposure to the putative factor leads to different risk of acquiring the outcome
• Dose response (biological gradient) is unlikely to be due to unknown confounding or bias
• E.g. The risk of leukaemia increased in survivors of the Hiroshima and Nagasaki atomic bombs the nearer they were to the hypocentre*

Question 16

Explain reversibility in the Bradford Hill Criteria

Answer 16

Reversibility – a causal link is very likely if removal or prevention of the putative factor leads to a reduced or non-existent risk of acquiring the outcome

Question 17

Using an example, explain coherence of theory in the Bradford Hill Criteria

Answer 17

• A causal link is more likely if the observed association conforms with current knowledge
• Coherence with current paradigms / constructs / theories strengthens the case for a causal link
• E.g. The link between socio-economic deprivation and greater ill-health, mortality and lower life expectancy is now well established*

Question 18

Explain biological plausibility in the Bradford Hill Criteria

Answer 18

• A causal link is more likely if a biologically plausible mechanism is likely or demonstrated
• A biologically plausible mechanism strengthens the case for a causal link

Question 19

Using an example, explain analogy in the Bradford Hill Criteria

Answer 19

• A causal link is more likely if an analogy exists with other diseases, species or settings
• An analogy is easier to infer than a biologically plausible mechanism
• E.g. The epidemiology of Hepatitis B virus was successfully used to predict how HIV virus would spread*

Question 20

What is epidemiology?

Answer 20

Epidemiology is the study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to the control of health problems

Question 21

What are the two assumptions one makes in epidemiology?

Answer 21

• Disease does not occur at random
• Disease has causal and preventable factors that can be identified through systematic investigation

Question 22

Explain how the concepts of causality have evolved over the years

Answer 22

• Necessary, specific, sufficient agent → disease

⇓

• Host, environment and agent → disease

⇓

• Multi-factorial web of factors → disease

Question 23

Identify the four concepts in epidemiological reasoning

Answer 23

• Hypothesis
• Analytical Study
• Observed Associations
• Cause-Effect Relationship

Question 24

Describe the following four concepts in epidemiological reasoning:

• Hypothesis
• Analytical study
• Observed associations
• Cause-effect relationship

Answer 24

• Hypothesis – generated from observations and/or theories
• Analytical Study – systematic observations of comparisons
• Observed Associations – possible explanations of non-causal associations (chance, bias, confounding ± reverse causality)
• Cause-Effect Relationship – based on judgement of how the observed association fits in with evidence from other sources