Causation
When do we have enough evidence?
Sam Bracebridge
It is not the fall that kills you. It is
the sudden stop at the end.
Douglas Adams
Learning outcomes
By the end of the lecture you will be able to:
• List the Bradford-Hill criteria for causal
inference
• Advise if radioactivity from the Sellafield
nuclear plant causes childhood leukaemia
Sellafield nuclear plant
Anecdotal evidence
• Journalist: documentary on occupational
exposure
• Local population: higher number of cases
of childhood leukaemia (CL)
• Broadcast: excess CL due to radioactive
environmental contamination
LOCAL ANGER!!!!
National
Media
Government Action
Enquiry:
“Do radioactive discharges from
Sellafield cause childhood
leukaemia?”
Causal inference
Bradford Hill’s criteria (1965)
Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Alternate explanations considered
8. Specificity of the association
9. Consistency with other knowledge
Temporal Relationship
Exposure must precede disease
Essential criterion for causality
Knowledge of:
• Latency period
• Incubation period
Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Alternate explanations considered
8. Specificity of the association
9. Consistency with other knowledge
Strength of Association
Strong associations are more likely to be causal
than weak ones
Smoking > 20 cigarettes/day
 laryngeal carcinoma (RR 20)
BUT
• Bias, confounding?
Criteria for a Causal Relationship
1.
2.
3.
4.
5.
6.
7.
8.
9.
Temporal relationship
Strength of the association
Biologic plausibility
Dose–response relationship
Replication of the findings
Effect of removing the exposure
Alternate explanations considered
Specificity of the association
Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Biologic Plausibility
Is consistent with current biological and
medical common knowledge.
Smoking
Ingesting of chemicals and known
carcinogens
DNA mutations
lung cancer
Criteria for a Causal Relationship
1.
2.
3.
4.
5.
6.
7.
8.
9.
Temporal relationship
Strength of the association
Biologic plausibility
Dose–response relationship
Replication of the findings
Effect of removing the exposure
Alternate explanations considered
Specificity of the association
Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Dose-response Relationship
Risk increases with more intense/more
frequent exposure
But:
• Beware threshold doses
Criteria for a Causal Relationship
1.
2.
3.
4.
5.
6.
7.
8.
9.
Temporal relationship
Strength of the association
Biologic plausibility
Dose–response relationship
Replication of the findings
Effect of removing the exposure
Alternate explanations considered
Specificity of the association
Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Criteria for a Causal Relationship
1.
2.
3.
4.
5.
6.
7.
8.
9.
Temporal relationship
Strength of the association
Biologic plausibility
Dose–response relationship
Replication of the findings
Effect of removing the exposure
Alternate explanations considered
Specificity of the association
Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Effect of removing the exposure
A decrease in the outcome of interest is seen when the
exposure is removed
Criteria for a Causal Relationship
1.
2.
3.
4.
5.
6.
7.
8.
9.
Temporal relationship
Strength of the association
Biologic plausibility
Dose–response relationship
Replication of the findings
Effect of removing the exposure
Alternate explanations considered
Specificity of the association
Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Criteria for a Causal Relationship
1.
2.
3.
4.
5.
6.
7.
8.
9.
Temporal relationship
Strength of the association
Biologic plausibility
Dose–response relationship
Replication of the findings
Effect of removing the exposure
Alternate explanations considered
Specificity of the association
Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Specificity of the association
Strengthens evidence if the cause has ONLY
one effect.
abestosis
Asbestos exposure
mesothelioma
lung cancer
Criteria for a Causal Relationship
1.
2.
3.
4.
5.
6.
7.
8.
9.
Temporal relationship
Strength of the association
Biologic plausibility
Dose–response relationship
Replication of the findings
Effect of removing the exposure
Alternate explanations considered
Specificity of the association
Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Does radioactivity from Sellafield
cause childhood leukaemia?
YOU ARE ASKED TO GIVE AN
EXPERT OPINION
Exercise
• Read the paper
• Which criteria are reached?
• What is your conclusion ?
• What is your recommendation?
References
Gardner M. Father’s occupational exposure to radiation
and the raised level of childhood leukaemia near the
Sellafield nuclear plant. Env Health Perspectives. Vol
94, 5-7, 1991.
Rothman KJ; Epidemiology: an introduction. Oxford
University Press 2002, 94-101