Causation When do we have enough evidence?

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CausationWhen do we have enough evidence?
Sam Bracebridge
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• It is not the fall that kills you. It is the
  sudden stop at the end.
• Douglas Adams

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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

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Sellafield nuclear plant
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(No Transcript)
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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

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LOCAL ANGER!!!!
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National Media
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Government Action

• Enquiry
• Do radioactive discharges from Sellafield cause
  childhood leukaemia?

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Causal inference

• Bradford Hills criteria (1965)

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Causal Relationship

1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Doseresponse 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

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Temporal Relationship

• Exposure must precede disease
• Essential criterion for causality
• Knowledge of
• Latency period
• Incubation period

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Causal Relationship

1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Doseresponse 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

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Strength of Association

• Strong associations are more likely to be causal
  than weak ones
• Smoking gt 20 cigarettes/day
• ? laryngeal carcinoma (RR 20)
• BUT
• Bias, confounding?

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Criteria for a Causal Relationship

1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Doseresponse 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

L Gordis Epidemiology 4th revised edition, W.
Saunder publishers July 2008
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Biologic Plausibility

• Is consistent with current biological and medical
  common knowledge.
• Smoking
• Ingesting of chemicals and known carcinogens
  
• DNA mutations
• lung cancer

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Criteria for a Causal Relationship

1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Doseresponse 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

L Gordis Epidemiology 4th revised edition, W.
Saunder publishers July 2008
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Dose-response Relationship

• Risk increases with more intense/more frequent
  exposure
• But
• Beware threshold doses

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Criteria for a Causal Relationship

1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Doseresponse 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

L Gordis Epidemiology 4th revised edition, W.
Saunder publishers July 2008
20
Criteria for a Causal Relationship

1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Doseresponse 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

L Gordis Epidemiology 4th revised edition, W.
Saunder publishers July 2008
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Effect of removing the exposure

• A decrease in the outcome of interest is seen
  when the exposure is removed

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Criteria for a Causal Relationship

1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Doseresponse 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

L Gordis Epidemiology 4th revised edition, W.
Saunder publishers July 2008
23
Criteria for a Causal Relationship

1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Doseresponse 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

L Gordis Epidemiology 4th revised edition, W.
Saunder publishers July 2008
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Specificity of the association

• Strengthens evidence if the cause has ONLY one
  effect.

abestosis
Asbestos exposure
mesothelioma
lung cancer
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Criteria for a Causal Relationship

1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Doseresponse 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

L Gordis Epidemiology 4th revised edition, W.
Saunder publishers July 2008
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You are asked to give an expert opinion

• Does radioactivity from Sellafield cause
  childhood leukaemia?

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Exercise

• Read the paper
• Which criteria are reached?
• What is your conclusion ?
• What is your recommendation?

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References
Gardner M. Fathers 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