CausationWhen 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. 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

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. 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

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. 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

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

Criteria for a 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

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. 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

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

Criteria for a 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

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

Specificity of the association

Strengthens evidence if the cause has ONLY one effect.

Asbestos exposure mesothelioma

abestosis

lung cancer

Criteria for a 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

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

YOU ARE ASKED TO GIVE AN EXPERT OPINION

Does radioactivity from Sellafield cause childhood leukaemia?

Exercise

• Read the paper

• Which criteria are reached?

• What is your conclusion ?

• What is your recommendation?

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

References