1. Causation When do we have enough evidence? Sam Bracebridge

2. It is not the fall that kills you. It is the sudden stop at the end. Douglas Adams

3. 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

4. Sellafield nuclear plant

6. 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

7. LOCAL ANGER!!!!

8. National Media

9. Government Action Enquiry: Do radioactive discharges from Sellafield cause childhood leukaemia?

10. Causal inference Bradford Hills criteria (1965)

11. 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

12. Temporal Relationship Exposure must precede disease Essential criterion for causality Knowledge of: Latency period Incubation period

13. 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

14. 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?

15. 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 4 th revised edition, W. Saunder publishers July 2008

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

17. 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 4 th revised edition, W. Saunder publishers July 2008

18. Dose-response Relationship Risk increases with more intense/more frequent exposure But: Beware threshold doses

19. 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 4 th 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.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 4 th revised edition, W. Saunder publishers July 2008

21. Effect of removing the exposure A decrease in the outcome of interest is seen when the exposure is removed

22. 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 4 th 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.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 4 th revised edition, W. Saunder publishers July 2008

24. Specificity of the association Strengthens evidence if the cause has ONLY one effect. Asbestos exposure mesothelioma abestosis lung cancer

25. 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 4 th revised edition, W. Saunder publishers July 2008

26. YOU ARE ASKED TO GIVE AN EXPERT OPINION Does radioactivity from Sellafield cause childhood leukaemia?

27. Exercise Read the paper Which criteria are reached? What is your conclusion ? What is your recommendation?

28. 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 References