1. Association to Causation

2. Sequence of Studies Clinical observations Available data Case-control studies Cohort studies Randomized trials

3. Types of Associations Real Spurious

4. DEFINITIONS Observational study Causation Association Necessary Sufficient

5. Koch and Causation Postulates Why study association Web of causation Do we need a better way

6. Twelve Criteria for Causation Cause distributed at same level Incidence much higher in exposed population Exposure more frequent Disease should follow exposure Dose dependent Expected response Association should be the same Other cause-effect ruled out Control results in decreased disease Modification of host results in decrease Human vol. always + Findings should make sense

7. Factors in Causation of Disease Predisposing Enabling Precipitating Reinforcing

8. Web of Causation

9. Are Associations Always Connected to the Disease? NO, BUT ………………………….. Cigarette smoking and lung cancer Age and prostate cancer Car accidents and alcohol Tribal customs and kuru Agriculture and antibiotic resistance

10. Association Deals with ………………. Is concerned with ………. Is the degree of …………. Has to be scientifically proven ….. Your Assignment: fill in the blanks

11. Degrees of Association No assoc. Direct assoc. No possibility for association Possibly associated Associated Direct cause and effect

12. Guidelines for Judging Whether An Association Is Causal Temporal relationship Strength of the association Dose-response relationship Replication of the findings Biologic plausibility Consideration of alternate explanations Specificity of the association Consistency with other knowledge

13. Deriving Causal Inferences Arriving at causation from association For example, showing that Helicobacter pylori is directly linked to peptic ulcers

14. Perspectives Causation may be limited Subject to modification Perhaps more complex than realized Sometimes not measureable “Criteria” are really guidelines may be subjective