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Causation

Causation. Jay M. Fleisher. Causation. Two types of medical research Bench work Epidemiology Bench work usually describes the underlying biology of disease

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Causation

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  1. Causation Jay M. Fleisher

  2. Causation • Two types of medical research • Bench work • Epidemiology • Bench work usually describes the underlying biology of disease • Epidemiology either tests the results of bench work on human populations or provides input to the biomedical scientist on what we still do not know

  3. What does the term “ Causal” really mean?

  4. Example #1 - HIV and AIDS • Epidemiology identifies new disease caused by defect in immune system • Bench science identifies the infectious agent • Epidemiological studies confirm that agent causes disease in humans • Causation is proven

  5. Example #2 - What Causes an MI • Epidemiological studies combined with laboratory study identify risk factors • Cigarette smoking • Cholesterol • Elevated blood pressure • Stress • Family history • Obesity • Etc • Which of the above contribute the most risk • What are the relationships between risk factors

  6. Therefore: • The issue of causation is not as simple as it first appears • Thus, the need for a unifying concept of causation

  7. A Unifying Model of Causal Relationships

  8. The 2 Components: • Sufficient Cause • precedes the disease • if the cause is present, the disease always occurs • Necessary Cause • precedes the disease • if the cause is absent, the disease cannot occur

  9. The 4 Models of Causal Relationships

  10. 1. Necessary and Sufficient* Disease Only Factor A Sickle Cell Anemia Genetic factors * RARELY OCCUR

  11. 2. Necessary but Not Sufficient Factor A + Factor B Disease + Factor C

  12. 2. Necessary but Not Sufficient - Example Initiation + Latent Period Cancer + Promoter

  13. 3. Sufficient but Not Necessary Factor A Factor B Disease Factor C

  14. 3. Sufficient but Not Necessary - Example Ionizing Radiation or Benzene Leukemia or Electromagnetic Fields?

  15. 4. Neither Sufficient Nor Necessary Factor A + Factor B and/or + Disease Factor C Factor D and/or + Factor E Factor F

  16. 4. Neither Sufficient Nor Necessary - Example Smoking + Cholesterol and/or + MI HBP Fam. History and/or + Stress Obesity

  17. Therefore: • Concept of Necessary vs. Sufficient Causes provides a theoretical framework for causation of all disease • How do we actually assess whether a Risk Factor is indeed Causal

  18. Criteria for Assessing Causation • Temporal relationship • Exposure precedes the disease • Strength of the Association • Measured by the Relative Risk ( either the Rate Ratio or the Odds Ratio) • Dose-response Relationship • As the dose of exposure increases the risk of disease also increases • Example: Cigarette Smoking and Lung Ca • Replication of the Findings • Results replicated in other studies • Biologic plausibility • Does the association fit with what we know about the underlying biology • Sometimes we know little or nothing about the undelieing biology ( “Black Box” epidemiology • Consistency • Alternative explanation eliminated • Cessation effects • Specificity of the Association • Dose-response

  19. Criteria for Assessing Causation • Biologic plausibility • Does the association fit with what we know about the underlying biology • Sometimes we know little or nothing about the underlying biology ( “Black Box” epidemiology) • Example – Asbestosis and Lung Ca.. Only have theory of mechanism • Consideration of Alternate Explanations • If knowledge exists, rule out or make sure studies took into account • Cessation of Exposure • If exposure is reduced or eliminated Risk will decline • Example Ex-Smokers • Specificity of the Association • A specific agent is associated with only 1 disease • OK for infectious agents but falls apart with many Risk Factors for Chronic Illness • Example: Cigarette Smoking associated with several diseases

  20. Criteria for Assessing Causation • Consistency with other knowledge • If we have other knowledge regarding a Risk factor then this comes into play • Often we do not • Example: • Exposure to Electromagnetic fields is a POSSIBLE risk factor for Leukemia • This finding is new and the only other knowledge we have is from studies in changes in cells ( in vitro) • Again “ Black Box” epidemiology

  21. Temporal relationship Biologic plausibility Consistency Alternatives Cessation effects Specificity of association Strength of Association Dose-response Smoking before Ca Yes > 36 studies ? Yes Point of attack 25 x > 25+ cigarettes /day* Yes Criteria for Causation:Smoking and Lung Cancer *.Estimated that 80% of all Lung cancer due to Cigarette smoking

  22. The usual bit of humor

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