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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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Presentation on theme: "Causation Jay M. Fleisher. Causation Two types of medical research Bench work Epidemiology Bench work usually describes the underlying biology of disease."— Presentation transcript:

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* Only Factor A Disease * RARELY OCCUR Genetic factors Sickle Cell Anemia

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

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

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

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

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

16 4. Neither Sufficient Nor Necessary - Example Smoking+ + + and/or Cholesterol HBPFam. History StressObesity MI

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 Criteria for Causation: Smoking and Lung Cancer 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 *.Estimated that 80% of all Lung cancer due to Cigarette smoking

22 The usual bit of humor

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