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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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causation

Causation

Jay M. Fleisher

causation2
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
example 1 hiv and aids
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
example 2 what causes an mi
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
therefore
Therefore:
  • The issue of causation is not as simple as it first appears
  • Thus, the need for a unifying concept of causation
the 2 components
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
1 necessary and sufficient
1. Necessary and Sufficient*

Disease

Only Factor A

Sickle Cell Anemia

Genetic factors

* RARELY OCCUR

2 necessary but not sufficient
2. Necessary but Not Sufficient

Factor A

+

Factor B

Disease

+

Factor C

2 necessary but not sufficient example
2. Necessary but Not Sufficient - Example

Initiation

+

Latent Period

Cancer

+

Promoter

3 sufficient but not necessary
3. Sufficient but Not Necessary

Factor A

Factor B

Disease

Factor C

3 sufficient but not necessary example
3. Sufficient but Not Necessary - Example

Ionizing Radiation

or

Benzene

Leukemia

or

Electromagnetic

Fields?

4 neither sufficient nor necessary
4. Neither Sufficient Nor Necessary

Factor A

+

Factor B

and/or

+

Disease

Factor C

Factor D

and/or

+

Factor E

Factor F

4 neither sufficient nor necessary example
4. Neither Sufficient Nor Necessary - Example

Smoking

+

Cholesterol

and/or

+

MI

HBP

Fam. History

and/or

+

Stress

Obesity

therefore17
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
slide18

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
slide19

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
slide20

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
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

Criteria for Causation:Smoking and Lung Cancer

*.Estimated that 80% of all Lung cancer due to Cigarette smoking