Causation

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Causation

• Jay M. Fleisher

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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

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What does the term Causal really mean?
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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

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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

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Therefore

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

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A Unifying Model of Causal Relationships
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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

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The 4 Models of Causal Relationships
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1. Necessary and Sufficient
Disease
Only Factor A
Sickle Cell Anemia
Genetic factors
RARELY OCCUR
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2. Necessary but Not Sufficient
Factor A

Factor B
Disease

Factor C
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2. Necessary but Not Sufficient - Example
Initiation

Latent Period
Cancer

Promoter
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3. Sufficient but Not Necessary
Factor A
Factor B
Disease

Factor C
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3. Sufficient but Not Necessary - Example
Ionizing Radiation
or
Benzene
Leukemia

or
Electromagnetic Fields?
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4. Neither Sufficient Nor Necessary
Factor A

Factor B
and/or

Disease
Factor C
Factor D
and/or

Factor E
Factor F
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4. Neither Sufficient Nor Necessary - Example
Smoking

Cholesterol
and/or

MI
HBP
Fam. History
and/or

Stress
Obesity
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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

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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

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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

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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

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Criteria for CausationSmoking and Lung Cancer

• Smoking before Ca
• Yes
• gt 36 studies
• ?
• Yes
• Point of attack
• 25 x gt 25 cigarettes /day
• Yes

• Temporal relationship
• Biologic plausibility
• Consistency
• Alternatives
• Cessation effects
• Specificity of association
• Strength of Association
• Dose-response

.Estimated that 80 of all Lung cancer due to
Cigarette smoking
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The usual bit of humor
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