Title: Causation
1Causation
2Causation
- 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
3What does the term Causal really mean?
4Example 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
5Example 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
6Therefore
- The issue of causation is not as simple as it
first appears - Thus, the need for a unifying concept of causation
7A Unifying Model of Causal Relationships
8The 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
9The 4 Models of Causal Relationships
101. Necessary and Sufficient
Disease
Only Factor A
Sickle Cell Anemia
Genetic factors
RARELY OCCUR
112. Necessary but Not Sufficient
Factor A
Factor B
Disease
Factor C
122. Necessary but Not Sufficient - Example
Initiation
Latent Period
Cancer
Promoter
133. Sufficient but Not Necessary
Factor A
Factor B
Disease
Factor C
143. Sufficient but Not Necessary - Example
Ionizing Radiation
or
Benzene
Leukemia
or
Electromagnetic Fields?
154. Neither Sufficient Nor Necessary
Factor A
Factor B
and/or
Disease
Factor C
Factor D
and/or
Factor E
Factor F
164. Neither Sufficient Nor Necessary - Example
Smoking
Cholesterol
and/or
MI
HBP
Fam. History
and/or
Stress
Obesity
17Therefore
- 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
18Criteria 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
19Criteria 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
20Criteria 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
21Criteria 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
22The usual bit of humor
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