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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
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
What does the term “ Causal” really mean?
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
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: The issue of causation is not as
simple as it first appears Thus, the need for a unifying
concept of causation
A Unifying Model of Causal Relationships
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
The 4 Models of Causal Relationships
1. Necessary and Sufficient*
Only Factor A Disease
* RARELY OCCUR
Genetic factors Sickle Cell Anemia
2. Necessary but Not Sufficient
Factor A
Disease
+
+
Factor B
Factor C
2. Necessary but Not Sufficient - Example
Initiation
Cancer
+
+
Latent Period
Promoter
3. Sufficient but Not Necessary
DiseaseFactor B
Factor C
Factor A
3. Sufficient but Not Necessary - Example
Leukemia
or
Benzene
Electromagnetic Fields?
Ionizing Radiation
or
4. Neither Sufficient Nor Necessary
Factor A +
+
+
and/or
and/or
Factor B
Factor C Factor D
Factor E Factor F
Disease
4. Neither Sufficient Nor Necessary - Example
Smoking +
+
+
and/or
and/or
Cholesterol
HBP Fam. History
Stress Obesity
MI
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
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
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
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
*.Estimated that 80% of all Lung cancer due to Cigarette smoking
The usual bit of humor