Cause of Disease and

Causal Inference
1. Model of disease cause
Ecological Model (Epidemiologic Triangle)
Wheel Model
 Disease-Factor Model
Socioeconomic Factor

Biologic Factor

Environmental Factor Medical and Biologic

Disease
Factor
（ pathogenesis ）

Psycho- and behavioral

Factor

Health care Factor

Fig 2-3 Disease-Factor Model

 Causation Web Model
The multi-factorial etiology of disease
Chain of causation web of causation
2. Cause of Disease
Factors increasing disease
incidence rate of population
risk factors
sufficient cause
necessary cause
3. Conditions of disease development
Causal Factors
Biologic, physics and chemo- causal
factors
Host
Genetical, immune condition, age,
gender, race, character, psychological
and behavioral factors
Environment
Natural and social environment
4. Epidemiological methods
for etiology studies
Based on characteristics:
Observational study
descriptive study
analytic study:
case-control & cohort study
Experimental study
 Based on time:
Retrospective study and
prospective study
Case report
Ecological study
Cross-sectional study
Case-control study
Cohort study
Interventional study
5. Deriving inferences: from
association to causation
The multi-factorial etiology of
disease
To judge whether an association is
causal
No association
False association
Association exist: RR or OR is
statistically significant
Causal association
6. Criteria of causal inference
Time sequence of association:
Did the exposure occur before the disease
began?
Strength of association:
Is the rate of disease many times greater
among the exposed population, or is the
disease excess slight?
Dose-response relationship:
Does the association show a dose-response
effect?
Consistency (replication) of association :
Has the association been noted
consistently across many studies in different
people, places, circumstances and times?
 Biologic plausibility of association :
Does a pathophysiologic model of how the
exposure could cause the disease make
sense?
Is the association supported by generally
known facts about the natural history and
biology of the disease?

Experimental evidence:
Has the exposure caused this disease in an
animal model?
If there are no other epidemiologic or
experimental studies of this exposure-
disease relationship, has a causal association