Causation Concept

Principles of Epidemiology

Irwin Aras, M.D

Natural History of Disease

Natural history of disease = progression of
disease in an individual over time
When considering a single cause, we look at
4 stages

Susceptibility
Sub-clinical
Clinical
Recovery, disability or death

Henle-Koch Postulates
Sometimes called pure determinism
1. The agent is present in every case of the disease
2. It does not occur in any other disease as a chance
or nonpathogenic parasite (one agent one disease)
3. It can be isolated and if exposed to healthy
subjects will cause the related disease

Natural History of Disease (Fig 2.1, p. 34)

Natural History of HIV/AIDS

Fig 2.3 (p. 37)

Cause
Cause is not easily defined
Definitions are metaphysical

Rothman & Greenlands (1998) definition:

any event, act, or condition

preceding disease
without which disease would not have occurred
or would have occurred at later time

Causal Relationships
A causal pathway may be direct or indirect
In direct causation, A causes B without intermediate
effects
In indirect causation, A causes B, but with
intermediate effects
In human biology, intermediate steps are virtually
always present in any causal process

Causal Pies (Fig. 2.8, p. 43)

Note: there is more
than one sufficient
mechanism for a
given ailment

Sufficient / Component Cause

(Causal Pies)
A necessary cause - a factor found in all
cases
Contributing cause a non-necessary
factor that is needed in some cases
Sufficiency combination of factors that
make disease inevitable completed pie
(see next slide)

Sufficient / Component Cause (cont.)

The effect of a factor in a population
depends on prevalence of causal
complements
The effect of Mycobacterium exposure in a
fully immune population is nil (increases risk
by 0%)
The effect of Mycobacterium exposure in a
fully susceptible population is 100%

We cannot talk about cause in isolation

Types of Causal Relationships

Necessary and sufficient without the factor, disease never develops
With the factor, disease always develops (this situation rarely occurs)

Necessary but not sufficient the factor in and of itself is not

enough to cause disease
Multiple factors are required, usually in a specific temporal sequence (such
as carcinogenesis)

Sufficient but not necessary the factor alone can cause disease, but
so can other factors in its absence
Benzene or radiation can cause leukemia without the presence of the other

Neither sufficient nor necessary the factor cannot cause disease on

its own, nor is it the only factor that can cause that disease
This is the probable model for chronic disease relationships

Factors in Causation
All may be necessary but rarely sufficient to cause a
particular disease or state
Predisposing age, sex or previous illness may create a state of
susceptibility to a disease agent
Enabling low income, poor nutrition, bad housing or
inadequate medical care may favor the development of disease
Conversely, circumstances that assist in recovery or in health
maintenance may be enabling

Precipitating exposure to a disease or noxious agent

Reinforcing repeated exposure or undue work or stress may
aggravate an established disease or state

Causal Complement
A causal complement is a factor or set of factors that
complete a sufficient causal mechanism (pie)
e.g., Consider tuberculosis
The agent (Mycobacteria sp.) is necessary
Susceptibility is complementary

Multi-Causality
Every cause is interdependent on other
causal factors.
Cause is the cumulative effects of multiple
factors acting together (causal interaction)
Causal factors almost never act alone

Multi-causality requires a more

sophisticated view of incubation

Multi-causal incubation
Induction period = time between causal action and
disease initiation
Latency period = time between disease initiation and
detection
Empirical induction period = induction + latency

Genetic + Environmental Factors in

Causing a Heart Attack (Fig 2.5, p. 38)

Iceberg Phenomenon
Spectrum of illness
most ailments have a
broad range
manifestations &
severities
We often detect only
the tip of the iceberg
e.g., dog bite injuries:

Henle-Koch Postulates
Sometimes called pure determinism
1. The agent is present in every case of the
disease
2. It does not occur in any other disease as a
chance or nonpathogenic parasite (one agent
one disease)
3. It can be isolated and if exposed to healthy
subjects will cause the related disease

Hills Postulates
1. Strength of Association the stronger the association, the less
likely the relationship is due to chance or a confounding variable

2. Consistency of the Observed Association has the association

been observed by different persons, in different places, circumstances,
and times? (similar to the replication of laboratory experiments)

3. Specificity if an association is limited to specific persons, sites and

types of disease, and if there is no association between the exposure
and other modes of dying, then the relationship supports causation

4. Temporality the exposure of interest must precede the outcome by

a period of time consistent with any proposed biologic mechanism

5. Biologic Gradient there is a gradient of risk associated with the

degree of exposure (dose-response relationship)

Hills Postulates (cont)

6. Biologic Plausibility there is a known or postulated
mechanism by which the exposure might reasonably alter the
risk of developing the disease

7. Coherence the observed data should not conflict with

known facts about the natural history and biology of the
disease

8. Experiment the strongest support for causation may be

obtained through controlled experiments (clinical trials,
intervention studies, animal experiments)

9. Analogy in some cases, it is fair to judge cause-effect

relationships by analogy With the effects of thalidomide and
rubella before us, it is fair to accept slighter but similar
evidence with another drug or another viral disease in
pregnancy

Web of Causation for the Major Cardiovascular Diseases

Causation Web Model

Upstream
causes

Individual
level causes

Downstream
causes

Agent, Host, & Environment

Epidemiologic Variables
Person
Place
Time
I keep six honest serving men
(They taught me all I know);
Their names are what and why and when
And how and where and who.
(Kipling)

Person Variables
Example of a person variables: age and sex in relation to
recreational injuries (Fig 2.13, p. 50). Rates are per 1000
per year.

Place
Illustrative example: Regional Differences in
Breast Cancer Mortality (Table 2.14, p. 52)
Fig. 2.14 (p. 52) shows large regional difference in
breast cancer rates
Rate in U.S. = 20 per 100,000 in 1962
Rate in Japan = 4 per 100,000 in 1962
What is not shown: rates in Japanese-Americans
women increase with each generation
Conclusion: environment plays large role in determine
breast cancer risk

Time
Table 2.5: Examples of time variables
Fig 2.15

References
1. Proceeding : Epidemiology Kept Simple,
Chapter 2; Causal Concepts.
2. Proceeding : Dona Schneider, Ph.D, MPH,
FACE; Showing Cause, Intriduction to Study
Design; Lecture 4.
3. Rothman, K. J : Epidemiology An Introduction;
2002.
4. Murti, B : Prinsip dan Metode Riset
Epidemiologi; Edisi ke-2; 2003.