CAUSATION I

Bambang Udji Djoko Rianto

 Objective:

– describe the concepts of cause

– identify single & multiple causes
– interactions among multiple causes
– concepts of cause & effect as an association
– hierarchy of research design: cause-effects
relationship
 The concepts of cause

– something that brings about an effect or a result

– cq. etiology, pathogenesis, or mechanisms
– guiding for: prevention, diagnosis, & treatment
 Single and multiple causes

Koch’s postulate: infectious agent is the cause

• the organism:

– must be present in every disease

– must be isolated & grown in pure culture
– when inoculated into susceptible animal, cause
specific disease
– must be recovered from the animal & identified
 many diseases: Koch’s postulate -
 basic approach: particular cause result in disease
• smoking cigarettes causes:
– lung cancer,
– chronic obstructive pulmonary disease,
– peptic ulcer
– bladder cancer
– coronary artery disease
• coronary artery disease caused by:
– cigarette smoking
– hypertension
– hypercholesterolemia

• many factors act together to cause disease

– web of causation
 Proximity of cause to effect
The occurrence of disease is determined by:

– environmental
earlier in the chain
– behavior factors
of diseases events
– genetic

• referred as origins of disease

• more likely to be investigated
by epidemiologists
The knowledge of risk factors lead to:

– effective treatments & prevention

– can be applied without knowing the pathogenetic
mechanism of disease
 Interaction of multiple causes
Multiple cause act together:
– the resulting effect > effect of separate causes
– elucidation of cause > difficult when play a part,
single one predominant
– interact, substantial impact, by changing 1/ small
number of causes
 Effect modification:

• the strength of cause-effect relationship between

2 variables is different, according to the level of
some third variable: effect modifier
 Association and cause

– 2 factors: the suspected cause & effect obviously

must appear to be associated if they are to be
considered cause & effect
– not all association are as causal
 Hierarchy of research designs
Randomized controlled trial:

– to provide evidence cause & effect relationship for

treatments and prevention
– to show a particular agent causes a disease
– sometime not possible to use this design
– most potentially harmful agents or risk factors can
not be assigned at random
– sometime would be unethical, and removal of
potential risk factors is rarely possible
Randomized controlled trial (RCT):

– there are problems of long latent periods & large

numbers of subjects needed in clinical medicine
– so, RCT rarely feasible when studying causes
of disease, and observational studies must be
used instead
 Cohort studies
– the next best design to experiments
– to minimize the effects of selection & measurement
bias

Cross-sectional studies
– are vulnerable
– provide no direct evidence of the sequence of events
– guard against selection bias, but subject to
measurement, and confounding bias
 Evidence that an association is cause & effect:

1. Temporality : cause precedes effect

2. Strength : large relative risk/ Odd ratio
3. Dose-response : larger exposure to cause associated
with higher rates of disease
4. Reversibility : reduction in exposure associated
with lower rates of disease
5. Consistency : repeatedly observed by different
persons, places, circumstances &
times
6. Biologic plausibility : makes sense, according to
biologic knowledge of the
time
7. Specificity : one cause leads to one effect
8. Analogy : cause-effect relationship
already established for a similar
exposure/ disease
 Establishing cause: studies of populations

– characterized by average exposure of group

individuals: aggregate risk studies
– people are classified by the general level of exposure
in their environment
– the main problem: potential bias (ecological fallacy)
– people in a generally exposed group may not them-
selves be exposed to the risk
– there may be confounding factors
In aggregate risk studies:

– cause-effect relationship can be strengthened

if observation: made at > 2 points in time (before &
after)

In a time series study:

– the effect is measured at various points in time

– before and after the purposed cause has been
introduced
– the effect varies in a similar fashion
– if changes in purported cause are followed by
changes in purported effect, the association: less
spurious
In multiple time series study:

– suspected cause: introduced into several different

groups at various times
– measurements of effect and cause: same sequential
manner
– effect regularly follows suspected cause at various
times & places: stronger evidence of relationship
 Weighing the evidence

If there is conflicting of cause-effect evidence:

– decide the weight of the evidence lies
 Types of evidence for cause-effect relationship:

Strength Design Finding

Strong Clinical trial Temporality

Cohort study Strength
Case control study Reversibility
Cross-sectional Dose-response
Aggregate risk Consistency
Case series Biologic plausibility
Weak Case report Specificity
Analogy
 Concept of risk

– refers to the probability of some untoward event

– used in a more restricted sense to describe the
likelihood that people who are without a disease,
but are exposed to certain factors (risk factors),
will acquire the disease
Risk factors:

– factors that are associated with an increased risk

of becoming diseases

Exposure to risk factor:

– a person before becoming ill, come in contact

with or has manifested the factor in question
– exposure: at single point in time, or over a period
of time
– characterizing of chronic exposure: ever exposed,
current dose, largest dose, total cumulative dose,
years of exposure, years since first exposure, etc.
Various measure of dose tend to be related
each other:

– some show an exposure-disease relationship

– others do not

Appropriate measure:

– based on all about biologic effects of exposure

– pathophysiology of disease
Situation in which personal experience is insufficient
to establish a relationship between exposure and
disease

• Large & dramatic risks: easy to recognize the

exposure- disease relationship: follow rapid, certain,
and obvious way
- chickenpox, sunburn, aspirin overdose

• In chronic disease: the relationship: far less obvious

Situation in which personal experience is insufficient
to establish a relationship between exposure and
disease include:

– long latency period between exposure-disease

– frequent exposure to risk factor
– low incidence of disease
– small risk from exposure
– common disease
– multiple cause of disease
 The purpose of the risk factors study

1. To predict the occurrence of disease

2. Assumed incidence of disease in exposed & non
exposed person to risk factor
- sometime risk factor as mark of disease in
directly by associate with other determinant(s)
- risk factor is not caused of disease: marker
3. In diagnostic process
4. To prevent disease
Several scientific strategies for determining risk

1. Observational studies:
- gathers data, simply observing events
- without playing in active part
- only feasible studying most question of risk

a. Cohort
- a group of people who have something in
common when they are first assembled, and
who are then observed for a period of time
to see what happen to them
The basic design:

At risk exposure to risk factor disease

yes
exposed
no

people at time
risk
yes

not exposed

no
The likelihood of exposed persons to get the disease
relative to non-exposed persons is relative risk

: the ratio incidence in exposed persons to incidence in non

exposed persons
b. Case control studies:
- compare the frequency of a purported risk
factor in a group of cases & a group of control

The basic design:

exposure to disease
risk factor
yes
yes: cases
no
time
yes
no: control
no data collection present
 The measures effects for comparing risk
Several measures of association exposure-disease:
measures of effect:

1. Attributable risk (risk difference):

- what is the additional incidence (risk) of disease
following exposure, that experienced by people
who are not exposed ?
- the incidence of disease in exposed persons
minus the incidence in no exposed persons
- the additional incidence of disease related to
exposure, taking into account the background
incidence of disease, presumably from other
cause
2. Relative risk:

- how many times more likely are exposed

persons to get the disease relative to non
exposed persons ?
- the ratio of incidence in expected persons to
incidence in non exposed persons
- the strength association exposure-disease
- useful measure of effect for studies disease
etiology
3. Population risk (PR):

- how much does a risk factor contribute to

the overall rates of disease in groups of people
rather than individual ?
- for deciding which risk factors are particularly
important, & which are trivial to health of community
- in policy positions how to choose priorities for
deployment health care resources
- to estimate PR, take into account the frequency
with which members of a community are exposed
to a risk factor
4. Population attributable risk:

- is a measure of the excess incidence of disease

in a community that associated with the occurrence
of a risk factor
- is the product of the attributable risk & prevalence
of the risk factor in a population
5. Population attributable fraction

- the fraction of disease occurrence in a population

that is association with a particular risk factor
- obtained by dividing the population attributable risk
by the total incidence of disease in the population
Thank you