ASSOCIATION AND CAUSATION

The epidemiologist whose primary interest is to establish a "cause and

effect" relationship has to proceeds from demonstration of statistical
association to demonstration that the association is causal
Association may be defined as the concurrence of two variables more
often than would be expected by chance. But association does not
necessarily imply a causal relationship.
The concept of cause
A cause of a disease is an event, condition, characteristic or a
combination of these factors which plays an important role in producing
the disease. Logically a cause must be preceding a disease.
Association can be broadly grouped under three headings:
a. Spurious association
b. Indirect association
c. Direct (causal) association (i) one-to-one causal association (ii)
multifactorial causation.
a. Spurious association Sometimes an observed association between a
disease and suspected factor may not be real. For example, a study in UK
of 5174 births at home and 11,156 births in hospitals showed perinatal
mortality rates of 5.4 per 1000 in the home births, and 27.8 per 1000 in
the hospital births. Apparently, the perinatal mortality was higher in
hospital births than in the home births. It might be concluded that
homes are a safer place for delivery of births than hospitals. Such a
conclusion. is spurious or artifactual, because in general, hospitals
attract women at high risk for delivery because of their special
equipment and expertise, whereas this is not the case with home
deliveries. The high perinatal mortality rate in hospitals might be due to
this fact alone, and not because the quality of care was inferior.
b. Indirect association Many associations which at first appeared to be
causal have been found on further study to be due to indirect
association. The indirect association is a statistical association between a
characteristic (or variable) of interest and a disease due to the presence
of another factor, known or unknown, that is common to both the
characteristic and the disease. This third factor (i.e., the common factor)
is also known as the "confounding" variable. Since it is related both to
the disease and to the variable, it might explain the statistical
association between disease and a characteristic wholly or in part. Such
confounding variables (e.g., age, sex, social class) are potentially and
probably present in all data and represent a formidable obstacle to
overcome in trying to assess the causal nature of the relationship.
Examples of an indirect association is altitude and endemic goitre
endemic goitre is generally found in high altitudes, showing thereby an
association between altitude and endemic goitre. We know, that
endemic goitre is not due to altitude but due to environmental
deficiency of iodine. a common factor {i.e., iodine deficiency) can result
in an apparent association between two variables, when no association
exists. This amplifies the earlier statement that statistical association
does not necessarily mean causation.
c. Direct (causal) association
(i) One-to-one causal relationship Two variables are stated to be causally
related (AB) if a change in A is followed by a change in B. If it does not,
then their relationship cannot be causal. This is known as "one-to-one"
causal relationship. This model suggests that when the factor A is
present, the disease B must result. Conversely, when the disease is
present, the factor must also be present.
The proponents of the germ theory of disease insisted that the cause
must be: a. necessary, and b. sufficient for the occurrence of disease
before it can qualify as cause of disease. In other words, whenever the
disease occurs, the factor or cause must be present.
The cause is termed necessary if a disease cannot develop in its absence;
(necessary cause: The cause must be present for the outcome to
happen. However, the cause can be present without the outcome
happening).
The cause is termed sufficient cause when it is not usually a single factor,
but often comprises several components, and each sufficient cause has a
necessary cause as a component. A cause is termed sufficient when it
inevitably produces or initiates a disease; (sufficient cause: If the cause is
present the outcome must occur. However, the outcome can occur
without the cause being present).
In general, it is not necessary to identify all the components of a
sufficient cause before effective prevention can take place, since the
removal of one component may interfere with the action of the others
and thus prevent the disease.
the "necessary and sufficient" concept does not fit well for many
diseases. Taking for example tuberculosis, tubercle bacilli cannot be
found in all cases of the disease but this does not rule out the statement
that tubercle bacilli are the cause of tuberculosis.
In tuberculosis, it is wellknown that besides tubercle bacilli, there are
additional factors such as host susceptibility which are required to
produce the disease.
The concept of one-to-one causal relationship is further complicated by
the fact that sometimes, a single cause or factor may lead to more than
one outcome. In short, one-to-one causal relationship, although ideal in
disease aetiology, does not explain every situation.
(ii) Multifactorial causation: the causal thinking is different when we
consider a noncommunicable disease or condition (e.g., CHO) where the
aetiology is multifactorial. This situation is exemplified in lung cancer
where more than one aetiological factor (e.g., smoking, air pollution,
exposure to asbestos) can produce the disease independently. It is
possible as our knowledge of cancer increases, we may discover a
common biochemical event at the cellular level that can be produced by
each of the factors. The cellular or molecular factor will then be
considered necessary as a causal factor.
In the second model (Factor 1 + 2+ Factor 3 = outcome). A model of
multifactorial causation showing synergism the causal factors act
cumulatively to produce disease. This is probably the correct model for
many diseases. lt is possible that each of the several factors act
independently, but when an individual is exposed to 2 or more factors,
there may be a synergistic effect. From the above discussion.
In biological phenomena, the requirement that "cause" is both
"necessary" and "sufficient" condition is not easily reached, because of
the existence of multiple factors in disease aetiology.
Web of Causation
In many diseases, especially noncommunicable diseases, the causative
agent may be unknown or uncertain, yet there may be definite This
model is ideally suited in the study of chronic disease, where the disease
agent is often not known, but is the outcome of interaction of multiple
factors. The (web of causation) considers all the predisposing factors of
any type and their complex interrelationship with each other which
shows a variety of possible interventions that could be taken which
might reduce the occurrence of the chronic disease. An example of the
Web of causation in reference to ischemic heart disease is given in the
accompanying diagram.

The Epidemiological Triad

In epidemiology, there is a concept known as the “Epidemiological
Triad“, which describes the necessary relationship between vector, host,
and environment. When all three are present, the disease can occur.
Without one or more of those three factors, the disease cannot occur.
It’s a very simplistic but useful model. The occurrence and
manifestations of any disease, whether communicable or
noncommunicable, are determined by the interactions between the
agent, the host and the environment, which together constitute the
epidemiological triad . Each of these is treated as a separate component,
though many epidemiologists consider the agent as part of the biological
.environment of man

The causal pie model

An individual factor that contributes to cause disease is shown as a piece of a pie. After all
.the pieces of a pie fall into place, the pie is complete, and disease occurs

The individual factors are called component

causes. The complete pie, is called
a sufficient cause. A disease may have more than one sufficient cause, with each
sufficient cause being composed of several component causes that may or may not overlap.
A component that appears in every single pie or pathway is called a necessary cause,
.because without it, disease does not occur
Component causes A–E add up to sufficient causes I–III. Every sufficient cause consists of
different component causes. If and only if all the component causes that constitute the
causal pie of a sufficient cause are present, does the sufficient cause exist and does the
outcome occur. Hence, the effect of a component cause depends on the presence of its
complementary component causes, that is, its complementary set. I, II, and III can be
sufficient causes for the same outcome, or for different outcomes, in which case the
.outcomes are correlated through the component causes

ADDITIONAL CRITERIA FOR JUDGING CAUSALITY

In the absence of controlled experimental evidence to incriminate the
"cause", certain additional criteria have been evolved for deciding when
an association may be considered a causal association. An elegant
elucidation of these criteria appears in "Smoking and Health" the Report
of the Advisory Committee to the Surgeon General of the Public Health
Service in US (87). Bradford Hill (88, 89) and others (90) have pointed out
that the likelihood of a causal relationship is increased by the presence
of the following criteria.
1. Temporal association
2. Strength of association
3. Specificity of the association
4. Consistency of the association
5. Biological plausibility
6. Coherence of the association
To judge or evaluate the causal significance of an association, all the
above criteria must be utilized, no one of which by itself is self-sufficient,
but each adds to the quantum of evidence, and all put together
contribute to a probability of the association being causal.
1. Temporal association This criterion centers round the question:
Does the suspected cause precede the observed effect? A causal
association requires that exposure to a putative cause must
precede temporarily the onset of a disease.
2. Strength of association: In general, the larger the relative risk, the
greater the likelihood of a causal association. Furthermore, the
likelihood of a causal relationship is strengthened if there is a
 biological gradient or dose-response relationship - i.e., with
increasing levels of exposure to the risk factor, an increasing rise
in incidence of the disease is found.
3. Specificity of the association: The concept of specificity implies a
"one-to-one" relationship between the cause and effect. The
requirement of specificity is a most difficult criterion to establish
not only in chronic disease but also in acute diseases and
conditions. The reasons are: first, a single cause or factor can give
rise to more than one disease. Secondly, most diseases are due to
multiple factors with no possibility of demonstrating one-to-one
relationship. In short, specificity supports causal interpretation but
lack of specificity does not negate it
4. Consistency of the association: The association is consistent if the
results are replicated when studied in different settings and by
different methods. If there is no consistency, it will weaken a
causal interpretation. A consistent association has been found
between cigarette smoking and lung cancer.
5. Biological plausibility Causal association is supported if there is
biological credibility to the association. For example, the notion
that food intake and cancer are interrelated is an old one. The
positive association of intestine, rectum and breast cancers is
biologically logical, whereas the positive association of food and
skin cancer makes no biological sense suggesting that strength of
association by itself does not imply causality causal.
6. Coherence of the association: A final criterion for the appraisal of
causal significance of an association is its coherence with known
facts that are thought to be relevant. For example, the historical
evidence of the rising consumption of tobacco in the form of
cigarettes and the rising incidence of lung cancer are coherent.
The fall in the relative risk of lung cancer when cigarette smoking
is stopped, and the occurrence of lung cancer from occupational
exposure to other carcinogens such as asbestos and uranium and
the demonstrated increase in lung cancer risk when workers
exposed to these substances also smoked, enhance the
significance of a causal association.