Causality in Epidemiology

Dr E Govha
Department of Community Medicine
1
 Introduction
• A major goal of epidemiology is to assist in
the prevention and control of disease and
in the promotion of health by:

 discovering the causes of disease and the

ways in which they can be modified.

2
 Association

EXPOSURE

}
(Genetic/
Environmental Association
/Agent)

DISEASE or
OUTCOME

3
 Association

• Statistically significant relationship

between two variables

• Occurrence of one event is related to the

occurrence of another event

• May reflect chance, bias or cause

4
Calculating measures of association
Standard two-by-two table
Disease

Present Absent Total

Exposure Exposed a b a+b

to Risk
Factor Not c d c+d
exposed

Total a+c b+d a+b+c+d

5
 Measures of association
• Evaluated by means of an analytical study

• Common measures of association:

1. Incidence risk rate
2. Odds ratio
3. Attributable risk
4. Proportional attributable risk
5. X2 test
6. Regression coefficient
6
 Is the Association Causal?
.
EXPOSURE
(genetic/environment

}
al/agent
? Association

DISEASE or
OUTCOME

7
 Interpretation of Association
• Chance – Statistical inference

• Bias – Epidemiological judgment

• Cause – Criteria for causality

8
 Concept of cause
• An understanding of the causes of disease is
important in the health field not only for
prevention but also in diagnosis and the
application of treatment.
• A cause of a disease is an event, condition,
characteristic, or combination of these factors
which plays an important role in producing the
disease.
• Causality is a relative concept
9
 Sufficient-component cause model
(Rothman)
• The agent-host-environment model did not work well for
many non-infectious diseases
• Rothman in 1976, came up with the Causal Pies Model of
disease causation
• A cause could be sufficient or necessary
• Each sufficient cause is composed of several component
causes

U U U

A B A E B E 10
 Types of causes
Sufficient: A cause is termed sufficient when it
inevitably/certainly produces or initiates a disease.
•It is not usually a single factor, but often comprises
several components. e.g. cigarette smoking is one
component of the sufficient cause in lung cancer.
•In general, it is not necessary to identify all the
components of a sufficient cause before effective
prevention can take place
Necessary: A cause is termed necessary if a disease
cannot develop in its absence.
•Each sufficient cause has a necessary cause as a
11
component.
 Types of causal relations
Factor A Disease

Necessary and sufficient

]
Factor A
+
Factor B Disease
+
Factor C
Necessary but not sufficient 12
 Types of causal relations

Factor A
or
Factor B Disease

or
Factor C

Sufficient but not necessary

13
 Types of causal relations

Each factor is neither sufficient nor necessary

14
 Establishing the cause of a disease
causal
• Causal inference is the term used for the process
of determining whether observed associations
are likely to be causal; the use of guidelines and
the making of judgments are involved.

• Before an association is assessed for the

possibility that it is causal, other explanations
such as chance, bias and confounding have to be
excluded. 15
Evaluating causal associations

16
 Koch’s postulates
• Rules for determining whether an infectious agent
causes a particular disease.
1. Organism present in every case of the disease.
2. Organism - isolated & grown in pure culture.
3. If organism inoculated into a susceptible animal, it
causes the specific disease.
4. Organism can be recovered from the animal and
identified.
– Not useful non-communicable diseases.
– Historical interest only
17
 Limitations of Koch’s Postulate
• Anthrax was the first disease demonstrated to
meet these rules which have proved useful but
for most disease (infectious and non-infectious),
Koch’s rules for determining causation are
inadequate.
The causative organism may disappear when the
disease develops.
 Certain micro-organisms cannot (at the present
time) be grown in pure culture.
Not all organisms exposed to an infectious agent
will acquire the infection. 18
Hill’s criteria – guidelines for judging
whether an association is causal
• Bradford Hill (1965)
suggested a criteria
to be considered in
attempting to
distinguish causal
from non-causal
associations
Sir Austin
Bradford Hill,
1907 – 1991 19
 Hill’s criteria
1. Temporal relationship*
• Refers to the necessity for a cause to precede an
effect in time.
• This is usually self-evident, although difficulties
may arise in case-control and cross sectional
studies when measurements of the possible cause
and effect are made at the same time and the
effect may in fact alter the exposure.
• E.g. use of seat belt
20
 Concentration of airborne particles and
count of daily deaths - London - December
1952

3000 600

2000 Smoke pollution 400

n particles
Airpollutio

per day
Deaths
1000 Deaths 200

0 0
1 2 3 4 5 6 7 8 9 10
Day

21
From: Schwartz J. Environ Res 1994:64:36-52
 Hill’s criteria(cont)
2. Strength of association
•Hill’s argument is that strong association between
possible cause and effect are more likely to be causal than
weak associations .
•The fact that an association is weak does not rule out a
causal connection. example would be passive smoking and
lung cancer
3. Biological Plausibility*
•An association is plausible and more likely causal if
consistent with other knowledge.
•Problem with plausibility: it is too often not based on logic
or data, but only on prior beliefs.
22
•Lack of which may be a reflection of medical knowledge.
 Hill’s criteria(cont)
4. Dose-response relationship
•Higher levels of exposure are associated with an increased
risk of disease
•A dose-response relationship occurs when changes in the
level of a possible cause are associated with changes in the
prevalence or incidence of the effect
5. Reversibility
•When the removal of a possible cause results in a reduced
disease risk, the likelihood of the association being causal
is strengthened.
•Cessation of smoking reduces the risk of developing lung
Cancer 23
Alcohol intake and breast cancer –
Meta-analysis

24
Collaborative Group on Hormonal Factors in Breast Cancer. Br J Cancer 2002;87:1234-45
 Effect of stopping smoking on lung cancer
death rates
1.4
Anual death rate / 1000

1.2
1
0.8
men

0.6
0.4
0.2
0
1 2 3 4 5 6 7 8 9 10 11 12
Years stopped smoking

25
From: Doll R, Hill AB. Br Med J 1964;1:1399-1410
 Hill’s criteria(cont)
6. Consistency - Replication of findings*
•Refers to the repeated observation of an
association in different populations under different
circumstances obtained from different studies.
•Lack of consistency, however, does not rule out a
causal association, because different exposure
levels and other conditions may reduce the impact
of the causal factor in other causes. 

26
 Hill’s criteria(cont)
7. Specificity
• Disease only found in people exposed to
suspected agent 
8. Experimental Evidence
• Rare in human diseases
9. Analogy
• Similar drugs cause similar things
11. Alternative explanations (confounding)*
12. Consistency with other knowledge
27
 Making a decision
• No single criteria completely reliable alone
• Evidence may be conflicting
• Weigh the available evidence
• Criteria not equally important
• Need adequate strength of association
• Correct temporal relationship is essential
• Increased likelihood if different types of evidence
point to same conclusion
• Increased certainty as more evidence becomes
available
• Make a reasonable decision, but keep mind open
to new evidence 28
 Causal inference
• Hill’s criteria to establish causality

• Kochi’s postulate

•Sufficient-component cause model

• Evidence-based approach

29
 Causal criteria
• Strength of the association
• Consistency
• Specificity
• Temporality
• Biologic gradient
• Biologic plausibility
• Coherence
• Experimental evidence
• Analogy
30
Hill AB. Proc R Soc Med 1965;58:295-300
 Causal criteria - comments
• All individual criteria, with the exception of
temporal relationship, have been questioned
– Criteria apply, but no causal effect
– Criteria do not apply, but causal effect

• Establishing a causal effect is a judgment based on

the consideration of all available evidence

31
32
 Self evaluation
Q1: Out of all the mentioned criteria, the one factor,
although not in itself sufficient, that is necessary to
demonstrate causality is:
a. Dose-response b. Temporality
c. Strength of association d. Specificity
Q2: True or False:
Just as a strong association between an exposure and
outcome is indicative of a causal relationship, a weak
association between the two suggests a non-causal
relationship. 33
 Evidence that HIV causes AIDS
• Before appearance of HIV, AIDS-like
syndromes were rare; today they are
common in HIV-infected individuals
• AIDS & HIV are invariable linked in
time, place & population group
• Main risk factors for AIDS have existed
for years
• Many studies agree that a single factor
HIV predicts whether a person will
develop AIDS 34
 HIV causes AIDS (cont.)
• Sero-surveys show AIDS is common where
HIV antibodies are common
• Cohort studies – Immunosuppression &
AIDS-defining illnesses occurred in HIV
infected
– 715 homosexual men followed for 8.6 years
• Immunological profile of AIDS – low CD4+ T
Cell count – rare in HIV –ve
• Nearly everyone with AIDS has antibodies to
HIV
35
 HIV causes AIDS (cont.)
• HIV detected in virtually everyone with AIDS
– PCR tests found HIV in blood, semen & vaginal
secretions
• HIV fulfills Koch’s postulates as the cause of
AIDS
– 4 laboratory workers
• Infectious agent found in all cases of disease
• Isolated from the host’s body
• Agent cause disease when injected
• Isolated in new host – sequenced same strain
– Also in MTCT, Haemophilia, IVDU, - serial
blood samples 36
 HIV causes AIDS (cont.)
• New born babies have no behavioural risk factors but 15 –
40% become infected
• HIV infected twin develops AIDS while non-infected twin
does not
• Increased mortality among haemophiliacs
– 1900 to 1920 life expectancy = 40 years
– 1971 to 1980 life expectancy = 68 years
– 1981 to 1990 life expectancy decrease to 49 years
• Transfusion acquired AIDS cases – similar HIV strains in
recipient & donor
• Sex partners of HIV +ve haemophiliacs & transfusion
recipients develop HIV without other risk factors
37
 HIV causes AIDS (cont.)
• HIV infects and kills CD4+ T lymphocytes in vitro
& in vivo
• Increase HIV correlate with progression to AIDS
and decreased immunologic responses
• HIV is similar to other lentivriuses that cause
immunodeficiency in animal hosts – FIV, SIV

38
THANK YOU

39