Causal Inference in Epidemiology

Ahmed Mandil, MBChB, DrPH

Prof of Epidemiology
High Institute of Public Health
University of Alexandria

Headlines

Levels of causality
Definitions
Koch's postulates (1877)
Hill's criteria (1965)
Susser's criteria (1988, 1991)

Relating

Exposures: causes, risk factors,

independent variables to
Outcomes: effects, diseases, injuries,
disabilities, deaths, dependent
variables
Statistical association versus
biological causation: cause-effect
relationship

Levels / Types of causality

Molecular / Physiological
Personal / Social
Deterministic / probabilistic
What aspect of environment (broadly
defined) if removed / reduced /
controlled would reduce outcome /
burden of disease

Definitions (I)

Deduction: reasoned argument proceeding from

the general to the particular.
Induction: any method of logical analysis that
proceeds from the particular to the general.
Conceptually bright ideas, breakthroughs and
ordinary statistical inference belong to the realm
of induction.
Induction period: the period required for a
specific cause to produce the disease (healthrelated outcome). Usually longer with NCDs

Definitions (II)

Association (relationship): statistical dependence between

two or more events, characteristics or other variables.
Positive association implies a direct relationship, while
negative association implies an inverse one. The presence
of a statistical association alone does not necessarily imply
a causal relationship.
Causality (causation / cause-effect relationship): relating
causes to the effects they produce.
Cause: an event, condition, characteristic (or a
combination) which plays an important role / regular /
predicable change in occurrence of the outcome (e.g.
smoking and lung cancer)
Causes may be genetic and / or environmental (e.g.
many NCDs including: diabetes, cancers, COPD, etc)

Definitions (III)
Deterministic causality: cause closely
related to effect, as in necessary /
sufficient causes
Necessary cause: must always PRECEDE the
effect. This effect need not be the sole result
of the one cause
Sufficient cause: inevitably initiates or
produces an effect, includes component
causes
Any given cause may be necessary, sufficient,
both, neither (examples)

Definitions (IV)

Component causes: together they

constitute a sufficient cause for the
outcome in question. In CDs, this may
include the biological agent as well as
environmental conditions (e.g. TB,
measles, ARF/RHD). In NCDs, this may
include a whole range of genetic,
environmental as well as personal /
psychosocial / behavioral characteristics
(e.g. diabetes, cancers, IHD)

Definitions (V)

Probabilistic Causality: in epidemiology,

most associations are rather weak (e.g.
relationship between high serum cholesterol
and IHD), which is neither necessary nor
sufficient
Multiple causes result in what is known as
web of causationor chain of causation
which is very common for
noncommunicable / chronic diseases

Effect Measures /
Impact Fractions

Effect measures (e.g. odds ratio, risk ratio)

and impact fractions (e.g. population
attributable risk) are closely related to the
strength of association
The higher effect measures (away from
unity) and population attributable risk
(closer to 100 %) the more the exposure is
predictive of the outcome in question
E.g. PAR of 100 % means that a factor is
necessary

Deterministic causality (I)

Deterministic causality (II)

Deterministic causality (III)

Deterministic causality (IV)

Deterministic causality (V)

Deterministic causality (VI)

Definitions (IV)

Predisposing factors: factors that prepare, sensitize,

condition or otherwise create a situation
(such as level
of immunity or state of susceptibility) so that the host tends
to react in a specific fashion to a disease agent, personal
interaction, environmental stimulus or specific incentive.
Examples: age, sex, marital status, family size, education,
etc. (necessary, rarely sufficient).
Precipitating factors: those associated with the definitive
onset of a disease, illness, accident, behavioral response,
or course of action.
Examples: exposure to specific
disease, amount or level of an infectious agent, drug,
physical trauma, personal interaction,
occupational
stimulus, etc.
(usually necessary).

Weighing Evidence

At individual level: clinical judgment (which

management scheme)
At population level: epidemiological
judgment (which intervention)
When weighing evidence from
epidemiological studies, we use causal
criteria (usually applied to a group of
articles, to deal with confounding) e.g. Hills /
Sussers criteria, which were preceded by
Kochs postulates (on infectious diseases)

Koch stated that four postulates should be met before a

causal relationship can be accepted between a particular
bacterial parasite (or disease agent) and the disease in
question. These are:
1. The agent must be shown to be present in every case
of the disease by isolation in pure culture.
2. The agent must not be found in cases of other
disease.
3. Once isolated, the agent must be capable of
reproducing the disease in experimental animals.
4. The agent must be recovered from the experimental
disease produced.

Hill's Criteria (1897 - 1991)

The first complete statement of the epidemiologic criteria
of a causality is attributed to Austin Hill (1897 - 1991).
They are:
1.
Consistency (on replication)
2.
Strength (of association)
3.
Specificity
4.
Dose response relationship
5.
Temporal relationship (directionality)
6.
Biological plausibility (evidence)
7.
Coherence
8.
Experiment

Consistency (I)

Consistency (II)

Meta-analysis is an good method for

testing consistency. It summarizes
odds ratios from various studies,
excludes bias
Consistency could either mean:

Exact replication (as in lab sciences,

impossible in epidemiological studies)
Replication under similar circumstances
(possible)

Strength of Association

Expressions of Strength of Association

Quantitatively:

Effect measure (OR, RR): away from unity (the

higher, the stronger the association)
P-value (at 95% confidence level): less than 0.05
(the smaller, the stronger the association)

Qualitatively:

Accept alternative hypothesis: an association

between the studied exposure and outcome exists
Reject null hypothesis: no association exists

Dose-response relationship (I)

Dose-response relationship (II)

Time-order (temporality, directionality)

Time order

Specificity of Outcome

Specificity of Exposure

Coherence

Theoretical: compatible with pre-existing

theory
Factual: compatible with pre-existing
knowledge
Biological: compatible with current
biological knowledge from other species or
other levels of organization
Statistical: compatible with a reasonable
statistical model (e.g. dose-response)

Biological Coherence (I)

Biological Coherence (II)

Susser's criteria (I)

Mervyn Susser (1988) used similar

criteria to judge causal relationships.
In agreement with previous authors,
he mentioned that two criteria have
to be present for any association that
has a claim to be causal: i.e. time
order (X precedes Y); and direction
(X leads to Y).

Sussers Criteria (II)

Rejection of a hypothesis can accomplished

with confidence by only three criteria: time
order, consistency, factual incompatibility or
incoherence.
Acceptance or affirmation can be achieved
by only four, namely: strength, consistency,
predictive performance, and statistical
coherence in the form of regular exposure/
effect relation.

Comparison of Causal Criteria

References
1.

2.

3.

4.

5.
6.

Porta M. A dictionary of epidemiology. New York, Oxford:

Oxford University Press, 2008.
Rothman KJ (editor). Causal inference. Chestnut Hill:
Epidemiology Resources Inc., 1988.
Hill AB. The environment and disease: Association or
causation. Proceedings of the Royal Society of
Medicine 1965; 58: 295-300.
Susser MW. What is a cause and how do we know one ? A
grammar for pragmatic epidemiology. American Journal
of Epidemiology 1991; 133: 635- 648.
Paneth N. Causal inference. Michigan State University.
Rothman J, Greenland S. Modern epidemiology. Second
edition. Lippincott - Raven Publishers, 1998.

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Thank you for your kind attention