This document discusses approaches for studying disease etiology, including ecological studies, case-control studies, and cohort studies. It explains that ecological studies examine the relationship between characteristics at a group level but cannot determine individual exposure. The document also discusses different types of causal relationships such as necessary and sufficient, necessary but not sufficient, and sufficient but not sufficient. Finally, it outlines nine guidelines for determining whether an observed association is likely causal, including temporal relationship, strength of association, dose-response relationship, replication of findings, biological plausibility, and specificity of association.

1. From Association to Causation:
Deriving Inferences from
Epidemiologic Studies
Dr. Faiza Abou El-Soud
Professor - Community Health Nursing,
Menoufiya University - Egypt

2. I. Identify the approaches for
studying diseases etiology
II. Determine the ecologic studies
III. Discuss type of association
IV. Explain type of causal relationships

3. I. Approaches for Studying
Diseases Etiology
• Expose animals to risk factors such as carcinogens in
control lab:
– Control the exposure dose
– Control other environmental conditions and
genetic factors
– Keep lost to follow-up to minimum
• Can we conclude data across species and from animal
to human population?

4. Approaches to Etiology in
Human Population
• build on unplanned or natural
experiments – People exposed to risk for non-study
purposes.
e.g. exposure to atomic bomb radiation in Hiroshima
and Nagasaki

5. Approaches to Etiology in
Human Population
•

6. Approaches to Etiology in
Human Population
Two steps process is followed in carrying out studies and
evaluating evidence
1.Determining association between an exposure or
characteristics and the risk of a disease
• Studies of characteristics: ecological studies
• Studies of characteristics: case control & cohort
2. If association exist - Determine whether the observed
association is likely to be a causal one.

7. II. Determine the Ecologic Studies
Example (1)

8. Ecologic studies : Interpretation
• • the average dietary fat consumption for a country,
the breast cancer incidence.
• • No information on individuals
(outcome - breast cancer . exposure - high dietary fat intake).
• • Evaluate to members of a group, characteristics that
they in fact do not possess as individuals (ecologic fallacy)

9. Ecologic studies : Homework
Answer: “the observed association is between pregnancy during an
influenza epidemic and subsequent leukemia in the offspring of that
pregnancy.
It is not known if the mothers of any of these children actually had
influenza during their pregnancy”.

10. Type of Association

11. Type of Association

12. A. Type of Causal Relationships

13. A. Type of Causal Relationships
(i)• Necessary and sufficient
– Without that factor the diseases never develops,
and in its presence the disease always develops.
– This situation rarely occurred .

14. A. Type of Causal Relationships
(ii)• Necessary, but not sufficient
– Factor is necessary but not sufficient to produce
the disease e.g. Tubercle bacillus
– Multiple factors are required, often in a specific
temporal sequence.

15. A. Type of Causal Relationships
(iii)• Sufficient, but not necessary
– The factor alone can produce the disease, but so
can other factors.
• Radiation, benzene – either can produce leukemia
• Cancer does not develop in everyone who has experienced
radiation or benzene exposure

16. A. Type of Causal Relationships
(iii)• Neither sufficient nor necessary
– More complex model
– Probably most accurately represents the causal relationships
that operate in most chronic diseases

17. Guidelines for Judging Whether an
Association is Causal
1. Temporal relationship
2. Strength of association
3. Dose response relationship
4. Replication of findings
5. Biologic plausibility
6. Consideration of alternate explanations
7. Cessation of exposure
8. Consistency with other knowledge
9. Specificity of the association

18. Guidelines for Judging Whether an
Association is Causal
1. Temporal relationship
2. Strength of association
3. Dose response relationship
4. Replication of findings
5. Biologic plausibility
6. Consideration of alternate explanations
7. Cessation of exposure
8. Consistency with other knowledge
9. Specificity of the association

19. 1.Temporal relationship
• Exposure to the factor must occurred before
the disease developed.
• It is easy to establish a temporal relationship
in a than
in a and .
• Length of the interval between the exposure
and disease (asbestos in lung cancer).

20. Figure: Temporal relationship

21. 2. Strength of association
• Strength of association is measured by
- Relative Risk or
- Odds Ratio.
• The stronger the association, the more likely the
relation is causal

22. 3. Dose response relationship
• As the dose of exposure increase, the risk of
disease also increases.
• If a dose response relationship is present, it is
strong evidence for a causal relationship.
• Absence of dose response relationship
rule out a causal relationship.
• In some cases a threshold may exist

23. Figure: Dose response relationship

24. 4. Replication of findings
• If the relationship is causal, we would
to find it consistently in different studies and
in different population.
• It is expected to be present in subgroups of
the population.

25. 5. Biologic plausibility
• Coherence with the current body of biologic knowledge
• Sometimes, epidemiological observation preceded
biologic knowledge
E.g. on Rubella and congenital
cataracts preceded any knowledge of teratogenic
viruses
• If epidemiological findings are not consistent with the
existing knowledge - interpreting the meaning of
observed might be

26. 6. Consideration of alternate
explanations
• Explanation of a relationship as causal or due to
confounding.
• The extent to which the investigators have taken
other possible explanations into account and the
extent to which they have ruled out such
explanations are important considerations.

27. 7. Cessation of exposure
• If a is a cause of a diseases, the of the
disease to decline when exposure to the factor is
reduced or eliminated.

28. 8. Consistency with other
knowledge
• If a relationship is causal, we would
the findings to be consistent with other data.

29. 9. Specificity of the association
• An association is specific when
only
– The weakest point of the guideline – should be
.
– Smoking is linked with lung, pancreatic & bladder
cancers; heart disease, emphysema …
– When specificity of an association is found, it
provides additional support for a causal inference
– With a dose response relationship, absence of
specificity in no way negates a causal relationship.

30. Thank You