Causation – Seminar

Jørn Olsen

20 November, 2014
Causes – the C-word in epidemiology

• We study associations but we estimate effects

because we are interested in causes

AXIOMS
1. (Some) diseases have causes
2. Some of these causes are avoidable
3. Therefore some diseases are preventable

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• But what is causation?

• How do causes operate?

• And how can they be detected?

• First the history: Hume – Mackie - Rothman

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Hume – one object E followed by another object D

E D rarely if ever seen

E D the necessary part

- circular if the exposure is part of the definition
of the diseases

E D the sufficient part

seen but not often
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• And monocausal effects are rare, even a
simple – press the switch, the light is on - has
a sequence of causes from distal to proximal
• and
• Causes act in a probalistic manner, why?
• Causes usually have delayed effects, why?

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• Mackie – Rothman causal model explains why
causes act probalistic.

Asb.
Smoke Smoke G2
asb G3
G1

The probability of getting L.C. if you smoke is a

function of the frequency of other component causes
Asb, G1 and G2.
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The induction time is the time it takes to
complete a causal field and latency time is the
time it takes for the disease to surface to clinical
detection.
INUS conditions.
Is the model true? More important is – does it
work? Inspire to better understanding, more
research. Shows why etiologic fractions sum up to
more than 100%
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• Gwas studies indicate a very complex genetic
set of causes perhaps that is why we see so
few gene-environmental interactions.

• Problems in meta-analyses. No reason to

expect simple additive or multiplicative effects
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 Counterfactual

E D
Hume’s second definition.
Or, in other words, where the first object had not been
the second would never exist.
• Leads to counterfactual analysis of causation and a
possible definition of causation. Leads also to the RCT
and other designs that can provide the expected
disease occurence among exposed had they not been
exposed

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 Current definition of causation
• E is causing D if E increases the probability of
D
• Or like
• E is causing D if E blocks the estrogen receptor
leading to ... D in the presence of E

• Epidemiology versus toxicology in public

health
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If E is a cause of D in a population it must be true
for at least one person that he or she would not
have had this disease at this time if he or she had
not been exposed.

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Counterfactual reasoning implies we can
imagine a world where the exposure is not
present.
Counterfactual reasoning also tells us why we
do not compare cases and controls in a case-
control study.
We try to reconstruct the IR among exposed
and not exposed.
We try to imagine what would be the disease
occurrence among the exposed had they not
been exposed and we use not exposed for
that well knowing that they are surrogates for
counterfactual observation time. 12
Causes are upstream or downstream.
Many sexual contacts cause cervical cancer?
Cervical cancer is caused by a specific variant of
HPV?
Both levels of causation can be used in prevention.
Down stream causes may become rather trivial –
accident research for example

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Causes may be presented graphically – as done
by using DAGs.

Put simply, causality has been mathematized.

Judea Pearl: Causality. Cambridge University

Press, 2010.

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DAGs also illustrate situations where causal inference
is justified.
A randomizes trial, incl. Mendelian Randomiza-tion.
R E D

Nothing feeds into R and R only affects E (incl. a

gene?). No backdoor path – closed at E. If R is
associated with D there is a causal link between E
and D.
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 Causal types

E1 G1
G2 G3
E2 E3

People without G1,G 2,G3 (2 out of 3) are immune

People with G 2,and G3 are doomed
People with G1 are causative

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 Quantification of causes

• Even if diseases have many causes – OK to

focus on one.
• The causes of interest are those that can be
manipulated – Følling’s Disease.

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 Do we need a concept of causation? The
surgeons point of view
• If someone kicks me in the back and it hurts –
I know what causes the pain and I want
revenge - not a lecture in philosophy

• Use causal concepts but leave the nature of

causation to philosophers?
• Perhaps but leaves much of the basic theory in
the dark.

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Causal interpretation problem
(CIP)
– Alex Broadbent

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• If nobody in the population smoked the risk of
L.C. in that population would be 50% less

• - But estimate is too high what would replace

smoking?

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• Counterfactual; a cause makes a
difference: Had it been different or
absent, then the effect would have
been different or absent (AB).

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“A measure of causal strength is a measure of
the net difference in outcome explained by the
exposure.
To explain a difference in outcome such that the
outcome in group A is greater than the outcome
in group B by degree, u , we must have a
difference in exposure which could at least
explain this degree, u.” (AB).
Strength of association is a causal criterium

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• A result, claim, theory, inference, or other
scientific output is stable if and only if
a) It is not known to be contradicted by good
scientific evidence

and

b) Given best current scientific knowledge, it

would probably not be seen contradicted by
good scientific evidence, if good research
were to be done on the topic (AB)
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• The ‘What could possibly go wrong?’

• When you have eliminated all other

explanations what remains must be the truth.

• Sherlock Holmes

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 Conclusions
• The Mackie/Rothman causal model has been
useful in providing an understanding (true or
false) of many of the concepts we use. It
inspires to new theories and hypotheses.
• DAGs has been useful in understanding how
causes operate and in helping separating out
causal paths of interest from causal paths of
no interest.

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• Counterfactuals has focused our attention on
what we aim at in our designs and analyses.

• Cross over design, case-only designs, sib

studies etc. – not only RCTs.

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