Professional Documents
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Research Questions/Hypotheses
Big Picture
Look for links between exposure & disease
to intervene and prevent disease
Big Picture
On a population basis
An increase in the level of a causal factor
will be accompanied by an increase in the
incidence of disease (all other things
being equal).
If the causal factor is eliminated or
reduced, the frequency of disease will
decline
Exposure
[ Agent ]
[ Vector/Vehicle ]
Disease
Injury Epidemiology
Studies are undertaken to demonstrate
a link [association] between an agent /
condition and an injury outcome
Exposure
Disease
Exposure
Disease
Issues to consider
Etiology (cause) of chronic disease is often
difficult to determine
Many exposures cause more than one
outcome
Outcomes may be due to a multiple
exposures or continual exposure over time
Causes may differ by individual
Exposure
OR
Genetic Background
OR
Combination of Both
Association
? Causation ?
Experimental studies
in vitro systems
animal studies in controlled environments
Allows for
control of precise dose
control of environmental conditions
loss to follow up kept to a minimum
Problems with
extrapolating data to human populations
human diseases with no good animal models
Clinical pathologies
ASOSIASI VS KAUSASI
Untuk memutuskan apakah eksposur A
menyebabkabn penyakit B, kita pertama
kali harus menemukan apakah dua
variabel itu berasosiasi, misal apakah
CAUSAL
ASSOCIATION
CAUSALITY OR CAUSAL
ASSOCIATION
BERHUBUNGAN DENGAN CAUSE EFFECT
RELATIONSHIPS
UNTUK
MENENTUKAN SEBERAPA BERBEDA
SUATU KONDISI (MIS: FAKTOR
RISIKO) BERHUBUNGAN DENGAN
KONDISI LAINNYA (MIS: PENYAKIT)
MENENTUKAN PENYEBAB ATAU
ETIOLOGI
2. If an association is demonstrated,
determine whether the observed
association is likely to be a causal one
using pre-determined criteria.
Exposure
Disease
Additional Factors
Web of Causation
There is no single cause
Causes of disease are interacting
Illustrates the interconnectedness
of possible causes
RS Bhopal
Understanding Causality
Types of Association
causal
noncausal
direct
indirect
sufficient
necessary
TYPES OF ASSOCIATION
A. Not statistically
associated (independent)
B. Statistically associated
1. Noncasually (secondarily
associated)
2. Causially associated
a. Indirectly associated
b. Directly casual
Non-Causal (due to
confounding)
Coffee Consumption
Real
Association
Spurious
Associatio
n
Smoking
Real
Association
Pancreatic Cancer
Pancreatic Cancer
HUBUNGAN KAUSAL
DIRECT vs INDIRECT
DIRECT (LANGSUNG):
FAKTOR
OUTCOME
Indirect
Factor 1
Factor 2
Factor 3
Factor 4
Disease
Disease
Indirect
High cholesterol
Artery thickening
Hemostatic factors
Cystic Fibrosis
Myocardial infarction
Steps in causality
Need to answer 2 major questions
Is there actually an association?
If there is an association, is it
likely to be causal?
Understanding Causality
Temporal relationship
Strength of association
Dose response
relationship
Replication of the
findings
Biologic plausibility
Consideration of
alternate explanations
Cessation of exposure
Specificity of the
association
Consistency with
other knowledge
1.
2.
3.
4.
5.
6.
7.
8.
9.
Strength
Consistency
Specificity
Temporality
Biological gradient
Plausibility
Coherence
Experimentation
Analogy
Hills Postulates
1.
2.
3.
4.
5.
7.
Coherence the observed data should not conflict with known facts about
the natural history and biology of the disease
8.
9.
Criteria 1: Strength
Relative risk as a measure of strength
Stronger RRs carry more weight
More difficult to explain away by confounders
KRITERIA KAUSAL
Postulat Hill (1)
1. Kekuatan asosiasi
asosiasi yang lebih kuat, kurang
mungkin berhubungan secara
kebetulan atau suatu variabel
perancu (confounding)
KEKUATAN
Apakah asosiasi itu kuat?
Perokok berat berasosiasi dengan
duapuluh kali lipat lebih tinggi tingkat
kanker paru-paru, dan dua kali lipat
tingkat penyakit jantung.
Asosiasi merokok dengan kanker paru
karena itu lebih kuat dari pada asosiasi
dengan penyakit jantung.
Asosiasi yang lebih kuat lebih
memungkin, itu adalah jadi sebab
sebenarnya.
Criterion 1: Strength
Stronger associations are less
easily explained by confounding
than weak associations
Ratio measures (like RR, SMR,
OR) are the best way to quantify
the strength of an association
Example: An RR of 10 is much
stronger evidence for causality
than an RR of 2
Strength of association
Which odds ratio would you be more likely to
infer causation from?
OR#1:
OR = 1.4
OR#2:
OR = 9.8
OR#3:
OR = 6.6
Criteria 2: Consistency
Similar findings
using diverse methods
in different populations
under a variety of circumstances
KRITERIA KAUSAL
Postulat Hill
2. Konsistensi Asosiasi yang diamati
Mempunyai asosiasi yang diamati
oleh orang yang berbeda, tempat,
persoalan dan waktu yang berbeda?
(mirip dengan replikasi eksperimen
laboratorium)
KONSISTENSI
Konsistensi dapat juga berarti :
Replikasi pasti, sebagai ilmu
laboratorium, atau
Replikasi dalam banyak persoalan
yang berbeda.
Dalam epidemiologi, replikasi pasti
adalah tidak mungkin (impossible)
Criterion 2: Consistency
Consistency: studies using
diverse methods in different
populations under a variety of
circumstances lead to similar
conclusions
Example: Ecological, cohort,
and case-control done by
independent researchers
studying different populations
all showed a strong association
between smoking and lung
cancer.
KRITERIA KAUSAL
Postulat Hill (2)
3. Spesifisitas
Jika suatu asosiasi terbatas pada
orang, tempat dan tipe penyakit
tertentu (spesifik), dan jika tidak
ada asosiasi antara ekposur dan
model lain kematian, kemudian
hubungan itu mendukung kausasi
Criteria 3: Specificity
Factor leads to a specific disease
Requires knowledge at cellular level
Converse is NOT true
Some casual relations are non-specific
e.g., smoking causes multiple diseases
SPESIFISITAS
Kausalitas diperkuat jika eksposur
diasosiasikan dengan suatu penyakit
spesifik, dan bukan dengan
keseluruhan varitas penyakitpenyakit
Contoh 1.
Asbestos sebab penyakit paru-paru spesifik,
asbestosis, dapat dibedakan dari berbagai
penyakit paru-paru lainnya.
Tetapi eksposure timbal pada tingkat rendah
dihubungkan dengan IQ (Intelligent Quotient)
yang lebih rendah daripada suatu sindrom otak
yang dapat dibedakan.
Jadi timbal (Pb = Plumbum = timah hitam)
lebih tidak tentu sebagai sebab karena
kemungkinan rancu dengan sebab-sebab yang
lain, ini bukan efek yang spesifik, IQ rendah
(misal SES = Social Economic Status).
Criterion 3: Specificity
The factor is linked to a
specific causal mechanism
Example: Smoking is linked to
physical and chemical
carcinogenesis of epithelial
cells
Comment: Mechanisms are
difficult to establish when there
is a vacuum of knowledge
Aristotle
(384 322 BCE)
KRITERIA KAUSAL
Postulat Hill
4.
Temporalitas/Urutan waktu
Eksposur yang menjadi
perhatian harus mendahului
outcome (penyakit) menurut
periode waktu yang konsisten
dengan berbagai usulan
mekanisme biologik
URUTAN WAKTU
Ini kriteria yang sangat penting secara
sederhana menyatakan bahwa orang
harus mengetahui pasti bahwa sebab
mendahului akibat dalam waktu.
Kadang-kadang ini sulit mengetahui ,
terutama dalam studi kroseksional
(penelitian survei).
Contoh 1.
Studi telah menemukan hubungan
terbalik antara tekanan darah seseorang
dengan kadar kalsium serum. Tetapi
yang mana sebab dan yang mana akibat?
Urutan waktu dapat juga menjadi tidak
tentu bila penyakit mempunyai periode
laten yang panjang, dan bila eksposur
mungkin juga mewakili efek durasi yang
panjang.
Criterion 4: Temporality
Exposure precedes disease by a reasonable
amount of time
Lead encephalopathy scenario 1:
Gerstman
Chapter 16
68
KRITERIA KAUSAL
Postulat Hill (3)
5. Gradien biologik
Ada suatu gradien risiko
berhubungan dengan derajat
eksposur (hubungan dosisrespons)
Hubungan Dosis-respons
Jika suatu gradien teratur risiko
penyakit ditemukan paralel terhadap
gradien eksposur (misal: perokok ringan
mendapat kanker paru pada tingkat
menengah antara bukan perokok dengan
perokok berat) kemungkinan hubungan
kausal diperjelas.
Dosis-respons umumnya dipikirkan
sebagai suatu sub-kategori kekuatan.
Contoh:
Untuk setiap peningkatan
jumlah rokok yang dihisap,
risiko kanker paru meningkat.
Biological Gradient
There is evidence of a dose-response relationship
Changes in exposure are related to a trend in
relative risk
Gerstman
Chapter 16
74
KRITERIA KAUSAL
Postulat Hill (3)
6. Plausibilitas biologik
Diketahui atau ada mekanisme
yang dipostulasikan menurut
ekposur yang mungkin
beralasan setelah risiko
perkembangan penyakit
Criteria 6: Plausibility
Plausible = makes sense in face of
known biological and and other
facts
But what of new previously
unexplained associations?
Where does new knowledge
come from?
Criterion 6: Plausibility
Plausible mechanism
in face of known
biological facts
Plausibility (defined):
appearing worthy of
belief
Gerstman
Chapter 16
77
KRITERIA KAUSAL
Postulat Hill (4)
7. Koherens
Data yang diamati tidak harus
konflik dengan fakta yang
diketahui tentang riwayat
alamiah dan biologi penyakit
KOHERENS
Apakah asosiasi sesuai (cocok) dengan
pengetahuan biologis?
Seseorang harus mencari dukungan
pemeriksaan laboratorium, atau
dari aspek kondisi biologi yang lain.
Criteria 7: Coherence
Do the facts cohere
(i.e., to stick
together)?
Criterion 7: Coherence
All facts stick together to
form a coherent whole.
Example: Epidemiologic,
pharmacokinetic,
laboratory, clinical, and
biological data create a
cohesive picture about the
smoking and lung cancer.
Gerstman
Chapter 16
81
KRITERIA KAUSAL
Postulat Hill (4)
8. Eksperimen
Dukungan yang paling kuat untuk
mendukung penyebab mungkin
dapat diperoleh melalui
ekperimen yang dikontrol
(percobaan klinis, studi
intervensi, percobaan hewan)
Criteria 8: Experimentation
Experimental evidence should support
observational studies
Types of experiments
Epidemiologic (trials)
In vitro
Animal models
Natural experiments
Criterion 8:
Experimentation
Experimental evidence
supports the
epidemiologic evidence
In vitro and in vivo
experiments
Experimentation is
often not possible in
humans
Animal models of
human disease
Gerstman
Chapter 16
84
KRITERIA KAUSAL
Postulat Hill (5)
9. Analogi
Pada beberapa kasus, adalah wajar
menilai hubungan sebab akibat
menurut analogi.
Dengan efek talidomid dan rubella
sebelum kita, adalah wajar bersikap
menerima tetapi pembuktian yang mirip
dengan obat atau virus yang
menyebabkan penyakit pada kehamilan
CONTOH:
Adanya penanda (marker) serologis
infeksi Hepatitis B dihubungkan dengan
laju peningkatan yang besar kanker hati.
Bahwa infeksi Hepatitis B adalah sebab
yang benar dari kanker hati, juga
ditunjang oleh penemuan genom viral
dalam berbagai kanker hati.
Criteria 9: Analogy
Similarities among things that are
otherwise different
e.g., before HIV was discovered,
epidemiologists noticed that AIDS and
Hepatitis B had analogous risk groups
Evidence of similar transmission
Note: analogy is a weak form of
evidence
Criterion 9: Analogy
Similarities among things
that are otherwise different
Weak form of evidence
Example: Before the HIV
was discovered,
epidemiologists noticed that
AIDS and Hepatitis B had
analogous risk groups,
suggesting similar types of
agents and transmission
Gerstman
Chapter 16
89
Temporal relationship
Biologic plausibility
Consistency
Alternatives
Cessation effects
Specificity of
association
Strength of
Association
Dose-response
Smoking before Ca
Yes
> 36 studies
?
Yes
Point of attack
25 x > 25+
cigarettes /day*
Yes
DIRECT
ASSOCIATION
NO
ASSOCIATION
NO POSSIBILITY FOR POSSIBILITY
ASSOCIATION
ASSOCIATED
-Physically not
possible
-Scientifically/
medically not
probable
-Statistically
not associated
-Remote
cause-effect a
possibility
-Not
statistically
associated at
an acceptable
level (50%60%)
-Secondarily
association
ASSOCIATED
-Cause-effect
associated
exists
-Causally
associated
but an indirect
association
-Scientifically
connected
Statistically
associated
but not
causative
association
DIRECT CAUSEEFFECT
-Causality
assurance
-Association
affirmed
-Scientifically
and
biomedically
proven
-Physically
possible
-Statistically
proven
Judging Causality
Weigh weaknesses
in data and other
explanations
RS Bhopal
Weigh quality
of science and
results of causal
models
Chapter 16
From Association to Causation
(Causal Inference)
Gerstman
Chapter 16
99
References
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