Etiologic research Study of the causes of disease. Dr.dr. Siti Setiati, SpPD(K). Major Types of Clinical Epidemiologic Research. Etiologic research. The research question Is there a relation between a determinant (risk factor) and a diseaseoutcome? Research question for causal relation!.
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Etiologic researchStudy of the causes of disease
Dr.dr. Siti Setiati, SpPD(K)
The research question
versus
This lecture: observational research
disease +
cohort
without
disease
outcome
determinant +
disease 
disease +
determinant 
disease 
time
start study
diseaseoutcome
Example of a research question:
Is hypertension a risk factor for MI?
MI +
cohort
without
myocardial
infarction
hypertension +
MI 
MI +
hypertension 
MI 
time
1948
1998
MI +
MI 
hypertension +
a
b
a/a+b=probability of MI for hypertension + = Incidence+
hypertension 
c
d
c/c+d=probability of MI for hypertension  = Incidence 
Relative Risk (RR) = incidence + / incidence 
How do you get a cohort?
How do you follow the cohort?
How do you find the diseaseoutcome?
Start here
Exposure
Outcome
+
**
Free of
outcome

*
+

to
t1
Start here
Exposure
Outcome
+
**
Free of
outcome

*
+

to
t1
determinant
diseaseoutcome
determinant +
disease +
(patients)
determinant 
determinant +
disease –
(controls)
determinant 
time
start study
CreutzfeldtJakob’s Disease
What research question?
Why case control?
beef +
patients
with CJD
beef 
beef +
controls from
hospital
beef 
time
start study
CJD +
CJD 
beef +
a
b
beef 
c
d
Odds Ratio
b/d = odds beef+ in controls
a/c = odds beef+ in cases
= a x d / b x c
How do you find patients?
How to select a control group?
How do you assess exposure to determinant?
Exposure
Outcome
Start here
+
Case

Population
+
Control

determinant
diseaseoutcome
Disease
YesNo
Yes ab
Determinant
No cd
Example 1 (Risk Ratio)
In the randomized prospective Heart Outcomes Prevention Evaluation (HOPE) study (1) the effect of Ramipril on the risk of cardiovascular (CV) events was investigated by calculating the ratio between the incidence proportions of CV events in Ramipril treated and in placebo treated patients.
With CV eventsWithout CV events
Ramipril group (n=4645) 651 3994
Placebo group (n=4652) 826 3826
Relative measures of effect
 Proportion of patients with CV events in the Ramipril group:
651/ 4645=0.14 (14%).
 Proportion of patients with CV events in the placebo group:
826/ 4652=0.18 (18%).
The RiskRatio(RR) is: 0.14/0.18= 0.78
The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensinconvertingenzyme inhibitor, ramipril, on cardiovascular events in highrisk patients. N Engl J Med 2000; 342: 145153
Relative measures of effect
Example 2 (the odds ratio)
Knoll et al. (3) investigated the association between vascular access thrombosis and thrombophilia. They considered 107 patients with access thrombosis (cases) and 312 patients without fistula thrombosis (controls). Overall, among the 107 patients with access thrombosis, 59 had evidence of thrombophilia and 48 did not while among the 312 without access thrombosis 122 had thrombophilia and 190 did not.
 Odds of thrombophilia in patients with vascular access thrombosis :
59/48=1.229
 Odds of thrombophilia in patients without vascular access thrombosis :
122/190=0.642
The odds ratio (OR) is: 1.229/0.642= 1.91
Knoll GA, Wells PS, Young D, et al. Thrombophilia and the risk for hemodialysis vascular access thrombosis. J Am SocNephrol 2005;16:11081114.
(controls = 10% random sampling from cohort)
Disease
YesNo
Yes 440300 740
Determinant
No 212350 562
Disease
YesNo
Yes aPY1
Determinant
No cPY0
a/py1
RR = c/py0
Disease
YesNo
Yes 44022.008 py Determinant
No 21221.235 py
RR = (440/22.008) / (212/21.235) = 2.0
Advantages:
1. only realistic study design for uncovering etiology in rare diseases
2. important in understanding new diseases
3. commonly used in outbreak investigation
4. useful if induction period is long
5. relatively inexpensive
Disadvantages:
1. Susceptible to bias if not carefully designed(and matched)
2. Especially susceptible to exposure misclassification
3. Especially susceptible to recall bias
4. Restricted to single outcome
5. Incidence rates not usually calculable
6. Cannot assess effects of matching variables
Susan is expecting her first baby in two months. She has been reading about the potential benefits and harms of giving newborn babies vitamin K injections. She is alarmed by reports that vitamin K injections in newborn babies may cause childhood leukaemia. She asks you if this is true and, if so, what the risk for her baby will be.
Type : Aetiology
P : newborn babies
I : vitamin K injection
C : 
O : Risk of childhood leukaemia
THANK YOU