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8/12/2019 Exposure Disease
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Exposure Disease?
Exposed cases from a population
If the same people, at the same time,had not been exposed would they still have become cases?
Observed
Expected
Comparison
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Analytical epidemiology Important considerations
Estimation of the right thing Internal validity: Bias, confounding
Retrieval of most information for least cost Efficieny: Precision, resources, time-scale
Means to obtain the right answer
Proper study design Proper analysis Proper interpretation
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Comparisons are fundamental
Different solutions with differentreference groups:
Experimental study design Randomized controlled trial (RCT)
Observational study design Cohort study Case-control study
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Cohort study
What is a cohort? Originally: one of 10 divisions of a Roman legion Group of individuals
Sharing some characteristics
Followed up for specified period of time Examples:
Birth cohort Cohort of guests at barbecue Occupational cohort of chemical plant workers The cohort of this course
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Cohort study
Cases
Compare disease in exposed to disease in unexposed
Source population
Exposed
Unexposed
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Reference group: Cohort study
Unexposed Information on disease in
unexposed Free of disease at beginning of
follow-up
At risk of disease (e.g. notimmune)
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Cohort study Relative risk (RR)
RR = AR in exposed
=a / (a+b)
AR in unexposed c / (c+d)
Disease No disease Total
Exposed a b a+b
Unexposed c d c+d
RR is a gold standard effect measure!
Attack rate, AR = diseased / total (AR is a risk)
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t i m e
Exposure Study starts Disease
Prospective cohort study
t i m e
ExposureStudy starts Disease
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Retrospective cohort study
Exposure
t i m e
Disease Study starts
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Case-control studySource population
Exposed
Unexposed
Cases
Controls =representative sampleof source population
Compare exposure in cases to exposure in controls
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Reference group: Case-control study
Controls Information on exposure in source
population Representative sample of source
population Same inclusion/exclusion criteria as
cases At risk of disease
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Case-control study Odds ratio (OR)
Cases Controls
Exposed a b
Unexposed c d
OR =
Odds of exposure incases
=a / c
=a d
Odds of exposure incontrols b / d b c
Odds of exposure = exposed / unexposed
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RR versus ORDisease No disease Total
Exposed a b a+b
Unexposed c d c+d
RR =a / (a+b)
=a (c+d)
c / (c+d) c (a+b)
OR = a / c = a db / d b c
Ifd
=c+d
then OR=RRb a+b
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Types of case-control studies
Retrospective Different control selection strategies
1. Traditional, exclusive / cumulative design
2. Case-cohort, inclusive design
3. Risk-set / density sampling
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Case-control study:Traditional, exclusive / cumulative
design Controls from disease-free people in
the end OR estimates RR when disease is rare
( 10%)
t i m e
Exposure Disease Cases
Controls
l d
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Case-control study:Case-cohort, inclusive design
Controls from all people in thebeginning
Controls could also be cases OR estimates RR
t i m e
Exposure CasesDisease
Controls
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Case-control study:Risk-set / density sampling
Controls from all people when caseoccurs
Controls could also be cases OR estimates RR
t i m e
ExposureDisease
Case
Control
DiseaseCase
Control
DiseaseCase
Control
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Matching in case-control studies
Frequency matching (n:m), e.g. age group Individual matching (1:1), e.g. birth date
Age strata(yrs)
CasesControls
Unmatched Matched
0-14 50 10 50
15-29 30 25 3030-44 15 25 15
45- 5 40 5
Total 100 100 100
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Matching in case-control studies Makes the distribution of the matching variable
(confounder) similar for cases and controls Stratified comparison when controlling for the matching
variable (confounder) become more efficient
Matched controls are a biased, not representative, sampleof the source population This bias must be taken into account with a matched
analyses Mantel-Haenszel formula for OR Conditional logistic regression
Matching variables cannot be studied Do not match unless you have to
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Sources of controls Population (e.g. register)
Reduce risk of selection bias for controls Neighbourhood, friends, family
Matching for social factors Overmatching underestimation?
Random digit dialling Selection bias?
Hospital Selection bias?
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Cohort or case-control study?
Cohort study Gold standard Risk of inefficieny (large
cohorts,long follow-up)
Use when: High attack rate
Rare exposure Multiple diseases
Case-control study Often more efficient Risk of selection bias
for controls
Use when: Low attack rate
Rare disease Multiple exposures
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Retrospective or prospective design?
Retrospective design Cases and healthy
people may reportexposure differently
(recall bias) Temporal relationship
exposure-disease maybe difficult to determine
(reversed causality)
Prospective design Maybe impossible Time- and resource-
consuming
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Cohort or case-control study?
RR =29 / 53
=0.55
= 2.3 (95%CI 1.2-4.5)8 / 34 0.24
Outbreak of gastroenteritis after eatingin restaurant, 37 of 87 visitors ill
Disease No disease Total
Exposed 29 24 53
Unexposed 8 26 34
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Cohort or case-control study?
Increase in Legionella cases in theNetherlands, 23 cases in a week
Cases ControlsExposed 17 21
Unexposed 6 30
OR =17 / 6
=17 30
= 4.0 (95%CI 1.2-14.5)21 / 30 21 6
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Further reading
Epidemiology: An Introduction, chapter 4Kenneth J. RothmanOxford University Press, 2002Acknowledgement:M. Kivi; EPIET