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Advanced course in field epidemiology
Health Protection Surveillance Centre Ireland
Objectives To strengthen understanding of various epidemiological studies available in field epidemiology James Stuart & Alain Moren, June 2006
Presentations on methods
Study design Reference group Counfounding and effect modification Matching Mesures or impact Alternative designs Introduction to multivariable analysis How to interpret data How to make an oral scientifi presentation
Case studies
Smoking and lung cancer Trichinosis Toxic shock syndrom Tiramisu
Presentations from participants
One each day Evening session?
Epidemiological studies Two types
Observation Experiment
James Stuart & Alain Moren, June 2006
Experiment
Exposure assigned Exposed Not exposed Disease occurrence Unethical to perform experiments on people if exposure is harmful
If exposure not harmful Treatment Preventive measure (vaccination) R andomised C ontrolled T rial Blinded Doses Time period Risk - effect No bias If not possible Left with observation of experiments designed by Nature Cohort studies Case control studies
Cohort studies
marching towards outcomes
What is a cohort?
One of 10 divisions of a Roman legion Group of individuals
-
sharing same experience followed up for specified period of time
Examples
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birth cohort cohort of guests at barbecue
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occupational cohort of chemical plant workers EPIET cohort 10
follow-up period
end of follow-up
Calculate measure of frequency:
Cumulative incidence
-
Incidence proportion
-
Attack rate (outbreak)
Incidence density
Cohort studies
Purpose
-
Study if an exposure is associated with outcome(s)?
Estimate risk of outcome in exposed and unexposed cohort Compare risk of outcome in two cohorts
Cohort membership
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Being at risk of outcome(s) studied Being alive and free of outcome at start of follow-up
exposed
Cohort studies
unexposed
exposed
Cohort studies
Incidence among exposed unexposed Incidence among unexposed
Presentation of cohort data: 2x2 table
ill not ill 49 49 98 ate ham did not ham 4 6 10
Presentation of cohort data: Population at risk
Does HIV infection increase risk of developing TB among a population of drug users?
HIV + HIV Population Cases (f/u 2 years) 215 8 289 1 Source: Selwyn et al., New York, 1989
Presentation of cohort data: Person-years at risk
Tobacco smoking and lung cancer, England & Wales, 1951 Person-years Cases Smoke 102,600 133 Do not smoke 42,800 3 Source: Doll & Hill
Presentation of data: Various exposure levels
Daily number of cigarettes smoked Person-years at risk Lung cancer cases > 25 15 - 24 1 - 14 none 25,100 38,900 38,600 42,800 57 54 22 3
Prospective cohort study
Exposure Study starts Disease occurrence Study starts Exposure Disease occurrence
time time
Retrospective cohort studies Exposure Disease occurrence Study starts
time
Recipe: Cohort study
Identify group of
-
exposed subjects unexposed subjects
Follow up for disease occurrence Measure incidence of disease Compare incidence between exposed and unexposed group
Our objective is to compare:
an incidence rate in an exposed population to the rate that would have been observed in the same population, at the same time if it had not been exposed
Principle of case control studies
Source population Exposed Unexposed
Source population Exposed Unexposed
Cases
Source population Exposed Unexposed Sample
Cases Controls
Source population Exposed Unexposed Sample Cases Controls = Sample of the denominator Representative with regard to exposure Controls
Intuitively if the frequency of exposure is higher among cases than controls then the incidence rate will probably be higher among exposed than non exposed.
Case control study
Exposure ?
?
Disease Controls Retrospective nature
Distribution of cases and controls according to exposure in a case control study Exposed Not exposed Total % exposed Cases a c a + c a/(a+c) Controls b d b + d b/(b+d)
Distribution of myocardial infarction cases and controls by oral contraceptive use Oral contraceptives Yes No Total % exposed Myocardial Infarction 693 307 1000 69.3% Controls 320 680 1000 32 %
Distribution of myocardial infarction cases and controls by amount of physical activity Physical activity >= 2500 Kcal < 2500 Kcal Total % exposed Myocardial Infarction 190 176 366 51.9% Controls 230 136 366 62.8 %
Volvo factory, Sweden, 3000 employees, Cohort study 200 cases of gastroenteritis Water Consumption YES NO Total Cases 150 50 200 Controls ?
?
200
Two types of case control studies
Exploratory New disease New risk factors Several exposures "Fishing expedition" Analytical Precise a single hypothesis Dose response
exposed
Cohort studies
Incidence among exposed unexposed Incidence among unexposed
Effect measures in cohort studies
Absolute measures
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Risk difference (RD) I e - I ue
Relative measures
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Relative risk (RR) Rate ratio Risk ratio I I e ue I e = incidence in exposed I ue = incidence in unexposed
ate ham did not eat ham ill not ill Incidence 49 49 98 50 % 4 6 10 40 % Risk difference 50% - 40% = 10% Relative risk 50% / 40% = 1.25
Does HIV infection increase risk of developing TB among drug users?
Exposure HIV + HIV - Population (f/u 2 years) 215 298 Cases 8 1 Incidence (%) 3.7 0.3 Relative Risk 11
Vaccine efficacy (VE)
Status Pop. Vaccinated Unvaccinated 301,545 298,655 Total 600,200 Cases Cases per 1,000 150 515 0.49 1.72 RR 0.28 Ref. 665 1.11 = 72% VE = 1 - RR = 1 - 0.28
Various exposure levels
Exposure level High Medium Low Population Cases Incidence at risk N 1 N 2 N 3 a a a 1 2 3 I I I 1 2 3 Unexposed N ne c I ue
Exposure level High Medium Low
Various exposure levels
Population Cases Incidence RR at risk N 1 N 2 N 3 a a a 1 2 3 I I I 1 2 3 RR RR RR 1 2 3 Unexposed N ne c I ue Reference
Cohort study: Tobacco smoking and lung cancer, England & Wales, 1951 Cigarettes smoked/d > 25 15 - 24 1 - 14 none Source: Doll & Hill Person-years at risk Cases Rate per 1000 p-y Rate ratio 25,100 38,900 38,600 42,800 57 54 22 3 2.27 1.39 0.57 0.07 32.4 19.8 8.1 Ref.
A cohort study allows to calculate indicators which have a clear, precise meaning.
The results are immediately understandable.
Cohort studies Rate Rate difference Rate Ratio (strength of association) Case control studies No calculation of rates Proportion of exposure Any way of estimating Rate ratio ?
E Cases Population denominator a P 1 E c P 0 I 1 = a / P 1
}
I 1 / I 0 = ----- a /P 1 c /P 0 I 0 = c /P 0 Cases Population sample E a P 1 /10 E c P 0 /10 I 1 = a ------- P 1 / 10 c I 0 = ------- P 0 /10
}
I 1 / I 0 = ----- a /P 1 c /P 0
Source population Cases Pop.
E a E c P 1 P 0 I 1 = a / P 1
}
I 1 / I 0 = ----- a /P 1 c /P 0 I 0 = c /P 0 E Cases a E c = sample Controls b P 1 -- P 0 b = --- d d
Source population Cases Pop.
E a P 1 I 1 = a / P 1 E E c c E Cases a d P 0 b = sample Controls P 1 I 0 = c /P 0 b
}
I 1 / I 0 a /P 1 a . P 0 a . d = ------ = ------- = ----- = a / c ----- c /P 0 c . P 1 c . b b / d Since d/b = P 0 / P 1 -- = --- P 0 d
Case control study design Cases Controls E a b Odds ratio a --- c b -- d = a x d --- --- b x c E c d
Radiation Exp Breast cancer Total Cases Rate RR
28010 41 14.6
1.9
Unexp.
19017 15 7.9
Ref.
Source: Rothman
Radiation Exp Breast cancer Total Cases Rate RR
28010 41 14.6
1.9
Controls OR
280 1.9
Unexp.
19017 15 7.9
Ref.
190 Ref.
Source: Rothman
Distribution of myocardial infarction in cases and controls by recent oral contraceptive use Oral contraceptives Yes No Total % exposed Myocardial Infarction 693 307 1000 69.3% Controls 320 680 1000 32 % OR 4.8
Ref.
Distribution of myocardial infarction in cases and controls by amount of physical activity Physical activity >= 2500 Kca l < 2500 Kcal Total % exposed Myocardial Infarction 190 176 366 51.9% Controls 230 136 366 62.8 % OR 0.64
Ref.
Distribution of cases of endometrial cancer by estrogen use Estrogen use Cases Controls Odds ratio High a1 b1 a1d/b1c Low None a2 c b2 d a2d/b2c Reference
Relation of Hepatocellular Adenoma to duration of oral contraceptive use in 79 cases and 220 controls Months of OC use Cases Controls Odds ratio 0-12 13-36 37-60 61-84 >= 85 Total 7 11 20 21 20 79 Source: Rooks et al. 1979 121 49 23 20 7 220 Ref.
3.9
15.0
18.1
49.7
Limitations of case-control studies
Cannot compute directly relative risk Not suitable for rare exposure Temporal relationship exposure-disease difficult to establish
Biases +++
-
control selection recall biases when collecting data
Loss of precision due to sampling
Disadvantages of cohort studies
Large sample size Latency period Lost to follow Exposure can change Multiple exposure = difficult Ethical considerations Cost Time consuming
Advantages of case control studies
Rare diseases Several exposures Long latency Rapidity Low cost Small sample size Available data No ethical problem
Strengths of cohort studies
Can directly measure
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incidence in exposed and unexposed groups true relative risk Well suited for rare exposure Temporal relationship exposure-disease is clear Less subject to selection biases
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outcome not known (prospective)
Strengths of cohort studies
Can examine multiple effects for a single exposure population outcome 1 exposed N e unexposed N ne I I e1 ue1 outcome 2 I e2 I ue2 outcome 3 I e3 I ue3 RR 1 RR 2 RR 3
The cohort study is the gold-standard of analytical epidemiology
Alain Moren CASE-CONTROL STUDIES HAVE THEIR PLACE IN EPIDEMIOLOGY but if cohort study possible, do not settle for second best