analytical epidemiology disease frequency study design: cohorts & case control choice of a...
TRANSCRIPT
![Page 1: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/1.jpg)
Analytical epidemiology
Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference
Alain Moren, 2006
Stratification- Effect modification - Confounding
Matching Significance testing Multivariable analysis
![Page 2: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/2.jpg)
Exposure Outcome
Third variable
![Page 3: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/3.jpg)
Two main complications
(1) Effect modifier
(2) Confounding factor
- useful information
- bias
![Page 4: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/4.jpg)
To analyse effect modification
To eliminate confounding
Solution = stratification stratified analysis
Create strata according to categories inside the range of values taken by third variable
![Page 5: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/5.jpg)
Variation in the magnitude of measure of effect across levels of a third variable.
Effect modification is not a bias butuseful information
Effect modifier
Happens when RR or OR is different between strata (subgroups of population)
![Page 6: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/6.jpg)
Effect modifier
• To identify a subgroup with a lower or higher risk
• To target public health action
• To study interaction between risk factors
![Page 7: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/7.jpg)
AR NV - AR VVE = -----------------------------
AR NV
VE = 1 - RR
Vaccine efficacy
![Page 8: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/8.jpg)
Vaccine efficacy
Status Pop. Cases Cases
per 1000 RR
V 301 545 150 0.49 0.28
NV 298 655 515 1.72 Ref.
Total 600 200 665 1.11
VE = 1 - RR = 1 - 0.28
VE = 72%
![Page 9: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/9.jpg)
Vaccine efficacy by age group
![Page 10: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/10.jpg)
Effect modification
Different effects (RR) in different strata (age groups)
VE is modified by age
Test for homogeneity among strata (Woolf test)
![Page 11: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/11.jpg)
Oral contraceptives (OC) and myocardial infarction (MI)
Case-control study, unstratified data
OC MI Controls OR
Yes 693 320 4.8No 307 680 Ref.
Total 1000 1000
![Page 12: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/12.jpg)
![Page 13: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/13.jpg)
Physical activity and MI
![Page 14: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/14.jpg)
![Page 15: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/15.jpg)
*
*
*
**
40 50 60 70 80
1
2
3
4
5
6
Relative risk (RR) of dying from coronary heart disease for smoking physicians, by age groups, England & Wales,
RR
AgeDoll et Hill, 1966
302010
Effect (OR or RR) is a function of the effect modifier
Effect function
![Page 16: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/16.jpg)
Any statistical test to help us?
• Breslow-Day
• Woolf test
• Test for trends: Chi square
Heterogeneity
![Page 17: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/17.jpg)
Confounding
Distortion of measure of effect because of a third factor
Should be prevented
Needs to be controlled for
![Page 18: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/18.jpg)
Simpson’s paradox
Hats Fit Do not fit % fit
Red 17 3 85%
Blue 9 1 90%
![Page 19: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/19.jpg)
Hats Fit Do not fit % fit
Red 1 9 10%
Blue 3 17 15%
Second table
![Page 20: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/20.jpg)
Hats Fit Do not fit % fit
Red 18 12 60%
Blue 12 18 40%
Day 2, one table only
![Page 21: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/21.jpg)
Cases of Down syndroms by birth order
0
20
40
60
80
100
120
140
160
180
1 2 3 4 5
Birth order
Cases per 100 000 live births
![Page 22: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/22.jpg)
Cases of Down Syndrom by age groups
0100200300400500600700800900
1000
< 20 20-24 25-29 30-34 35-39 40+
Age groups
Cases per 100000 live
births
![Page 23: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/23.jpg)
Birthorder
Age ormother
Downsyndrom
![Page 24: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/24.jpg)
0100200300400500600700800900
1000
Cases per 100000
1 2 3 4 5
Birth order
Cases of Down syndrom by birth order and mother's age
![Page 25: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/25.jpg)
Confounding
Exposure Outcome
Third variable
To be a confounding factor, 2 conditions must be met:
Be associated with exposure - without being the consequence of exposure
Be associated with outcome - independently of exposure
![Page 26: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/26.jpg)
To identify confounding
Compare crude measure of effect (RR or OR)
to
adjusted (weighted) measure of effect (Mantel Haenszel RR or OR)
![Page 27: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/27.jpg)
Are Mercedes more dangerous than Porsches?
Type Total Accidents AR % RR
Porsche 1 000 300 30 1.5
Mercedes 1 000 200 20 Ref.
Total 2 000 500 25
95% CI = 1.3 - 1.8
![Page 28: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/28.jpg)
Crude RR = 1.5Adjusted RR = 1.1 (0.94 - 1.27)
![Page 29: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/29.jpg)
Car type Accidents
Confounding factor:Age of driver
![Page 30: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/30.jpg)
Age Porsches Mercedes
< 25 years 550 (55%) 300 (30%)
>= 25 years 450 700
Chi2 = 127.9
Age Accidents No accidents< 25 years 370 (44%) 480
>= 25 years 130 (11%) 1020
Chi2 = 270.7
![Page 31: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/31.jpg)
Exposure OutcomeHypercholesterolaemia Myocardial infarction
Third factorAtheroma
Any factor which is a necessary step in the causal chain is not a confounder
![Page 32: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/32.jpg)
Salt Myocardial infarction
Hypertension
![Page 33: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/33.jpg)
10 - 20 %
Any statistical test to help us?
When is ORMH different from crude OR ?
![Page 34: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/34.jpg)
How to prevent/control confounding?
Prevention– Restriction to one stratum– Matching
Control– Stratified analysis– Multivariable analysis
![Page 35: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/35.jpg)
Mantel-Haenszel summary measure
Adjusted or weighted RR or OR
Advantages of MH
• Zeroes allowed
OR MH = -------------------
kSUM (ai di / ni)
i=1
kSUM (bi cci / ni)
i=1
![Page 36: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/36.jpg)
OR MH = -------------------
kSUM (ai di / ni)
i=1
kSUM (bi cci / ni)
i=1
![Page 37: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/37.jpg)
Examples of stratified analysis
![Page 38: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/38.jpg)
Effect modifierBelongs to natureDifferent effects in different strataSimpleUsefulIncreases knowledge of biological mechanismAllows targeting of PH action
Confounding factorBelongs to study
Weighted RR different from crude RRDistortion of effectCreates confusion in dataPrevent (protocol)
Control (analysis)
![Page 39: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/39.jpg)
How to conduct a stratified analysis
Perform crude analysisMeasure the strength of association
List potential effect modifiers and confounders
Stratify data according topotential modifiers or confounders
Check for effect modification
If effect modification present, show the data by stratum
If no effect modification present, check for confoundingIf confounding, show adjusted dataIf no confounding, show crude data
![Page 40: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/40.jpg)
How to define strata
In each stratum, third variable is no longer a confounder
Stratum of public health interest
If 2 risk factors, we stratify on the different levels of one of them to study the second
Residual confounding ?
![Page 41: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/41.jpg)
Logical order of data analysis
How to deal with multiple risk factors:
Crude analysis
Multivariate analysis
1. stratified analysis
2. modelling
linear regression
logistic regression
![Page 42: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/42.jpg)
A train can mask a second train
A variable can mask another variable
![Page 43: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/43.jpg)
![Page 44: Analytical epidemiology Disease frequency Study design: cohorts & case control Choice of a reference group Biases Impact Causal inference Alain Moren,](https://reader035.vdocuments.net/reader035/viewer/2022062417/5515320555034673228b581a/html5/thumbnails/44.jpg)
What happened?
Tables
% FittingHatColour
Hat fitting higher in Table I (83%) vs table II (13%)
Blue and red hats not evenly distributed between the 2 tables - table I, 33 % blue - table II, 66 % blue