1. Summary of Measures and Design
Hein Stigum
Presentation, data and programs at:
Nov-19
H.S.

2. Epidemiological measures
Frequency
prevalence
incidence
Association
Risk difference
Risk ratio
Odds ratio
Potential impact
Attributable fraction
How much disease?
More disease
among exposed?
We have covered ..
We turn now to Association measures
Does smoking cause lung cancer? We measure the strength of the association between the risk factor (smoking) and the disease.
assoc. measures are calculated from freq measures
Important cause?
Nov-19
H.S.

3. Time E,D No time E → D prospective E ← D retrospective Present time
Nov-19
H.S.

4. Cohorts Closed cohort Open cohort Count persons Count person-time
start
end
end
start
Count persons
Count person-time
Closed cohort with time varying covariates
start
end
Count person-time
Nov-19
H.S.

5. Mathematical concepts
Proportion (risk)
Rate
Odds
2 math quatities
prop: fraction, numerator (top) is part of denominator (bottom)
ex: females in class , no dimension, 0-1
rate: change in one quantity per change in another (time),
ex: speed, drive 100 km in 2 h then average speed is 50 km/h, dimension, no upper bound
Statistical concept:
risk: probability, no dimension,
ex: flip coin
Nov-19
H.S.

6. Frequency measures ! Name Equation Type Unit Prevalence risk
cases/person
Incidence Proportion
(Cumulative Incidence)
Incidence Rate
rate
cases/person-time
Odds
odds !
Nov-19
H.S.

7. Disease frequency depicted
Show:
Prevalence
Incidence proportion, closed pop, no loss to follow up
Incidence rate, takes observation time into account, (could also have loss to follow up)
H.S.

8. Association measures
Nov-19
H.S.

9. Association measures More disease among exposed?
Compare frequency among exposed1 and unexposed0
Difference: RD=IP1-IP0 0=no effect
Ratio: RR=IP1/IP0 1=no effect
Frequency
Association or Effect
Difference
Ratio
Risk
Risk Difference, RD
Risk Ratio, RR
Rate -
Rate Ratio, RR, IRR, (HRR)
Odds
Odds Ratio, OR
Dekoder til bakkenett: 1 kr vs 0.5 kr
Situation 0-1
Can use all 3 types of measures, ex=incidence prop
2 types:
null value=no association
RR=2 means exposed twize the risk
Nov-19
H.S.

10. Adjusted measures
Remove the effect of confounders in regression models
Frequency
Association or Effect
Difference
Ratio
Risk
RD:
RR:
Rate -
IRR:
Odds
OR:
Linear-binomial
Log-binomial
Cox, Poisson
Logistic
Standardize freq measures on sex and age
Remove effect of sex and age on association measures in regression
glm=generalized linear models
Nov-19
H.S.

11. Being bullied, 3 models Bullied=17%
glm bullied Island Norway Finland Denmark sex age, family(binomial) link(logit)
glm bullied Island Norway Finland Denmark sex age, family(binomial) link(log)
glm bullied Island Norway Finland Denmark sex age, family(binomial) link(identity)
Bullied=17%
After OR/RR, what is the prevalence of bullying?
After RD, what is the risk of being bullied if girls from Finland?
Nov-19
H.S.

12. Designs Aims Designs Disease occurrence Exposure-Disease association
Cross-sectional studies
Cohort studies
Case-control studies
Case-Cohort
Nested Case Control
Traditional Case Control
Aim: find association
Designs: unit of analysis, time for finding exposure and disease
Nov-19
H.S.

13. The 2 by 2 table
Nov-19
H.S.

14. The 2 by 2 table The lowest number sets the precision
=.13
To increase power:
In a cohort study: oversample unexposed
In a case control study: oversample disease
To increase power:
Cohort: balance exposure
Case-Control: balance disease
Nov-19
H.S.

15. Cohort
Nov-19
H.S.

16. Disease frequency depicted=
Risk time
Show:
Prevalence
Incidence proportion, closed pop, no loss to follow up
Incidence rate, takes observation time into account, (could also have loss to follow up)
Nov-19
H.S.

17. Cohort: Risk, Odds and Rate
Full Cohort, 3 year Risk:
Balance?
Full Cohort, Rate:
3 years follow up time
subject followed for 3 years, 0.017*3 appr=0.05
95% CI
Gene-Diabetes as cohort:
Gene freq 5% * dis freq 1%=0.05%
Number in exposed, diseased cell= *0.05%=50
Nov-19
H.S.

18. 1) Case-Cohort Case-Control studies: Inside an existing cohort
2) Nested Case-Control
3) Traditional Case-Control
Inside an existing cohort
At the end of an imaginary cohort
1) Case-Cohort
Nov-19
H.S.

19. Case-Cohort .
controls
Prospective
Nov-19
H.S.

20. Case-Cohort, Risk Full Cohort, Risk: Case-Cohort, Risk: In practice:
CHD N + -
Exercise
100
1 900
2 000
Inactive
800
7 200
8 000
10 000
Frequency
Pseudo Risk
0.50
1.00
Association RR
0.50 1
Risk time: 3*2000=6000 get a bit less
3*8000=24 000
RR (Rate Ratio) almost equal to Risk Ratio
3 year risk=1-exp(-3*rate) app=3*rate
In practice:
Count: person time
Analyze: Cox model
Sample controls from
healthy at start
Nov-19
H.S.

21. 2) Nested Case-Control
Nov-19
H.S.

22. . . . . Nested Case-Control case case controls controls risk set
Prospective
Nov-19
H.S.

23. Nested Case-Control, Rate
Full Cohort, Rate:
Nested Case-Control:
CHD
Risk time + -
Exercise
100
1900
5 850
Inactive
800
7200
22 800
28 650
Frequency
Pseudo Rate
0.171
0.351
Association
IRR
0.49 1
Sample controls from
risk time
Analyze:
Conditional logistic model
Nov-19
H.S.

24. 3) Traditional Case Control
Nov-19
H.S.

25. Traditional Case-Control.
controls
Retrospective
Nov-19
H.S.

26. Traditional Case-Control
Full Cohort, Odds:
Trad. Case-Control, Odds:
CHD + -
Exercise
100
1 900
Inactive
800
7 200
Frequency
Pseudo Odds
0.53
1.11
Association OR
0.47 1
Sample controls from
non-disease at end
Analyze: Logistic model
Nov-19
H.S.

27. Case-Control studies Cohort studies Case-Control studies
Measure the exposure experience of the entire population
Case-Control studies
Measure the exposure experience of a sample of the source population of cases
Key assumption
Sample controls independent of exposure ( same sampling fraction)
Prospective or retrospective
Nov-19
H.S.

28. Summing up ! Measures Designs Cohort full cohort
Frequency
Association or Effect
Difference
Ratio
Risk RD RR
Rate -
IRR
Odds OR !
Designs
Cohort full cohort
Case-Control all cases + sample of healthy
Case-Cohort sample at start
Nested Case-Control sample during
Trad. Case-Control sample at end
of follow up
Nov-19
H.S.