Case-control study 1 : Design and odds ratio

1. Case-control study 1:Design and odds ratio Preben Aavitsland (partly based on Epiet 2004)

2. Contents • Monday 1 • Design: Case-control study as a smarter cohort study • The odds ratio • Tuesday 2 • Choosing cases and controls • Matching • Power calculation • Wednesday • Case-control studies in outbreaks • Thursday 3 • Bias and confounding • Analysis

3. Why case-control study • Best way to acquire knowledge about causes and protective factors of disease • Both for outbreaks and endemic diseases • Easy to perform and analyse • Needs thorough planning • Next step after surveillance and outbreak investigations

4. Source population

5. The cohort study exposed unexposed

6. Occurrence amongexposed (I1 or R1) Occurrence amongunexposed (I0or R0) The cohort study exposed a unexposed b

7. The cohort study: calculation Exposed I1= a / Nt1 = 16 / 125 pyar Unexposed I0= b / Nt0 = 8 / 120 pyar IRR = I1 = a / Nt1 = 16/125 pyar = 1.92 I0 b / Nt0 8/120 pyar

8. Problems of cohort • Large sample size required • At least if disease is rare • Latency period • Time consuming • Loss to follow up • Changing exposure over time • Only one exposure • Ethical considerations • Cost

9. That is whythe case-control study is smarter • Gives the same measure of causal effect as the cohort study (risk ratio RR or incidence rate ratio IRR) • It is called odds ratio (OR) • Easier, quicker, cheaper, smarter

10. Source population Exposed Unexposed The case-control study

11. Source population Exposed Cases Unexposed

12. Source population Exposed Sample Cases Unexposed Controls

13. Source population Exposed Sample Cases Unexposed Cases = the same as in cohort study Controls = sample of the source population, with representative distribution of exposed and unexposed persons (or person-time) Controls

14. Source population a b Exposed Sample Cases Unexposed c d Controls

15. Source population a b Exposed Sample Cases Unexposed d / Nt0 = c / Nt1 because sampled independent of exposure 24 / 120 = 25 / 125 c d Controls

16. The case-control study: calculation IRR = I1 = a / Nt1 I0 b / Nt0 = a . Nt0 b Nt1 = a . d b c d = c Nt0 Nt1 Nt0= d Nt1 c = 16 . 24 = 1.9225 8

17. Saving resources with case-control study • In stead of following a cohort of 245 people for one year to wait for the 24 cases • We investigated the 24 cases in order to divide them between • exposed a = 16 and • unexposed b = 8 • We chose 49 controls and investigated them in order to divide them between • exposed c = 25 and • unexposed d = 24 • The result • exactly the same as cohort study, but much easier

18. The odds ratio (OR) • OR = Incidence rate ratio (IRR) • OR = Risk ratio (RR) • Cross product ratio: ad / bc

19. Summary of the case-control study • Imagine a source population • Consists of exposed and unexposed people • Gives rise to cases (same as if cohort study) • Control group is a sample from this source population • Independent of exposure status • Same distribution of exposed persons (person-time) as in source population • Determine exposure status of cases and controls • Calculate odds ratio • = risk ratio or incidence rate ratio if a cohort had been done

20. Challenges in case control study • No measure of disease occurrence • Not risk R or incidence rate IR • Difficult to define source population • Difficult to sample controls correctly • Independently from exposure • Recall bias • Cases remember differently from controls