1. Choosing a reference group Dublin June 2006

2. comparing disease incidence in exposed and unexposed (reference) comparing exposure in cases and exposure in controls (reference) comparing disease incidence in different time-periods in a population Making comparisons fundamental to epidemiology

3. difficulty in selecting reference group most often applies to finding the right “controls” for case control study constraints of time and resource Field epidemiology

4. Who are the right controls?

5. Controls should be representative of the population from which cases arise (source population) identified as cases if they had the disease under study have the same exclusion and restriction criteria as cases

6. Who is the source population? start with your case definition this leads to source population and criteria for controls

7. Case definition Resident of Galway with isolate of Salmonella typhimurium in faecal sample during May 2005. Exclusion: Travel abroad in week before illness Control definition?

8. Selecting controls population random from register/list/directory stratified (age/sex/general practice) neighbourhood friends family hospital

9. Population controls

10. aim for random sample of population giving rise to cases best if taken from population registers ideally registers should –be complete –contain the cases –be readily accessible –identify control characteristics e.g. age

11. or... random digit dialling using residential directories or mobile numbers (e.g. add 5 to case number) quick and easy but may be bias in selection telephone ownership availability geographial area participation

12. or… stratification for example same age same sex same primary care doctor stratification in study design is called “matching”

13. Neighbourhood controls - advantages no need for population register similar socio- economic status

14. Neighbourhood controls - disadvantages low co-operation may be time consuming and expensive might be too similar to cases

15. Friends / family controls - advantages good matching for social factors good cooperation quick and efficient validity established in food poisoning investigations

16. Friends / family controls - disadvantages if exposure same as cases may not detect causal association = overmatching

17. Hospital controls

18. Hospital controls - advantages useful if cases identified from hospital (or other disease) register easily identified and available population cost and time efficient

19. Hospital controls - disadvantages may be different catchment populations for different diseases overmatching on exposures linked to other diseases (e.g. smoking and lung cancer)

20. Sample size sample size calculation often limited by the number of cases and controls available unusual to select more than 3 or 4 controls per case as little extra power gained beyond this number

21. Controls may not be easy to find

22. Which reference group ? 12 cases of E. coli O157 in children aged 1- 8 years across Dublin since 1 st June 2006. You conduct a case control study Who would be your controls? Please discuss with your neighbourhood control

23. Key points in choosing controls review pros and cons of available options aim to minimise bias, taking account of resources and urgency controls from population register have advantages but no control group is perfect

24. Be prepared to defend your choice…

25. …and do the study!

26. References Rothmann KJ, Greenland S. Modern epidemiology. Lippincott-Raven 1998. Hennekens CH, Epidemiology in Medicine. Lippincott- Williams and Wilkins 1987. Gregg MB. Field epidemiology. Oxford University Press 1996. Wacholder S, McLaughlin JK, Silverman DT, Mandel JS. Selection of controls in case control studies I-III. Am J Epidemiol 1992; 135: 1019-50.