1. SEARO – CSR Training on Outbreak Investigation Selecting Comparison Groups

2. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Learning Objectives At the end of the session, the participants will be able to: –Explain the rationale for selecting comparison groups –Enumerate criteria for selecting comparison groups –Identify individuals who can be selected –Identify location where to select members of comparison groups –Describe how to choose comparison groups –Explain the power of the study

3. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Comparison Group Two denominators according to the kind of study: Case-control - control group Cohort - cohort of non-exposed or reference group

4. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Planning: controls for case-control study 1.WHY – choose a group of controls 2.WHICH – criteria for selection 3.WHO and WHERE – to choose a group of controls 4.HOW – to select controls 5.HOW MANY Groups of controls Few controls

5. SEARO – CSR Training on Outbreak Investigation WHY choose comparison groups? Selecting comparison groups

6. SEARO – CSR Training on Outbreak Investigation a c Exposed Not exposed CASES What can we compute?

7. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation 1.If we have these cases Simple observation of exposure (percentage) Example: Trichinellosis Eating porkCases No.% exp Yes9090% No10 Total100

8. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Exposed Not exposed a c CASES CONTROLS b d What can we compute?

9. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Example: Trichinellosis Eating pork CasesControls No.% expNo.% exp Yes9090%4040% No1060 Total100 2) If we have a group of controls Comparing two exposures (percentages)

10. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation In a case-control study, a group of CONTROLS allows To define –The EXPECTED FREQUENCY of exposure to a risk factor To compare –The TWO PROPORTIONS of exposure to the same risks between CASES and a group of CONTROL To measure –The DEGREE of ASSOCIATION between exposure and disease

11. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation a Exposed CASES b HEALTHY What can we compute?

12. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Example: Asbestos Exposed Asbestos Cancer Pleura Healthy subjects TotalIncidence Yes5836,73236,7901.6/1,000 Simple observation If we have the following exposed subjects

13. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation CASES a Exposed b HEALTHY c Not exposed d What can we compute?

14. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Example: Asbestos If we have a group of reference of NOT EXPOSED Exposed Asbestos Cancer Pleura Healthy subjects TotalIncidence Yes5836,73236,7901.6/1,000 No4299,958100,0000.4/1,000 We can compare two incidences

15. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation In a cohort study, reference group allows To define –The EXPECTED FREQUENCY of the disease To compare –The TWO INCIDENCE RATES between the EXPOSED and a group of individuals NOT EXPOSED to the risk factor under study To measure –The DEGREE of ASSOCIATION between the factor or risk and the disease (computing relative risk)

16. SEARO – CSR Training on Outbreak Investigation WHICH criteria for selection? HOW to select ? Selecting comparison groups

17. SEARO – CSR Training on Outbreak Investigation Characteristics of controls They DON’T HAVE the disease They have the same characteristics in terms of person, time, place in relation to the study population –They could have been cases if they had the same disease –Distribution of the exposure in the study population –Selected independently from the exposure status

18. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Rum and Tourists in Guadeloupe Hospital of Pointre-à-Pitre, Haiti Consumption of Rum Cases (car accidents) No.% exp Yes5050% No50 Total100

19. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Rum and Tourists in Guadeloupe Hospital of Pointre-à-Pitre, Haiti Consumption of Rum Cases (Tourists) Controls (hospitalized Haitians) No.% expNo.% exp Yes5050%9090% No5010 Total100

20. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Consumption of Rum Cases (Tourists) Controls (hospitalized Haitians) Odds Ratio No.% expNo.% exp Yes5050%9090%0.11 [0.01 – 1.2] No5010 Total100 Rum and Tourists in Guadeloupe Hospital of Pointre-à-Pitre, Haiti Conclusion: The rum is not a risk factor for car accidents among tourists and may even be protective!!!

21. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Consumption of Rum Cases (Tourists) Controls (hospitalized tourists) Odds Ratio No.% expNo.% exp Yes5050%3030%2.33 [1.3 – 4.2] No5070 Total100 Rum and Tourists in Guadeloupe Hospital of Pointre-à-Pitre, Haiti Conclusion: Completely the opposite of the previous slide

22. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation The CONTROLS should be at risk for the disease as the CASES In case-control studies

23. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Pork and Trichinellosis Melun Prison, France, 1985* Eating Pork Cases Trichinellosis Controls (Maghrebins) Odds Ratio No.% expNo.% exp Yes1890%210% 81 [10 – 640] No218 Total20 Conclusion: The consumption of pork multiplies the risk of getting Trichinellosis by 81. * Ancelle, T., et al. Two outbreaks of Trichinosis caused by Horsemeat in France in 1985. American Journal of Epidemiology Vol. 127, No. 6: 1302-1311

24. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Pork and Trichinellosis Melun Prison, 1985 Eating Pork Cases Trichinellosis Controls (prisoners same race as cases) Odds Ratio No.% expNo.% exp Yes1890%1785% 1.6 [0.2 – 11] No23 Total20 Conclusion: Pork is not a risk factor The maghrebins did not have the same chance to be exposed to the risk factor as the cases

25. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Criteria for the selection of a reference group in a cohort study The non exposed subjects need to be selected from the same population as those exposed same «UNIVERSE» as exposed Otherwise: SELECTION BIAS which cannot be controlled at the time of analysis

26. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Criteria for the selection of a reference group in a cohort study The UNEXPOSED subjects should have: a.The same possibility to be followed-up as the exposed b.Be defined with the same criteria of Time, Place and Person c.The same probability to develop the disease AS THE EXPOSED

27. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Vaccination against Haemophilus influenzae in Alaska VaccinatedCases of Otitis H. influenzae Healthy subjects Attack Rate (AR) Relative Risk (RR) Yes (inuits)307030%1.5 [0.9 – 2.5] No (whites)208020% Conclusion: The children immunized have a greater risk (1.5 times) of getting H. Influenzae otitis

28. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Vaccination against Haemophilus influenzae in Alaska VaccinatedCases of Otitis H. influenzae Healthy subjects Attack Rate (AR) Relative Risk (RR) Yes (inuits)307030%0.37 [0.3 – 0.5] No (inuits)802080% Conclusion: The vaccination has a protective effect The children from the white population are much better nourished, much better treated and have a lower risk to become sick compared to the inuits

29. SEARO – CSR Training on Outbreak Investigation WHO to choose? WHERE to choose? Selecting comparison groups

30. SEARO – CSR Training on Outbreak Investigation What group to select in a case-control study? Other patients in the ward outpatient laboratory Specific group family members friends neighbors colleagues Community, general population

31. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Hospitalized patients as controls Advantages –Easy identification Time Cost –Motivation +++ –Few non-respondents –Same demographic and social origin as the cases Disadvantages –May not be representative of the whole population e.g., smoke more, drink more, etc. –The disease of the controls has the risk to be associated to the risk factor being studied

32. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation CASESCONTROLS a Smokers b Lung cancer Cardiovascular pathology c Non- Smokers d

33. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Community sample of population selected at random Advantages –The highest level of comparison –Controls are healthy Disadvantages –Difficult to obtainTime ++ Cost + –Motivation -- –No respondents ++

34. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Specific groups selected close to the cases: family members, neighbors, friends colleagues Advantages –Healthy subjects –More representative –Easy to find Time -- Cost -- –Motivation ++ –Few non-respondents Disadvantages –Too similar to the cases –Percent of exposure very close to the one of the cases Risk of overmatching

35. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation What kind of reference group to select in a cohort study? 1.Retrospective cohort –Universe closed, pre-defined –The whole population, sample –School, prison, ship, airplane, etc

36. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation What kind of reference group to select in a cohort study? 2.Prospective cohort –General population, sample –Social-professional group a.External cohort not exposed e.g., cotton labors/ asbestos b.Internal cohort with different levels of exposure e.g., uranium mine

37. SEARO – CSR Training on Outbreak Investigation How many? Selecting comparison groups

38. SEARO – CSR Training on Outbreak Investigation Relation between number of controls by cases and power of the study FactorCasesControlsORCI 95% X1050% 420% 40.8 – 20.9 No X10 16 Total20 One (1) control/ case FactorCasesControlsORCI 95% X1050% 820% 41.1 – 15.3 No X10 32 Total20 40 Two (2) control/ case

39. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Relation between number of controls by cases and power of the study Con/ case casecontrolsORCI 95% 120 4 0.8 – 20.9 220404 1.1 – 15.3 320604 1.2 – 13.6 420804 1.3 – 12.8 5201004 1.3 – 12.3

40. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation Relation between number of controls by cases and power of the study

41. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation CONCLUSION 1.A control is as important as the case 2.The “right” control is much more difficult to select than the case 3.An error in the selection of controls can have much more consequences in the validity of the study BIAS

42. Selecting comparison groups SEARO – CSR Training on Outbreak Investigation