1. Case Control Studies Dr Amna Rehana Siddiqui Department of Family and Community Medicine October 17, 2010

2. Objectives 1.To understand the basic design features of case control study 2. To list the advantages and disadvantages of case control studies 3.To calculate the odds ratio as a measure of association in case control studies

3. Types of Study Designs DesignStudy Type Case reportObservational - Descriptive Case seriesObservational - Descriptive Cross sectionalObservational - Descriptive/Analytic Case controlObservational - Analytic CohortObservational - Analytic Clinical trialExperimental - Analytic 3

4. Basic Question in Analytic Epidemiology Are exposure and disease linked? Direction of inquiry in case control study Exposure Risks e.g smoking Disease e.g. Myocardial Infarction (MI)

5. Design of Case Control Study The investigator selects cases with the disease (MI) and appropriate controls without the disease and obtains data regarding past exposure to possible etiologic factors (smoking & other ) in both groups then compares the frequency of exposure of the two groups.

6. Proportion of smoking in cases and controls controls cases Arrows show the extent of smoking among cases and controls Smoking

7. Proportion of exposure in cases and controls controls cases Arrows show the extent of factor among cases and controls Saturated fat intake Saturated fat intake

8. Study Design: Case Control -Exposure data collected retrospectively -Feasible where disease outcomes are rare -Case ascertainment system is present -More than one exposure can be studied -Control selection from the source population -Multiple controls possible; e.g. 2 controls/case) -Efficient in Cost and time

9. Study Design Cases Controls Myocardial infarction OTHER ILLNESS/ Free of any illness EXPOSED SMOKED NOT EXPOSED NEVER SMOKED EXPOSED SMOKED NOT EXPOSED NEVER SMOKED Proportions of exposed and unexposed in cases and controls

10. Example MI Cases Controls Smokers110150 Never smokers 90250 Total200400 % smokers 55% 37.5% If Cancer is related to smoking then more cases than controls would be smokers

11. Selection of Cases Source of cases / hospital based / other Incident or prevalent Representative Homogenous criteria for case definition Certainty of diagnosis

12. Selection of cases Source population Hospital Physicians clinic Registries Community Risk factors could be unique to any one particular source especially from a hospital/clinic

13. Selection of Cases Incident cases; could take long time to wait to identify cases Early deaths before or after diagnosis may prevent determination of risk factors Prevalent cases; large pool of cases survival bias, change in exposures

14. Selection of Controls Highly important for valid results Whether; Controls be similar to cases in all aspects except the occurrence of disease OR Representative of all persons without the disease in population from which the cases have arisen

15. Selection of Controls Sources of Controls Probability sample of a total population Neighborhood controls Sibling/ best friend control Hospitalized controls

16. Measures of association Odds ratio: A ratio of one odds to another Odds of exposure in a case = probability of exposure (smoking) probability of no exposure (not smoking) Odds of exposure in a control = probability for exposure (smoking) probability for no exposure (not smoking)

17. Odds Ratio If any event takes place with a probability ‘p’ then the odds in the favor of event are ‘p/1-p’ to 1 If p=2/3 then the odds of event are 2/3 / 1/3 = 2 to1 =Prob (exposure|cases)/[1-prob(exposure|cases)] Prob(expsoure|controls)/[1-prob(exposure|controls)] Odds Ratio is equivalent to Relative Risk (RR), only when the disease is rare. As incidence is not derived in case control studies then RR can not be derived from these studies.

18. Calculating Odds Ratio MI Cases Controls Smokers110150 Never smokers 90250 Total200400 % smokers 55% 37.5% Odds of exposure in cases=0.55/1-0.55 = 1.22 Odds of smoking in controls=0.38/ 1-0.38 = 0.61 Odds Ratio= 1.22/0.61 = 2 Interpretation: Odds of smoking in cases are two times more than the odds of smoking in controls

19. Calculating Odds Ratio MI Cases Controls Smokers110150 Never smokers 90250 Total200400 % smokers 55% 37.5% Odds of exposure in cases=0.55/1-0.55 = 1.22 Odds of smoking in controls=0.38/ 1-0.38 = 0.61 Odds Ratio= 1.22/0.61 = 2 Interpretation: Odds of smoking in cases are two times more than the odds of smoking in controls

20. ODDS RATIO Odds ratio ~ cross product ratio CasesControls Exposed 110 150 Not exposed 90 250 OR= a/b = 110/90 = ad/bc = [(110*250)/(150*90)] = 27500 = 2 c/d 150/250 13500 Odds of exposure in cases : two times compared to controls

21. Interpretation of (OR) odds ratio > 1 means the exposure is a risk factor. = 1 means the exposure is not associated with the disease. < 1 means the exposure is protective

22. Factors considered in Design Selection bias in selection of controls if selection is related to exposure in any way; bias will occur Recall bias; cases tend to recall more than controls; a high OR could be a biased estimate Interviewer bias; interviewers would keenly interview cases to obtain information compared to controls Matching of cases and controls can be done on certain variables; e,g. age, gender, location, ethnicity Multiple controls increase the power of study as usually done on rare diseases and few cases are available during a specified time e.g. any cancer.

23. Advantages and Disadvantages Advantages Efficient in time & cost Etiology of long latency period can be studied e.g. chronic diseases Multiple exposures could be studied Disadvantages Errors in Case definitions and in characterization of exposure Disease and exposure have already occurred and potential for bias remains - selection - recall - interviewer

24. Example of Case Control Study Toxic Shock Syndrome Thirty-five patients were matched for age and menstruation to 105 controls: 34 of 35 cases (versus 80 of 105 controls) used tampons during every menstrual period; nine of 35 cases (versus 64 of 105 controls) practiced contraception. Make a two by two tables and Calculate Odds Ratios