1. Case Control Study Dr. Ashry Gad Mohamed MB, ChB, MPH, Dr.P.H. Prof. Of Epidemiology

2. Descriptive Analytical Case report Case series Cross section Ecological Case control Cohort Observational Experimental Study Designs Animal Experiment Human Intervention Clinical trial

3. Case control study - Observational study - Analytical study - Unit of observation and analysis: individual

4. Target population Cases Controls Exposed Not exposed Exposed Not exposed

5. Selection of cases Definition of cases is first task of the investigator in case control studies. The definition may be Simple e.g. cleft lip. Complex e. g. hypertension A variety of methods may be used alone or in combination to establish the presence of the disease.

6. It is often recommended to choose incident (newly diagnosed) cases 1-Exposure is recent and easy to recall. 2-The etiological milieu of incident cases is relatively homogeneous. 3-To avoid the possibility that in long term survivors the exposure may occur after the onset of the disease.

7. Sources of cases Cases admitted to or discharged from a hospital, clinic or any health care facility. Cases reported or diagnosed during a survey or surveillance system Incident cases in a going cohort study Death certificates with recorded cause of death. Employment records. Institutional records

8. Selection of controls It is crucial to set up control group (s) of people who do not have the specified disease condition in order to obtain estimates of the frequency of the attribute or risk factor for comparison with its frequency among cases.

9. Methods for selecting controls A-Through matching for relevant criteria Pair-wise matching For each case, a specific comparison subject (s) with similar values of the matching factors is (are) selected. Frequency matching The overall distribution of matching factors parallels the distribution in case group.

10. Advantages of matching In some situations there are natural partners for comparison e.g. identical twins. Matching may account for extraneous variables Matching may improve the statistical precision of study results

11. Disadvantages of matching when there are a large number of matching variables, it may be difficult to find suitable controls. Unmatched cases and controls cannot be analyzed. Overmatching may lead to an underestimation of study effect. Matching may increase the costs of the study.

12. B-Through random or stratified sampling. No restriction. No matching. Allow confounders to act.

13. Sources of control 1-Hospital controls Advantages of hospital controls Subjects are easily accessible. Patients usually have time to participate. Patients are often motivated to cooperate with investigators. Controls and cases may be drawn from similar social and geographical environment. Differential recalls of prior exposure is likely to be minimized.

14. Disadvantages of hospital controls Differential hospitalization patterns may introduce selection bias. Difficult to blind disease status from cases and controls. An underestimate of the study effect may be obtained if control’s disease is etiologically similar to cases’ disease.

15. 2-Community controls A probability sample of a defined population, if cases do belong to that population or a sample of relatives or associates of cases or neighborhood controls. Advantages of community controls Reduction of selection bias. Generalization of study results is more valid. May provide convenient control of extraneous variables.

16. Disadvantages of community controls Time and money consuming. May suffer low participation rate. Cases and control may exhibit differential recall of prior exposures.

17. How many controls per case? Ideal : 1 : 1 In case of Rare Cases Increase Controls. 1 : 4 More than 4 controls add little to study power 4 91.5 5 92.4 6 93.0 7 93.4

18. Collection of data Self reported (self administered questionnaire) or by interview. Revision of records (medical or occupational). Biological markers (lab.records).

19. Quality control in case control study. Standardization of methods and circumstances of data collection. Observers are better to collect the data blindly. Observations should be objective.

20. Analysis of case control study Because population at risk is absent we can not calculate relative risk as it is based on incidence, however it can be estimated by means of odds ratio (OR) which is the ratio of odds of exposure among diseased to the odds of exposure among controls.

21. Exposure for each case and control Disease status Cases Controls Exposure Yes NO BA DC B+DA+C

22. Calculating Odds (number exposed  number unexposed) Odds (Cases) = A/C Odds (controls) = B/D Odds Ratio = (A/C) / (B/D) = AD/BC

23. OR>1 OR<1OR=1 Odds of exposure for cases are greater than the odds of exposure for controls Odds of exposure for cases are less than the odds of exposure for controls Odds of exposure are equal among cases and controls Odds comparison between cases and controls Exposure increases disease risk (Risk factor) Exposure reduces disease risk (Protective factor) Particular exposure is not a risk factor Exposure as a risk factor for the disease?

24. Disease Status No CHD (Controls) CHD (Cases) 176112 22488 400200 Smoker Non smoker Total Odds Ratio= AD BC = 112 X 224 176 X 88 = 1.62 Example

25. Odds Ratio = 1.62 The risk of CHD is 62% higher among smokers 95% CI = 1.13 – 2.31 Sig.

26. Advantages of case control study Efficient sampling of rare diseases. Rapid evaluation of chronic diseases. Requires less money and personnel Little problem of attrition

27. Disadvantages of case control study Not practical for rare exposures. Historical information often can not be validated. Relevant cofactors may be difficult to control. Temporality may be obscured. Selective survival may bias the comparison.