1. CHP400: Community Health Program- lI Research Methodology STUDY DESIGNS Observational / Analytical Studies Case Control Studies Present: Disease Past: Exposure Cross - section Cohort Case - control Present: Disease & Exposure Present: Exposure Future: Disease nbmmb Time is Key 

2. Content Definition and importance of Case - Control Studies Design Selecting Cases Selecting Controls Assessing Exposure: Odds Ratio (OR) Advantages Disadvantages

3. STUDY DESIGNS Experimental Observational Animal Experiment Human Intervention Clinical trial Analytical Case control Descriptive Case report Case series Cross section Ecological Cohort Research Methodology Case Control Studies

4. STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies Definition: It is a type of observational analytic epidemiologic investigation in which subjects are selected on the basis of whether they do or do not have the particular disease under study.

5. STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies Importance: The most frequently undertaken analytical epidemiological studies The only practical approach for identifying risk factors for rare diseases They are best suited to the study of diseases for which medical care is sought, such as cancers or hip fracture

6. Design : At baseline: Selection of cases (disease) and controls (no disease) based on disease status Exposure status is unknown Retrospective design – lacks temporality! STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

7. Design : Target Population Diseased (Cases) Not Diseased (Controls) Exposed Not Exposed Exposed Not Exposed STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

8. Design : YES NO TIME OUTCOME/DISEASE EXPOSURE ? ? STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies 

9. Selecting Cases: Select cases after the diagnostic criteria and definition of the disease is clearly established Selected cases should be representative of all cases STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

10. The study need not include all cases in the population Cases may be selected from hospitals, clinics, disease registries, screenings, etc. STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies Selecting Cases:

11. Incident cases are preferable to prevalent cases for reducing (a) recall bias and (b) over-representation of cases of long duration The most desirable way to obtain cases is to include all incident cases in a defined population over a specified period of time STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

12. Selecting Controls: Controls should come from the same population at risk for the disease as the cases Controls should be representative of the target population STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

13. Selecting Controls: Multiple controls can be used to add statistical power when cases are difficult to obtain Using more than one control group lends credibility to the results More than 3 controls for a case is usually not cost-efficient STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

14. Selecting Controls: Sources of cases and controls Spouses, siblings or associates of cases Any of the above methods Sample of patients in the same hospital who do not have the disease All cases diagnosed in a single hospital Sample of patients in all hospitals who do not have the disease All cases diagnosed in all hospitals Non-cases in a sample of the population All cases diagnosed in a sample of the population Sample of general population All cases diagnosed in the community CONTROLSCASES

15. Assessing Exposure: Exposure is usually an estimate unless past measurements are available It has to be assumed that the exposure incurred at the time the disease process began (this may not be valid) STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

16. Assessing Exposure: Exposure estimates are subject to recall bias and interviewer bias Some protection may be afforded by blinding interviewers and carefully phrasing interview questions Potential confounders need to be accurately assessed in order to be controlled in the analysis STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

17. Analysis: Odds Ratio (OR) A ratio that measures the odds of exposure for cases compared to controls Odds of exposure = number exposed  number unexposed OR Numerator: Odds of exposure for cases OR Denominator: Odds of exposure for controls STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

18. Analysis: Odds Ratio (OR) 400200Total 22488 Non- smoker 176112 Smoker Exposure Status No CHD (Controls) CHD cases (Cases) Disease Status Odds Ratio == ad bc 112 x 224 176 x 88 = 1.62 a b cd STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies a c b d =

19. Exposure increases disease risk (Risk factor) Exposure is not a risk factor nor a protective factor Exposure reduces disease risk (Protective factor) Exposure as a risk factor for the disease? Odds of exposure for cases are greater than the odds of exposure for controls Odds of exposure are equal among cases and controls Odds of exposure for cases are less than the odds of exposure for controls Odds comparison between cases and controls OR>1OR=1OR<1 Interpreting the Odds Ratio (e.g)

20. Analysis: Odds Ratio (OR) The odds of exposure for cases are 1.62 times the odds of exposure for controls. Those with CHD are 1.62 times more likely to be smokers than those without CHD Interpreting the Odds Ratio STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

21. Possible Sources of Bias and Error Information on the potential risk factor (exposure) may not be available: - either from records - or the study subjects’ memories STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

22. Cases may search for a cause for their disease and thereby be more likely to report an exposure than controls (recall bias) The investigator may be unable to determine with certainty whether the suspected agent caused the disease or whether the occurrence of the disease caused the person to be exposed to the agent STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies cont.

23. Identifying and assembling a case group representative of all cases may be unduly difficult Identifying and assembling an appropriate control group may be unduly difficult STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies cont.

24. Analysis: Odds Ratio (OR) ORs, P-Values and 95% CIs for Case-Control Study with 3 Different Sample Sizes Sample Size Parameter Computed n=20n=50n=500 OR2.0 p-value0.5000.2000.001 95% CIs0.5, 7.70.9, 4.71.5, 2.6 STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

25. Advantages: Quick and easy to complete, cost effective Most efficient design for rare diseases Usually requires a smaller study population than a cohort study Several exposures can be studied. STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

26. Disadvantages: Uncertainty of exposure-disease time relationship Inability to provide a direct estimate of risk Not suitable for studying rare exposures Subject to biases (recall & selection bias) STUDY DESIGNS Research Methodology Observational / Analytical Studies Case - Control Studies

27. Summary Case-control study: Observational, analytic study. Most frequently undertaken analytical studies Quick and easy to complete, cost effective Most efficient design for rare diseases Subjects are selected on the basis of presence or absence disease under study Odds Ratio (OR)