Case Control Studies in Epidemiology

1. Case-Control Studies Principles of Epidemiology Lecture 10 Dona Schneider , PhD, MPH, FACE

2. PHCO 0502 Principles of Epidemiology (Schneider) Case-Control Studies Type of analytic study Unit of observation and analysis: Individual (not group)

3. PHCO 0502 Principles of Epidemiology (Schneider) Case-Control Studies Case-control studies are the most frequently undertaken analytical epidemiological studies They are 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

4. PHCO 0502 Principles of Epidemiology (Schneider) Design At baseline: Selection of cases (disease) and controls (no disease) based on disease status Exposure status is unknown Retrospective design lacks temporality !

5. PHCO 0502 Principles of Epidemiology (Schneider) Case Control Study Design Target Population Diseased (Cases) Not Diseased (Controls) Exposed Not Exposed Exposed Not Exposed

6. PHCO 0502 Principles of Epidemiology (Schneider) Selecting Cases Select cases after the diagnostic criteria and definition of the disease is clearly established Study cases should be representative of all cases

7. PHCO 0502 Principles of Epidemiology (Schneider) Selecting Cases (cont.) The study need not include all cases in the population Cases may be located from hospitals, clinics, disease registries, screenings, etc.

8. PHCO 0502 Principles of Epidemiology (Schneider) Selecting Cases (cont.) 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

9. PHCO 0502 Principles of Epidemiology (Schneider) 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

10. PHCO 0502 Principles of Epidemiology (Schneider) Selecting Controls (cont.) Controls estimate the exposure rate to be expected in cases if there were no association between exposure and disease

11. PHCO 0502 Principles of Epidemiology (Schneider) Selecting Controls (cont.) Multiple controls can be used to help add statistical power when cases are unduly 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

12. 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 CONTROLS CASES

13. PHCO 0502 Principles of Epidemiology (Schneider) 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)

14. PHCO 0502 Principles of Epidemiology (Schneider) Assessing Exposure (cont.) 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

15. PHCO 0502 Principles of Epidemiology (Schneider) 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

16. PHCO 0502 Principles of Epidemiology (Schneider) 400 200 Total 224 88 Non- smoker 176 112 Smoker Exposure Status No CHD (Controls) CHD cases (Cases) Disease Status Calculating the Odds Ratio Odds Ratio = = AD BC 112 x 224 176 x 88 = 1.62

17. PHCO 0502 Principles of Epidemiology (Schneider) Exposure increases disease risk (Risk factor) Particular exposure is not a risk 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>1 OR=1 OR<1

18. PHCO 0502 Principles of Epidemiology (Schneider) Interpreting the Odds Ratio or The odds of exposure for cases are 1.62 times the odds of exposure for controls.

19. PHCO 0502 Principles of Epidemiology (Schneider) Interpreting the Odds Ratio Those with CHD are 62% more likely to be smokers than those without CHD Those with CHD are 1.62 times more likely to be smokers than those without CHD or

20. PHCO 0502 Principles of Epidemiology (Schneider) 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 Information on potentially important confounding variables may not be available either from records or the study subjects memories

21. PHCO 0502 Principles of Epidemiology (Schneider) Possible Sources of Bias and Error (cont.) 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

22. PHCO 0502 Principles of Epidemiology (Schneider) Possible Sources of Bias and Error (cont.) 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

23. Nested Case-Control Study Initial Data and/or Serum, Urine, or Other Specimens Obtained Subgroup Selected as Controls Cases CASE-CONTROL STUDY Population Develop Disease Do Not Develop Disease Years

24. ORs, P-Values and 95% CIs for Case- Control Study with 3 Different Sample Sizes Sample Size Parameter Computed n=20 n=50 n=500 OR 2.0 2.0 2.0 p-value 0.500 0.200 0.001 95% CIs 0.5, 7.7 0.9, 4.7 1.5, 2.6

25. PHCO 0502 Principles of Epidemiology (Schneider) Advantages of Case-Control Studies Quick and easy to complete, cost effective Most efficient design for rare diseases Usually requires a smaller study population than a cohort study

26. PHCO 0502 Principles of Epidemiology (Schneider) Uncertainty of exposure-disease time relationship Inability to provide a direct estimate of risk Not efficient for studying rare exposures Subject to biases (recall & selection bias) Disadvantages of Case-Control Studies