1. Case-Control Studies (Retrospective Studies)

2. What is a cohort?

3. A group of individuals who share a common characteristic, e.g. all of the individuals born in one year (a birth cohort) or a group of individuals entered in a prospective study or clinical trial. The term always carries a connotation that: individuals are observed over a period of time and that summary statistics describe the experience of real individuals rather than mathematical abstractions, e.g., a cohort study or a cohort life table. Cohort

4. WERE EXPOSED HAVE THE DISEASE WERE NOT EXPOSED WERE EXPOSED WERE NOT EXPOSED DO NOT HAVE THE DISEASE “CASES”“CONTROLS” Design of a Case-Control Study

5. When is a Case-Control Study Warranted? Useful as a first step when searching for an adverse health outcome Useful when disease being investigated is rare

6. Retrospective Studies Disadvantages information not easily available difficult to validate quality of survey bias in selection possible misconception of factors causing disease recall may be flawed

7. Retrospective Studies Advantages inexpensive easy requires fewer subjects useful for rate of disease or diseases with long latency periods can check for more than one risk factor useful for drug induced illness

8. Selection of Cases and Controls Variety of sources avoid bias Choose incidence or prevalent cases? Controls must represent general population can be hospitalized or non-hospitalized

9. Problems in Control Selection Controls must be carefully selected otherwise, results may be confounded Coffee and pancreatic cancer study Apparent dose-response relationship between coffee consumption and pancreatic cancer Cases = confirmed diagnosis of pancreatic cancer Controls = from all patients hospitalized at same time and by same attending physicians as cases Difficult to know if disease caused by coffee drinking or some factor closely related to coffee drinking (confounding factor)

10. Problems in Control Selection (cont.) Coffee and pancreatic cancer study (cont.) One such confounding factor was cigarette smoking --- most smokers are coffee drinkers --- and cigarette smoking is a known risk factor for pancreatic cancer To rule out effect of smoking, the data was stratified for smoking history and reanalyzed Current smokers Never smokers and the dose-response relationship with coffee consumption held for both groups

11. Problems in Control Selection (cont.) Coffee and pancreatic cancer study (cont.) Objective in control group is to have level of coffee consumption approximate that in general population --- and thus, that cases demonstrate excessive coffee consumption Problem was that attending physicians referring both cases and controls were gastroenterologists Controls may have reduced coffee consumption because of their gastrointestinal problems, e.g., esophagitis or peptic ulcer disease Controls coffee intake may be abnormally low compared to general population

12. Problems in Control Selection (cont.) Coffee and pancreatic cancer study (cont.) Therefore, the dose-response relationship differences between cases and controls may not be due to cases drinking more coffee, but rather, controls drinking less coffee than expected Conclusion: when difference in exposure is observed between cases and controls, controls must not have a level of exposure that is significantly higher or lower than the general population

13. Matching Concern that cases and controls may differ in characteristics or exposures other than that observed in the study To overcome this problem, we can match cases in controls in regard to potential factors of concern Matching selects controls that are similar to cases in characteristics such as age, race sex, socioeconomic status, occupation, etc.

14. Matching Group matching (frequency matching) proportion of controls with a given characteristic (variable) is identical to proportion of cases with the same characteristic Individual matching (matched pairs) for each case, a control is selected who is similar to the case for a given variable(s)

15. Problems with Matching Practical problems attempting to match too many characteristics (variables) Conceptual problems once controls are matched to cases according to a given characteristic (variable), that characteristic can not be studied, because matching artificially establishes identical proportions for that characteristic among cases and controls

16. Recall (Interview) Problems Limitations in recall Recall bias One group (e.g., mothers with child with birth defect) may clearly remember (recall) an event (e.g., mild respiratory infection) Other group (e.g., mothers with healthy child) may not recall any such event

17. Use of Multiple Controls Same type 2, 3, or even 4 controls for each case (i.e., increasing the ratio of matched controls to cases), increases the power of the study Different types where there is concern that the controls may differ in some way from what is “expected” in the general population