1. Case-Control Studies(Retrospective Studies)

2. What is a cohort?

3. Cohort 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 summarystatistics describe the experience of real individuals rather than mathematical abstractions, e.g., a cohort study or a cohort life table.

4. WERE EXPOSED WERE NOT EXPOSED WERE EXPOSED WERE NOT EXPOSED HAVE THE DISEASE 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 StudiesDisadvantages • 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 StudiesAdvantages • 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