Case-Control Studies

1. Case-Control Studies

2. Case-control studies 2 “TROHOC” STUDIES This disparaging term was given to case-control studies because their logic seemed backwards (trohoc is ?? spelled backwards) and they seemed more prone to bias than other designs. No basis for this derogation. Case-control studies are a logical extension of cohort studies and an efficient way to learn about associations.

3. Case-control studies 3 Introduction Hypothesis: Pesticide exposure increases the risk of breast cancer. Consider a hypothetical prospective cohort study of 89,949 women aged 34-59; 1,439 breast cancer cases identified over 8 years of follow-up Blood drawn on all 89,949 at beginning of follow-up and frozen Exposure: Level of pesticides (e.g. DDE) in blood characterized as high or low

4. Introduction Results

5. Case-control studies 5 Introduction Practical Problem: Quantifying pesticide levels in the blood is very expensive -- it's not practical to analyze all 89,949 blood samples To be efficient, analyze blood on all cases (N=1,439) but just take a sample of the women who did not get breast cancer, say two times as many cases (N=2,878)

6. Case-control studies 6 Introduction

7. Case-control studies 7

8. Case-control studies 8 When is it desirable to conduct a case-control study? When exposure data are expensive or difficult to obtain - Ex: Pesticide study described earlier When disease has long induction and latent period - Ex: Cancer, cardiovascular disease

9. Case-control studies 9 When is it desirable to conduct a case-control study? When the disease is rare Ex: Studying risk factors for birth defects When little is known about the disease Ex. Early studies of AIDS When underlying population is dynamic Ex: Studying breast cancer on Cape Cod

10. Cases Criteria for case definition should lead to accurate classification of disease Efficient and accurate sources should be used to identify cases: existing registries, hospitals What do the cases give you? Think of the standard 2 X 2 table:

11. Case-control studies 11

12. Case-control studies 12 Where do you get the information for the denominators in a case control study? THE CONTROLS. A case-control study can be considered a more efficient form of a cohort study. Cases are the same as those that would be included in a cohort study. Controls provide a fast and inexpensive means of obtaining the exposure experience in the population that gave rise to the cases.

13. Case-control studies 13 Controls Definition: A sample of the source population that gave rise to the cases. Purpose: To estimate the exposure distribution in the source population that produced the cases.

14. Case-control studies 14 Selecting Controls General population controls Most often used when cases are selected from a defined geographic population Sources: random digit dialing, residence lists, drivers’ license records Example: Upper Cape Cancer Study

15. Case-control studies 15 Selecting Controls Advantages of general population controls: Because of selection process, investigator is usually assured that they come from the same base population as the cases.

16. Case-control studies 16 Selecting Controls Disadvantages of general population controls Time consuming, expensive, hard to contact and get cooperation; may remember exposures differently than cases

17. Case-control studies 17 Selecting Controls Hospital controls Used most often when cases are selected from a hospital population

18. Case-control studies 18 Advantages of hospital controls Same selection factors that led cases to hospital led controls to hospital Easily identifiable and accessible (so less expensive than population-based controls) Accuracy of exposure recall comparable to that of cases since controls are also sick More willing to participate than population-based controls

19. Case-control studies 19 Disadvantages of hospital controls Since hospital based controls are ill, they may not accurately represent the exposure history in the population that produced the cases Hospital catchment areas may be different for different diseases

20. Case-control studies 20 What illnesses make good hospital controls? Those illnesses that have no relation to the risk factor(s) under study Example: Should respiratory diseases be used as controls for a study of smoking and myocardial infarction? Do they represent the distribution of smoking in the entire population that gave rise to the cases of MI?

21. Case-control studies 21 Selecting Controls Special control groups like friends, spouses, siblings, and deceased individuals. These special controls are rarely used. Some cases are not able to nominate controls because they have few appropriate friends, are widowed, or are only or adopted children. Dead controls are tricky to use because they are more likely than living controls to smoke and drink.

22. Case-control studies 22 Sampling a cohort population for controls: nested case-control study 1. Sample the population at risk at the start of the observation period *-------------------------------------------------------------------------* Start FU End FU ^^

23. Case-control studies 23 Sampling a cohort population for controls: nested case-control study 2. Sample population at risk as cases develop *-------------------------------------------------------------------------* Start FU End FU ^ ^ ^ ^^^ ^

24. Case-control studies 24 Sampling a cohort population for controls: nested case-control study 3. Sample survivors at the end of the observation period *------------------------------------------------------------------------* Start FU End FU ^^

25. Case-control studies 25 Recall nested case-control study on pesticides and breast cancer Hypothetical cohort study of 89,949 women; 1,439 breast cancer cases identified over 8 years of follow-up Blood drawn on all 89,949 at beginning of follow-up and frozen Exposure: Level of pesticides (e.g. DDE) in blood characterized as high or low

26. Case-control studies 26 Recall nested case-control study on pesticides and breast cancer

27. Case-control studies 27 Important consideration for selecting controls: “the would criterion” Review: Controls are a sample of the source population that gave rise to the cases. Purpose is to provide information on the exposure distribution in the source population. When selecting a control group consider the “WOULD CRITERION”: If a member of the control group actually had the disease under study WOULD he/she end up as a case in your study? Answer should be YES. Example: Spontaneous abortion study

29. Case-control studies 29 Analysis of case-control studies Definition of odds: the ratio of the probability of an event occurring to that of it not occurring Example: Probability of getting a heads on one coin toss = ½ = .50. Probability of NOT getting a heads on one coin toss = ½ = .50. Odds of getting a heads on a coin toss = .5/.5 = 1:1

30. Case-control studies 30 Analysis of case-control studies Two possible outcomes for an exposed person: case or not Odds=a/b Two possible outcomes for an unexposed person: case or not Odds=c/d Odds ratio = odds of an exposed person being a case = a/b = ad/bc odds of unexposed person being a case c/d Just like the incidence rate ratio and cumulative incidence ratio, the odds ratio is a ratio measure of association.

31. Analysis of case-control studies EXAMPLE: Case control study of spontaneous abortion and prior induced abortion (OUTCOME = spontaneous abortion; EXPOSURE = prior induced abortion)

32. Case-control studies 32 Analysis of case-control studies Odds of being a case among the exposed = 42/247 (a/b) Odds of being a case among the unexposed = 107/825 (c/d) Odds ratio = [(a/b) / (c/d)] = [(42/247) / (107/825)] = 1.3 Women with a history of induced abortion had a 30% increased risk of having a spontaneous abortion compared to women who never had an induced abortion.

33. Case-control studies 33 Strengths of case-control studies Efficient for rare diseases and diseases with long induction and latent period. Can evaluate many risk factors for the same disease. So, good for diseases about which little is known.

34. Case-control studies 34 Weaknesses of case-control studies Inefficient for rare exposures Vulnerable to bias because of retrospective nature of study May have poor information on exposure because retrospective Difficult to infer temporal relationship between exposure and disease How do these strengths and weaknesses compare to cohort studies?