1. CASE-CONTROL STUDIES Ass.Prof. Dr Faris Al-Lami MB,ChB MSc PhD FFPH
Dept. of Community Medicine/ College of Medicine/ Baghdad University

2. CASE-CONTROL STUDIES It is a type of observational analytic studies.
Study subjects are selected on the basis of whether they do (cases) or do not have (controls) the outcome under study.
The groups then compared for the proportion of having a history of exposure or characteristic of interest.

3. CASE-CONTROL STUDIES Disease Exposure a +c b+d Total Present Absent a
c+d
a +c
b+d N

4. Case-Control Studies – Timing
Exposure
Disease ?
Exposed
Unexposed
Yes (case)
No (control)
In a typical case-control study, the investigator begins the investigation after disease has occurred. The investigator enrolls cases (who have the disease), a group of people who do not have the disease (“controls”). The investigator then collects information about prior exposures from the cases and controls. In this way, case-control studies begin with disease and move “backwards” to exposure.
Investigator

5. Strengths: Suitable for diseases of long latency period
Quick and inexpensive (as compared to other analytic studies)
3. Suitable for rare diseases
4. Can examine multiple etiologic factors for a single outcome.
5. Requires fewer subjects at entry
6. Few ethical problems

6. Limitations- Usually cannot measure disease risk
Relies on recall or records for information on past exposures (potential recall bias)
May be difficult to determine that ‘cause’ preceded ‘effect’ (Temporal relationship)
Unsuitable for rare exposures
Selection bias
Information Bias
However, case-control studies have some disadvantages, too.
Usually you cannot measure disease risk.
Determination, selection, and enrollment of appropriate control group may be difficult (potential selection bias)
Case-control studies rely on participants’ recall or records for info on past exposures (potential recall bias)
Because both exposure and disease have already occurred, sometimes it can be difficult to determine that ‘cause’ preceded ‘effect’
Case-control studies are good for rare diseases, but they are not good for rare exposures. For a rare exposure, use s a cohort study.
And finally, case-control studies are less familiar to non-epidemiologists. At first glance, they seem kind of backwards. But most of the time they work!

7. Definition of Cases The definition of the cases should depend on:
1. Homogenous disease entity
2. Strict diagnostic criteria
Depending on certainty of diagnosis, and amount of criteria one can classify the diagnosis into definite, probable, and possible

8. Sources of Selection of the cases:
1. Hospital-based case control studies
The cases will be identified from the hospitals, or other health care facilities. These are common, relatively easy, and inexpensive.

9. Sources of Selection of the cases:
2. Population based case-control studies.
It involves locating and obtaining data from all affected individuals or a random sample from a defined population.

10. Types of controls:
1. Hospital control: consist of patients at the same hospital with conditions other than the disease under study.

11. Hospital control: Advantages:
Easily identified insufficient number, with minimal cost, and effort.
May come from the same catchments area
More willing to know about previous exposures than healthy people (less recall bias).
They are exposed to the same factors that make them select this particular hospital (less selection Bias)
More willing to cooperate than healthy people, (less non-response).

12. 1. Hospital control: Disadvantage
They are by definition ill and not healthy.
Hospitalized controls differ from general population
Control disease may be linked to exposure
The patient in the control should not have a disease that is related to the same risk factors of the disease under study (CA-lung, MI, Smoking)

13. 2. General population control
Used when the cases are chosen from the general population, and if the hospital control is not desirable or feasible.

14. 2. General population control Difficulties:
More costly and time consuming
Population lists are not always available
Difficult to contact healthy people with busy work

15. 2. General population control Difficulties:
The quality of information may differ from cases and control (more recall bias)
Less motivated to participate (more non-response)
Those who accept to participate may systematically differ from those who refused (volunteer Bias).

16. 3. Special Group Control Friends, relatives, neighbours of the cases .
They have the advantage of the general population control, in that they are healthy, but they are more willing to cooperate, and offer a degree of control on certain confounding factors as ethnic background, socioeconomic status, or environment

17. No. of Controls
When the number of cases and controls is large and the cost of obtaining them is similar we choose one control for every case (1:1 ratio), but if the number of cases is small then the number of controls can be increased and this will increase the power of the study , but this should not exceed 4:1.

18. Ascertainment of the disease, and exposure status
Outcome status can be made from death certificates, case sheets, discharging cards.
Exposure status can be obtained by interview, a questionnaire, or medical records.
Data collector should not aware of: who the case is, and who the control is and about the hypothesis under study to minimize the possibility of observational bias.

19. Step 4 — Measure of Association
Odds Ratio (OR)
Odds ratio
Good estimator of risk or rate ratio, especially for rare disease
Odds of exposure among cases divided by odds of exposure among controls
Once cases and controls have been enrolled and exposure information has been collected, you are ready to analyze the data. For a case-control study, the measure of association to use is the odds ratio. As we have discussed, it is a good estimator of the risk or rate ratio when the disease is uncommon. The odds ratio gets its name because technically it is the ratio of the odds of exposure among cases divided by the odds ratio of exposure among controls.

20. Odds Ratio = (a/c) / (b/d) = ad / bc
Measure of Association between Exposure and Outcome in Case-Control – 2-by-2 Table
Case
Exposed a
Unexposed c V1
Control b d V2
While technically the odds ratio is the ratio of odds (a/c) divided by (b/d/), it is much easier to calculate it (and to remember the formula) as ad/bc.
Odds Ratio = (a/c) / (b/d) = ad / bc

21. Example Cigarette Smoking Lung Cancer Total Cases Control Yes 70 30
100 No
200

22. Exercise ad 70 x 70 Odds Ratio= ------------=-----------------= 5.4
bc x 30
= OR (1± z/√x2)
95% CI =5.4 1± 1.96/ √32 =

23. Role of Bias in case control studies:
Selection Bias: occur when the inclusion of cases or controls into the study depends on the exposure of interest.
2. Observational Bias: error in obtaining, reporting, or recording of information by the investigator.

24. Role of Bias in case control studies:
3. Recall Bias: related to difference in the ways the cases and the controls will recall their exposure history. Cases are more likely to remember exposures than healthy controls.
4. Misclassification: refers to errors in the categorization of either the exposure or disease status.