Case-control studies are a type of observational research that compare individuals with a disease (cases) to those without (controls) to identify risk factors, and they are characterized by their retrospective nature. Key strengths include cost-effectiveness, suitability for rare diseases, and the ability to examine multiple risk factors simultaneously, while key weaknesses involve biases related to selection, recall, and data quality. Various case-control studies illustrate their application, such as investigating psychological stress's link to breast cancer and smoking's association with lung cancer.

1. CASE-CONTROL
STUDIES
By: Anmol Ayaz

2. Case-Control Studies
• Case-Control study design is a type of observational study.
• Case control studies are also known as "retrospective studies"
and "case-referent studies”.
• Case–control studies which compare two groups of subjects; a
healthy control group versus a case group displaying the disease
(James w. Hanson 2013).

4. Study Design
• Case-control studies identify subjects by outcome status at
the outset of the investigation.
• Outcomes of interest may be whether the subject has
undergone a specific type of surgery, experienced a
complication, or is diagnosed with a disease.
• Once outcome status is identified and subjects are
categorized as cases and controls (subjects without the
outcome but from the same source population) are selected.

5. Cont…
• Data about exposure to a risk factor or several risk factors
are then collected retrospectively, typically by interview,
abstraction from records, or survey.

6. Methodological Issues
◦ Selection of Cases
◦ Selection of Controls
◦ Matching
◦ Multiple Controls
◦ Bias in Case-Control Studies

7. Selection of Cases
• Sampling in a case-control study design begins with selecting the
cases.
• In a case-control study, the investigator has clearly defined
inclusion and exclusion criteria prior to the selection of cases.
• It is important to select cases that are representative of cases in the
target population to strengthen the study's external validity.

8. Cont.…
◦ For example,
if the outcome is having a disease, specific diagnostic criteria, disease subtype, stage of disease,
or degree of severity should be defined. Such criteria ensure that all the cases are homogenous.
Second, cases may be selected from a variety of sources, including hospital patients, clinic
patients, or community subjects.
Many communities maintain registries of patients with certain diseases and can serve as a
valuable source of cases

9. Selection of Controls
◦ Cases and controls should stem from the same source population.
◦ The investigator may also consider the control group to be an at-risk population, with the
potential to develop the outcome (disease).
◦ Because the validity of the study depends upon the comparability of these two groups, cases
and controls should otherwise meet the same inclusion criteria in the study.

10. Matching
This matching strategy is called individual matching. Age, sex, and race are often used to match cases
and controls because they are typically strong confounders of disease .
Multiple Controls
The study may be able to provide more information if multiple controls per case are selected.
This method increases the “statistical power” of the investigation by increasing the sample size. The
precision of the findings may improve by having up to about three or four controls per case (Bruce,
2008).

11. Bias in Case-Control Studies
◦ Evaluating exposure status can be the vulnerable point of case-control studies.
◦ Information about experience is typically collected by self-report, interview, or from recorded
information, it is subjective to recall bias, interviewer bias, or will rely on the completeness or
accuracy of recorded information.
◦ These biases decrease the internal validity of the investigation and should be carefully addressed and
reduced in the study design.

12.  Cost effective relative to other analytical studies such as cohort studies.
 Good for studying rare conditions or diseases.
 Effective for the study of diseases with long latency periods.
 Less time needed to conduct the study because the condition or disease has already occurred.
 Simultaneously look at multiple risk factors.
 Useful as initial studies to establish an association.
 Case-control studies are retrospective, and cases are identified at the beginning of the study;
therefore there is no long follow up period (as compared to cohort studies).

13. • Particularly prone to bias; especially selection, recall and observer bias.
• Retrospective studies have more problems with data quality because they rely on memory and people with a
condition will be more motivated to recall risk factors (also called recall bias).
• Not good for evaluating diagnostic tests because it’s already clear that the cases have the condition and the
controls do not.
• It can be difficult to find a suitable control group.
• Case-control studies are limited to examining one outcome.
• The temporal sequence between exposure and disease may be difficult to determine.

14. Examples of Case-Control Studies
Psychological stress and the risk of breast cancer: a case–control study
◦ The study was conduct to determine whether psychological stress, in the form of past life events and stress at
work, was associated with the development of breast cancer. (Kruk & Aboul Enein, 2004).
◦ The study was based on a case–control study of 257 women with breast cancer operated during 1993–1998
in Szczecin (Poland) hospitals and 565 controls, free of any cancer diagnosis.
◦ The subjects were sent a detailed questionnaire including questions on sociodemographic data; lifestyle
(lifetime recreational and sport activities, occupational physical activity, diet); reproductive history;
experience of psychological stress
◦ The subjects reported major stressful life events, stress of daily activity and experience of stress at work.
◦ Logistic regression analyses were used to estimate the odds ratios (ORs) with 95% confidence intervals
(CIs).

15. Cont.…
◦ They found that women with major life events, stress of daily activity, and depression had 3.7 times
higher risk for breast cancer, compared to those which did not experience such stress.
◦ Women who reported experience of stress at work had a nonsignificant 16% higher risk for breast
cancer compared with those who reported no stress .
◦ A higher proportion of cases (89.1%) than controls (71.1%) reported that their job was stressful, very
fretful or very responsible or experienced a major life event
◦ These findings suggest an association between major life events and breast cancer

16. A case–control study of psychological distress in
survivors of farmers' suicides in Wardha District in
central India (Bhise &Behere, 2016).
• To assess the psychological distress and its correlates in survivors of farmers’ suicides.
• Case–control study design was used in Wardha District of Vidarbha region in the central India. A
predesigned and pretested semi structured questionnaire was used to assess sociodemographic
variables.
• Self-Reporting Questionnaire-20 was used to evaluate psychological distress in 98 survivors of
farmers’ suicides and 98 age, sex, and occupation-matched controls.

17. Cont..
• Significantly higher proportion of survivors had psychological distress than controls.
• Female survivors, spouse and parents of suicide victims had a high risk of distress.
• Survivors of farmers’ suicides are suffering from significant psychological distress

18. Smoking and lung cancer study
• In their landmark study, Doll and Hill (1950) evaluated the association between smoking and lung
cancer.
• They included 709 patients of lung carcinoma (defined as cases). They also included 709 controls
from general medical and surgical patients.
• The selected controls were similar to the cases with respect to age and sex. Thus, they included 649
males and 60 females in cases as well as controls.

19. Cont..
◦ They found that only 0.3% of males were non-smokers among cases.
◦ However, the proportion of non-smokers among controls was 4.2%; the different was statistically significant
(P = 0.00000064).
◦ Similarly they found that about 31.7% of the female were non-smokers in cases compared with 53.3% in
controls; this difference was also statistically significant (0.01< p <0.02).

20. Odds Ratio
• The odds ratio is the “measure of association” for a case-control study. It quantifies the
relationship between an exposure and a disease in a case-control study.
• The odds ratio tells us how much higher the odds of exposure are among case-patients than
among controls.
• Once the odds ratio is determined, tests of statistical significance must be used to determine the
probability of finding an odds ratio as strong as or stronger than the one observed, if the
exposure is not truly related to the disease. This probability is called the “p-value.”
Other analysis
We can use logistic regression models for multivariate analysis in case-control studies

22. Interpreting Odd Ratios
◦ OR = 1 Odds of exposure among cases and controls are same -Exposure is not associated with
disease
◦ OR > 1 Odds of exposure among cases are higher than controls -Exposure is positively associated
with disease
◦ OR < 1 Odds of exposure among cases are lower than controls - Exposure is negatively associated
with disease.

23.  In case-control studies, participants are recruited on the basis of disease status. Thus, some of
participants have the outcome of interest (referred to as cases), whereas others do not have the
outcome of interest (referred to as controls).
 The investigator then assesses the exposure in both these groups.
 Case-control studies are less expensive and quicker to conduct (compared with prospective cohort
studies at least). The measure of association in this type of study is an odds ratio.
 This type of design is useful for rare outcomes and those with long latent periods. However, they
may also be prone to certain biases – selection bias and recall bias.