What Is A Case-control Study?

A case-control study is a type of observational study in which two existing groups differing in outcome are identified and compared on the basis of some supposed causal attribute. Case-control studies are often used to identify factors that may contribute to a medical condition by comparing subjects who have that condition/disease (the “cases”) with patients who do not have the condition/disease but are otherwise similar (the “controls”).

They require fewer resources but provide less evidence for causal inference than a randomized controlled trial.

Porta’s Dictionary of Epidemiology defines the case-control study as:

“an observational epidemiological study of persons with the disease (or another outcome variable) of interest and a suitable control group of persons without the disease (comparison group, reference group).

The potential relationship of a suspected risk factor or an attribute to the disease is examined by comparing the diseased and nondiseased subjects with regard to how frequently the factor or attribute is present (or, if quantitative, the levels of the attribute) in each of the groups (diseased and nondiseased).”

For example, in a study trying to show that people who smoke (the attribute) are more likely to be diagnosed with lung cancer (the outcome), the cases would be persons with lung cancer, the controls would be persons without lung cancer (not necessarily healthy), and some of each group would be smokers. If a larger proportion of the cases smoke than the controls, that suggests, but does not conclusively show, that the hypothesis is valid.

The case-control study is frequently contrasted with cohort studies, wherein exposed and unexposed subjects are observed until they develop an outcome of interest.

Examples of case-control studies include:

Cerebral Microbleeds in Multiple Sclerosis Evaluated on Susceptibility-weighted Images and Quantitative Susceptibility Maps: A Case-Control Study
The Glioma International Case-Control Study
Asthma as a risk factor for zoster in adults: A population-based case-control study
Exposure to Bovine Leukemia Virus Is Associated with Breast Cancer: A Case-Control Study

Case-control Group Selection

Controls need not be in good health; inclusion of sick people is sometimes appropriate, as the control group should represent those at risk of becoming a case. Controls should come from the same population as the cases, and their selection should be independent of the exposures of interest.

Controls can carry the same disease as the experimental group, but of another grade/severity, therefore being different from the outcome of interest. However, because the difference between the cases and the controls will be smaller, this results in a lower power to detect an exposure effect.

As with any epidemiological study, greater numbers in the study will increase the power of the study. Numbers of cases and controls do not have to be equal. In many situations, it is much easier to recruit controls than to find cases. Increasing the number of controls above the number of cases, up to a ratio of about 4 to 1, may be a cost-effective way to improve the study.

Explainer diagram Case Controls

Case-Control Study vs. Cohort on a Timeline. “OR” stands for “odds ratio” and “RR” stands for “relative risk”.
Credit: Kelidimari CC-BY 3.0

Case-control Study Strengths And Weaknesses

Case-control studies are a relatively inexpensive and frequently used type of epidemiological study that can be carried out by small teams or individual researchers in single facilities in a way that more structured experimental studies often cannot be. They have pointed the way to a number of important discoveries and advances.

The case-control study design is often used in the study of rare diseases or as a preliminary study where little is known about the association between the risk factor and disease of interest.

Compared to prospective cohort studies they tend to be less costly and shorter in duration. In several situations they have greater statistical power than cohort studies, which must often wait for a ‘sufficient’ number of disease events to accrue.

Case-control studies are observational in nature and thus do not provide the same level of evidence as randomized controlled trials. The results may be confounded by other factors, to the extent of giving the opposite answer to better studies. A meta-analysis of what were considered 30 high-quality studies concluded that use of a product halved a risk, when in fact the risk was, if anything, increased.

It may also be more difficult to establish the timeline of exposure to disease outcome in the setting of a case-control study than within a prospective cohort study design where the exposure is ascertained prior to following the subjects over time in order to ascertain their outcome status.

The most important drawback in case-control studies relates to the difficulty of obtaining reliable information about an individual’s exposure status over time. Case-control studies are therefore placed low in the hierarchy of evidence.

Rothman, K. (2012)
Epidemiology: An Introduction
Oxford, England: Oxford University Press. ISBN 978-0-19-513554-1