Case Control Study
A study that compares patients who have a disease or outcome of interest (cases) with patients who do not have the disease or outcome (controls), and looks back retrospectively to compare how frequently the exposure to a risk factor is present in each group to determine the relationship between the risk factor and the disease.
Case control studies are observational because no intervention is attempted and no attempt is made to alter the course of the disease. The goal is to retrospectively determine the exposure to the risk factor of interest from each of the two groups of individuals: cases and controls. These studies are designed to estimate odds.
Case control studies are also known as "retrospective studies" and "case-referent studies."
- Good for studying rare conditions or diseases
- Less time needed to conduct the study because the condition or disease has already occurred
- Lets you simultaneously look at multiple risk factors
- Useful as initial studies to establish an association
- Can answer questions that could not be answered through other study designs
- 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
Design pitfalls to look out for
Care should be taken to avoid confounding, which arises when an exposure and an outcome are both strongly associated with a third variable. Controls should be subjects who might have been cases in the study but are selected independent of the exposure. Cases and controls should also not be "over-matched."
Is the control group appropriate for the population? Does the study use matching or pairing appropriately to avoid the effects of a confounding variable? Does it use appropriate inclusion and exclusion criteria?
There is a suspicion that zinc oxide, the white non-absorbent sunscreen traditionally worn by lifeguards is more effective at preventing sunburns that lead to skin cancer than absorbent sunscreen lotions. A case-control study was conducted to investigate if exposure to zinc oxide is a more effective skin cancer prevention measure. The study involved comparing a group of former lifeguards that had developed cancer on their cheeks and noses (cases) to a group of lifeguards without this type of cancer (controls) and assess their prior exposure to zinc oxide or absorbent sunscreen lotions.
This study would be retrospective in that the former lifeguards would be asked to recall which type of sunscreen they used on their face and approximately how often. This could be either a matched or unmatched study, but efforts would need to be made to ensure that the former lifeguards are of the same average age, and lifeguarded for a similar number of seasons and amount of time per season.
Chambers, C. D., Hernandez-Diaz, S., Van Marter, L. J., Werler, M. M., Louik, C., & Jones, K. L. et al. (2006). Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. New England Journal of Medicine, 354(6), 579-587.
This study used a matched design, matching infants who had persistent pulmonary hypertension with infants who did not have it, and compared the rates of exposure to SSRIs.
Smedby, K. E., Hjalgrim, H., Askling, J., Chang, E. T., Gregersen, H., & Porwit-MacDonald, A. et al. (2006). Autoimmune and chronic inflammatory disorders and risk of non-hodgkin lymphoma by subtype. Journal of the National Cancer Institute, 98(1), 51-60.
This study matched patients with non-Hodgkin lymphoma (NHL) with control subjects and compared their history of autoimmune and chronic inflammatory disorders, markers of severity, and treatment. It found that the risk of NHL was increased in association with rheumatoid arthritis, primary Sjögren syndrome, systemic lupus erythematosus, and celiac disease.
Teo, K. K., Ounpuu, S., Hawken, S., Pandey, M., Valentin, V., & Hunt, D. et al. (2006). Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: A case-control study. Lancet, 368(9536), 647-658.
This study looked at the relation between risk of acute myocardial infarction and current or former smoking, type of tobacco, amount smoked, effect of smokeless tobacco, and exposure to secondhand smoke.
A patient with the disease or outcome of interest.
When an exposure and an outcome are both strongly associated with a third variable.
A patient who does not have the disease or outcome.
Each case is matched individually with a control according to certain characteristics such as age and gender. It is important to remember that the concordant pairs (pairs in which the case and control are either both exposed or both not exposed) tell us nothing about the risk of exposure separately for cases or controls.
The method of assignment of individuals to study and control groups in observational studies when the investigator does not intervene to perform the assignment.
The controls are a sample from a suitable non-affected population.
Now test yourself!
Case-control and Cohort studies: A brief overview
Posted on December 6, 2017
Tags: Case-control study, cohort study, outcome, study design
Case-control and cohort studies are observational studies that lie near the middle of the hierarchy of evidence. These types of studies, along with randomised controlled trials, constitute analytical studies, whereas case reports and case series define descriptive studies (1). Although these studies are not ranked as highly as randomised controlled trials, they can provide strong evidence if designed appropriately.
Case-control studies are retrospective. They clearly define two groups at the start: one with the outcome/disease and one without the outcome/disease. They look back to assess whether there is a statistically significant difference in the rates of exposure to a defined risk factor between the groups. See Figure 1 for a pictorial representation of a case-control study design. This can suggest associations between the risk factor and development of the disease in question, although no definitive causality can be drawn. The main outcome measure in case-control studies is odds ratio (OR).
Figure 1. Case-control study design.
Cases should be selected based on objective inclusion and exclusion criteria from a reliable source such as a disease registry. An inherent issue with selecting cases is that a certain proportion of those with the disease would not have a formal diagnosis, may not present for medical care, may be misdiagnosed or may have died before getting a diagnosis. Regardless of how the cases are selected, they should be representative of the broader disease population that you are investigating to ensure generalisability.
Case-control studies should include two groups that are identical EXCEPT for their outcome / disease status.
As such, controls should also be selected carefully. It is possible to match controls to the cases selected on the basis of various factors (e.g. age, sex) to ensure these do not confound the study results. It may even increase statistical power and study precision by choosing up to three or four controls per case (2).
Case-controls can provide fast results and they are cheaper to perform than most other studies. The fact that the analysis is retrospective, allows rare diseases or diseases with long latency periods to be investigated. Furthermore, you can assess multiple exposures to get a better understanding of possible risk factors for the defined outcome / disease.
Nevertheless, as case-controls are retrospective, they are more prone to bias. One of the main examples is recall bias. Often case-control studies require the participants to self-report their exposure to a certain factor. Recall bias is the systematic difference in how the two groups may recall past events e.g. in a study investigating stillbirth, a mother who experienced this may recall the possible contributing factors a lot more vividly than a mother who had a healthy birth.
A summary of the pros and cons of cohort studies are provided in Table 2.
Table 1. Advantages and disadvantages of case-control studies.
Cohort studies can be retrospective or prospective. Retrospective cohort studies are NOT the same as case-control studies.
In retrospective cohort studies, the exposure and outcomes have already happened. They are usually conducted on data that already exists (from prospective studies) and the exposures are defined before looking at the existing outcome data to see whether exposure to a risk factor is associated with a statistically significant difference in the outcome development rate.
Prospective cohort studies are more common. These studies define an exposure and recruit participants into two groups – those that have been subjected to it and those that have not. The study then follows these participants for a defined period to assess the proportion that develop the outcome/disease of interest. See Figure 2 for a pictorial representation of a cohort study design. Therefore, cohort studies are good for assessing prognosis, risk factors and harm. The outcome measure in cohort studies is usually a risk ratio / relative risk (RR).
Figure 2. Cohort study design.
Cohort studies should include two groups that are identical EXCEPT for their exposure status.
As a result, both exposed and unexposed groups should be recruited from the same source population. Another important consideration is attrition. If a significant number of participants are not followed up (lost, death, dropped out) then this may impact the validity of the study. Not only does it decrease the study’s power, but there may be attrition bias – a significant difference between the groups of those that did not complete the study.
Cohort studies can assess a range of outcomes allowing an exposure to be rigorously assessed for its impact in developing disease. Additionally, they are good for rare exposures, e.g. contact with a chemical radiation blast.
Whilst cohort studies are useful, they can be expensive and time-consuming, especially if a long follow-up period is chosen or the disease itself is rare or has a long latency.
A summary of the pros and cons of case-controls are provided in Table 1.
Table 2. Advantages and disadvantages of cohort studies.
The Strengthening of Reporting of Observational Studies in Epidemiology Statement (STROBE)
STROBE provides a checklist of important steps for conducting these types of studies, as well as acting as best-practice reporting guidelines (3). Both case-control and cohort studies are observational, with varying advantages and disadvantages. However, the most important factor to the quality of evidence these studies provide, is their methodological quality.
- Song, J. and Chung, K. Observational Studies: Cohort and Case-Control Studies. Plastic and Reconstructive Surgery. 2010 Dec;126(6):2234-2242.
- Ury HK. Efficiency of case-control studies with multiple controls per case: Continuous or dichotomous data. Biometrics. 1975 Sep;31(3):643–649.
- von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.Lancet 2007 Oct;370(9596):1453-14577. PMID: 18064739.
Having completed my fourth year as a medical student at the University of Liverpool, UK, I am currently intercalating in a Masters of Research (MRes) in Medicine at the University of Leeds, UK. I will be entering my sixth and final year of medicine in September 2017. My primary interests lie within Cardiology and Evidence Based Medicine.
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