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Quantitative study designs

Case Control

In a Case-Control study there are two groups of people: one has a health issue (Case group), and this group is “matched” to a Control group without the health issue based on characteristics like age, gender, occupation. In this study type, we can look back in the patient’s histories to look for exposure to risk factors that are common to the Case group, but not the Control group. It was a case-control study that demonstrated a link between carcinoma of the lung and smoking tobacco. These studies estimate the odds between the exposure and the health outcome, however they cannot prove causality. Case-Control studies might also be referred to as retrospective or case-referent studies. 

Stages of a Case-Control study

This diagram represents taking both the case (disease) and the control (no disease) groups and looking back at their histories to determine their exposure to possible contributing factors.  The researchers then determine the likelihood of those factors contributing to the disease.

(FOR ACCESSIBILITY: A case control study is likely to show that most, but not all exposed people end up with the health issue, and some unexposed people may also develop the health issue)

Which Clinical Questions does Case-Control best answer?

Case-Control studies are best used for Prognosis questions.

For example: Do anticholinergic drugs increase the risk of dementia in later life?
(See BMJ Case-Control study Anticholinergic drugs and risk of dementia: case-control study)

What are the advantages and disadvantages to consider when using Case-Control?

Advantages
  • Helps you find the source of an existing illness or epidemic. 
  • Cheap and quick to conduct this type of study. The health issue has already occurred, you don’t need a lab or special equipment. 
  • Few ethics issues as the patient already has the health condition 
  • Looks at multiple risk factors in a patient’s life (environment, work, diet).
Disadvantages
  • Patient recall about their history can be inaccurate (recall bias).
  • Patients aware of certain risk factors may focus on those and ignore other exposures.  
  • No randomisation is possible, lowering internal validity of the study.
  • Finding a Control group that matches the Case group appropriately can be difficult.
  • This study type does not prove a clear causal relationship between risk factors and illness, only calculates the odds. 
Opportunities
  • Particularly useful for rare conditions, it’s often the only option as it’s not appropriate to try to cause a disease using RCTs. 
  • Can be used to identify point of outbreak, looking into the past to see common exposure in the Case histories. 
  • Can look at many exposure factors of the patient’s environment, medical history, diet. This is  useful where no single aspect of the patient’s life has been narrowed down as a potential cause. 
Confounding*
  • If the health issue causes multiple common exposures, the study should attempt to differentiate between those exposures to identify which is more likely. For example, having a chronic illness may mean you spend more time in hospital environments, have a lower immune system, and suffer high levels of stress – so any of these could potentially be the cause of that chronic illness. The study must make an attempt to eliminate some of these exposures as causes if possible. 
  • If the Control group is overmatched and starts to develop the health issue.
  • If the Control group is under-matched and there aren’t enough comparable factors to differentiate what is specific to the Case population. For example, if you could not find female Controls to match female Cases, then you cannot assess whether gender is or isn’t a contributing risk factor. 

* Confounding occurs when the elements of the study design invalidate the result. It is usually unintentional. It is important to avoid confounding, which can happen in a few ways within Case-Control studies. This explains why it is lower in the hierarchy of evidence, superior only to Case Studies.

What does a strong Case-Control study look like?

A strong study will have:

  • Well-matched controls, similar background without being so similar that they are likely to end up with the same health issue (this can be easier said than done since the risk factors are unknown). 
  • Detailed medical histories are available, reducing the emphasis on a patient’s unreliable recall of their potential exposures. 

What are the pitfalls to look for?

  • Poorly matched or over-matched controls. 
    Poorly matched means that not enough factors are similar between the Case and Control. E.g. age, gender, geography. Over-matched conversely means that so many things match (age, occupation, geography, health habits) that in all likelihood the Control group will also end up with the same health issue! Either of these situations could cause the study to become ineffective. 
  • Selection bias: Selection of Controls is biased. E.g. All Controls are in the hospital, so they’re likely already sick, they’re not a true sample of the wider population. 
  • Cases include persons showing early symptoms who never ended up having the illness. 

Real World Examples

Smoking and carcinoma of the lung; preliminary report

  • Doll, R., & Hill, A. B. (1950). Smoking and carcinoma of the lung; preliminary report. British Medical Journal, 2(4682), 739–748. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2038856/
  • Key Case-Control study linking tobacco smoking with lung cancer
  • Notes a marked increase in incidence of Lung Cancer disproportionate to population growth.
  • 20 London Hospitals contributed current Cases of lung, stomach, colon and rectum cancer via admissions, house-physician and radiotherapy diagnosis, non-cancer Controls were selected at each hospital of the same-sex and within 5 year age group of each.
  • 1732 Cases and 743 Controls were interviewed for social class, gender, age, exposure to urban pollution, occupation and smoking habits.
  • It was found that continued smoking from a younger age and smoking a greater number of cigarettes correlated with incidence of lung cancer.

Anticholinergic drugs and risk of dementia: case-control study

  • Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y. K., Arthur, A., . . . Savva, G. M. (2018). Anticholinergic drugs and risk of dementia: case-control study. BMJ, 361, k1315. Retrieved from http://www.bmj.com/content/361/bmj.k1315.abstract.
  • A recent study linking the duration and level of exposure to Anticholinergic drugs and subsequent onset of dementia.
  • Anticholinergic Cognitive Burden (ACB) was estimated in various drugs, the higher the exposure (measured as the ACB score) the greater likeliness of onset of dementia later in life.
  • Antidepressant, urological, and antiparkinson drugs with an ACB score of 3 increased the risk of dementia. Gastrointestinal drugs with an ACB score of 3 were not strongly linked with onset of dementia.
  • Tricyclic antidepressants such as Amitriptyline have an ACB score of 3 and are an example of a common area of concern.

Omega-3 deficiency associated with perinatal depression: Case-Control study 

  • Rees, A.-M., Austin, M.-P., Owen, C., & Parker, G. (2009). Omega-3 deficiency associated with perinatal depression: Case control study. Psychiatry Research, 166(2), 254-259. Retrieved from http://www.sciencedirect.com/science/article/pii/S0165178107004398.
  • During pregnancy women lose Omega-3 polyunsaturated fatty acids to the developing foetus.
  • There is a known link between Omgea-3 depletion and depression
  • Sixteen depressed and 22 non-depressed women were recruited during their third trimester
  • High levels of Omega-3 were associated with significantly lower levels of depression.
  • Women with low levels of Omega-3 were six times more likely to be depressed during pregnancy.

References and Further Reading

Doll, R., & Hill, A. B. (1950). Smoking and carcinoma of the lung; preliminary report. British Medical Journal, 2(4682), 739–748. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2038856/

Greenhalgh, Trisha. How to Read a Paper: the Basics of Evidence-Based Medicine, John Wiley & Sons, Incorporated, 2014. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/deakin/detail.action?docID=1642418.

Himmelfarb Health Sciences Library. (2019). Study Design 101: Case-Control Study. Retrieved from https://himmelfarb.gwu.edu/tutorials/studydesign101/casecontrols.cfm  

Hoffmann, T., Bennett, S., & Del Mar, C. (2017). Evidence-Based Practice Across the Health Professions (Third edition. ed.): Elsevier. 

Lewallen, S., & Courtright, P. (1998). Epidemiology in practice: case-control studies. Community Eye Health, 11(28), 57. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1706071/ 

Pelham, B. W. a., & Blanton, H. (2013). Conducting research in psychology : measuring the weight of smoke /Brett W. Pelham, Hart Blanton (Fourth edition. ed.): Wadsworth Cengage Learning. 

Rees, A.-M., Austin, M.-P., Owen, C., & Parker, G. (2009). Omega-3 deficiency associated with perinatal depression: Case control study. Psychiatry Research, 166(2), 254-259. Retrieved from http://www.sciencedirect.com/science/article/pii/S0165178107004398

Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y. K., Arthur, A., … Savva, G. M. (2018). Anticholinergic drugs and risk of dementia: case-control study. BMJ, 361, k1315. Retrieved from http://www.bmj.com/content/361/bmj.k1315.abstract

Statistics How To. (2019). Case-Control Study: Definition, Real Life Examples. Retrieved from https://www.statisticshowto.com/case-control-study/ 

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