Lecture 4 - Case-control study

What is a case-control study?

Observational study of a persons with the disease of interest and a suitable control group of persons without the disease 

Are case-control studies retrospective or prospective?

Retrospective study

• Looks into the past from the present day

What is the goal of a case-control study?

Investigate how do diseased cases differ from non-diseased controls in terms of prior exposure history  

Why can case-control studies not be used to calculate incidence rates?

Cannot calculate disease incidence rates as the study does not follow a disease-free population over time 

What can case-control studies be used to calculate?

Odds ratio 

What is the calculation of Odds Ratio?

Odds of exposure in cases/Odds of exposure in controls 

• Equal to (Outcome-Exposed x No Outcome-Unexposed) / (No Outcome-Exposed x Outcome-Unexposed) 

An odds ratio of 1 means…

…means there is no association between exposure and disease 

An odds ratio of >1 indicates…

Indicates a positive association

An odds ratio of <1 indicates…

Indicates a potential protective effect

What are the two sources of cases for a case control study?

Population based

• Identify and recruit all cases from a defined population

Hospital cased

• Identify cases where you can find them

What are some key considerations when choosing the control group for a case-control study?

• Controls must be chosen to represent the population of individuals who would have been identified had they developed the disease  

• Any exclusion/restrictions on cases must be applied to the controls too 

  • E.g. Age restriction 

What are the advantages of population controls?

• Usually first choice

• Exclusion criteria are easy to apply

• Cases and controls from the same study base

• Representative of the whole study base

What are the disadvantages of population controls?

• Low participation rates → bias

• Inconvenience of finding controls

• Recall bias

• May not be motivated to take part

What are the advantages of hospitalised controls?

• Easy to identify

• Readily available in sufficient numbers

• Likely subject to same selection factors as cases

• More likely to cooperate

What are the disadvantages of hospitalised controls?

• By definition, they are ill

• Disease may have common aetiology or be on a causal pathway

• Specialist hospitals have wider geographic range 

What are the advantages of Neighbourhood controls?

• Selection doesn’t need a roster of people

• Avoids problems of using telephone lists 

• Possible risk factors varying geographically may be more balanced 

What are the disadvantages of Neighbourhood controls?

• Costly

• Possibly not representative of study base

• Possible over-matching if exposure is related to residence 

• Household sampling units increases selection chance of people living alone

What are the advantages of using friends as controls?

• Convenient and cheap

• Likely to be similar to the case

• Useful when friendship characteristics are unrelated to exposure 

What are the disadvantages of using friends as controls?

• Overmatching when friendship characteristics are related to exposure 

What are the advantages of using relatives as controls?

Useful if genetic factors are involved

What are the disadvantages of using relatives as controls?

Risk of overmatching

What is the purpose of matching?

Control for a confounding factor

• E.g. sex, date of birth, socio-economic status

What are the disadvantages of matching?

• Increased effort to find suitable controls 

• Exclusion of cases if no match found 

• Longer study duration 

What is over-matching?

• Matching variable is involved in mechanism 

  • E.g. smoking in lung cancer 

• Could be on causal pathway  

Why is increasing the number of control groups beyond four bad?

Diminishing returns beyond four control groups.

• Usually even one control group is enough

• Two or three are often used for rare diseases 

What is a nested case-control study?

Case-control study within another study (e.g. Cohort study)

• The cases which develop in the cohort study can be entered into the case-control study

What is a case-control study example?

Serum Vitamin D status in Migraine patients vs healthy controls.

• Investigated concentration of serum vitamin D from blood samples

What were the findings of the serum vitamin D and migraine patient case-control study?

Found significant negative association between migraines and serum vitamin D

• Decreasing odds of migraines with increasing serum vitamin D

What are the general advantages of case-control studies?

• Effectively investigates multiple potential risk factors

• Optimal for rare diseases

• Relatively quick

• Relative inexpensive 

• Yields estimates of relative risk

• Well suited for long latency periods 

What are the general disadvantages of case-control studies?

• Potential for selection bias

• Yields only relative risk and not absolute risk/incidence rates 

• Can only look at one disease

• Relies on past data, memory and records 

• Matching can be complex