Traditional case-control studies

Let's suppose we are at the end of the follow-up period and have Ce and Cu cases respectively, and Ne-Ce and Nu-Cu persons are still free of disease (non-cases) in the two cohorts. If the disease is rare, it is obvious that persons free of disease at the end of the study period reflect the exposure experience of the source population. If the disease is frequent, exposure among persons free of disease at the end of the study may be lower than in the source population (since exposure increases the risk of disease).

If the disease is rare, we can use a sample of non-cases at the end of the study period to estimate the risk ratio. Using non-cases to estimate the source population exposure experience is the principle of traditional case-control studies.

Let’s call “c” and “d”, respectively, the sample's number of exposed and unexposed. If sampling is done independently from the exposure status, we would expect that the disease is rare.

or equivalently

If the above is true, the risk ratio estimated from a traditional case-control study can be represented as:

The quantity ad/bc is the odds ratio. It represents the ratio of the odds of disease among exposed divided by the odds of disease among unexposed.

However, if the disease is not rare, a large part of Ne/Nu is represented by future cases, which are more likely to be exposed than non-cases. Consequently, the odds ratio may dramatically overestimate the risk ratio.

To illustrate this point, let’s now move to the example of a food-borne outbreak in a nursing home with 200 residents and 74 cases of gastroenteritis. The epidemic curve is consistent with a point common source of infection, and example 4 shows the results of a retrospective cohort study. It suggests that the risk of gastroenteritis is 3.4 times higher among residents who consumed a specific food item than those who did not.

Example 1: Occurrence of gastroenteritis among residents of nursing home A according to consumption of a specific food item.

Specific food item	Total	Cases	Risk	Risk ratio
Yes	60	44	73.3%	3.4
No	140	30	21.4%	Reference
Total	200	74	37.5%

Let’s suppose investigators would have preferred to conduct a traditional case-control study (case – non-case study) rather than a retrospective cohort. In a traditional case-control study, controls are selected from people who are free of the disease at the end of the study period. The OR is a good risk ratio estimate if the disease is rare.

Example 2: Consumption of a specific food item among cases and various samples of residents of a nursing home

Consumption	Cases	50% sample of non cases	OR	50% sample of source population	RR
Yes	44	8	10.1	30	3.4
NO	30	55		70

Using as controls a 50% sample of the non-cases, the odds ratio equals 10.1, overestimating the risk ratio by a factor of three. This should not come as a surprise, though. When selecting controls from non-cases, and since the disease is frequent (the overall risk of gastroenteritis is 37.5%), the control group no longer represents the exposure distribution in the source population. The frequency of exposure in the control group selected from non-cases is 7.3% and was 30% in the source population.

If instead we had done a case-cohort study and chosen a 50% random sample of the source population, the sample (if unbiased and ignoring random variation) would likely provide the same proportion of exposed (30%) as in the source population. The risk ratio obtained (3.4) would again be similar to the risk ratio observed in the cohort study.

When to use a traditional case-control study?

Traditional case-control studies are an easy and very convenient way to conduct epidemiological studies when the disease is rare. Because of its simplicity, it is the most popular method. It has been extremely useful to epidemiologists in the past 50 years. The odds ratio provides a good estimate of the risk ratio, provided that the disease is rare. However, it should not be used when disease incidence is high. This particularly applies to investigations of food-borne outbreaks with very high incidences.

NB. "Traditional case-control studies" are a type of case-control studies where controls are simply non-cases. For this reason, you may find them quoted as "case-non-case studies" in literature.

FEM PAGE CONTRIBUTORS 2007

Editor

Masja Straetemans

Original Authors

Alain Moren

Jean Claude Desenclos

Marta Valenciano

Arnold Bosman

Contributors

Arnold Bosman

Lisa Lazareck

Ioannis Karagiannis

Masja Straetemans