SeriesCompared to what? Finding controls for case-control studies
Section snippets
Aim of controls
Controls in a case-control study, which progresses backwards in time from outcome to exposure,3 indicate the background frequency of an exposure in individuals who are free of the disease in question. Controls do not need to be healthy; inclusion of sick people is sometimes appropriate. Indeed, exclusion of ill people as controls can distort (bias)4 the results.5 (Like healthy individuals, ill people can develop a different condition of interest.) The final point is key: controls in a
Where to find controls?
The investigator (and, ultimately, the reader) needs to determine the group of individuals from which cases and controls will be drawn. A known group11 consists of a defined population observed over a period (figure 2). This group might consist of passengers and crew on a week-long cruise of the Caribbean or all individuals living in Sweden over a decade. Cases are those who develop the disorder of interest and controls are those in the same group without the condition. Thus, case-control
Controls from a known group
When possible, random samples of people without the disease can serve as controls. Investigation of an outbreak of food-borne illness on a cruise ship generally uses a case-control approach. Cases are those who develop gastroenteritis; controls are those on board who do not. The study seeks to identify food exposures that are more common among the cases than the controls. Moreover, no one who had not eaten the suspect food should have become ill. On the ship, probability sampling among those
Neighbourhood controls
Neighbourhood controls generally are drawn in a specified pattern from the block in which the case lives. As always, selection of controls should be independent of the exposure of interest. To avoid selection bias, interviewers are given a specific pattern of houses to approach. Researchers have used two approaches to identify houses of controls: a population register or door-to-door canvassing.20, 21 A useful aid for the former is the cross-reference (also termed crisscross or reverse-street)
How many control groups?
Some authors have argued for using two separate control groups; if results are consistent, then findings are deemed more credible.14, 31 For example, a case-control study of oestrogen therapy and endometrial cancer used both hospital and community controls.32 In the unhappy circumstance of disparate results, however, which result should be ignored?15 Another immediate disadvantage is the added cost in time and resources. For example, in the case-control study of endometrial cancer cited above,32
How many controls per case?
Readers are sometimes surprised to discover large disparities between the numbers of cases and controls in a case-control report; clinicians intuitively expect similar group sizes.34 This inequality reflects attempts by investigators to increase the ability of the study to find differences of importance, should they exist. In unmatched case-control studies, having roughly equal numbers of cases and controls is most efficient if costs are similar for cases and controls. However, sometimes the
What to look for in controls
The validity of case-control studies depends on selection of appropriate control groups. Choosing controls might seem deceptively simple but it can be treacherous. Controls should reflect the background frequency of the exposure in the population. Hence, they should be similar in all important respects to cases, except that they do not have the disorder in question. Their selection must be independent of exposure.
When the study group of potential controls is known, a good approach is to take
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