Case-control studies are one of the most fre- quently used designs in epidemiology, having been de- fined as an efficient version of cohort studies1. Part of the validity of case-control studies resides in appropria- te selection of controls. There are two major groups of controls, viz., population and hospital, yet few studies have compared the two. It has been claimed that, if hospital controls are properly selected, there should be no important differences as against population controls in terms of the risks obtained for any given disease2.

This study sought to compare the characteristics of the above two groups of controls (hospital and population) recruited in the same public health district for two case-control studies on risk factors for lung cancer.

The two groups of controls were enrolled for two lung cancer studies. The objectives of the respective studies were: in one case, to analyze the effect of radon ex- posure3; and in the other, to analyze the effect of envi- ronmental and genetic risk factors of lung cancer4. In both studies, participation was restricted to subjects over 35 years and the sampling was performed based on sex frequency among cases.

A description of the study sample is shown in table 1. A total of 187 hospital and 241 population controls were included. There was a difference of six years in the mean age of the two groups, though the age range was similar. The percentage of individuals with secondary or higher education was likewise similar, but the percentage of individuals without any formal education was greater among hospital controls. Whereas the percentage of smokers was slightly higher among hospital controls, the number of cigarettes smoked per day and percentage of never-smokers was very much alike in both control groups. Alcohol consumption was higher among hospital controls, as was the percentage of drinkers.

Table 2 shows the probability of being a hospital control versus a population control. No important differen- ces were observed between both in smoking habit and occupational exposure to carcinogens. Important diffe- rences appeared for alcohol consumption. The risk of being a hospital control was 2.76-fold higher for moderate drinkers, rising to 4.83-fold for heavy drinkers, which means that the higher the alcohol consumption, the higher the likelihood of being selected as a hospital control.

Few studies have compared directly hospital and po- pulation controls, despite the amount of theoretical li- terature on the topic. These results indicate that both control types are comparable in terms of factors viewed as potential confounding variables in many epidemio- logic studies, e.g., educational level, number of cigarettes smoked per day, duration of smoking habit, and even risk occupations for lung cancer. The results also indicate, however, that there are important differences be- tween hospital and population controls regarding alcohol consumption, with hospital controls having a greater likelihood of being drinkers.

The use of population controls is acknowledged as being more appropriate than that of hospital controls for reasons of representativeness. Nevertheless, both have their advantages and their drawbacks. In the study region, public coverage covers approximately 95% of the population. The population controls were randomly selected on the basis of the census. There may be cer- tain differential characteristics between the 5% that makes no use of public health and the remaining 95%, in aspects such as economic level (educational level), tobacco use (the lower classes tend to smoke more than the higher classes), and perhaps employment in occupations posing a risk for lung cancer.

The basic problem of using hospital or population controls is that of comparability. In the present study, both control types were comparable except in alcohol consumption (and educational level). It might be thought that this is due to the medical profiles in res- pect of which hospital controls were selected. How- ever, none of these disorders (inguinal hernia, cataracts and orthopedic surgery in over 95% of controls) is, in principle, associated with alcohol consumption, so that they could not account for the differences observed. Another possible explanation might be non-response or participation bias. In general, participation by hospital controls tends to be higher than that of popula- tion controls. Hospital setting may increase participation, while the fact of being a healthy (and in many cases, a working) person reduces participation among popu- lation controls. Participation among hospital controls was 100%, whereas it was only 61.6% of the population controls. It may be that a higher proportion of heavier drinkers decline to participate among population than among hospital controls, which could account for the results obtained. Insofar as memory bias is concerned, hospital controls are reported to have as much time as cases do to think about the causes of their disease, thus preventing any possible differential information bias6. Drinkers may be more reluctant to participate when they are approached in their home environ- ment or because they are more difficult to locate in this setting.

Our study possesses a series of advantages; the two studies from which the controls were taken were de- signed to study the same disease. Consequently, the questionnaires used were essentially similar. Accordingly, it can be said that, in this particular instance of a case- control study -one in which the «cases» were hospital controls- the principle of comparable measures has been fulfilled7. A further advantage resides in the fact that, from the very outset, both studies were undertaken in the same public health district, a factor that would, a prio- ri, make both groups of controls highly comparable7. This means that the distribution of the different study expo- sures (and of other variables that have not been eva- luated) is exactly the same in the population base from which the two groups of controls were drawn. Both studies used the same inclusion and exclusion criteria (save for exclusion of individuals with previous respiratory di- seases in the population-based study).

The most important limitation is the lower participation of population controls, a finding in line with most previous studies. Controls were not recruited simul- taneously; instead, the population controls were en- rolled from 1992 through 1995, and the hospital controls from 1999 through 2000. We feel, however, that the habits studied hardly varied in the interval betwe- en the two studies.

The ideal control group rarely exists in epidemio- logic studies. In addition to theoretical work, empirical studies are needed to measure the impact of the dif- ferent biases that can appear, so that these can be pre- vented and corrected. However, even though appropriate selection of controls is problematic, the most serious limitations can be avoided by bearing a series of basic principles in mind8. Hospital controls are usually suit- able where hospital cases are used, but could not re- present the general population. Population controls, though generally preferable for reasons of validity, are expensive and difficult to obtain. Furthermore, for reasons of convenience, there is an important reason for not recruiting population controls, the need to ensure that the information bias that affects cases is similar9. In this study, while the characteristics of population and hospital controls were generally similar, differences were nevertheless observed in respect of alcohol consumption. Further studies are called for to ascertain whether there are differences between population or hospital controls, and for which diseases and popula- tions it would be more appropriate to use one or the other.

The authors declare no conflict of interests.

This work has been partly funded by two investigation grants, one from the Fondo de Investigaciones Sanitarias (FIS) (Health Research Fund) (grant FIS 92/0176) and the Galician Regional Health Authority (grant XUGA 91010).