3. general considerations for the analysis of case-control ... - IARC

INTRODUCTION 21
cording to age, sex and various risk factors at a point in (in fact during a brief period of)
time. This cannot be achieved in a follow-up study, even if a general population comprises
the study group (which is uncommon), unless new sub-cohorts are periodically added
to the persons under observation. The reason is that a follow-up study group gives a
broad picture of a cancer only at the start of the study. Thereafter, the group evolves
and certain subgroups, e.g., the young, "disappear"; another subgroup literally disappears
from the study - those lost to follow-up. On the other hand, the population-based
case-control study provides a "window" on the totality of a cancer. One example of
such a study relates to cancer of the bladder (Cole, 1973).
A second advantage of the case-control design is its efficiency, which is particularly
impressive in view of its high informativeness. Such studies may be done in a few weeks
if pre-existing data are used, but more often they take a year or two especially if the
subjects are interviewed. Furthermore, the cost of these studies has tended to be low
because only pre-existing or anamnestic data were gathered on relatively few subjects;
case-control studies usually include several hundred subjects compared with the many
thousands in follow-up studies. However, this low cost is becoming less characteristic of
case-control studies of cancer because the kind of data required is changing. Many
studies now require that interviews be supplemented with complex biochemical or other
types of analysis of biological specimens. Despite the increased cost, this change is
welcome for it is due to improvement in our understanding of the causes of cancer. On
the other hand, the use of biological specimens in case-control studies may sometimes
contribute nothing, or even be inappropriate, because the changes found may reflect
some pathophysiological effect of the cancer rather than a cause. The advantages, then,
of speed and low cost, while a general attribute of case-control studies, are not characteristic
of all of them. Moreover, speed and low cost are not unique to the case-control
study, and indeed the non-concurrent follow-up study is usually superior in these aspects.
A third advantage of the case-control study is its applicability to rare as well as common
diseases. In this context, all but the three most common cancers (those of the
breast, lung and colon in the western world) are "rare". In addition, the more rare
the cancer, the greater is the relative advantage of this design. A disease which is rare
in general, however, may not be rare in a special exposure group. If this is suspected
and if such a group can be identified from a period in the past, a non-concurrent followup
study should be considered.
A fourth advantage is that case-control studies (as well as follow-up studies) permit
evaluation of the causal significance of a rare exposure. This is often not appreciated,
and it is a common misconception that a case-control study is inappropriate for study of
a rare exposure. Insofar as the prevalence of an exposure makes it suitable or unsuitable
for a case-control study, it is not the general prevalence (i.e., among potential
controls) but that among the cases that is relevant. If a factor is rare, but nonetheless
accounts for a high proportion of the cancer, that is, if the factor is related to a high
population-attributable risk percent (Cole & MacMahon, 1971), it can be studied.
Indeed this is a circumstance that maximizes the efficiency of the case-control design
since it enables a small study to be quite powerful. One example is the case-control
study of eight young women with clear-cell adnocarcinoma of the vagina and 32 controls
(Herbst, Ulfelder & Poskanzer, 197 1). Similarly, a large fraction of mesotheliomas of
the pleura are related to exposure to asbestos (Greenberg & Lloyd Davies, 1974), and