Case-Only Design

Analytical studies are designed to test the hypotheses created by descriptive studies and to assess the cause–effect association. These studies are able to measure the effect of a specific exposure on the occurrence of an outcome over time. Depending on the nature of the exposure, whether it has been caused experimentally as an intervention on the study subjects or has happened naturally, without any specific intervention on the subjects, these studies may be divided into two major groups: observational and experimental studies. Each of these designs has its own advantages and disadvantages. In observational studies, by definition, the researcher is looking for causes, predictors, and risk factors by observing the phenomenon without doing any intervention on the subjects, whereas in experimental designs, there is an intervention on the study subjects. In practice, however, there is no clear-cut distinction between different types of study design in biomedical research. Case-only studies are genetics studies in which individuals with and without a genotype of interest are compared, with an emphasis on environmental exposure.

For evaluation of etiologic and influencing role of some factors (such as risk factors) on the occurrence of diseases, we necessarily need to have a proper control group. Otherwise, no inferential decision can properly be made on the influencing role of risk factors. One of the study designs with control subjects is case–control study. These studies are designed to assess the cause–effect association by comparing a group of patients with a (matched) group of control subjects in terms of influencing or etiologic factors.

Some concerns in case–control studies, including control group and appropriate selection of control subjects, expensive cost for examining risk markers in both cases and controls (particularly in genetic studies), and the time-consuming process of such studies, have led to the development of the case-only method in studying the gene–environment interaction in human diseases. Investigators studying human malignancies have broadly used this method in recent years.

The case-only method was originally designed as a valid approach to the analysis and screening of genetic factors in the etiology of multifactorial diseases and also to assessing the gene–environment interactions in the etiology. In a case-only study, cases with and without the susceptible genotype are compared with each other in terms of the existence of the environmental exposure.

To conduct a case-only design, one applies the same epidemiological approaches to case selection rules as for any case–control study. The case-only study does not, however, have the complexity of rules for the selection of control subjects that usually appears in traditional case–control studies. The case-only method also requires fewer cases than the traditional case–control study. Furthermore, the case-only design has been reported to be [Page 115]more efficient, precise, and powerful compared with a traditional case–control method.

Although the case-only design was originally created to improve the efficiency, power, and precision of the study of the gene–environment interactions by examining the prevalence of a specific genotype among case subjects only, it is now used to investigate how some other basic characteristics that vary slightly (or never vary) over time (e.g., gender, ethnicity, marital status, social and economic status) modify the effect of a time-dependent exposure (e.g., air pollution, extreme temperatures) on the outcome (e.g., myocardial infarction, death) in a group of cases only (e.g., decedents).

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