1 - Clinical research design: analytical studies

Summary

Analytic studies are used to define the relationship between a disease and its etiology or factors that may alter the course or manifestations of the disease. While these studies provide measures of the association between a risk factor, an exposure or a gene and a disease, Glynn points out that the association may also be due to chance, the result of an inherent bias or confounding. Analytic studies usually take the form of observational investigations, but can also include randomized clinical trials. All aspects of the disease pathway may be investigated in this fashion.

Disease pathway

The model of the classical disease pathway (Figure 1.1) offers a way of conceptualizing how and when factors act in the process of disease. Etiology refers to a specific cause, while pathogenesis defines the mechanism by which the etiology results in disease. The period between exposure to the cause and the initiation of the disease process is referred to as the induction period. This period of time is dependent on the etiology or cause; no specific time period can be defined. The period between the induction of disease and its detection has been termed by Rothman as the latency period.

In many neurologic disorders both the latency and induction periods may be lengthy. Associations between factors and disease may indicate where influences act in the disease pathway. For example, risk factors that act during the induction period will, most likely, have direct effects on risk. Traumatic head injury is an example of a risk factor that is considered by some to increase the risk of Alzheimer's disease by promoting the extracellular release of β-amyloid in the brain.