Imaging biomarkers: from research to patient care—a shift in view

Excerpt

The term “biomarker” is increasingly being used with different meanings in the scientific literature. In some cases it is used to indicate either a molecular probe or a technology or a method used to assess a biological variable in relation to an abnormal processes. However, according to the working group of the National Institutes of Health Director’s Initiative on Biomarkers and Surrogate Endpoints, a biomarker is “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” [1] This definition, in which a distinction between a tool and the variable measured by the tool is implicit, places a major emphasis on the measurement used as a marker of a biological state. This emphasis can be better appreciated if one considers the classification system for biomarkers developed by the same working group. Type 0 biomarkers are markers of the natural history of a disease and correlate longitudinally with known clinical indices, such as symptoms over the full range of disease states. Type I markers capture the effects of an intervention in accordance with the mechanism of action of the drug, even though the mechanism might not be known to be associated with clinical outcome. Type II markers are considered surrogate endpoints, i.e. biomarkers that are intended to substitute for a clinical endpoint that is expected to predict clinical benefit (or harm, or lack of benefit or harm) based on epidemiologic, therapeutic, pathophysiologic, or other scientific evidence. A surrogate endpoint and a clinical endpoint are not unassociated; in fact, changes induced by a therapy on a surrogate endpoint are expected to reflect changes in a clinically meaningful endpoint. A definition has also been proposed to distinguish biomarkers from clinical endpoints, defined as a characteristic or variable that reflects how a patient feels, functions, or survives. With these considerations in mind one can better appreciate the role of imaging biomarkers, those that hinge on the use of radiology, and nuclear medicine methods and tools. …