The uses of biomarkers in drug development.

Although the value of "surrogate biomarkers" (strictly speaking, those biomarkers that can serve as surrogate primary endpoints in registration trials) is significant, such biomarkers are few. However, "nonsurrogate biomarkers" are increasingly being used to reduce the risks of drug development. Any given biomarker is usually useful for only one of four types of risk reduction: that associated with (1) an inappropriate dosing regimen; (2) enrollment of nonresponsive subjects into clinical trials; (3) an inability to detect an efficacy signal quickly and reliably in chronic disorders; or (4) delayed recognition of potential side effects and/or toxicity. A biomarker suitable for one purpose is usually not suitable for the other three. Although these considerations apply to all drug development, both the need and availability of appropriate biomarkers in each category vary between therapeutic areas. The focus is on diseases of the brain.