Evidence from biomarkers and surrogate endpoints

Abstract

The use of physiological, anatomical, and other biological tests is commonplace in the practice of medicine. In neurology, objectively measured tests termed biomarkers (BMs) are playing an increasing role in diagnosis and management of disease, both in clinical practice and in experimental therapeutics. This article will discuss the various applications of BMs to the assessment of therapies for neurological diseases and will use examples from neurological diseases to elucidate the strengths and potential weaknesses of BMs. As the understanding of the pathophysiology of many neurological diseases has improved, new BMs have been developed, and efforts have been made to use these as proxies for clinical endpoints. A BM used in this manner is referred to as a surrogate endpoint (SE). There are many potential advantages and disadvantages of using SEs in the evaluation of new therapies, and these will be reviewed as well. Furthermore, the evidence required for the development of an SE and the nature of the evidence that can be derived from the use of BMs and SEs will be discussed.

FIG. 1.

Surrogate endpoints. The validation of a surrogate endpoint requires data from both basic science (mechanism) and clinical trials.

FIG. 2.

Proposed terminology for neurodegenerative disorders. Clinical measures are used in neurodegenerative disorders to assess both symptomatic therapies (clinical endpoints) and potential neuroprotective therapies (clinical markers). Surrogate endpoints may substitute for clinical endpoints, whereas surrogate markers may substitute for clinical markers (see text). Surrogate endpoints and surrogate markers are both biomarkers.