ABSTRACT
The goal of any intervention in medicine, for example the administration of a drug or a change in lifestyle, is to reduce mortality or morbidity, or to improve quality of life. However, establishing whether any given intervention has such effects can be time-consuming and costly. Rather than assess the effects of interventions on outcomes that are relevant to patients, surrogate endpoints are often substituted, in an attempt to improve the efficiency with which interventions are evaluated. The realization that the use of surrogate endpoints is likely to gather pace, as the underlying pathophysiology of different diseases is elucidated and the number of candidate drugs rises, prompted a working party at the National Institutes of Health (NIH) in the USA to formally define the terms biological marker, clinical endpoint and surrogate endpoint
(Box 7.1).1 The term intermediate (or non-ultimate) end-point is also sometimes used. An intermediate endpoint is a true clinical endpoint, but is not the ultimate endpoint of disease. For example, the main clinical endpoints of ischaemic heart disease are the occurrence of myocardial infarction, heart failure and death. Exercise tolerance might be considered a surrogate endpoint for these, but at the same time may also be considered a clinical endpoint in its own right, given that it is an important determinant of how a patient feels and functions.
