A surrogate endpoint is one that is measured in place of the biologically definitive or clinically meaningful endpoint. A surrogate endpoint usually tracks the progress or extent of the disease.
Investigators choose a surrogate endpoint when the definitive endpoint is inaccessible due to cost, time, or difficulty of measurement. The problem with a surrogate endpoint in a clinical trial is determining whether it is valid (i.e., is it strongly associated with the definitive outcome?)
Piantadosi (2005) gives the following characteristics of a useful surrogate endpoint:
- It can be measured simply and without invasive procedures
- It is related to the causal pathway for the definitive endpoint
- It yields the same statistical inference as that for the definitive endpoint
- It should be responsive to the effects of treatments
The disease affects the surrogate endpoint, which in turn affects the definitive endpoints.
Examples of surrogate endpoints include CD4 counts in AIDS patients, tumor size reduction in cancer patients, blood pressure in cardiovascular disease, and intraocular pressure in glaucoma patients. The response variables in translational research are surrogate endpoints.
Surrogate endpoints can potentially shorten and increase the efficiency of clinical trials. If, however, the surrogate is imprecisely associated with definitive endpoints, the use of the surrogate can lead to misleading results.