Clinical criteria for surrogacy–Boissel et al. (1992) as modified by Espeland et al. (2005)
| Efficiency | The surrogate marker should be relatively easy to evaluate, preferably by noninvasive means, and more readily available than the gold standard; the time course of changes in the surrogate marker should precede that of the endpoints so that disease and/or disease progression may be established more quickly via the surrogate; clinical trials based on surrogates should require fewer resources, less participant burden, and a shorter time frame |
| Linkage | The quantitative and qualitative relationship between the surrogate marker and the clinical endpoint should be established on the basis of epidemiologic and clinical studies; the nature of this relationship may be understood in terms of its pathophysiology or in terms of an expression of joint risk |
| Congruence | The surrogate should produce parallel estimates of risk and benefits that are related to the target disease process as endpoints; individuals with and without vascular disease should exhibit differences in surrogate marker measurements; in intervention studies, anticipated clinical benefits should be deducible from the observed changes in the surrogate marker |