Table 3

Criteria for surrogate endpoints in chemoprevention trialsa

End point fits expected biological mechanism
· Differentially expressed in normal and high-risk tissue
· On or closely linked to causal pathway for cancer (e.g., expression increases/decreases with severity of dysplasia)
· Modulated by chemopreventive agents
· Latency is short compared with cancer
End point and assay provide acceptable sensitivity, specificity, and accuracy
· Assay for biomarker is standardized and validated
· Dose-related response to the chemopreventive agent is observed
· Statistically significant difference can be observed between levels in treatment groups and controls
Biomarker is easily measured
· Biomarker can be obtained by noninvasive or relatively noninvasive techniques
· Assay for biomarker is not technically difficult
Biomarker modulation correlates to decreased cancer incidence (i.e., the biomarker is validated as a surrogate end point, preferably in clinical studies. Animal studies may provide strong supportive evidence for validation)
  • a Adapted from reference 3 .