Table 2.

Prentice²⁵ Criteria for Individual Patient–Level Surrogacy

Criterion	Description	Assessment
1	Treatment must have significant effect on clinical end point (ie, survival)	Treatment effect on survival was assessed using stratified log-rank test
2	Treatment must have significant effect on proposed biomarker	Treatment effect on surrogate was assessed using stratified score statistic from proportional odds regression model
3	Biomarker must have significant impact on clinical end point	Weighted c-index was used to quantify discriminatory power of surrogate with respect to survival; heuristically, for any two patients, c-index measures probability that patient classified as lower risk by surrogate also has longer survival time; values range between 0.5 and 1.0, with value 0.5 indicating that surrogate provides no information on survival time ranking
4	Full effect of treatment on clinical end point must be captured by biomarker	To show that after accounting for surrogate, treatment had no residual effect on survival, test for conditional independence was undertaken between survival model that included both patient surrogate and treatment assignment and survival model based solely on surrogate; Data Supplement provides details and results of this test