Validation of surrogate end points in multiple randomized clinical trials with failure time end points

Before a surrogate end point can replace a final (true) end point in the ev aluation of an experimental treatment, it must be formally 'validated'. The validation will typically require large numbers of observations. It is the refore useful to consider situations in which data are available from sever al randomized experiments. For two normally distributed end points Buyse an d co-workers suggested a new definition of validity in terms of the quality of both trial level and individual level associations between the surrogat e and true end points. This paper extends this approach to the important ca se of two failure time end points, using bivariate survival modelling. The method is illustrated by using two actual sets of data from cancer clinical trials.