How a biomarker can become an acceptable substitution criteria?

How a biomarker can become an acceptable substitution criteria ? Numerous biomarkers of the treatment activity are now available as a result of the fascinating progresses in biology and biotechnology. Together with the rapidly growing understanding of the mechanisms of action of new agents, these biomarkers provide promising tools to evaluate early the effect of treatments against cancer. It is tempting to use these new markers of activity as primary endpoints to evaluate new treatments in the context of randomized clinical trials. Nevertheless, a mandatory preliminary step is to demonstrate that the two endpoints carry the same information in order to validate whether the biomarker is a surrogate of the final endpoint. We illustrate on several examples in prostate, gastric and early breast cancer that it is important to distinguish two levels of information: the individual level that allows to monitor a patient to anticipate treatment failure, and the trial level that enables to predict the treatment effect on the final endpoint based on the treatment effect measured on the surrogate endpoint. In several cases, the formal validation turned out to be disappointing despite strong biological rational.