[Methodological approaches of clinical studies with targeted therapies].

The development of molecular targeted therapies requires some specific methodological approaches. Dose-limiting toxicities are rare in phase I studies the maximal tolerated dose is rarely established. On the contrary, the biological active dose is often determined as the dose inducing biological effect on the target without significant clinical toxicity. Several designs of phase II are described (selection phase II, randomized phase II, stratified phase II...). All of them are indicated in specific situations. The discontinuation treatment studies and the validation of biomarkers (as surrogate endpoints or as classifiers) are the two main particularities of phase III studies designed for the assessment of molecular targeted therapies.