Clinical drug development in thromboembolic diseases: regulatory and methodological approach.

Coinciding in time with the expiration of the patent of enoxaparin and clopidogrel, a number of new antithrombotics (anticoagulants and antiplatelets with new mechanisms of action) have been developed or are still under development for both venous and arterial thromboembolic complications. The effect of antithrombotic drugs is a continuum where a fine tune assessment of the ischemic events that are intended to be prevented and bleeding complications derived naturally from the own mechanism of action of the administered agent is essential. This paper discusses relevant aspects of pivotal studies aimed to support the marketing authorisation application of new antithrombotics for the prophylaxis or treatment of venous thromboembolism on one hand, and arterial thromboembolism on the other hand (acute coronary syndromes and stroke and systemic embolic events in patients with atrial fibrillation). General methodological issues and tools to assess efficacy and safety parameters and problems encountered in the way they are measured and classified are discussed.