Pulmonary hypertension trials: how can we do better?

Conducting clinical trials on pulmonary hypertension in the US and Western Europe has become increasingly difficult and costly because of many challenges. These include a limited patient population that makes recruitment difficult. Recruiting internationally has helped, but can add variability. The choice of end points is important but ideal end points that reflect pathogenesis of the disease are not available. The 6-min walk distance has been used in most trials to date, but recent trials have used an 'event-driven' design, in which combined outcomes are used to reflect progression of the disease. This design has advantages but requires many hundreds of patients and may take up to several years. Thus, there is still a role for functional or hemodynamic end points to enable testing of more new agents. Assuring the safety and scientific integrity of clinical trials without excessive regulation will also help facilitate the evaluation of additional therapies for this devastating disease.