• Ioana R Preston, Samy Suissa, and Marc Humbert.
• Pulmonary and Critical Care Division, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA. 2 Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, 3 Dept of Medicine, McGill University, Montreal, and 4 Dept of Epidemiology and Biostatistics, McGill University, Montreal, Canada. 5 Université Paris-Sud, AP-HP, Service de Pneumologie, Hôpital Bicêtre, Inserm U999, Le Kremlin Bicêtre, France.
• Eur Respir Rev. 2013 Dec 1; 22 (130): 495-502.

AbstractThe past two decades have seen significant improvements in the management of patients with pulmonary arterial hypertension (PAH). Although outcome has improved, long-term prognosis remains unsatisfactory. The development of new treatment options is clearly important. Equally important is testing new agents in trials designed to provide robust evidence for sustained clinical benefits enabling clinicians to determine the optimal treatment strategy for individual patients. End-points such as the change in 6-min walk distance (6MWD) have been pivotal in the registration trials of currently available PAH-specific therapies. However, as current clinical trials enrol patients with milder disease, many already on background therapy, there is growing evidence that change from baseline in 6MWD is a weak surrogate of outcome in PAH. In addition, while short-term trials allowed for the rapid approval of PAH therapies in the past, there is increasing recognition that clinical trials for new agents must provide evidence of long-term benefits. Clinical trials need to evolve to provide the long-term, clinically relevant data required to appropriately assess new therapies. Event-driven long-term morbidity and mortality trials are currently underway, and will provide robust data on the frequency and timing of events, and are likely to reflect the future of clinical trial design in PAH.

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