Research and treatment of pulmonary vascular diseases pose distinct challenges. Despite these hurdles (or perhaps because of them), a cadre of basic scientists, geneticists, physiologists, clinical researchers and clinicians have dedicated themselves to the study and care of patients with pulmonary vascular disease. The European Respiratory Journal (ERJ) series “Advances in Pathobiology, Diagnosis, and Treatment of Pulmonary Hypertension” 1–10 comprehensively categorises the achievements of these individuals and concludes this month with a fitting finale. Peacock et al. 11 (this issue of the ERJ) and Hoeper et al. 12 have written statements from recent conferences focused on the methodology of randomised controlled trials (RCTs) in pulmonary arterial hypertension (PAH); until recently, a seemingly quixotic discussion. As with all important research, these documents potentially raise more questions than they answer.
The availability of bosentan (an endothelin‐1 receptor antagonist) and other safe, effective therapies for PAH led the working groups to reevaluate the ethical and scientific merit of using untreated placebocontrol arms in RCTs 2, 13–15. This is a very controversial area faced by researchers in other conditions with preexisting effective therapies, such as congestive heart failure (CHF) 16–19. In general, it is considered to be ethical to perform such trials if: 1) the patient is fully informed about the alternatives; and 2) there is minimal risk of irreversible or severe morbidity, or mortality, posed by withholding effective therapy.
While the former concern is relatively straightforward, the working groups recognised the difficulty in defining the boundaries of the latter. As the success of future placebocontrolled trials in this rare disease will depend on patients' and physicians' willingness to enrol in such trials, future study designs will have to be acceptable to both groups. Such acceptability may be important to investigate before initiating …