title: End-points and clinical trial design in pulmonary arterial hypertension: have we made progress?
abstract: There is enormous interest in the treatment of pulmonary arterial hypertension (PAH), so it is appropriate to consider the design of trials of new therapies and the end-points to be measured when trying to decide whether or not a therapy is effective. In May 2003, the first meeting devoted solely to the discussion of end-points and trial design in PAH was held in Gleneagles, UK. At that time, most of the randomised controlled trials in PAH had used 6-min walking distance and/or resting haemodynamics as their primary end-points. The present article considers the progress that has been made since 2003. It deals with aspects of clinical trial design (such as noninferiority, superiority and withdrawal trials), considers end-points used in previous and current studies (such as 6-min walking distance, time to clinical worsening, haemodynamics, imaging and plasma brain natriuretic peptide), and considers what end-points might be used in the future. The second end-points meeting was held in Turnberry, UK, in June 2007. It had a similar format to the first meeting. Much of what is presented here is a summary of the workshops from that meeting. An attempt has been made to both summarise the current state of end-points and trial design and suggest new ways in which they could be improved. The present article forms one of a series being published in the European Respiratory Journal on pulmonary hypertension.
authors: Scottish Pulmonary Vascular Unit, Regional Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow G81 4HX, UK. apeacock@udcf.gla.ac.uk
authors: A J
authors: AJ
authors: Peacock
authors: R
authors: R
authors: Naeije
authors: N
authors: N
authors: Galiè
authors: L
authors: L
authors: Rubin
mesh_terms: D002986:Clinical Trials as Topic; D004452:Echocardiography / Q000379:methods; D023381:Endpoint Determination; D005080:Exercise Test; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012129:Respiratory Function Tests; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome