title: End points and clinical trial design in pulmonary arterial hypertension.
abstract: New and emerging therapies might provide benefit in patients with pulmonary arterial hypertension. Their efficacy and safety will be compared with existing combination therapies in randomized clinical trials. Appropriate end points for these trials need to be identified: these will include exercise testing, the composite end point of time to clinical worsening, and hemodynamic markers, including advanced imaging modalities and biomarkers. Quality-of-life questionnaires are useful and important secondary end points; pulmonary arterial hypertension-specific questionnaires are currently being developed. Advantages and disadvantages of various trial designs, including placebo-controlled monotherapy or add-on trials, noninferiority studies, and withdrawal trials are also discussed.
authors: Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan. Electronic address: vmclaugh@med.umich.edu.
authors: Vallerie V
authors: VV
authors: McLaughlin
authors: Divisions of Pulmonary Sciences and Critical Care Medicine, and Cardiology, University of Colorado Health Sciences Center, Denver, Colorado.
authors: David B
authors: DB
authors: Badesch
authors: Center for Pulmonary Vascular Disease, Department of Pneumology, Gasthuisberg University Hospital, Leuven, Belgium.
authors: Marion
authors: M
authors: Delcroix
authors: Department of Biostatistics, University of Washington, Seattle, Washington.
authors: Thomas R
authors: TR
authors: Fleming
authors: National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland.
authors: Sean P
authors: SP
authors: Gaine
authors: Pulmonary Hypertension Center, Institute of Cardiology, University of Bologna, Bologna, Italy.
authors: Nazzareno
authors: N
authors: Galiè
authors: Department of Clinical Cardiology, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: J Simon R
authors: JSR
authors: Gibbs
authors: Pulmonary and Critical Care Medicine, University of California San Diego School of Medicine, La Jolla, California.
authors: Nick H
authors: NH
authors: Kim
authors: Liu Center for Pulmonary Hypertension, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors: Ronald J
authors: RJ
authors: Oudiz
authors: Department of Respiratory Medicine, Scottish Pulmonary Vascular Unit, University of Glasgow, Glasgow, Scotland, United Kingdom.
authors: Andrew
authors: A
authors: Peacock
authors: Institute of Cardiology and Pulmonology, Laval University, Sainte-Foy, Québec, Canada.
authors: Steeve
authors: S
authors: Provencher
authors: Centre des Maladies Vasculaires Pulmonaires, Hôpital Antoine Béclère, Clamart, France.
authors: Olivier
authors: O
authors: Sitbon
authors: Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina.
authors: Victor F
authors: VF
authors: Tapson
authors: Department of Internal Medicine, University of Giessen Lung Center, Giessen, Germany.
authors: Werner
authors: W
authors: Seeger
mesh_terms: D002986:Clinical Trials as Topic; D023381:Endpoint Determination; D005080:Exercise Test; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012129:Respiratory Function Tests; D016896:Treatment Outcome