End points and clinical trial design in pulmonary arterial hypertension.
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.
McLaughlin
Vallerie V
VV
Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan. Electronic address: vmclaugh@med.umich.edu.
Badesch
David B
DB
Divisions of Pulmonary Sciences and Critical Care Medicine, and Cardiology, University of Colorado Health Sciences Center, Denver, Colorado.
Delcroix
Marion
M
Center for Pulmonary Vascular Disease, Department of Pneumology, Gasthuisberg University Hospital, Leuven, Belgium.
Fleming
Thomas R
TR
Department of Biostatistics, University of Washington, Seattle, Washington.
Gaine
Sean P
SP
National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland.
Galiè
Nazzareno
N
Pulmonary Hypertension Center, Institute of Cardiology, University of Bologna, Bologna, Italy.
Gibbs
J Simon R
JSR
Department of Clinical Cardiology, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Kim
Nick H
NH
Pulmonary and Critical Care Medicine, University of California San Diego School of Medicine, La Jolla, California.
Oudiz
Ronald J
RJ
Liu Center for Pulmonary Hypertension, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
Peacock
Andrew
A
Department of Respiratory Medicine, Scottish Pulmonary Vascular Unit, University of Glasgow, Glasgow, Scotland, United Kingdom.
Provencher
Steeve
S
Institute of Cardiology and Pulmonology, Laval University, Sainte-Foy, Québec, Canada.
Sitbon
Olivier
O
Centre des Maladies Vasculaires Pulmonaires, Hôpital Antoine Béclère, Clamart, France.
Tapson
Victor F
VF
Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina.
Seeger
Werner
W
Department of Internal Medicine, University of Giessen Lung Center, Giessen, Germany.
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