title: Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration.
abstract: BACKGROUND
  A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial.
  
  
  METHODS
  A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus β-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will be made available online (http://www.ctsu.ox.ac.uk/research/meta-trials).
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. Electronic address: alex.pitcher@cardiov.ox.ac.uk.
authors.forename: Alex
authors.initials: A
authors.lastname: Pitcher
authors.affiliation: Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Oxford, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Emberson
authors.affiliation: Children's Hospital Boston and Harvard Medical School, Boston, MA.
authors.forename: Ronald V
authors.initials: RV
authors.lastname: Lacro
authors.affiliation: New England Research Institutes, Watertown, MA.
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Sleeper
authors.affiliation: National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
authors.forename: Mario
authors.initials: M
authors.lastname: Stylianou
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Lynn
authors.initials: L
authors.lastname: Mahony
authors.affiliation: National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
authors.forename: Gail D
authors.initials: GD
authors.lastname: Pearson
authors.affiliation: Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Groenink
authors.affiliation: Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Mulder
authors.affiliation: Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.affiliation: Center for Medical Genetics and Department of Cardiology, University Hospital Ghent, Ghent, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: De Backer
authors.affiliation: Center for Medical Genetics, University Hospital Ghent, Ghent, Belgium.
authors.forename: Anne M
authors.initials: AM
authors.lastname: De Paepe
authors.affiliation: Centre for Inherited Cardiovascular Diseases, IRCCS Foundation, San Matteo Hospital, Pavia, Italy.
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
authors.affiliation: Clinical Trials and Evaluation Unit, Royal Brompton & Harefield NHS Trust, London, UK.
authors.forename: Guliz
authors.initials: G
authors.lastname: Erdem
authors.affiliation: John Radcliffe Hospital, Oxford, UK.
authors.forename: Xu Yu
authors.initials: XY
authors.lastname: Jin
authors.affiliation: Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Flather
authors.affiliation: UCL Institute of Cardiovascular Science, The Heart Hospital, London, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mullen
authors.affiliation: Department of Cardiac and Vascular Sciences, St George's Hospital, University of London, London, UK.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Child
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Forteza
authors.affiliation: Marfan Sydrome Unit, Department of Cardiology, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Arturo
authors.initials: A
authors.lastname: Evangelista
authors.affiliation: Department of Pediatrics and Adult Congenital Heart Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Hsin-Hui
authors.initials: HH
authors.lastname: Chiu
authors.affiliation: Department of Pediatrics and Adult Congenital Heart Center, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Mei-Hwan
authors.initials: MH
authors.lastname: Wu
authors.affiliation: Children's Heart Centre, British Columbia's Children's Hospital, Vancouver, British Columbia, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Sandor
authors.affiliation: Massachusetts General Hospital, Boston, MA.
authors.forename: Ami B
authors.initials: AB
authors.lastname: Bhatt
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Creager
authors.affiliation: Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Devereux
authors.affiliation: Center for Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Loeys
authors.affiliation: John Radcliffe Hospital, Oxford, UK.
authors.forename: J Colin
authors.initials: JC
authors.lastname: Forfar
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
authors.affiliation: Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Hugh
authors.initials: H
authors.lastname: Watkins
authors.affiliation: Inserm LVTS U1148, Departement de Génétique, Hôpital Xavier Bichat-Claude Bernard, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.affiliation: Centre National de Référence pour le syndrome de Marfan et apparentés, INSERM LVTS U1148, Service de Cardiologie, AP-HP Hôpital Bichat, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jondeau
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, and the Howard Hughes Medical Institute, Baltimore, MD.
authors.forename: Harry C
authors.initials: HC
authors.lastname: Dietz
authors.affiliation: Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Oxford, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Baigent
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000188:drug therapy*; D015201:Meta-Analysis as Topic; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
chemical_list: D057911:Angiotensin Receptor Antagonists