title: Twenty-two points to consider for clinical trials in systemic sclerosis, based on EULAR standards.
abstract: OBJECTIVE
  SSc is clinically and aetiopathogenically heterogeneous. Consensus standards for more uniform trial design and selection of outcome measures are needed. The objective of this study was to develop evidence-based points to consider (PTCs) for future clinical trials in SSc.
  
  
  METHODS
  Thirteen international SSc experts experienced in SSc clinical trial design were invited to participate. One researcher with experience in systematic literature review and three trainees were also included. A systematic review using PubMed and the Cochrane Central Register of Controlled Trials was conducted and PTCs when designing clinical trials in SSc were developed. As part of that development we conducted an Internet-based Delphi exercise regarding the main points to be made in the consensus statement. Consensus was defined as achieving a median score of ≥7 of 9.
  
  
  RESULTS
  By consensus, the experts decided to develop PTCs for each individual organ system. The current document provides a unifying outline on PTCs regarding general trial design, inclusion/exclusion criteria and analysis. Consensus was achieved regarding all the main points of the PTCs.
  
  
  CONCLUSIONS
  Using European League Against Rheumatism suggestions for PTCs, a general outline for PTCs for controlled clinical trials in SSc was developed. Specific outlines for individual organ systems are to be published separately. This general outline should lead to more uniform and higher-quality trials and clearly delineate areas where further research is needed.
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA. defurst@mednet.ucla.edu.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA. Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Div
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: Sangmee
authors.initials: S
authors.lastname: Bae
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Bodukam
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Clements
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Czirjak
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Denton
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Walker
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA. Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Div
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Seibold
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: Manjit
authors.initials: M
authors.lastname: Singh
authors.affiliation: Division of Rheumatology, University of Michigan Scleroderma Program, Ann Arbor, MI, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA, Department of Rheumatology A, Paris Descartes University, Cochin Institut, INSERM U1016, Cochin Hospital, Paris, France, Department of Medicine, Crozer Chester Medical Center, Upland, PA, USA, Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, Centre for Rheumatology, Royal Free Hospital, London, UK, Department of Rheumatology, University Hospital Zurich, Zurich, Deparment of Rheumatology, Basel University, Basel, Switzerland, Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, Department of Medicine, Denothe Centre, University of Florence, Florence, Italy, Department of Rheumatology and Clinical Immunology, Justus-Liebrig University Giessen, Kerckhoff Clinic, Bad Beuheinn, Germany, Scleroderma Research Consultants, Avon, CT and Department of Internal Medicine, Rochester General Health System, Rochester, NY, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Tyndall
mesh_terms: D002986:Clinical Trials as Topic / Q000941:ethics / Q000592:standards* / Q000639:trends*; D003697:Delphi Technique; D005060:Europe; D019317:Evidence-Based Medicine; D006801:Humans; D017063:Outcome Assessment, Health Care; D018579:Patient Selection; D012595:Scleroderma, Systemic / Q000628:therapy*; D013997:Time Factors
keywords: clinical trials; points to consider; systemic sclerosis