Twenty-two points to consider for clinical trials in systemic sclerosis, based on EULAR standards

Dinesh Khanna; Daniel E Furst; Yannick Allanore; Sangmee Bae; Vijay Bodukam; Philip J Clements; Maurizio Cutolo; Laszlo Czirjak; Christopher P Denton; Oliver Distler; Ulrich A Walker; Marco Matucci-Cerinic; Ulf Müller-Ladner; James R Seibold; Manjit Singh; Alan Tyndall

doi:10.1093/rheumatology/keu288

Twenty-two points to consider for clinical trials in systemic sclerosis, based on EULAR standards

Rheumatology (Oxford). 2015 Jan;54(1):144-51. doi: 10.1093/rheumatology/keu288. Epub 2014 Aug 13.

Authors

Dinesh Khanna¹, Daniel E Furst², Yannick Allanore³, Sangmee Bae¹, Vijay Bodukam¹, Philip J Clements¹, Maurizio Cutolo¹, Laszlo Czirjak¹, Christopher P Denton¹, Oliver Distler¹, Ulrich A Walker¹, Marco Matucci-Cerinic³, Ulf Müller-Ladner¹, James R Seibold¹, Manjit Singh¹, Alan Tyndall¹

Affiliations

¹ 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.
² 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.
³ 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

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.

Conclusion: 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.

Keywords: clinical trials; points to consider; systemic sclerosis.

Publication types

Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Clinical Trials as Topic / ethics
Clinical Trials as Topic / standards*
Clinical Trials as Topic / trends*
Delphi Technique
Europe
Evidence-Based Medicine
Humans
Outcome Assessment, Health Care*
Patient Selection
Scleroderma, Systemic / therapy*
Time Factors