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

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

PMID: 25125594
PMCID: PMC4269793
DOI: 10.1093/rheumatology/keu288

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

Dinesh Khanna et al. Rheumatology (Oxford). 2015 Jan.

. 2015 Jan;54(1):144-51.

doi: 10.1093/rheumatology/keu288. Epub 2014 Aug 13.

Authors

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

PMID: 25125594
PMCID: PMC4269793
DOI: 10.1093/rheumatology/keu288

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.

PubMed Disclaimer

References

1. Charles C, Clements PJ, Furst DE. Systemic sclerosis: hypothesis-driven treatment strategies. Lancet. 2006;367:1683–91. - PubMed
1. Furst DE. Outcome measures in rheumatologic clinical trials and systemic sclerosis. Rheumatology. 2008;47(Suppl 5):v29–30. - PubMed
1. Khanna D, Lovell DJ, Giannini E, et al. Development of a provisional core set of response measures for clinical trials of systemic sclerosis. Ann Rheum Dis. 2008;67:703–9. - PMC - PubMed
1. White B, Bauer EA, Goldsmith LA, et al. Guidelines for clinical trials in systemic sclerosis (scleroderma). I. Disease-modifying interventions. The American College of Rheumatology Committee on Design and outcomes in clinical trials in systemic sclerosis. Arthritis Rheum. 1995;38:351–60. - PubMed
1. Abraham DJ, Varga J. Scleroderma: from cell and molecular mechanisms to disease models. Trends Immunol. 2005;26:587–95. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials