Defining appropriate outcome measures in pulmonary arterial hypertension related to systemic sclerosis: A Delphi consensus study with cluster analysis

Authors

  • Oliver Distler,

    1. University Hospital Zurich, Zurich, Switzerland
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    • Dr. Distler has received consultancies and/or speaking fees (less than $10,000 each) from Actelion and Encysive.

  • Frank Behrens,

    1. J. W. Goethe University, Frankfurt, Germany
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  • David Pittrow,

    1. Technical University, Dresden, Germany
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  • Doerte Huscher,

    1. German Rheumatism Research Centre, Berlin, Germany
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  • Christopher P. Denton,

    1. Royal Free and University College Medical School, London, UK
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    • Dr. Denton has received consultancies and honoraria (less than $10,000 each) from Actelion and Encysive.

  • Ivan Foeldvari,

    1. General Hospital Eilbek, Eilbek, Germany
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    • Dr. Foeldvari has received consultancies (less than $10,000 each) from Encysive and Roche.

  • Marc Humbert,

    1. Hôpital Antoine Beclere, Assistance Publique Hôpitaux de Paris, and Université Paris-Sud 11, Clamart, France
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    • Dr. Humbert has received consultancies and honoraria (less than $10,000 each) from Actelion, Bayer Schering, GSK, Novartis, Pfizer, and United Therapeutics.

  • Marco Matucci-Cerinic,

    1. University of Florence, Florence, Italy
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    • Dr. Matucci-Cerinic has received consultancies and/or speaking fees (less than $10,000 each) from Actelion, Encysive, Schering Plough, BMS, and Wyeth, and research grants from Actelion, Encysive, and Schering Plough.

  • Peter Nash,

    1. University of Queensland, Queensland, Australia
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    • Dr. Nash has received speaking fees and honoraria (less than $10,000) from Actelion and research grants from Actelion.

  • Christian F. Opitz,

    1. DRK-Kliniken Berlin, Westend, Berlin, Germany
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    • Dr. Opitz has received consultancies and/or honoraria (less than $10,000 each) from Actelion, Encysive, GSK, Pfizer, and Bayer Schering.

  • Lewis J. Rubin,

    1. University of California, San Diego
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    • Dr. Rubin has received consultancies (more than $10,000 each) from NHBLI, Actelion, Pfizer, United Therapeutics, Gilead, Aires, Bayer Schering Pharma, MondoBiotech, Novartis, Jerini AG, EPIX Pharmaceuticals, Broncus Technologies, Solvay, Cogentus, and GeneraMedix, investor consultancies from Gerson Lehrman Group, MEDACorp, Guidepoint Global Advisors, Piper Jaffray, and Citigroup, investment research from Vista Research and Concert Pharmaceuticals, research grants from NHBLI, Actelion, MondoBiotech, Gilead, United Therapeutics, Pfizer, and MD Primer, and holds stock in United Therapeutics.

  • James R. Seibold,

    1. University of Michigan Scleroderma Program, Ann Arbor
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  • Daniel E. Furst

    Corresponding author
    1. David Geffen School at University of California, Los Angeles
    • Division of Rheumatology, Department of Medicine, David Geffen School at UCLA, 1000 Veteran Avenue, Room 32-59, Los Angeles, CA
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  • Participants of the Delphi Survey are shown in Appendix A.

Abstract

Objective

Outcome measures for pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) are only partially validated. The aim of the present study was to establish an expert consensus regarding which outcome measures are most appropriate for clinical trials in PAH-SSc.

Methods

Sixty-nine PAH-SSc experts (rheumatologists, cardiologists, pulmonologists) rated a list of disease domains and measurement tools in an Internet-based 3-stage Delphi consensus study. In stages 2 and 3, the medians of domains and measurement tools and frequency distributions of ratings, along with requests for re-ratings, were distributed to respondents to provide feedback. A final score of items was identified by means of cluster analysis.

Results

The experts judged the following domains and tools as most appropriate for randomized controlled trials in PAH-SSc: lung vascular/pulmonary arterial pressure and cardiac function both measured by right heart catheterization and echocardiography, exercise testing measured by 6-minute walking test and oxygen saturation at exercise, severity of dyspnea measured on a visual analog scale, discontinuation of treatment measured by (serious) adverse events, quality of life/activities of daily living measured by the Short Form 36 and Health Assessment Questionnaire disability index, and global state assessed by physician measured by survival.

Conclusion

Among experts in PAH-SSc, a core set of outcome measures has been defined for clinical trials by Delphi consensus methods. Although these outcome measures are recommended by this expert group to be used as an interim tool, it will be necessary to formally validate the present measures, as well as potential research measures, in further studies.

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