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Outcome Measurements in Scleroderma:
Results from a Delphi Exercise
HASHIM GAZI, JANET E. POPE, PHILIP CLEMENTS, THOMAS A. MEDSGER, RICHARD W. MARTIN, PETER A. MERKEL, BASHAR KAHALEH, FRANK A. WOLLHEIM, MURRAY BARON, MARY ELLEN CSUKA, PAUL EMERY, JILL F. BELCH, SAMINA HAYAT, EDWARD V. LALLY, JOSEPH H. KORN, LÁSZLÓ CZIRJÁK, ARIANE HERRICK, ALEXANDER E. VOSKUYL, PIUS BRUEHLMANN, MURAT INANC, DANIEL E. FURST, CAROL BLACK, MICHAEL H. ELLMAN, LARRY W. MORELAND, NAOMI F. ROTHFIELD, VIVIEN HSU, MAUREEN MAYES, KEVIN M. McKOWN, THOMAS KRIEG, and JAMES R. SEIBOLD ABSTRACT. Objective. To obtain a consensus on the minimal clinically relevant treatment effect in various scleroderma disease outcome measures to be used in future clinical trials. Methods. A Delphi consensus building exercise using a survey was sent out to members of the Scleroderma Clinical Trials Consortium (SCTC). The 65 SCTC members were divided into 2 groups. Group 1 was informed, in a cover letter, of the usual American College of Rheumatology 20% response results in randomized trials using effective biologic treatments for rheumatoid arthritis, while Group 2 was not. The first round of the exercise presented the scleroderma experts with a survey composed of 95 questions/clinical scenarios divided into 8 categories. These included situations where the treatment group improved, or worsened, or where some outcome measures improved, while others worsened. From the responses of this first round, a mean, mode, median, and range of responses for each of the 95 questions was obtained. This information was sent out, in the second round of the Delphi exercise, only to those respondents who answered the first round. The respondent's previous answer and the mean and range from the first round were provided for each question. It gave respondents the option to change any of their initial responses. The median of their responses in the second round was used to calculate the values for the minimal clinically relevant treatment effect. Results. Thirty-two of the 65 SCTC members returned the first round of the Delphi exercise. Twenty-eight members returned the second round. Intraclass correlation coefficients between responses to round 1 and 2 were calculated for the questions. These varied from 0.99 (excellent agreement) to 0.02 (poor agreement). The p value was under 0.09 for 9 questions and under 0.19 for 20 questions. Standard deviations (SD) were calculated and were found to be lesser for each of the questions in round 2 when compared to the SD in responses from round 1, thus indicating a movement towards a consensus by the second round. An average of 33% of the responses were changed by the respondents in the second round of the Delphi exercise to a value closer to the median/average of the first round's responses. A range in required values for the minimal clinically relevant treatment effect for Modified Rodnan skin score is 3 to 7.5 units, Health Assessment Questionnaire Disability Index (HAQ-DI) 0.2 to 0.25 units, HAQ pain 0.2 to 0.3 units, MD global (100 mm visual analog scale) 8 to 13, patient global assessment 10 to 12, and diffusing capacity (percentage predicted) 9 to 10. The scenarios were especially weighted towards overall disease modification, thus organ-specific measures, such as 6 minute walk time (which has been used in many pulmonary artery hypertension trials), forced vital capacity, and a dyspnea rating (which may be important in scleroderma lung trials), were not included in the survey. Conclusion. Our study begins to address the current deficiency in our knowledge of appropriate values for the minimal clinically relevant treatment effect in various scleroderma disease outcome measures. A consensus could be achieved, or at least a range of minimal clinically relevant treatment effect values could be found for several outcome measurements. Of course, this consensus statement will be modified by evidence as it accrues in each consensus area. (First Release Feb 1 2007; J Rheumatol 2007;34:501-9) Key Indexing Terms:
SYSTEMIC SCLEROSIS From the Division of Rheumatology, Department of Medicine, The University of Western Ontario, London, Ontario, Canada. Supported by the Summer Research Training Program of the Schulich School of Medicine at the University of Western Ontario, London, Ontario, Canada. H. Gazi, BA, Medical Student, Schulich School of Medicine; J.E. Pope, MD, MPH, FRCPC, Professor of Medicine and Epidemiology and Biostatistics, Division of Rheumatology, Department of Medicine, The University of Western Ontario; P. Clements, MD, Professor of Medicine, University of California, Los Angeles, Los Angeles, California; T.A. Medsger, MD, Department of Medicine, Division of Rheumatology, University of Pittsburgh, Pittsburgh, Pennsylvania; R.W. Martin, MD, College of Human Medicine, Michigan State University, Grand Rapids, Michigan; P.A. Merkel, MD, MPH, Boston University School of Medicine, Boston, Massachusetts; B. Kahaleh, MD, Professor, Chief of Rheumatology, Medical College of Ohio, Toledo, Ohio, USA; F.A. Wollheim, MD, PhD, Department of Rheumatology, Lund University Hospital, Lund, Sweden; M. Baron, MD, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; M.E. Csuka, MD, Professor of Medicine, Department of Rheumatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; P. Emery, BA, MA, MBChir, MRCP, MD, FRCP, Professor of Medicine, Leeds University, Academic Unit of Musculoskeletal Disease, Leeds; J.F. Belch, MD, Reader and Consultant Physician, Ninewells Hospital and Medical School, Dundee, United Kingdom; S. Hayat, MD, Department of Medicine — Rheumatology, Louisiana State University, Shreveport, Louisiana; E.V. Lally, MD, Chief, Division of Rheumatology, Brown University School of Medicine, Providence, Rhode Island; J.H. Korn, MD, Boston University School of Medicine, Boston, Massachusetts, USA; L. Czirják, MD, DSc, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary; A. Herrick, MBChB, MD, FRCP, University of Manchester, Manchester, UK; A.E. Voskuyl, MD, PhD, VU University Medical Center, Amsterdam, The Netherlands; P. Bruehlmann, MD, Department of Rheumatology and Physical Medicine, University Hospital, Zurich, Switzerland; M. Inanc, MD, Department of Internal Medicine, Division of Rheumatology, University of Istanbul, Istanbul, Turkey; D.E. Furst, MD, University of California, Los Angeles, Los Angeles, California, USA; C. Black, MD, Centre for Rheumatology, Royal Free Hospital, London, UK; M.H. Ellman, MD, The University of Chicago, Chicago, Illinois; L.W. Moreland, MD, Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, Alabama; N.F. Rothfield, MD, Professor of Medicine, Chief, Division of Rheumatic Diseases, University of Connecticut Health Center, Farmington, Connecticut; V. Hsu, MD, Director, Scleroderma Program, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, Piscataway, New Jersey; M. Mayes, MD, MPH, Division of Rheumatology and Clinical Immunogenetics, University of Texas–Houston Medical School, Houston, Texas; K.M. McKown, MD, University of Wisconsin–Madison, Madison, Wisconsin, USA; T. Krieg, MD, Professor, Department of Dermatology, University of Cologne, Cologne, Germany; J.R. Seibold, MD, Department of Internal Medicine/Rheumatology, University of Michigan, Ann Arbor, Michigan, USA. Address reprint requests to Prof. J.E. Pope, Rheumatology Center, St. Joseph's Health Care London, 268 Grosvenor Street, Box 5777, London, Ontario N6A 4V2, Canada. E-mail: janet.pope@sjhc.london.on.ca Accepted for publication October 13, 2006.
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