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Development of Draft Validation Criteria for a Soluble Biomarker to Be Regarded as a Valid Biomarker Reflecting Structural Damage Endpoints in Rheumatoid Arthritis and Spondyloarthritis
Clinical Trials
WALTER P. MAKSYMOWYCH, ROBERT LANDEWÉ, MAARTEN BOERS, PATRICK GARNERO, PIET GEUSENS, HANI EL-GABALAWY, DICK HEINEGARD, VIRGINIA KRAUSE, STEFAN LOHMANDER, JOHN MATYAS, TORE SAXNE, DÉSIRÉE van der HEIJDE ABSTRACT. Objective. Recent work has shown that several soluble biomarkers, detectable in peripheral blood, synovial fluid, and/or urine, reflect remodeling of joint tissues and may therefore constitute outcome measures that reflect joint damage. Consequently, it is now desirable to begin the process of developing criteria for validation of a soluble biomarker as an outcome measure reflecting structural damage progression in trials of disease-modifying therapies for rheumatoid arthritis (RA) and spondyloarthritis (SpA). Our objective was to develop validation criteria for a soluble biomarker to be regarded as a valid biomarker reflecting radiological endpoints in RA and SpA clinical trials. Methods. A special interest group was established comprising investigators with expertise in soluble biomarker assay development as well as in outcomes research. This project was initiated by means of a Delphi consensus exercise. A list of draft criteria was first generated following a review of a US National Institutes of Health (NIH) 2000 white paper (available at: http://www.niams.nih.gov/ne/oi/ oabiomarwhipap.htm) that focused on biomarkers in OA, and these were organized under subject headings relevant to the OMERACT filter: truth, discrimination, and feasibility. Additional criteria were solicited from the working group. This was followed by 3 rounds of voting. Results. A list of 31 criteria was generated prior to voting. The first 2 rounds of voting resulted in cumulative agreement that 19 criteria be retained and 4 discarded, while discrepancies were recorded for 8 criteria. In the third round of voting, cumulative agreement was achieved to retain 5 of the 8 discrepant criteria, so that the final list included 24 criteria. Conclusion. A draft set of criteria for validation of a soluble biomarker to be regarded as reflecting radiological damage endpoints in clinical trials has been proposed on the basis of consensus. (J Rheumatol 2007;34:634-40) Key Indexing Terms:
BIOMARKER From the Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, University of Maastricht, Maastricht, The Netherlands; Department of Clinical Epidemiology, VU University Medical Centre, Amsterdam, The Netherlands; INSERM Research Unit 664, Lyon, France; Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Division of Rheumatology, Lund University Hospital, Lund, Sweden; Department of Medicine, Duke University, Durham, North Carolina, USA; Department of Orthopedics, Clinical Sciences, Lund University, Lund, Sweden; and Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada. Prof. Maksymowych is a Senior Scholar of the Alberta Heritage Foundation for Medical Research. W.P. Maksymowych, FRCPC, Professor, Department of Medicine, University of Alberta; R. Landewé, MD, PhD, Associate Professor, Department of Medicine, University of Maastricht; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology, VU University Medical Centre, Amsterdam; P. Garnero, PhD, DSc, Director of Research, INSERM Research Unit 664 and Molecular Markers, Synarc, Lyon; P. Geusens, MD, PhD, Professor, Department of Medicine, University of Maastricht; H. El-Gabalawy, MD, FRCPC, Professor, Department of Medicine, University of Manitoba; D. Heinegard, MD, PhD, Professor, Division of Rheumatology, Lund University Hospital; V. Krause, MD, PhD, Associate Professor, Department of Medicine, Duke University; S. Lohmander, MD, PhD, Professor, Department of Orthopedics, Clinical Sciences, Lund University; J. Matyas, PhD, Professor, Department of Cell Biology and Anatomy, University of Calgary; T. Saxne, MD, PhD, Professor, Department of Rheumatology, Lund University Hospital; D. van der Heijde, MD, PhD, Professor, Department of Medicine, University of Maastricht. Address reprint requests to Prof. W.P. Maksymowych, 562 Heritage Medical Research Building, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter.maksymowych@ualberta.ca
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