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Testing of the Preliminary OMERACT Validation Criteria for a Biomarker to Be Regarded as Reflecting Structural Damage Endpoints in Rheumatoid Arthritis Clinical Trials: The Example of C-Reactive Protein
STEPHANIE O. KEELING, ROBERT LANDEWÉ, DESIREE van der HEIJDE, JOAN BATHON, MAARTEN BOERS, PATRICK GARNERO, PIET GEUSENS, HANI EL-GABALAWY, ROBERT D. INMAN, VIRGINIA B. KRAUS, TORE K. KVIEN, PHILIP J. MEASE, MIKKEL OSTERGAARD, CHRIS RITCHLIN, SILJE W. SYVERSEN, and WALTER P. MAKSYMOWYCH ABSTRACT. Objective. A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker extensively studied in RA, was then used to test these criteria. Our objectives were: (1) To assess the strength of evidence in support of CRP as a soluble biomarker reflecting structural damage in RA according to the draft validation criteria. (2) To assess the strength of recommendation for inclusion of individual criteria in the draft set. Methods. A systematic literature review was conducted to elicit evidence in support of each specific criterion composing the 14-criteria draft set. A summary of the key literature findings per criterion was presented to both the working group and to participants in a special interest soluble biomarker group at OMERACT 8. Participants at OMERACT 8 were asked to rate the strength of evidence and the strength of the recommendation in support of each individual criterion on a 0–10 numerical rating scale. Working group members not present at OMERACT voted by a Web-based survey. Results. Minimal data were extracted from the literature pertaining to those criteria listed under the category of truth. Ratings for strength of evidence were moderate to low (< 7) for CRP as a biomarker reflecting structural damage in RA; this was true for all criteria except those listed under the category of feasibility and 2 listed under the category of discrimination pertaining to assay reproducibility and evidence regarding sources of variability. Ratings for strength of recommendation for inclusion of each of the 14 criteria in the draft set were high (> 7) except for those criteria listed under the category of truth. Conclusion. The draft criteria serve as a useful template in the evaluation of the strength of evidence in support of a particular soluble biomarker as reflecting structural damage in RA. (J Rheumatol 2007;34:623-33) Key Indexing Terms: SOLUBLE BIOMARKER From the Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, University of Maastricht, Maastricht, The Netherlands; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; 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; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA; Diakonhjemmet Hospital, University of Oslo, Oslo, Norway; University of Washington School of Medicine, Seattle, Washington, USA; Copenhagen University Hospitals, Herlev, Denmark; and University of Rochester School of Medicine, Rochester, Minnesota, USA. W.P. Maksymowych is a Senior Scholar of the Alberta Heritage Foundation for Medical Research. S.O. Keeling, FRCPC, Assistant Professor, Department of Medicine, University of Alberta; R. Landewé, MD, PhD, Associate Professor, Department of Medicine, University of Maastricht; D. van der Heijde, MD, PhD, Professor, Department of Medicine, University of Maastricht; J. Bathon, MD, Professor, Department of Medicine, The Johns Hopkins University School of Medicine; 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, France; P. Geusens, MD, PhD, Professor, Department of Medicine, University of Maastricht; H. El-Gabalawy, FRCPC, Professor, Department of Medicine, University of Manitoba; R.D. Inman, FRCPC, Professor, Department of Medicine, University of Toronto; V.B. Kraus, MD, PhD, Associate Professor, Department of Medicine, Duke University Medical Center; T.K. Kvien, MD, Professor of Rheumatology, Diakonhjemmet Hospital, University of Oslo; P.J. Mease, MD, Clinical Professor, Swedish Medical Center and University of Washington School of Medicine, Seattle; M. Ostergaard, MD, PhD, DMedSci, Professor, Copenhagen University Hospitals at Herlev and Hvidovre; C.T. Ritchlin, MD, Associate Professor in Rheumatology/Arthritis, University of Rochester School of Medicine; S.W. Syversen, MD, PhD Student, Diakonhjemmet Hospital, University of Oslo; W.P. Maksymowych, FRCPC, Professor, Department of Medicine, University of Alberta. 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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