title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. walter.maksymowych@ualberta.ca
authors.forename: Walter P
authors.initials: WP
authors.lastname: Maksymowych
authors.forename: Robert
authors.initials: R
authors.lastname: Landewe
authors.forename: Maarten
authors.initials: M
authors.lastname: Boers
authors.forename: Patrick
authors.initials: P
authors.lastname: Garnero
authors.forename: Piet
authors.initials: P
authors.lastname: Geusens
authors.forename: Hani
authors.initials: H
authors.lastname: El-Gabalawy
authors.forename: Dick
authors.initials: D
authors.lastname: Heinegard
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Kraus
authors.forename: Virginia
authors.initials: V
authors.lastname: Krause
authors.forename: Stefan
authors.initials: S
authors.lastname: Lohmander
authors.forename: John
authors.initials: J
authors.lastname: Matyas
authors.forename: Tore
authors.initials: T
authors.lastname: Saxne
authors.forename: Desiree
authors.initials: D
authors.lastname: van der Heijde
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000473:pathology*; D015415:Biomarkers; D032921:Consensus; D003697:Delphi Technique; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000592:standards*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D025241:Spondylarthritis / Q000097:blood / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers