title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Stephanie O
authors.initials: SO
authors.lastname: Keeling
authors.forename: Robert
authors.initials: R
authors.lastname: Landewe
authors.forename: Desiree
authors.initials: D
authors.lastname: van der Heijde
authors.forename: Joan
authors.initials: J
authors.lastname: Bathon
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: Robert D
authors.initials: RD
authors.lastname: Inman
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Kraus
authors.forename: Tore K
authors.initials: TK
authors.lastname: Kvien
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
authors.forename: Mikkel
authors.initials: M
authors.lastname: Ostergaard
authors.forename: Chris
authors.initials: C
authors.lastname: Ritchlin
authors.forename: Silje W
authors.initials: SW
authors.lastname: Syversen
authors.forename: Walter P
authors.initials: WP
authors.lastname: Maksymowych
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis*; D032921:Consensus; D003697:Delphi Technique; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000592:standards*; D011237:Predictive Value of Tests
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein