title: Testing of the OMERACT 8 draft validation criteria for a soluble biomarker reflecting structural damage in rheumatoid arthritis: a systematic literature search on 5 candidate biomarkers.
abstract: OBJECTIVE
  To test the OMERACT 8 draft validation criteria for soluble biomarkers by assessing the strength of literature evidence in support of 5 candidate biomarkers.
  
  
  METHODS
  A systematic literature search was conducted on the 5 soluble biomarkers RANKL, osteoprotegerin (OPG), matrix metalloprotease (MMP-3), urine C-telopeptide of types I and II collagen (U-CTX-I and U CTX-II), focusing on the 14 OMERACT 8 criteria. Two electronic voting exercises were conducted to address: (1) strength of evidence for each biomarker as reflecting structural damage according to each individual criterion and the importance of each individual criterion; (2) overall strength of evidence in support of each of the 5 candidate biomarkers as reflecting structural damage endpoints in rheumatoid arthritis (RA) and identification of omissions to the criteria set.
  
  
  RESULTS
  The search identified 111 articles. The strength of evidence in support of these biomarkers reflecting structural damage was low for all biomarkers and was rated highest for U-CTX-II [score of 6.5 (numerical rating scale 0-10)]. The lowest scores for retention of specific criteria in the draft set went to criteria that refer to the importance of animal studies, correlations with other biomarkers reflecting damage, and an understanding of the metabolism of the biomarker.
  
  
  CONCLUSIONS
  Evidence in support of any of the 5 tested biomarkers (MMP-3, CTX-I, CTX-II, OPG, RANKL) was inadequate to allow their substitution for radiographic endpoints in RA. Three of the criteria in the draft criteria set might not be required, but few omissions were identified.
authors: Heritage Medical Research Building, University of Alberta, Edmonton, Alberta, Canada.
authors: Silje W
authors: SW
authors: Syversen
authors: Robert
authors: R
authors: Landewe
authors: Désirée
authors: D
authors: van der Heijde
authors: Joan M
authors: JM
authors: Bathon
authors: Maarten
authors: M
authors: Boers
authors: Vivian P
authors: VP
authors: Bykerk
authors: Oliver
authors: O
authors: Fitzgerald
authors: Dafna D
authors: DD
authors: Gladman
authors: Patrick
authors: P
authors: Garnero
authors: Piet
authors: P
authors: Geusens
authors: Hani
authors: H
authors: El-Gabalawy
authors: Robert D
authors: RD
authors: Inman
authors: Virginia
authors: V
authors: Kraus
authors: Tore K
authors: TK
authors: Kvien
authors: Philip J
authors: PJ
authors: Mease
authors: Mikkel
authors: M
authors: Ostergaard
authors: Christopher J
authors: CJ
authors: Ritchlin
authors: Paul-Peter
authors: PP
authors: Tak
authors: William J
authors: WJ
authors: Taylor
authors: Walter P
authors: WP
authors: Maksymowych
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology*; D015415:Biomarkers / Q000097:blood*; D003245:Consensus Statements as Topic; D006801:Humans; D007596:Joints / Q000473:pathology*; D011237:Predictive Value of Tests; D011859:Radiography; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers