title: Proposal for levels of evidence schema for validation of a soluble biomarker reflecting damage endpoints in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, and recommendations for study design.
abstract: OBJECTIVE
  At OMERACT 8 a framework for levels of evidence was proposed for the validation of biomarkers as surrogate outcome measures. We aimed to adapt this scheme in order to apply it in the setting of soluble biomarkers proposed to replace the measurement of damage endpoints in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). We also aimed to generate consensus on minimum standards for the design of longitudinal studies aimed at validating biomarkers.
  
  
  METHODS
  Before the meeting, the Soluble Biomarker Working Group prepared a preliminary framework and discussed various models for association and prediction related to the statistical strength domain. In addition, 3 Delphi exercises addressing longitudinal study design for RA, PsA, and AS were conducted within the working group and members of the Assessments in SpondyloArthritis International Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). This formed the basis for discussions among OMERACT 9 participants.
  
  
  RESULTS
  The proposed framework was accepted by consensus. In the study design domain a requirement for both prospective observational studies and randomized controlled trials (RCT) in different drug classes was noted. A template for determining the level of statistical strength was proposed. The addition of a new domain on biomarker assay performance was considered essential, and participants suggested that for any biomarker this domain should be addressed first, i.e., before starting clinical validation studies. Participants agreed on most elements of a longitudinal study design template. Where consensus was lacking the working group has drafted solutions that constitute a basis for prospective validation studies.
  
  
  CONCLUSIONS
  The OMERACT 9 Soluble Biomarker Group has successfully formulated a levels of evidence scheme and a study design template that will provide guidance to conduct validation studies in the setting of soluble biomarkers proposed to replace the measurement of damage endpoints in RA, PsA, and AS.
authors: Heritage Medical Research Building, University of Alberta, Edmonton, Alberta, Canada. walter.maksymowych@ualberta.ca
authors: Walter P
authors: WP
authors: Maksymowych
authors: Oliver
authors: O
authors: Fitzgerald
authors: George A
authors: GA
authors: Wells
authors: Dafna D
authors: DD
authors: Gladman
authors: Robert
authors: R
authors: Landewé
authors: Mikkel
authors: M
authors: Ostergaard
authors: William J
authors: WJ
authors: Taylor
authors: Robin
authors: R
authors: Christensen
authors: Paul-Peter
authors: PP
authors: Tak
authors: Maarten
authors: M
authors: Boers
authors: Silje W
authors: SW
authors: Syversen
authors: Joan M
authors: JM
authors: Bathon
authors: Christopher J
authors: CJ
authors: Ritchlin
authors: Philip J
authors: PJ
authors: Mease
authors: Vivien P
authors: VP
authors: Bykerk
authors: Patrick
authors: P
authors: Garnero
authors: Piet
authors: P
authors: Geusens
authors: Hani
authors: H
authors: El-Gabalawy
authors: Daniel
authors: D
authors: Aletaha
authors: Robert D
authors: RD
authors: Inman
authors: Virginia Byers
authors: VB
authors: Kraus
authors: Tore K
authors: TK
authors: Kvien
authors: Désirée
authors: D
authors: van der Heijde
mesh_terms: D001168:Arthritis / Q000097:blood* / Q000473:pathology*; D015535:Arthritis, Psoriatic / Q000097:blood / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000473:pathology; D015415:Biomarkers / Q000097:blood*; D019317:Evidence-Based Medicine / Q000592:standards*; D006801:Humans; D007596:Joints / Q000473:pathology*; D008137:Longitudinal Studies; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000473:pathology
chemical_list: D015415:Biomarkers