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.
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.
Maksymowych
Walter P
WP
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. walter.maksymowych@ualberta.ca
Landewe
Robert
R
Boers
Maarten
M
Garnero
Patrick
P
Geusens
Piet
P
El-Gabalawy
Hani
H
Heinegard
Dick
D
Kraus
Virginia B
VB
Krause
Virginia
V
Lohmander
Stefan
S
Matyas
John
J
Saxne
Tore
T
van der Heijde
Desiree
D
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
D015415:Biomarkers