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.

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.

Reappraisal of OMERACT 8 draft validation criteria for a soluble biomarker reflecting structural damage endpoints in rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis: the OMERACT 9 v2 criteria.

Objectives: A draft set of criteria for the validation of soluble biomarkers reflecting damage endpoints was proposed at OMERACT 8. At OMERACT 9 we aimed to scrutinize the necessity for each of these criteria according to the objectives of the working group.

Methods: The OMERACT 8 draft criteria and the principle objectives of the validation process were clarified at a meeting of the working group in London, December 2007.

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.

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.