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. A new framework was proposed after the following steps were conducted: (A) A systematic review of the literature focusing on the draft criteria and a preselected group of biomarkers (MMP3, CTX-II, RANKL, OPG, CTX-I) followed by a Delphi consensus exercise addressing the importance of individual criteria and identification of omissions in the draft set. (13) Formal debate its well as group discussion centered oil the key arguments for inclusion/exclusion of specific criteria. (C) Onsite interactive electronic voting on the importance of specific criteria. The framework was presented and discussed at OMERACT 9 in both breakout and plenary sessions followed by a vote on its acceptance. Results. The objectives of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis biomarkers in relation to their predictive validity for damage endpoints was clarified and supported by OMERACT 9 participants. The OMERACT 8 draft validation criteria were reformulated into an essential category focused on criteria addressin the OMERACT Filter elements of discrimination 9 (incorporating truth) and feasibility, and a desirable but nonessential category of other criteria addressing, truth. This revised draft set was endorsed by participants at OMERACT 9. Conclusion. A revised set of validation criteria has been drafted by consensus at OMERACT 9 that focuses on the performance characteristics of biomarker assays, the importance of addressing potential confounders, and the essential requirement for clinical validation studies. (J Rheumatol 2009; 36:1785-91. doi: 10.3899/jrheum.090346

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. 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. Conclusion. 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. (J Rheumatol 2009:36:1792-9;, doi. 10.3899/jrheum.090347