Updating the OMERACT Filter: Implications for Imaging and Soluble Biomarkers

Abstract

Objective. The Outcome Measures in Rheumatology (OMERACT) Filter provides a framework for the validation of outcome measures for use in rheumatology clinical research. However, imaging and biochemical measures may face additional validation challenges because of their technical nature. The Imaging and Soluble Biomarker Session at OMERACT 11 aimed to provide a guide for the iterative development of an imaging or biochemical measurement instrument so it can be used in therapeutic assessment. Methods. A hierarchical structure was proposed, reflecting 3 dimensions needed for validating an imaging or biochemical measurement instrument: outcome domain(s), study setting, and performance of the instrument. Movement along the axes in any dimension reflects increasing validation. For a given test instrument, the 3-axis structure assesses the extent to which the instrument is a validated measure for the chosen domain, whether it assesses a patient-centered or disease-centered variable, and whether its technical performance is adequate in the context of its application. Some currently used imaging and soluble biomarkers for rheumatoid arthritis, spondy-loarthritis, and knee osteoarthritis were then evaluated using the original OMERACT Filter and the newly proposed structure. Breakout groups critically reviewed the extent to which the candidate biomarkers complied with the proposed stepwise approach, as a way of examining the utility of the proposed 3-dimensional structure. Results. Although there was a broad acceptance of the value of the proposed structure in general, some areas for improvement were suggested including clarification of criteria for achieving a certain level of validation and how to deal with extension of the structure to areas beyond clinical trials. Conclusion. General support was obtained for a proposed tri-axis structure to assess validation of imaging and soluble biomarkers; nevertheless, additional work is required to better evaluate its place within the OMERACT Filter 2.0

How to Choose Core Outcome Measurement Sets for Clinical Trials: OMERACT 11 Approves Filter 2.0

“…Filter 2.0 Session 5 -Biomarkers and Imaging 24 . How best to work with patient research partners, from both a technical viewpoint and an interpersonal viewpoint, was considered by several breakout groups.…”

Development and Reliability of the Joint Tissue Activity and Damage Examination for Quantitation of Structural Abnormalities by Musculoskeletal Ultrasound in Hemophilic Joints

“…Two‐dimensional measurements of osteochondral and soft tissue evaluation in musculoskeletal medicine have become increasingly attractive, since they take advantage of the high spatial and tissue contrast resolution inherent to continuously improving US technology, enabling precise measurements in 0.1‐ to 0.2‐mm increments with higher‐frequency transducers (>12 MHz). Here we report the intra‐ and inter‐rater reliability as well as inter‐operator reliability of the JADE protocol, incorporating direct measurements by hemophilia care providers trained in musculoskeletal US, in alignment with OMERACT recommendations for the validation of imaging protocols . Reliability is defined as the ability of a measurement to be replicated and mathematically illustrated by a value between 0 and 1, with values closer to 1 representing stronger reliabilities .…”

“…Here we report the intra-and inter-rater reliability as well as inter-operator reliability of the JADE protocol, incorporating direct measurements by hemophilia care providers trained in musculoskeletal US, in alignment with OMERACT recommendations for the validation of imaging protocols. [21][22][23][24] Reliability is defined as the ability of a measurement to be replicated and mathematically illustrated by a value between 0 and 1, with values closer to 1 representing stronger reliabilities. 38 Most of the assessments and measurements exceeded values of 0.70, which provides confidence that the JADE protocol is suitable for implementation in hemophilia practice and can serve as an objective imaging outcome measure in clinical studies, evaluating effects of new therapies on the progression or resolution of individual pathologic findings.…”

“…Toward that end, several semiquantitative musculoskeletal US scoring algorithms have been proposed, especially for the detection of early changes . However, these scoring algorithms lack iterative validation processes (“truth, discrimination, and feasibility”), as proposed by Outcome Measures in Rheumatology (OMERACT) . Additionally, scoring algorithms are relatively subjective, may have ceiling effects in advanced hemophilic arthropathy, and do not permit the following of individual findings in hemophilic joints, which may be central to patients’ specific presentations but outside the scoring algorithms.…”

“…The OMERACT guidelines are considered the “reference standard” for validating imaging protocols for the assessment of arthritic changes, and following those guidelines appeared essential to provide confidence that the JADE parameters would bear relevance as outcome tools. OMERACT is a widely accepted international initiative, whereby the cornerstones of validation are composed of correct tissue annotation, the establishment of intra‐rater, inter‐rater, and inter‐operator reliability, and clinical applicability for specific disease states and patient cohorts, emulating the OMERACT filter components truth, discrimination, and feasibility . Along OMERACT recommendations, we recently established the extent of pathologic tissue discrimination with musculoskeletal US specific to hemophilic joints by comparison with conventional and ultrashort time‐to‐echo magnetic resonance imaging …”