P. Tugwell

Updating the OMERACT Filter: Implications for imaging and soluble biomarkers

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, spondyloarthritis, 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.

OMERACT Filter Evidence Supporting the Measurement of At-work Productivity Loss as an Outcome Measure in Rheumatology Research.

Objective. Indicators of work role functioning (being at work, and being productive while at work) are important outcomes for persons with arthritis. As the worker productivity working group at OMERACT (Outcome Measures in Rheumatology), we sought to provide an evidence base for consensus on standardized instruments to measure worker productivity [both absenteeism and at-work productivity (presenteeism) as well as critical contextual factors]. Methods. Literature reviews and primary studies were done and reported to the OMERACT 12 (2014) meeting to build the OMERACT Filter 2.0 evidence for worker productivity outcome measurement instruments. Contextual factor domains that could have an effect on scores on worker productivity instruments were identified by nominal group techniques, and strength of influence was further assessed by literature review. Results. At OMERACT 9 (2008), we identified 6 candidate measures of absenteeism, which received 94% endorsement at the plenary vote. At OMERACT 11 (2012) we received over the required minimum vote of 70% for endorsement of 2 at-work productivity loss measures. During OMERACT 12 (2014), out of 4 measures of at-work productivity loss, 3 (1 global; 2 multiitem) received support as having passed the OMERACT Filter with over 70% of the plenary vote. In addition, 3 contextual factor domains received a 95% vote to explore their validity as core contextual factors: nature of work, work accommodation, and workplace support. Conclusion. Our current recommendations for at-work productivity loss measures are: WALS (Workplace Activity Limitations Scale), WLQ PDmod (Work Limitations Questionnaire with modified physical demands scale), WAI (Work Ability Index), WPS (Arthritis-specific Work Productivity Survey), and WPAI (Work Productivity and Activity Impairment Questionnaire). Our future research focus will shift to confirming core contextual factors to consider in the measurement of worker productivity.

Toward the development of a core set of outcome domains to assess shared decision-making interventions in rheumatology : results from an OMERACT Delphi survey and consensus meeting

Objective. The aim of this Outcome Measures in Rheumatology (OMERACT) Working Group was to determine the core set of outcome domains and subdomains for measuring the effectiveness of shared decision-making (SDM) interventions in rheumatology clinical trials. Methods. Following the OMERACT Filter 2.0, and based on a previous literature review of SDM outcome domains and a nominal group process at OMERACT 2014, (1) an online Delphi survey was conducted to gather feedback on the draft core set and refine its domains and subdomains, and (2) a workshop was held at the OMERACT 2016 meeting to gain consensus on the draft core set. Results. A total of 170 participants completed Round 1 of the Delphi survey, and 116 completed Round 2. Respondents came from 29 countries, with 49% being patients/caregivers. Results showed that 14 out of the 17 subdomains within the 7 domains exceeded the 70% criterion (endorsement ranged from 83% to 100% of respondents). At OMERACT 2016, only 8% of the 96 attendees were patients/caregivers. Despite initial votes of support in breakout groups, there was insufficient comfort about the conceptualization of these 7 domains and 17 subdomains for these to be endorsed at OMERACT 2016 (endorsement ranged from 17% to 68% of participants). Conclusion. Differences between the Delphi survey and consensus meeting may be explained by the manner in which the outcomes were presented, variations in participant characteristics, and the context of voting. Further efforts are needed to address the limited understanding of SDM and its outcomes among OMERACT participants.

OMERACT Quality-adjusted Life-years (QALY) Working Group: Do Current QALY Measures Capture What Matters to Patients?

Objective. To understand the limitations with current patient-reported outcome measures (PROM) used to generate quality-adjusted life-years (QALY) in rheumatology, and set a research agenda. Methods. Two activities were undertaken. The first was a scoping review of published studies that have used PROM to generate QALY in rheumatology between 2011 and 2016. The second was an interactive “eyeball test” exercise at Outcome Measures in Rheumatology 13 that compared subdomains of widely used generic PROM, as identified through the scoping review, to subdomains of the Assessment of SpondyloArthritis Health Index (ASAS-HI) condition-specific PROM for ankylosing spondylitis. Results. The scoping review included 39 studies. Five different PROM have been used to generate QALY in rheumatology; however, the EQ-5D and Short Form 6 Dimensions (SF-6D) were used most frequently (in 32 and 9 of included studies, respectively). Special interest group participants identified energy/drive and sleep as 2 key subdomains of the ASAS-HI instrument that may be missed by the EQ-5D, and sexual function as potentially missed by the SF-6D. Participants also expressed concerns that aspects of the process of care and non-health outcomes may be missed. Three ways of incorporating additional subdomains were discussed, including using an alternative generic PROM, modifying an existing generic PROM with “bolt-on” subdomain(s), and generating societal weights for a condition-specific PROM. Conclusion. Three priorities for future research were identified: understanding whether the EQ-5D and SF-6D identify what matters to patients with different rheumatic conditions, analyzing how much patients value process or non-health outcomes, and identifying which approaches to incorporating a greater number of subdomains into the QALY are being undertaken in other disease areas.

An OMERACT Initiative Toward Consensus to Identify and Characterize Candidate Contextual Factors: Report from the Contextual Factors Working Group

Objective. The importance of contextual factors (CF) for appropriate patient-specific care is widely acknowledged. However, evidence in clinical trials on how CF influence outcomes remains sparse. The 2014 Outcome Measures in Rheumatology (OMERACT) Handbook introduced the role of CF in outcome assessment and defined them as “potential confounders and/or effect modifiers of outcomes in randomized controlled trials.” Subsequently, the CF Methods Group (CFMG) was formed to develop guidance on how to address CF in clinical trials. Methods. First, the CFMG conducted an e-mail survey of OMERACT working groups (WG) to analyze how they had addressed CF in outcome measurement so far. The results facilitated an informed discussion at the OMERACT 2016 CFMG Special Interest Group (SIG) session, with the aim of gaining preliminary consensus regarding an operational definition of CF and to make a first selection of potentially relevant CF. Results. The survey revealed that the WG had mostly used the OMERACT Handbook and/or the International Classification of Functioning, Disability and Health (ICF) definition. However, significant heterogeneity was found in the methods used to identify, refine, and categorize CF candidates. The SIG participants agreed on using the ICF as a framework along with the OMERACT Handbook definition. A list with 28 variables was collected including person-related factors and physical and social environments. Recommendations from the SIG guided the CFMG to formulate 3 preliminary projects on how to identify and analyze CF. Conclusion. New methods are urgently needed to assist researchers to identify and characterize CF that significantly influence the interpretation of results in clinical trials. The CFMG defined first steps to develop further guidance.

OMERACT Endorsement of Patient-reported Outcome Instruments in Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

Objective. The antineutrophil cytoplasmic antibody–associated vasculitides (AAV) are multiorgan diseases. Patients with AAV report impairment in their health-related quality of life (HRQOL) and have different priorities regarding disease assessment compared with physicians. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group previously received endorsement for a core set of domains in AAV. Two approaches to measure patient-reported outcomes (PRO) were presented at OMERACT 2016. Methods. A novel 5-step tool was used to facilitate assessment of the instruments by delegates: the OMERACT Filter 2.0 Instrument Selection Algorithm, with a red-amber-green checklist of questions, including (1) good match with domain (face and content validity), (2) feasibility, (3) do numeric scores make sense (construct validity)?, (4) overall ratings of discrimination, and (5) can individual thresholds of meaning be defined? Delegates gave an overall endorsement. Three generic Patient-Reported Outcomes Measurement Information System (PROMIS) instruments (fatigue, physical functioning, and pain interference) and a disease-specific PRO, the AAV-PRO (6 domains related to symptoms and HRQOL), were presented. Results. OMERACT delegates endorsed the use of the PROMIS instruments for fatigue, physical functioning, and pain interference (87.6% overall endorsement) and the disease-specific AAV-PRO instrument (89.4% overall endorsement). Conclusion. The OMERACT Vasculitis Working Group gained endorsement by OMERACT for use of the PROMIS and the AAV-PRO in clinical trials of vasculitis. These instruments are complementary to each other. The PROMIS and the AAV-PRO need further work to assess their utility in longitudinal settings, including their ability to discriminate between treatments of varying efficacy in the setting of a randomized controlled trial.

THU0677 Outcome measurement instruments for safety in rheumatology: a scoping review of available instruments to inform the omeract safety working group

Background International scientific networks have raised concerns about inadequate reporting of safety outcomes in randomised trials and systematic reviews. Outcome Measures in Rheumatology (OMERACT) has previously developed an adaptation of the US National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE), the RCTC (Rheumatology Common Toxicity Criteria) to collect adverse events in rheumatology clinical trials. To respond to the need to also report safety outcomes from the patient perspective, the Safety Working Group is developing a core outcome set, followed by a core outcome measurement set. A scoping review of available instruments for measuring safety outcomes is needed to inform this work. Objectives To identify candidate measurement instruments for safety outcomes in rheumatology clinical trials. Methods A systematic search was performed in the MEDLINE database (via PubMed) in January 2017 using MeSH terms covering synonyms for adverse events, rheumatology and measurement instruments and the Boolean operator AND to combine them. Full-text articles about the development or evaluation of instruments for measuring safety in rheumatology were eligible. One reviewer (LK) screened for eligibility based on title and abstracts. Two reviewers (LK and RC) screened the full text articles. Results Of 434 unique references identified, 19 were read in full-text, and 8 were included (see figure). The instruments identified were: Glucocorticoid Toxicity Index (GTI), Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC), Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI flare index (cSFI), the BioSecure questionnaire, Rheumatology Common Toxicity Criteria (RCTC), OMERACT 3x3, and the Stanford Toxicity Index (STI). These instruments were specific for substance (GTI, BioSecure questionnaire), setting (PREOS-PC), condition (cSFI), or not fully validated (RCTC, OMERACT 3x3, STI).Figure 1 Conclusions The instruments identified are either too specific, or require further development/evaluation, for the purpose of standardizing measurement of safety in rheumatology clinical trials. Thus, we will proceed to gain consensus on the domains that must be measured to develop a core outcome set. Disclosure of Interest None declared