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Objectives: To explore which core domain is best associated with the American College of Rheumatology (ACR) 20% response in trials assessing the effect of targeted interventions in rheumatoid arthritis (RA)., Methods: A meta-epidemiological study was performed on randomised trials investigating biologics and targeted agents compared with placebo or conventional disease-modifying antirheumatic drugs in patients with RA. The main outcome measures were ORs for the ACR 20% response and at least one of the eight core domains according to the existing RA core outcome set (COS) analysed based on standardised mean differences., Results: 115 trials involving 55 422 patients with RA were eligible. The OR for achieving ACR 20% response was 3.19 (95% CI 2.96 to 3.44) for the experimental interventions relative to the comparators. The median number of COS domains reported was 6; 18 trials reported only 1 domain, 17 all 8. Univariable meta-regression analyses indicated that each of the eight core domains was significantly associated with ACR 20% response, yet improvements in physical disability explain a successful ACR 20% response the most. Including only trials reporting on all eight core domains, univariable meta-regression analyses proved improvement in fatigue to explain a successful ACR 20% response the most., Conclusions: Within this dataset, it is evident that the conclusions concerning our primary objective were significantly influenced by both the amount and characteristics of missing data. Our data suggest that fatigue could be more important for the primary endpoint than previously assumed, but this is based on limited data., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objective: To develop a set of detailed definitions for foundational domains commonly used in OMERACT (Outcome Measures in Rheumatology) core domain sets., Methods: We identified candidate domain definitions from prior OMERACT publications and websites and publications of major organizations involved in outcomes research for six domains commonly used in OMERACT Core Domain Sets: pain intensity, pain interference, physical function, fatigue, patient global assessment, and health-related quality of life. We conducted a two-round survey of OMERACT working groups, patient research partners, and then the OMERACT Technical Advisory Group to establish their preferred domain definitions. Results were presented at the OMERACT 2023 Methodology Workshop, where participants discussed their relevant lived experience and identified potential sources of variability giving the needed detail in our domain definitions., Results: One-hundred four people responded to both rounds of the survey, and a preferred definition was established for each of the domains except for patient global assessment for which no agreement was reached. Seventy-five participants at the OMERACT 2023 Methodology Workshop provided lived experience examples, which were used to contextualise domain definition reports for each of the five domains., Conclusion: Using a consensus-based approach, we have created a detailed definition for five of the foundational domains in OMERACT core domain sets; patient global assessment requires further research. These definitions, although not mandatory for working groups to use, may facilitate the initial domain-match assessment step of instrument selection, and reduce the time and resources required by future OMERACT groups when developing core outcome sets., Competing Interests: Declaration of competing interest COB, MB, RC, CH, CLH, SG, FK, BJS, GAW - No conflicts DEB: Member of Management team at OMERACT, co-chair of methods group and technical advisory group of OMERACT. PC: Member, OMERACT Management Committee. AB: Received research grants for Abbvie and Lilly and fees for lectures or consultations from Abbvie, UCB, Novartis, Galapagos and Pfizer, all to her department and unrelated to the topic of this manuscript. EC has received research grants from Bio-Cancer, Biogen, Novartis, Pfizer, Roche, Sanofi and UCB, consultancy from Abbvie, Amgen, Biogen, Biocon, Chugai Pharma, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck Serono, Novartis, Pfizer, Regeneron, Roche, RPharm and Sanofi, speakers fee from Abbvie, Amgen, Bristol Myer Squibbs, Chugai Pharma, Eli Lilly, Fresenius Kai, Galapagos, Gilead, Janssen, Novartis, Pfizer, Regeneron, RPharm, Roche, Sanofi, and UCB. AD has the following relationships unrelated to the conduct of this study: Chair of the International Myositis Assessment & Clinical Studies Group (not for profit) Chair of the Radiological Society of North America (RSNA) Annual Planning Committee for Pediatric Radiology (not for profit), Co-Chair of the American College of Radiology (ACR) Pediatric Imaging Research Committee (not for profit), Chair of the Bias in Recruitment, Hiring, Promotion, Awards Committee of the Canadian Association of Radiology (not for profit), and PI of research grants from Novo Nordisk, the Terry Fox Foundation, the PSI Foundation, the Society of Pediatric Radiology, and the Garron Family Cancer Centre, unrelated to the topic of this manuscript. MADA: Grants from Abbvie, Amgen, Pfizer. Royalties or licenses from Elsevier. Consulting fees from Abbvie, Amgen, BMS, Galapagos, Novartis, Lilly, Janssen, UCB. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Amgen, BMS, Galapagos, Novartis, Lilly, Janssen, UCB. Support for attending meetings and/or travel from Janssen, Novartis. BH: OMERACT 2023 conference in Colorado Springs. Paid by OMERACT to support my role a Patient Research Partner. CJ: Seed funding grants for unrelated project (pilot trial of opioids used after total joint replacement surgery) from ANZMUSC ($19,956), Arthritis Australia ($20,000) and Wiser Healthcare ($4000). Casual payments from OMERACT for hours spent creating an unrelated e-learning series (technician role) in 2022–2023. Registration, flight and accommodation costs covered by OMERACT for attendance at OMERACT Colorado Springs 2023. Current member of ECR committee of ANZMUSC SLM reports: Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca, Pfizer; Investigator on clinical trials for Sanofi, GSK, Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer, UCB, Novartis and AbbVie; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. SLM is supported in part by the NIHR Leeds Biomedical Research Centre. The views expressed in this article are those of the authors and not necessarily those of the NIHR, the NIHR Leeds Biomedical Research Centre, the National Health Service or the UK Department of Health and Social Care. AM: Consulting fees from Sanofi, Abbvie, Amgen. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Sobi, Sanofi, Abbvie. Registration, flight and accommodation costs covered by OMERACT for attendance at OMERACT Colorado Springs 2023. LJM is a paid staff member of OMERACT. LSS is on the Management Committee of OMERACT and is Chair, Finance Committee of OMERACT. YY (Katy)L is supported by National Medical Research Council of Singapore. AbbVie, DKSH, Janssen, Novartis and Pfizer- Speaker fee and honorarium paid to me. AbbVie, DKSH, Janssen, Novartis and Pfizer - Research sponsorship paid to institution. APLAR: Travel and accommodation to APLAR congresses. GRAPPA: Travel and accommodation to GRAPPA congresses. Co-Chair of Scientific Committee of Asia Pacific League of Associations of Rheumatology, APLAR - No payment. Education committee of Group for Research and Assessment for Psoriasis and Psoriatic Arthritis, GRAPPA -No payment. PT: Consulting Fees from Reformulary Group. An independent Committee Member for clinical trial Data Safety Monitoring Boards for FDA approved trials being conducted by: UCB Biopharma GmbH & SPRL, Parexel International, Prahealth Sciences. I am [unpaid] Chair of the Management Group of a registered non-profit independent medical research organization, OMERACT, whose goal is to improve and advance the health outcomes for patients suffering from musculoskeletal conditions. OMERACT receives arms-length funding from 11 companies: Abbvie, Astra Zenaca, Aurinia, BMS, Centrexion, GSK, Horizon Pharma Inc, Janssen, Novartis, Pfizer & Sparrow. ZT: Leadership or fiduciary role in other board, society, committee or advocacy group: Co-chair American College of Rheumatology Criteria development subcommittee., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To generate candidates for contextual factors (CFs) for each CF type (i.e., Effect Modifying Contextual Factors (EM-CFs), Outcome Influencing Contextual Factors (OI-CFs), and Measurement Affecting Contextual Factors (MA-CFs)) considered important within rheumatology., Methods: We surveyed OMERACT working groups and conducted a Special Interest Group (SIG) session at the OMERACT 2023 meeting, where the results were reviewed, and additional CFs suggested., Results: The working groups suggested 44, 49, and 21 generic EM-CFs, OI-CFs, and MA-CFs, respectively. SIG participants added 49, 44, and 55 factors, respectively., Conclusion: Candidate CFs were identified, next step is a consensus-based set of endorsed (important) CFs., Competing Interests: Declaration of competing interest Amye Leong reports unpaid leadership or fiduciary roles at the Arthritis Foundation, the United States Bones and Joint Initiative and the FDA Patient Engagement Advisory Committee. Annelies Boonen reports a research grant from Abbvie and honoraria from Abbvie, Pfizer, UCB, Novartis and Galapagos for lectures or advisory boards, all to her department. Dorthe Bang Berthelsen reports PhD Scholarships from Odense University Hospital and from the Faculty of Health Sciences, University of Southern Denmark. Francis Guillemin reports grant by Novartis, paid to his institution. Irene van der Horst-Bruinsma reports travel support for EULAR 2023 by Pfizer and unpaid membership in the ASAS advisory board. Maria A. Lopez-Olivo reports grants or contracts from the National Cancer Institute, the Rheumatology Research Foundation and the Duncan Family Institute for Cancer Prevention and Risk Assessment, and consulting fees from the American Cancer Society. Niti Goel reports that she is an owner of stock in Abcuro and UCB and that she is a former employee of TrialSpark, Inc. Peter Tugwell reports consulting fees from the Reformulary Group, being independent Committee Member for clinical trial Data Safety Monitoring Boards for UCB Biopharma GmbH & SPRL, Parexel International and PRA Health Sciences and being chair of the Management Group of OMERACT, a registered non-profit independent medical research organization. OMERACT receives arms-length funding from eleven companies (Abbvie, Astra Zenaca, Aurinia, BMS, Centrexion, GSK, Horizon Pharma Inc, Janssen, Novartis, Pfizer, Sparrow). Rieke Alten reports personal and institutional payments from BMS, Galapagos, Janssen, Lilly, Novartis, Pfizer and UCB as wells as institutional payments from Abbvie and Amgen, support for attending meetings from Celltrion, Lilly and UCB, and membership of an advisory board for Pfizer. Saurab Sharma was supported by the International Association for the Study of Pain John J. Bonica Postdoctoral Fellowship (2021-2023) and travel support to the International Association for the Study of Pain (IASP) Congress in Toronto (2022) both unrelated to the current work. Victor S. Sloan reports consulting fees from Boehringer-Ingelheim, stock in UCB Pharma and as an employee of the Peace Corps states: “This is my personal work, and does not reflect the opinion of the Peace Corps or the United States Government.”. The other authors have no conflict of interest relevant to the content of this study., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Clinical studies with work participation (WP) as an outcome domain pose particular methodological challenges that hamper interpretation, comparison between studies and meta-analyses., Objectives: To develop Points to Consider (PtC) for design, analysis and reporting of studies of patients with inflammatory arthritis that include WP as a primary or secondary outcome domain., Methods: The EULAR Standardised Operating Procedures were followed. A multidisciplinary taskforce with 22 experts including patients with rheumatic diseases, from 10 EULAR countries and Canada, identified methodologic areas of concern. Two systematic literature reviews (SLR) appraised the methodology across these areas. In parallel, two surveys among professional societies and experts outside the taskforce sought for additional methodological areas or existing conducting/reporting recommendations. The taskforce formulated the PtC after presentation of the SLRs and survey results, and discussion. Consensus was obtained through informal voting, with levels of agreement obtained anonymously., Results: Two overarching principles and nine PtC were formulated. The taskforce recommends to align the work-related study objective to the design, duration, and outcome domains/measurement instruments of the study (PtC: 1-3); to identify contextual factors upfront and account for them in analyses (PtC: 4); to account for interdependence of different work outcome domains and for changes in work status over time (PtC: 5-7); to present results as means as well as proportions of patients reaching predefined meaningful categories (PtC: 8) and to explicitly report volumes of productivity loss when costs are an outcome (PtC:9)., Conclusion: Adherence to these EULAR PtC will improve the methodological quality of studies evaluating WP., Competing Interests: Competing interests: AB: research grants from Abbvie and Celgene and honoraria for consultancy or speakers honoraria from UCB, Biogen, Sandoz, Eli Lilly and Galapagos (all to her department); EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, AbbVie and Lilly; FPS: research grant from AbbVie, Novartis; consultancy or speaking fees: AbbVie, Angelini, AstraZeneca, Biogen, Eli Lilly, Laboratórios Vitória, MSD, Novartis, Tecnimed, UCB; SR: research grant from MSD; consultancy or speaking fees: AbbVie, Eli Lilly, MSD, Novartis, Sanofi, UCB; JKW: consultancy fees from Celgene, Eli Lilly, Novartis; RW: consultancy and speakers bureau Celltrion and Galapagos/Gilead., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To describe the Outcome Measures in Rheumatology (OMERACT) stepwise approach to select and develop an imaging instrument with musculoskeletal ultrasound (US) as an example., Methods: The OMERACT US Working Group (WG) developed a 4-step process to select instruments based on imaging. Step 1 applies the OMERACT Framework Instrument Selection Algorithm (OFISA) to existing US outcome measurement instruments for a specific indication. This step requires a literature review focused on the truth, discrimination, and feasibility aspects of the instrument for the target pathology. When the evidence is completely unsatisfactory, Step 2 is a consensus process to define the US characteristics of the target pathology including one or more so-called "elementary lesions". Step 3 applies the agreed definitions to the image, evaluates their reliability, develops a severity grading of the lesion(s) at a given anatomical site, and evaluates the effect of the acquisition technique on feasibility and lesion(s) detection. Step 4 applies and assesses the definition(s) and scoring system(s) in cross-sectional studies and multicenter trials. The imaging instrument is now ready to pass a final OFISA check., Results: With this process in place, the US WG now has 18 subgroups developing US instruments in 10 different diseases. Half of them have passed Step 3, and the groups for enthesitis (spondyloarthritis, psoriatic arthritis), synovitis, and tenosynovitis (rheumatoid arthritis) have finished Step 4., Conclusion: The US WG approach to select and develop outcome measurement instruments based on imaging has been repeatedly and successfully applied in US, but is generic for imaging and fits with OMERACT Filter 2.1.

Objective: Outcome Measures in Rheumatology (OMERACT) Filter 2.1 revised the process used for core outcome measurement set selection to add rigor and transparency in decision making. This paper describes OMERACT's methodology for instrument selection., Methods: We presented instrument selection processes, tools, and reporting templates at OMERACT 2018, introducing the concept of "3 pillars, 4 questions, 7 measurement properties, 1 answer." Truth, discrimination, and feasibility are the 3 original OMERACT pillars. Based on these, we developed 4 signaling questions. We introduced the Summary of Measurement Properties table that summarizes the 7 measurement properties: truth (domain match, construct validity), discrimination [test-retest reliability, longitudinal construct validity (responsiveness), clinical trial discrimination, thresholds of meaning], and feasibility. These properties address a set of standards which, when met, answer the one question: Is there enough evidence to support the use of this instrument in clinical research of the benefits and harms of treatments in the population and study setting described? The OMERACT Filter 2.1 was piloted on 2 instruments by the Psoriatic Arthritis Working Group., Results: The methodology was reviewed in a full plenary session and facilitated breakout groups. Tools to facilitate retention of the process (i.e., "The OMERACT Way") were provided. The 2 instruments were presented, and the recommendation of the working group was endorsed in the first OMERACT Filter 2.1 Instrument Selection votes., Conclusion: Instrument selection using OMERACT Filter 2.1 is feasible and is now being implemented.

Objective: To update the 1997 OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society International) core domain set for clinical trials in hip and/or knee osteoarthritis (OA)., Methods: An initial review of the COMET database of core outcome sets (COS) was undertaken to identify all domains reported in previous COS including individuals with hip and/or knee OA. These were presented during 5 patient and health professionals/researcher meetings in 3 continents (Europe, Australasia, North America). A 3-round international Delphi survey was then undertaken among patients, healthcare professionals, researchers, and industry representatives to gain consensus on key domains to be included in a core domain set for hip and/or knee OA. Findings were presented and discussed in small groups at OMERACT 2018, where consensus was obtained in the final plenary., Results: Four previous COS were identified. Using these, and the patient and health professionals/researcher meetings, 50 potential domains formed the Delphi survey. There were 426 individuals from 25 different countries who contributed to the Delphi exercise. OMERACT 2018 delegates (n = 129) voted on candidate domains. Six domains gained agreement as mandatory to be measured and reported in all hip and/or knee OA clinical trials: pain, physical function, quality of life, and patient's global assessment of the target joint, in addition to the mandated core domain of adverse events including mortality. Joint structure was agreed as mandatory in specific circumstances, i.e., depending on the intervention., Conclusion: The updated core domain set for hip and/or knee OA has been agreed upon. Work will commence to determine which outcome measurement instrument should be recommended to cover each core domain.

Objective: To describe the Outcome Measures in Rheumatology (OMERACT) Filter 2.1 methodology for core domain set selection., Methods: The "OMERACT Way for Core Domain Set selection" framework consists of 3 stages: first, generating candidate domains through literature reviews and qualitative work, then a process of consensus to obtain agreement from those involved, and finally formal voting on the OMERACT Onion. The OMERACT Onion describes the placement of domains in layers/circles: mandatory in all trials/mandatory in specific circumstances (inner circle); important but optional (middle circle); or research agenda (outer circle). Five OMERACT working groups presented their core domain sets for endorsement by the OMERACT community. Tools including a workbook and whiteboard video were created to assist the process. The methods workshop at OMERACT 2018 introduced participants to this framework., Results: The 5 OMERACT working groups achieved consensus on their proposed core domain sets. After the Methodology Workshop training exercise at OMERACT 2018, over 90% of participants voted that they were confident that they understood the process of core domain set selection., Conclusion: The methods described in this paper were successfully used by the 5 working groups voting on domains at the OMERACT 2018 meeting, demonstrating the feasibility of the process. In addition, participants at OMERACT 2018 expressed increased confidence and understanding of the core domain set selection process after the training exercise. This methodology will continue to evolve, and we will use innovative technology such as whiteboard videos as a key part of our dissemination and implementation strategy for new methods.

Objective: The Outcome Measures in Rheumatology (OMERACT) Filter 2.0 framework was developed in 2014 to aid core outcome set development by describing the full universe of "measurable aspects of health conditions" from which core domains can be selected. This paper provides elaborations and updated concepts (OMERACT Filter 2.1)., Methods: At OMERACT 2018, we discussed challenges in the framework application caused by unclear or ambiguous wording and terms and incompletely developed concepts., Results: The updated OMERACT Filter 2.1 framework makes benefits and harms explicit, clarifies concepts, and improves naming of various terms., Conclusion: We expect that the Filter 2.1 framework will improve the process of core set development.

What Is Known: Currently, medication bottles with an electronic cap are frequently used to measure medication adherence. This system is termed medication event monitoring system (MEMS). To our knowledge, the optimal method to summarize data from MEMS has not yet been determined., Objective: Look for best practices on how to quantify adherence data from MEMS., Methods: Review of PubMed, Embase and Cochrane databases for the articles on medication adherence with MEMS., Results: Of 1493 identified articles, 207 were included in this review. The MEMS cap was used for a median of 3 months (IQR: 4; range: 1 week to 24 months) in various health conditions. Many different outcome measures were used. Most studies computed an adherence score, expressed as the percentage of days on which the correct dose of medication was taken. The threshold to mark people as adherent was most frequently, arbitrarily, set at 80% (range: 67%-95%). We found no data to support a specific threshold., Discussion: Although the commonly used definition of adherence has face validity, we found no validation studies, and not all studies used the same cut-off for adherence. Ideally, a cut-off should be defined and validated in the context of the specific drug and its pharmacokinetic and dynamic characteristics, and perhaps other contextual factors, rather than generically. In addition, there was large heterogeneity in the definition of what "correct intake" of medication is., What Is New and Conclusion: Outcome measures for MEMS data lacked standardization, and no demonstrable effort to validate any definition against a relevant clinical outcome is available. Consensus on the definition of adherence is urgently needed., (© 2018 The Authors. Journal of Clinical Pharmacy and Therapeutics Published by John Wiley & Sons Ltd.)

Objective: The Outcome Measures in Rheumatology (OMERACT) 3×3 method analyzes the occurrence of benefit and harm simultaneously at the individual patient level. We applied this method to 2 recent rheumatoid arthritis (RA) trial data sets., Methods: The Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) and the Rheumatoid Arthritis Comparison of Active Therapies (RACAT) randomized trial outcomes for safety were defined according to OMERACT as having no adverse events (AEs), non-serious AEs, and serious AEs. Treatment efficacy was defined as good, moderate, or no response. A good treatment response without any AEs was labeled an unqualified success, and no treatment response but at least 1 AE was considered an unmitigated failure. The association between benefit and harm was assessed by chi-square or exact tests, as appropriate., Results: In TEAR, 612 of 755 patients had response data at 48 weeks: 14% of patients experienced unqualified success and 9% had unmitigated failure, with no difference between the treatment arms. Treatment response and AE rates were not correlated. In RACAT, 309 of 353 patients had response data at 48 weeks: 6% of patients experienced unqualified success and 11% had unmitigated failure, with no differences between the treatment arms. Response and AE rates were negatively correlated. The frequency of AEs and serious AEs increased as response decreased (P = 0.008)., Conclusion: We found some evidence that clinical response may be reduced by the co-occurrence of AEs., (© 2018 American College of Rheumatology.)

To standardize outcome reporting in clinical trials of patients with nonspecific low back pain, an international multidisciplinary panel recommended physical functioning, pain intensity, and health-related quality of life (HRQoL) as core outcome domains. Given the lack of a consensus on measurement instruments for these 3 domains in patients with low back pain, this study aimed to generate such consensus. The measurement properties of 17 patient-reported outcome measures for physical functioning, 3 for pain intensity, and 5 for HRQoL were appraised in 3 systematic reviews following the COSMIN methodology. Researchers, clinicians, and patients (n = 207) were invited in a 2-round Delphi survey to generate consensus (≥67% agreement among participants) on which instruments to endorse. Response rates were 44% and 41%, respectively. In round 1, consensus was achieved on the Oswestry Disability Index version 2.1a for physical functioning (78% agreement) and the Numeric Rating Scale (NRS) for pain intensity (75% agreement). No consensus was achieved on any HRQoL instrument, although the Short Form 12 (SF12) approached the consensus threshold (64% agreement). In round 2, a consensus was reached on an NRS version with a 1-week recall period (96% agreement). Various participants requested 1 free-to-use instrument per domain. Considering all issues together, recommendations on core instruments were formulated: Oswestry Disability Index version 2.1a or 24-item Roland-Morris Disability Questionnaire for physical functioning, NRS for pain intensity, and SF12 or 10-item PROMIS Global Health form for HRQoL. Further studies need to fill the evidence gaps on the measurement properties of these and other instruments.

Objective: The Outcome Measures in Rheumatology (OMERACT) working group on the patients' perspective on remission in rheumatoid arthritis (RA) has been working on this topic since 2010. At OMERACT 2016, progress and preliminary data on validity of measurement instruments for pain, fatigue, and independence in remission in RA were presented, and future directions were explored., Methods: A special interest group was organized, in which the current data on the patients' perspective on remission were presented. The ongoing study that aimed to validate measurement instruments for pain, fatigue, and independence in a state of low disease activity or remission was presented, and preliminary data on construct validity and discriminative capacity were evaluated cross-sectionally., Results: At OMERACT 2016, the progress of the working group and preliminary data from 142 of the anticipated 300 patients were presented. Selected instruments significantly correlated with the Disease Activity Score in 28 joints (construct validity) and all instruments except 1 discriminated between patients in and patients not in remission. The subsequent discussion mainly focused around 3 points: (1) the formulation of patient perceived remission, (2) the duration of remission, and (3) the measurement of the domain independence. An informal vote indicated a slight preference for working toward modifying the current remission criteria by adding patient-reported outcomes (PRO), or by substituting the patient's global assessment with 1 or more PRO., Conclusion: More evidence on measuring patients' perspective on remission in RA is needed before an informed decision can be made regarding development or modification of remission definitions.

Objective: Failure to report harmful outcomes in clinical research can introduce bias favoring a potentially harmful intervention. While core outcome sets (COS) are available for benefits in randomized controlled trials in many rheumatic conditions, less attention has been paid to safety in such COS. The Outcome Measures in Rheumatology (OMERACT) Filter 2.0 emphasizes the importance of measuring harms. The Safety Working Group was reestablished at the OMERACT 2016 with the objective to develop a COS for assessing safety components in trials across rheumatologic conditions., Methods: The safety issue has previously been discussed at OMERACT, but without a consistent approach to ensure harms were included in COS. Our methods include (1) identifying harmful outcomes in trials of interventions studied in patients with rheumatic diseases by a systematic literature review, (2) identifying components of safety that should be measured in such trials by use of a patient-driven approach including qualitative data collection and statistical organization of data, and (3) developing a COS through consensus processes including everyone involved., Results: Members of OMERACT including patients, clinicians, researchers, methodologists, and industry representatives reached consensus on the need to continue the efforts on developing a COS for safety in rheumatology trials. There was a general agreement about the need to identify safety-related outcomes that are meaningful to patients, framed in terms that patients consider relevant so that they will be able to make informed decisions., Conclusion: The OMERACT Safety Working Group will advance the work previously done within OMERACT using a new patient-driven approach.

Background: In cooperation with the Core Outcome Measures in Effectiveness Trials (COMET) initiative, the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) initiative aimed to develop a guideline on how to select outcome measurement instruments for outcomes (i.e., constructs or domains) included in a "Core Outcome Set" (COS). A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population., Methods: Informed by a literature review to identify potentially relevant tasks on outcome measurement instrument selection, a Delphi study was performed among a panel of international experts, representing diverse stakeholders. In three consecutive rounds, panelists were asked to rate the importance of different tasks in the selection of outcome measurement instruments, to justify their choices, and to add other relevant tasks. Consensus was defined as being achieved when 70 % or more of the panelists agreed and when fewer than 15 % of the panelists disagreed., Results: Of the 481 invited experts, 120 agreed to participate of whom 95 (79 %) completed the first Delphi questionnaire. We reached consensus on four main steps in the selection of outcome measurement instruments for COS: Step 1, conceptual considerations; Step 2, finding existing outcome measurement instruments, by means of a systematic review and/or a literature search; Step 3, quality assessment of outcome measurement instruments, by means of the evaluation of the measurement properties and feasibility aspects of outcome measurement instruments; and Step 4, generic recommendations on the selection of outcome measurement instruments for outcomes included in a COS (consensus ranged from 70 to 99 %)., Conclusions: This study resulted in a consensus-based guideline on the methods for selecting outcome measurement instruments for outcomes included in a COS. This guideline can be used by COS developers in defining how to measure core outcomes.

Objective: During OMERACT 12, a workshop was held with the aim to endorse a core set of domains for 3 settings: clinical trials of symptom and structure modification and observational studies. Additional goals were to endorse a core set of contextual factors for these settings, and to define preliminary instruments for each core domain. Finally, an agenda for future research in hand osteoarthritis (OA) was to be proposed., Methods: Literature reviews of preliminary instruments for each core domain of the proposed core set for hand OA in the settings described above. Literature review of radiographic scoring methods and modern imaging in hand OA were also performed. Proposed contextual factors for a core set were identified through 2 Delphi exercises with participation of hand OA experts, patient partners, and OMERACT participants., Results: Results from Delphi exercises and systematic literature reviews were presented and discussed. It was agreed that a preliminary core domain set for the setting clinical trials of symptom modification should contain at least "pain, physical function, patient global assessment, joint activity and hand strength." The settings clinical trial of structure modification and observational studies would in addition include structural damage. Preliminary instruments for the proposed domains were agreed on. A list of prioritized contextual factors was defined and endorsed for further research. A research agenda was proposed for domain instrument validation according to the OMERACT Filter 2.0., Conclusion: Preliminary core sets for clinical trials of symptom and structure modification and observational studies in hand osteoarthritis, including preliminary instruments and contextual factors, were agreed upon during OMERACT 12.

Objective: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of linked multisystem life- and organ-threatening diseases. The Outcome Measures in Rheumatology (OMERACT) vasculitis working group has been at the forefront of outcome development in the field and has achieved OMERACT endorsement of a core set of outcomes for AAV. Patients with AAV report as important some manifestations of disease not routinely collected through physician-completed outcome tools; and they rate common manifestations differently from investigators. The core set includes the domain of patient-reported outcomes (PRO). However, PRO currently used in clinical trials of AAV do not fully characterize patients' perspectives on their burden of disease. The OMERACT vasculitis working group is addressing the unmet needs for PRO in AAV., Methods: Current activities of the working group include (1) evaluating the feasibility and construct validity of instruments within the PROMIS (Patient-Reported Outcome Measurement Information System) to record components of the disease experience among patients with AAV; (2) creating a disease-specific PRO measure for AAV; and (3) applying The International Classification of Functioning, Disability and Health to examine the scope of outcome measures used in AAV., Results: The working group has developed a comprehensive research strategy, organized an investigative team, included patient research partners, obtained peer-reviewed funding, and is using a considerable research infrastructure to complete these interrelated projects to develop evidence-based validated outcome instruments that meet the OMERACT filter of truth, discrimination, and feasibility., Conclusion: The OMERACT vasculitis working group is on schedule to achieve its goals of developing validated PRO for use in clinical trials of AAV.

Background: General recommendations for a reference case for economic studies in rheumatic diseases were published in 2002 in an initiative to improve the comparability of cost-effectiveness studies in the field. Since then, economic evaluations in osteoarthritis (OA) continue to show considerable heterogeneity in methodological approach., Objectives: To develop a reference case specific for economic studies in OA, including the standard optimal care, with which to judge new pharmacologic and non-pharmacologic interventions., Methods: Four subgroups of an ESCEO expert working group on economic assessments (13 experts representing diverse aspects of clinical research and/or economic evaluations) were charged with producing lists of recommendations that would potentially improve the comparability of economic analyses in OA: outcome measures, comparators, costs and methodology. These proposals were discussed and refined during a face-to-face meeting in 2013. They are presented here in the format of the recommendations of the recently published Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, so that an initiative on economic analysis methodology might be consolidated with an initiative on reporting standards., Results: Overall, three distinct reference cases are proposed, one for each hand, knee and hip OA; with diagnostic variations in the first two, giving rise to different treatment options: interphalangeal or thumb-based disease for hand OA and the presence or absence of joint malalignment for knee OA. A set of management strategies is proposed, which should be further evaluated to help establish a consensus on the "standard optimal care" in each proposed reference case. The recommendations on outcome measures, cost itemisation and methodological approaches are also provided., Conclusions: The ESCEO group proposes a set of disease-specific recommendations on the conduct and reporting of economic evaluations in OA that could help the standardisation and comparability of studies that evaluate therapeutic strategies of OA in terms of costs and effectiveness., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aims to investigate how well the Assessment of SpondyloArthritis international Society (ASAS)/Outcome Measures in Rheumatology Clinical Trials (OMERACT) core set and response criteria for ankylosing spondylitis (AS) have been implemented in randomized controlled trials (RCTs) testing pharmacological and non-pharmacological interventions. A systematic literature search was performed up to June 2013 looking for RCTs in patients with axial spondyloarthritis (SpA) (AS and non-radiographic axial SpA). The assessed domains and instruments belonging to the core sets for disease-controlling anti-rheumatic therapy (DC-ART) and symptom-modifying anti-rheumatic drugs (SMARDs) were extracted. Results were reported separately for those trials published until 2 years after the publication of the core set (1 April 2001; 'control trials') and those trials published at least 2 years after the publication date ('implementation trials'). One hundred twenty-three articles from 99 RCTs were included in the analysis, comparing 48 'control trials' and 51 'implementation trials'. Regarding DC-ART core set, the following domains were significantly more frequently assessed in the 'implementation group' in comparison to the 'control group': 'physical function' (100 vs 41.7 %; p ≤ 0.001), 'peripheral joints/entheses' (100 vs 33.3 %; p ≤ 0.001) and 'fatigue' (100 vs 0 %; p ≤ 0.001). Three instruments were significantly more used in the 'implementation group': Bath Ankylosing Spondylitis Functional Index (BASFI) (100 vs 8.3 %; p = ≤ 0.001), CRP (92.3 vs 58.3 %; p = 0.01) and Bath Ankylosing Spondylitis Metrology Index (BASMI) (53.8 vs 0 %; p = 0.001). Regarding SMARD core set domains, physical function (92 vs 23 %; p ≤ 0.001) and fatigue (84 vs 17 %; p ≤ 0.001), as well as the instruments BASFI (88 vs 14 %; p ≤ 0.001) and BASMI (52 vs 0 %; p ≤ 0.001), increased significantly in the 'implementation group'. Twenty per cent of trials from the 'implementation group' but none from the 'control group' included all domains of the core set. In conclusion, this study provides evidence for the implementation of the ASAS/OMERACT core set in RCTs of both DC-ART and SMARD. This applies to the use of the domains and, to a lesser extent, to the specific instruments.

Background: Lack of standardization of outcome measures limits the usefulness of clinical trial evidence to inform health care decisions. This can be addressed by agreeing on a minimum core set of outcome measures per health condition, containing measures relevant to patients and decision makers. Since 1992, the Outcome Measures in Rheumatology (OMERACT) consensus initiative has successfully developed core sets for many rheumatologic conditions, actively involving patients since 2002. Its expanding scope required an explicit formulation of its underlying conceptual framework and process., Methods: Literature searches and iterative consensus process (surveys and group meetings) of stakeholders including patients, health professionals, and methodologists within and outside rheumatology., Results: To comprehensively sample patient-centered and intervention-specific outcomes, a framework emerged that comprises three core "Areas," namely Death, Life Impact, and Pathophysiological Manifestations; and one strongly recommended Resource Use. Through literature review and consensus process, core set development for any specific health condition starts by identifying at least one core "Domain" within each of the Areas to formulate the "Core Domain Set." Next, at least one applicable measurement instrument for each core Domain is identified to formulate a "Core Outcome Measurement Set." Each instrument must prove to be truthful (valid), discriminative, and feasible. In 2012, 96% of the voting participants (n=125) at the OMERACT 11 consensus conference endorsed this model and process., Conclusion: The OMERACT Filter 2.0 explicitly describes a comprehensive conceptual framework and a recommended process to develop core outcome measurement sets for rheumatology likely to be useful as a template in other areas of health care., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Behçet syndrome (BS) is a multisystem vasculitis that is most active during young adulthood, causing serious disability and significant impairment in quality of life. Differences in the disease course, severity, and organ involvement between patients, depending on the age at presentation and sex, makes it impossible to determine a single management strategy. The diversity and variability in the outcome measures used in clinical trials in BS makes it difficult to compare the results or inform physicians about the best management strategy for individual patients. There is a large unmet need to determine or develop validated outcome measures for use in clinical trials in BS that are acceptable to researchers and regulatory agencies. We conducted a systematic review to describe the outcomes and outcome measures that have been used in clinical trials in BS. This review revealed the diversity and variability in the outcomes and outcome measures and the lack of standard definitions for most outcomes and rarity of validated outcome tools for disease assessment in BS. This systematic literature review will identify domains and candidate instruments for use in a Delphi exercise, the next step in the development of a core set of outcome measures that are properly validated and widely accepted by the collaboration of researchers from many different regions of the world and from different specialties, including rheumatology, ophthalmology, dermatology, gastroenterology, and neurology.

The conduct of randomized controlled trials for vasculitis, especially for the antineutrophil cytoplasmic antibody-associated vasculitides [AAV, granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis], has been greatly advanced by the development, use, and acceptance of validated outcome measures. Trials have subsequently provided the opportunity to validate and refine reliable, valid outcome measures for these multisystemic and relapsing rare diseases. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group was formed in 2004 to foster development of validated and widely accepted outcomes in vasculitis using data-driven analyses, a dedication to building consensus, and adherence to, and guidance by, the principles of the OMERACT approach. This work led to the endorsement by OMERACT of the core set of domains and associated outcome measures for AAV. Next steps for the study of existing outcome tools in AAV include better definition of response criteria through development of more data-driven weighting of the elements of activity and damage assessment. The Working Group is now also embarking on a series of linked projects to develop validated patient-reported outcomes for use in clinical research in vasculitis. Additionally, the Working Group is studying how current methods of disease assessment and plans for new outcomes can be informed by the conceptual framework of the International Classification of Function of the World Health Organization. The success of the Group's work in AAV has also led to a formal process for developing outcomes for the large vessel vasculitides (Takayasu arteritis and giant cell arteritis) and Behçet disease.

Objective: To determine the extent to which participants at the Outcome Measures in Rheumatology (OMERACT) 11 meeting agree that instruments used in clinical trials to measure OMERACT core outcome domains in acute gout fulfill OMERACT filter requirements of truth, discrimination, and feasibility; and where future research efforts need to be directed., Methods: Results of a systematic literature review and analysis of individual-level data from recent clinical studies of acute gout were presented to OMERACT participants. The information was discussed in breakout groups, and opinion was defined by subsequent voting in a plenary session. Endorsement was defined as at least 70% of participants voting in agreement with the proposition (where the denominator excluded those participants who did not vote or who voted "don't know")., Results: The following measures were endorsed for use in clinical trials of acute gout: (1) 5-point Likert scale and/or visual analog scale (0 to 100 mm) to measure pain; (2) 4-point Likert scale for joint swelling; (3) 4-point Likert scale for joint tenderness; and (4) 5-point Likert scale for patient global assessment of response to treatment. Measures for the activity limitations domain were not endorsed., Conclusion: Measures of pain, joint swelling, joint tenderness, and patient global assessment in acute gout were endorsed at OMERACT 11. These measures should now be used in clinical trials of acute gout.

Background: The development and application of standardised sets of outcomes to be measured and reported in clinical trials have the potential to increase the efficiency and value of research. One of the most notable of the current outcome sets began nearly 20 years ago: the World Health Organization and International League of Associations for Rheumatology core set of outcomes for rheumatoid arthritis clinical trials, originating from the OMERACT (Outcome Measures in Rheumatology) Initiative. This study assesses the use of this core outcome set by randomised trials in rheumatology., Methods: An observational review was carried out of 350 randomised trials for the treatment of rheumatoid arthritis identified through The Cochrane Library (up to and including September 2012 issue). Reports of these trials were evaluated to determine whether or not there were trends in the proportion of trials reporting on the full set of core outcomes over time. Researchers who conducted trials after the publication of the core set were contacted to assess their awareness of it and to collect reasons for non-inclusion of the full core set of outcomes in the study., Results: Since the introduction of the core set of outcomes for rheumatoid arthritis, the consistency of measurement of the core set of outcomes has improved, although variation in the choice of measurement instrument remains. The majority of trialists who responded said that they would consider using the core outcome set in the design of a new trial., Conclusions: This observational review suggests that a higher percentage of trialists conducting trials in rheumatoid arthritis are now measuring the rheumatoid arthritis core outcome set. Core outcome sets have the potential to improve the evidence base for health care, but consideration must be given to the methods for disseminating their availability amongst the relevant communities.

The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence-based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence-based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long-term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research., (© 2012 John Wiley & Sons A/S.)

Content validity of patient-reported outcome measures (PROs) has been a focus of debate since the 2006 publication of the U.S. FDA Draft Guidance for Industry in Patient Reported Outcome Measurement. Under the auspices of the Patient Reported Outcomes Measurement Information System (PROMIS) initiative, a working meeting on content validity was convened with leading PRO measurement experts. Platform presentations and participant discussion highlighted key issues in the content validity debate, including inconsistency in the definition and evaluation of content validity, the need for empirical research to support methodological approaches to the evaluation of content validity, and concerns that continual re-evaluation of content validity slows the pace of science and leads to the proliferation of study-specific PROs. We advocate an approach to the evaluation of content validity, which includes meticulously documented qualitative and advanced quantitative methods. To advance the science of content validity in PROs, we recommend (1) development of a consensus definition of content validity; (2) development of content validity guidelines that delineate the role of qualitative and quantitative methods and the integration of multiple perspectives; (3) empirical evaluation of generalizability of content validity across applications; and (4) use of generic measures as the foundation for PROs assessment.

Objective: To summarize evidence for and endorsement of serum urate (SU) as having fulfilled the OMERACT filter as a soluble biomarker in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10)., Methods: Data were presented to support the use of SU as a soluble biomarker in chronic gout and specifically the ability to utilize it to predict future patient-reported outcomes., Results: SU was accepted as having fulfilled the OMERACT filter by 78% of voters. However, consensus was not obtained regarding its use as a soluble biomarker in chronic gout. Although the majority of the criteria for a soluble biomarker were fulfilled, the key criterion of association of the biomarker with outcomes was not agreed upon. It was agreed that the appropriate choice of endpoint must be linked to its clinical importance to the individual with the disorder and its temporal relationship to the intervention. Appropriate outcomes in chronic gout may therefore include gout flares, reduction in tophi, and patient-reported outcomes., Conclusion: SU is a critical outcome measure. It has the potential to fulfil criteria for a soluble biomarker. Further analyses of existing data from randomized controlled trials will be required to determine whether SU can predict future important outcomes, in particular disability.

There has been a marked increase in the past 15 years in the number and quality of clinical trials in the idiopathic inflammatory vasculitides, especially the small-vessel vasculitides known as antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis [AAV; granulomatosis, with polyangiitis (Wegener's)]. These trials have been conducted by multicenter, international groups in Europe and the United States with financial support provided by government agencies and biopharmaceutical companies. This increased clinical trial activity in vasculitis has been accompanied by the development and validation of new outcome measures--a challenging process for these complex, multiorgan system diseases. The international OMERACT Vasculitis Working Group has developed and implemented an iterative research agenda that has utilized accumulated experience and datasets from several multicenter clinical trials and large cohort studies. This work has led to the development, evaluation, validation, and endorsement, through the OMERACT consensus and validation processes, of a "core set" of outcome measurements for use in clinical trials of AAV. The core set includes domains of disease activity, damage assessment, patient-reported outcomes, and mortality; there is at least one validated outcome measurement instrument available for each domain. This report reviews the domains of illness in AAV included in the OMERACT core set, describes the instruments validated to measure these domains, and presents the approved core set.

Giant cell (GCA) and Takayasu's arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms. Although some clinical features are more common in one or the other disorder and the ages of initial presentation differ substantially, there is enough clinical and histopathologic overlap between these disorders that some investigators suggest GCA and TAK may be 2 processes within the spectrum of a single disease. There have been few randomized therapeutic trials completed in GCA, and none in TAK. The lack of therapeutic trials in LVV is only partially explained by the rarity of these diseases. It is likely that the lack of well validated outcome measures for LVV and uncertainties regarding trial design contribute to the paucity of trials for these diseases. An initiative to develop a core set of outcome measures for use in clinical trials of LVV was launched by the international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative include: (1) to review the literature and existing data related to outcome assessments in LVV; (2) to obtain the opinion of experts and patients on disease content; and (3) to formulate a research agenda to facilitate a more data-based approach to outcomes development.

Objective: To develop a simple system to assess benefit and harm of treatment on a single scale. Harm and benefit signals from trials need to be placed in the proper perspective to decide on the value of a treatment. Several systems have been developed for assessment, but few attempt to incorporate both benefit and risk in the same metric while retaining enough simplicity to aid patients and clinicians in their decision making., Study Design and Setting: We designed a very simple 3 x 3 table (Outcome Measures in Rheumatology [OMERACT] 3 x 3) that comprises three ranks for both beneficial and harm outcomes: for benefit, these are "none," "substantial," and "(near) remission"; for harm, these are "none," "severe," and "(near) death." Patients are ranked both for benefit and harm and subsequently counted in a 3 x 3 table., Results: The system was feasible when applied to one trial dataset (patient-level information) and a meta-analysis. To become applicable as a tool, several issues need to be resolved in further development, especially the definitions and cutoffs for the ranks., Conclusion: A simple 3 x 3 table to rank both benefit and harm outcomes is feasible. For rheumatology this will be further developed in the context of the OMERACT initiative.

Objective: Traditional outcome measures in randomized controlled trials (RCT) include well-established response criteria as well as ACR EULAR responses using Disease Activity Score 44 (DAS44)/DAS28 to assess improvement; however, a measure to assess worsening of disease has yet to be developed. This special interest group (SIG) was established to develop an evidence-based, consensus-driven standard definition of "flare" in rheumatoid arthritis (RA)., Methods: At OMERACT 8, the need for a standardized definition of RA flare was recognized; interested individuals developed a proposal to form a SIG. A literature review was performed to identify publications and abstracts with flare definitions applied in RA, JIA, and lupus RCT as well as concerning patient perspectives on disease worsening. A SIG was held at OMERACT 9 with breakout sessions for patients and investigators., Results: The RA flare SIG was attended by about 120 participants, including 11 patients. Patients and investigators held separate breakout sessions to discuss various aspects of disease worsening. The following consensus was obtained at OMERACT 9: a working definition of flare should indicate worsening of disease activity (88%), persistence, and duration as critical elements (77%), and consideration of change or increase in therapy (74%)., Conclusion: A working definition of RA flare was developed based on these votes: flare is any worsening of disease activity that would, if persistent, in most cases lead to initiation or change of therapy; and a flare represents a cluster of symptoms of sufficient duration and intensity to require initiation, change, or increase in therapy. Using this working definition, evaluation of candidate domains will be conducted via Delphi exercise and further informed by patient focus groups. Validation of candidate definitions in appropriate RCT will be required.

The past decade has seen a substantial increase in the number and quality of clinical trials of new therapies for vasculitis, including randomized, controlled, multicenter trials that have successfully incorporated measures of disease activity and toxicity. However, because current treatment regimens for severe disease effectively induce initial remission and reduce mortality, future trials will focus on any of several goals including: (a) treatment of mild-moderate disease; (b) prevention of chronic damage; (c) reduction in treatment toxicity; or (d) more subtle differences in remission induction or maintenance. Thus, new trials will require outcome measure instruments that are more precise and are better able to detect effective treatments for different disease states and measure chronic manifestations of disease. The OMERACT Vasculitis Working Group comprises international clinical investigators with expertise in vasculitis who, since 2002, have worked collaboratively to advance the refinement of outcome measures in vasculitis, create new measures to address domains of illness not covered by current research approaches, and harmonize outcome assessment in vasculitis. The focus of the OMERACT group to date has been on outcome measures in small-vessel vasculitis with an overall goal of creating a core set of outcome measures for vasculitis, each of which fulfills the OMERACT filter of truth, discrimination, feasibility, and identifying additional domains requiring further research. This process has been informed by several ongoing projects providing data on outcomes of disease activity, disease-related damage, multidimensional health-related quality of life, and patient-reported ratings of the burden of vasculitis.

At OMERACT 8 in May 2006 in Malta, the International Classification of Functioning, Disability and Health (ICF) was introduced as a universal model and a universal classification to describe human functioning. The potential usefulness of the ICF for the OMERACT process was highlighted and reported in a position paper following the OMERACT 8 meeting. Since then representatives of several OMERACT working groups with an interest in the ICF joined an OMERACT-ICF reference group. Most members had experience with the ICF and worked further to integrate the ICF into OMERACT. We describe the main roles of the ICF in the OMERACT process and the challenges when practice confronts theory.

We sought to identify instruments assessing sleep quality that measure the domains of sleep applicable to rheumatoid arthritis (RA) patients and are feasible to use and have appropriate reliability, validity, and responsiveness properties. A systematic review of sleep instruments was conducted. In particular, domains related to sleep that were assessed in the instruments were identified and evaluated. Feasibility characteristics and psychometric properties of instruments were reviewed. At OMERACT 9, the preparatory work was described at the plenary session of the Patient Perspective Workshop, and the tasks of 3 breakout groups in ranking and scoring the domains and sleep instruments were outlined. Each breakout group considered different aspects of sleep: sleep domains, feasibility, and psychometric properties. The rapporteur for each breakout group reported back to the plenary on the domains and sleep instruments that achieved the highest rank/score. The systematic review identified 45 sleep instruments of interest. Based on these instruments, 14 domains of sleep were identified. The top ranked domains were: Sleep Adequacy (1), Sleep Maintenance (2), Sleep Initiation (3) and Daytime Functioning (4). The top ranked instruments on feasibility were: Athens Insomnia Scale (2.3), Medical Outcome Study (MOS) Sleep (4.0), Insomnia Severity Index (4.9), and Women's Health Insomnia Rating Scale (5.5). The highest scored instruments on psychometric properties were: Athens Insomnia Scale (13.6), Sleep Assessment Questionnaire (13), Pittsburgh Sleep Diary (12), and MOS Sleep (11). Sleep domains have been reviewed, and several sleep instruments have been identified. These instruments should be considered for use in planned clinical trials of RA patients to assess their applicability.

Objective: To validate the definitions of minimal disease activity (MDA) in patients with rheumatoid arthritis (RA) and to compare abatacept to control with respect to patients attaining a state of MDA., Methods: Two randomized controlled trials comparing abatacept to control in patients with RA were considered: ATTAIN and AIM. Core set measures, Disease Activity Score 28-joint count (DAS28), and, for AIM, radiographic scores were available. The core set and DAS-based definitions for MDA were calculated and the number of patients in the treatment groups meeting the definitions was compared to determine sensitivity of the criteria to treatment differences and patient severity. The number of times achieving MDA was compared to the change in Health Assessment Questionnaire (HAQ), and for the AIM study compared to change in radiographic scores., Results: For both definitions of MDA, the change in radiographic scores showed a continual decrease in progression the more often a patient was in MDA. The change in HAQ, for both studies, showed a similar consistent improvement - the longer a patient was in MDA, then the better the HAQ score. Significantly more patients in the abatacept group met the core set and DAS-based definition of MDA than in the control group., Conclusion: The presence and persistence of MDA was associated with slowing of radiographic progression and improvement in the HAQ, providing support for discriminative and predictive validity of the measure. The MDA results were consistent with other efficacy analyses indicating a treatment advantage for abatacept.

Objective: To assess whether the American College of Rheumatology response criteria ACR20 should be replaced by another definition of response with enhanced discriminant validity., Methods: We worked with statisticians to define over 100 different ways of defining response, including dichotomous definitions (e.g., ACR20; ACR50; ACR70; low disease activity), ordinal definitions (EULAR response; ACR20, ACR50, ACR70), disease activity indexes [Disease Activity Score (DAS); Disease Activity Index, SDAI], continuous definitions (mean percentage improvement in all core set measures; nACR, ACRn), and hybrid definitions (ACR20, ACR50, ACR70 defined for a patient as 0, 1, 2, 3 scale with continuous measures between intervals) along with variations on each of these approaches (e.g., percentage vs absolute change in DAS; e.g., measures requiring vs not requiring joint count improvement). To test clinical validity, we administered a survey using patients from a trial who had various levels of improvement and asked rheumatologists whether and by how much these patients improved. For Sn-to-Chge, we are collecting data from large disease modifying antirheumatic drug multicenter trials in rheumatoid arthritis and ranking candidate definitions of response on their average p values in distinguishing active treatment from placebo or combination compared to single comparator., Results: We surveyed 52 rheumatologists about which trial patients had improved and by how much. Trial data were obtained and tested for sensitivity to change., Conclusion: A rigorous data-driven consensus process was used to reassess the ACR20.

The concepts of minimal clinically important improvement (MCII) and patient acceptable symptomatic state (PASS) could help in interpreting results of trials involving patient-reported outcomes by translating the response at the group level (change in mean scores) into more clinically meaningful information by addressing the patient level as "therapeutic success (yes/no)." The aims of the special interest group (SIG) at OMERACT 8 were to discuss specific issues concerning the MCII and PASS concepts, especially the wording of the external anchor questions used to determine the MCII and PASS estimates, and to move toward a consensus for the cutoff values to use as the MCII and PASS in the different outcome criteria. The purpose of this SIG at OMERACT 8 was to inform participants of the MCII and PASS concepts and to agree on MCII and PASS values for pain, patient global assessment, and functional impairment.

Since healthcare resources are scarce, choices have to be made on how they will be allocated. The use of economic evaluations using cost-effectiveness analyses has increased rapidly as policymakers have realized their value in maximizing the population's benefits (in terms of length of life and health status) within a given budget. Following efforts by OMERACT to create reference case definitions for the conduct of economic evaluation in rheumatoid arthritis, osteoporosis, and osteoarthritis, we review various methodological areas and research decisions that could benefit from a consensus between researchers, clinicians, and drug developers in terms of an ankylosing spondylitis (AS) reference case. Ten methodological issues are presented that will be important for future development of evaluations. Tentative proposals to define the issues in a reference case for AS are made, along with recommendations for further research.

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., Conclusion: 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.

Objective: A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker extensively studied in RA, was then used to test these criteria. Our objectives were: (1) To assess the strength of evidence in support of CRP as a soluble biomarker reflecting structural damage in RA according to the draft validation criteria. (2) To assess the strength of recommendation for inclusion of individual criteria in the draft set., Methods: A systematic literature review was conducted to elicit evidence in support of each specific criterion composing the 14-criteria draft set. A summary of the key literature findings per criterion was presented to both the working group and to participants in a special interest soluble biomarker group at OMERACT 8. Participants at OMERACT 8 were asked to rate the strength of evidence and the strength of the recommendation in support of each individual criterion on a 0-10 numerical rating scale. Working group members not present at OMERACT voted by a Web-based survey., Results: Minimal data were extracted from the literature pertaining to those criteria listed under the category of truth. Ratings for strength of evidence were moderate to low (< 7) for CRP as a biomarker reflecting structural damage in RA; this was true for all criteria except those listed under the category of feasibility and 2 listed under the category of discrimination pertaining to assay reproducibility and evidence regarding sources of variability. Ratings for strength of recommendation for inclusion of each of the 14 criteria in the draft set were high (> 7) except for those criteria listed under the category of truth., Conclusion: The draft criteria serve as a useful template in the evaluation of the strength of evidence in support of a particular soluble biomarker as reflecting structural damage in RA.

"What to measure" refers to domains stable over time. "How to measure" is constantly evolving. Lacking a common terminology and common underlying conceptual model of functioning and disability, what and how to measure have been described differently in the various OMERACT Core Sets. With the approval of the International Classification of Functioning, Disability and Health (ICF) by the World Health Assembly in 2001, we now have a universally conceptual model that integrates the biomedical and societal model of functioning and disability. The so-called ICF Core Sets can be used as a basis for the further specification of OMERACT domains addressing aspects of functioning. In line with the successful approach taken by OMERACT, it is suggested to comprehensively specify the domain "function" when defining "what should be measured," and only then to recommend how to measure or which health status measure to use. We recommend comparing the specifications of domains addressing aspects of functioning of OMERACT Core Sets already established with the ICF Core Sets, and examine whether the ICF Core Sets may be useful for the further specification of these domains.

Objective: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders., Methods: After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop., Results: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful., Conclusion: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery, development, and approval.

The complexity of assessing disease activity, disease status, and damage in the vasculitides reflects the multisystemic pathologic manifestations of these often chronic illnesses. Major progress has been made in the past decade in the development of validated and widely accepted outcome measures for use in clinical trials. Over time, these tools have been regularly revised, expanded, and supplemented with new measures of disease prognosis and damage. As a result clinical research in this area has become increasingly complex. This article critically reviews the current status of tools for assessing disease activity and damage in "ANCA-associated" vasculitides (Wegener's granulomatosis and microscopic polyangiitis), summarizes the current level of validation of each measure, addresses central problems and controversies to be considered during development of new vasculitis assessment tools, and proposes a series of research agendas for consideration by the vasculitis research community.