Remission in Rheumatoid Arthritis: Working Toward Incorporation of the Patient Perspective at OMERACT 12.

OBJECTIVE: The treatment of rheumatoid arthritis (RA) should target patient-relevant outcomes, making patient perspective on remission essential. In 2010, patients, physicians, health professionals, and researchers at the Outcome Measures in Rheumatology (OMERACT) conference developed an ambitious research agenda to study the concept of remission. Qualitative research has since helped us understand the concept of remission from the patient perspective. METHODS: During OMERACT 12, the OMERACT working group on patient perspective on remission in RA elaborated on data generated to date and discussed the methodological challenges ahead. Challenges included (1) selection of domains, (2) choice of a patient remission definition or a single domain to add to the current remission definition, and (3) the importance of pain in defining remission from a patient perspective. RESULTS: Focus in the coming years will be on increasing our understanding by identifying the most important domains from the patient perspective regarding remission and investigating how these domains can be measured. Investigation into the Rheumatoid Arthritis Impact of Disease questionnaire, disease flare, as well as the concordance of domains from our ongoing remission survey is appropriate. More data and further discussions are needed to decide on the next steps. CONCLUSION: Progress summarized over 4 years highlights the main methodological challenges discussed within the working group on patient perspective on remission in RA during OMERACT 12.

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.

Reliability and sensitivity to change of the Bristol Rheumatoid Arthritis Fatigue scales.

OBJECTIVE: To examine the reliability (stability) and sensitivity of the Bristol Rheumatoid Arthritis Fatigue scales (BRAFs) and patient-reported outcome measures (PROMs) developed to capture the fatigue experience. The Multi-Dimensional Questionnaire (BRAF-MDQ) has a global score and four subscales (Physical Fatigue, Living with Fatigue, Cognitive Fatigue and Emotional Fatigue), while three numerical rating scales (BRAF-NRS) measure fatigue Severity, Effect and Coping. METHODS: RA patients completed the BRAFs plus comparator PROMs. Reliability (study 1): 50 patients completed questionnaires twice. A same-day test-retest interval (minimum 60 min) ensured both time points related to the same 7 days, minimizing the capture of fatigue fluctuations. Reliability (study 2): 50 patients completed the same procedure with a re-worded BRAF-NRS Coping. Sensitivity to change (study 3): 42 patients being given clinically a single high dose of i.m. glucocorticoids completed questionnaires at weeks 0 and 2. RESULTS: The BRAF-MDQ, its subscales and the BRAF-NRS showed very strong reliability (r = 0.82-0.95). BRAF-NRS Coping had lower moderate reliability in both wording formats (r = 0.62, 0.60). The BRAF-MDQ, its subscales and the BRAF-NRS Severity and Effect were sensitive to change, with effect sizes (ESs) of 0.33-0.56. As hypothesized, the BRF-NRS Coping was not responsive to the pharmaceutical intervention (ES 0.05). Preliminary exploration suggests a minimum clinically important difference of 17.5% for improvement and 6.1% for fatigue worsening. CONCLUSION: The BRAF scales show good reliability and sensitivity to change. The lack of BRAF-NRS Coping responsiveness to medication supports the theory that coping with fatigue is a concept distinct from severity and effect that is worth measuring separately.

Patient perspective workshop: moving towards OMERACT guidelines for choosing or developing instruments to measure patient-reported outcomes.

The workshop Choosing or Developing Instruments held at the Outcome Measures in Rheumatology (OMERACT) 10 meeting was designed to help participants think about the underlying methods of instrument development. Conference pre-reading material and 3 brief introductory presentations elaborated the issues, and participants broke into discussion groups before reconvening to share insights, engage in a more general discussion of the issues, and vote on recommendations. Tradeoffs between using current imperfect measures and the long and complex process of developing new instruments were considered, together with the need for rigor in patient-reported outcome (PRO) instrument development. The main considerations for PRO instrument development were listed and a research agenda for action produced. As part of the agenda for action, it is recommended that researchers and patient partners work together to tackle these issues, and that OMERACT bring forward proposals for acceptable instrument development protocols that would meet an enhanced "Truth" statement in the OMERACT Filter.

OMERACT 10 Patient Perspective Virtual Campus: valuing health; measuring outcomes in rheumatoid arthritis fatigue, RA sleep, arthroplasty, and systemic sclerosis; and clinical significance of changes in health.

This workshop reviewed progress in a number of areas related to patient perspective outcomes that were not specifically included within other areas of the program. A substantial review of the work of the valuing health outcomes group (the "QALY" working group) with participation and feedback from the plenary audience resulted in guidance to refocus on the use of patient preferences in the elaboration of more robust outcome measures for patient-reported outcomes and life impact measures. Progress and developments in the areas of fatigue and sleep in rheumatoid arthritis, outcome measures in hip and knee arthroplasty clinical trials, and scleroderma were outlined, and the challenge of truly understanding the nature of clinically important improvement was reviewed.

Developing a construct to evaluate flares in rheumatoid arthritis: a conceptual report of the OMERACT RA Flare Definition Working Group.

Rheumatoid arthritis (RA) patients and healthcare professionals (HCP) recognize that episodic worsening disease activity, often described as a "flare," is a common feature of RA that can contribute to impaired function and disability. However, there is no standard definition to enable measurement of its intensity and impact. The conceptual framework of the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Definition Working Group includes an anchoring statement, developed at OMERACT 9 in 2008: "flare in RA" is defined as worsening of signs and symptoms of sufficient intensity and duration to lead to change in therapy. Subsequently, domains characterizing flare have been identified by comprehensive literature review, patient focus groups, and patient/HCP Delphi exercises. This led to a consensus regarding preliminary domains and a research agenda at OMERACT 10 in May 2010. The conceptual framework of flare takes into account validated approaches to measurement in RA: (1) various disease activity indices (e.g., Disease Activity Score, Clinical Disease Activity Index, Simplified Disease Activity Index); (2) use of patient-reported outcomes (PRO); and (3) characterization of minimally clinically detectable and important differences (MCDD, MCID). The measurement of RA flare is composed of data collection assessing a range of unique domains describing key features of RA worsening at the time of patient self-report of flare, and then periodically for the duration of the flare. The components envisioned are: (1) Patient self-report using a "patient global question" with well characterized and validated anchors; (2) Patient assessment using a flare questionnaire and PRO available at the time of each self-report; (3) Physician/HCP assessment of disease activity status; and (4) Physician's determination whether to change treatment. In randomized controlled trials and observational studies, such a conceptual approach is intended to lead to a valid measure of this outcome/response, thus expanding an understanding of the true impact of a therapy to limit disease activity. Clinically, this approach is intended to enhance patient-HCP communication. This article describes the conceptual framework being used by the OMERACT RA Flare Definition Working Group in developing a standardized method for description and measurement of "flare in RA" to guide individual patient treatment.

Identifying preliminary domains to detect and measure rheumatoid arthritis flares: report of the OMERACT 10 RA Flare Workshop.

BACKGROUND: While disease flares in rheumatoid arthritis (RA) are a recognized aspect of the disease process, there is limited formative research to describe them. METHODS: The Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Definition Working Group is conducting an international research project to understand the specific characteristics and impact of episodic disease worsening, or "flare," so that outcome measures can be developed or modified to reflect this uncommonly measured, but very real and sometimes disabling RA disease feature. Patient research partners provided critical insights into the multidimensional nature of flare. The perspectives of patients and healthcare and research professionals are being integrated to ensure that any outcome measurement to detect flares fulfills the first OMERACT criteria of Truth. Through an iterative data-driven Delphi process, a preliminary list of key domains has been identified to evaluate flare. RESULTS: At OMERACT 10, consensus was achieved identifying features of flare in addition to the existing core set for RA, including fatigue, stiffness, symptom persistence, systemic features, and participation. Patient self-report of flare was identified as a component of the research agenda needed to establish criterion validity for a flare definition; this can be used in prospective studies to further evaluate the Discrimination and Feasibility components of the OMERACT filter for a flare outcome measure. CONCLUSION: Our work to date has provided better understanding of key aspects of the RA disease process as episodic, potentially disabling disease worsening even when a patient is in low disease activity. It also highlights the importance of developing ways to enhance communication between patients and clinicians and improve the ability to achieve "tight control" of disease.

Developing a standardized definition for disease "flare" in rheumatoid arthritis (OMERACT 9 Special Interest Group).

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.

Incorporating the patient perspective into outcome assessment in rheumatoid arthritis--progress at OMERACT 7.

The Patient Perspective Workshop at OMERACT 7 addressed the question of assessing the outcomes of intervention in rheumatoid arthritis (RA) from the perspective of those who experience the disease. A particular emphasis at this workshop was placed on fatigue, but other areas included well-being, real-time assessment, patient priorities, and needs in early and late disease. Through a series of overview presentations, discussion groups, and plenary sessions, workshop participants (who included 19 patients) clarified what is known and what are the outstanding issues for future research. The importance of further work on clarifying the validity of fatigue measurements in RA has been confirmed, and with at least one suitable instrument available there will be strong pressure to include fatigue in a redefined core set of outcome measures in RA. In the other 4 areas covered there are important issues that can be addressed by enquiry and experiment and that together provide a challenging research agenda. At the final plenary session the OMERACT conference endorsed, by a large majority, the proposal that fatigue may warrant consideration for inclusion in the OMERACT core set for RA.