OMERACT consensus-based operational definition of contextual factors in rheumatology clinical trials: A mixed methods study

Objectives: To develop an operational definition of contextual factors (CF) [1]. Methods: Based on previously conducted interviews, we presented three CF types in a Delphi survey; Effect Modifying -, Outcome Influencing - and Measurement Affecting CFs. Subsequently, a virtual Special Interest Group (SIG) session was held for in depth discussion of Effect Modifying CFs. Results: Of 161 Delphi participants, 129 (80%) completed both rounds. After two rounds, we reached consensus (≥70% agreeing) for all but two statements. The 45 SIG participants were broadly supportive. Conclusion: Through consensus we developed an operational definition of CFs, which was well received by OMERACT members

Incidence and cost of new onset diabetes mellitus among U.S. wait-listed and transplanted renal allograft recipients.

Abstract This study sought to determine 1) the incidence and costs of new onset diabetes mellitus (NODM) associated with maintenance immunosuppression regimens following renal transplantation and 2) whether the mode of dialysis pretransplant or the type of calcineurin inhibition used for maintenance immunosuppression affected either the incidence or cost of NODM. The study examined the United States Renal Data System\u27s clinical and financial records from 1994 to 1998 of all adult, first, single-organ, renal transplantations in either 1996 or 1997 with adequate financial records. It used the second diagnosis of diabetes in previously nondiabetic patients to identify NODM. While NODM had an incidence of approximately 6% per year among wait-listed dialysis patients, NODM over the first 2 years post-transplant had an incidence of almost 18% and 30% among patients receiving cyclosporine and tacrolimus, respectively. By 2 years post-transplant, Medicare paid an extra $21500 per newly diabetic patient. We estimated the cost of diabetes attributable to maintenance immunosuppression regimens to be$2025 and $3308 for each tacrolimus patient and$1137 and $1611 for each cyclosporine patient at I and 2 years post-transplant, respectively

Validation of OMERACT preliminary rheumatoid arthritis flare domains in the NOR-DMARD study

Objective Domains identified as a result of qualitative research and Delphi exercises to assess rheumatoid arthritis (RA) flare include pain, function, swollen and tender joints, patient and physician global, laboratory measures, participation, stiffness, self-management and fatigue. Here we examine aspects of construct and content validity of these domains in a longitudinal observational study. Methods A total of 1195 patients with RA treated with non-biological disease-modifying antirheumatic drugs (DMARDs) or biologics were eligible for the analyses. Working definitions of ‘flare’ included patient-reported worsening between 3 and 6 months (primary) and treatment change at 6 months (DMARDs and/or systemic corticosteroids) (secondary). Available outcome measures were mapped to the flare domains. Changes between 3 and 6 months were compared between patients with and without ‘flare’. Convergent and divergent construct validity and content validity were assessed by correlation analyses and logistic regression analysis, respectively. Results Applying the flare working definition based on patient-reported worsening, standardised mean differences (SMDs) were >0.5 for the majority of outcomes. The largest SMDs were observed for Pain visual analogue scale (1.30), SF-36 Bodily pain (1.24), Patient global (1.20) and morning stiffness intensity (1.17). The flare working definition based on treatment change yielded lower SMDs (<0.5 for most variables). Consistently stronger intradomain than corresponding interdomain correlations supported convergent and divergent validity of the domains. Conclusions Probing a flare definition via outcome measures, the identified flare domains discriminated well between patients with and without worsening. Interdomain and intradomain correlation and logistic regression analyses provide further support for construct and content validity of the identified flare domains

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. The Journal of Rheumatology Copyright © 2009. All rights reserved

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. The Journal of Rheumatology Copyright © 2011. All rights reserved

Identifying core domains to assess flare in rheumatoid arthritis: An OMERACT international patient and provider combined Delphi consensus

Objectives: For rheumatoid arthritis (RA), there is no consensus on how to define and assess flare. Variability in flare definitions impairs understanding of findings across studies and limits ability to pool results. The OMERACT RA Flare Group sought to identify domains to define RA flares from patient and healthcare professional (HCP) perspectives. Methods: Flare was described as a worsening of disease activity of sufficient intensity and duration to consider a change in therapy. International patients and HCPs participated in separate and combined rounds of Delphi exercises to rate candidate flare domains previously generated in patient focus groups. Core domains were defined as those with ≥70% ratings of being 'essential' according to the third/final Delphi exercise. Results: The final Delphi included 125 RA patients from 10 countries and 108 HCPs from 23 countries who rated 14 domains. Patients had a mean (±SD) age of 56±12 years and disease duration of 18±12 years. HCPs included physicians from clinical practice/research and industry, allied health providers and researchers with 17±11 years experience. Core domains comprised: pain (93%), function (89%), swollen joints (84%), tender joints (81%), participation (81%), stiffness (79%), patient global assessment (76%) and self-management (75%). Fatigue (68%), which did not reach group consensus, will receive additional consideration. Conclusions: As part of the process to develop a measure for RA flare, patients and HCPs agreed on eight core domains. Next steps include identifying items to assess domains and conducting studies to validate and refine a new measure