Abstract
Discussion and voting at OMERACT 9 confirmed 5 essential domains for outcomes of acute gout: pain, joint swelling, joint tenderness, patient global assessment and activity limitations. For studies in chronic gout 7 essential domains are: serum urate, acute gout attacks, tophus burden, health-related quality of life, activity limitations, pain, and patient global assessment. Implications of patient perspectives, discretionary domains for specific studies, measurement instruments and a possible responder index are under study.
There has been increased interest and attention paid to gout, motivated in part by improved understanding of the pathogenesis of gouty inflammation1, new insights into the genetics of hyperuricemia2,3 and the introduction and investigation of potentially important new interventions4,5. Previous meetings of investigators in the OMERACT gout group6 have highlighted the paucity of validated outcome measures for evaluation of either acute gout or the longterm management of chronic gout in clinical trials. As an important first step, it was necessary to define the relevant domains for outcome measurement in both of these contexts. At the second meeting of a special interest group (SIG) at OMERACT 8 in 2006 a preliminary list of proposed domains was developed and published7.
Taylor, et al8 followed this with a modified Delphi exercise to assess the importance of the domains proposed by the SIG. During 3 iterations, 30 rheumatologists and 3 industry representatives rated the domains for both acute and chronic gout. Consensus was defined as a UCLA RAND disagreement index of less than 1. Outcome domains considered essential for acute gout were pain, patient global, physician global, joint swelling, joint tenderness, and functional disability. Essential domains for chronic gout were listed as serum urate, flares, tophus regression, health related quality of life, functional disability, pain, patient global, physician global, work disability, and joint inflammation.
Methods
A two-and-half hour workshop at OMERACT 9 addressed domains for both acute and chronic gout and some initial evaluation of measures. A 15-minute presentation reviewed the current state of the proposed domains. Two separate, hour-long breakout groups discussed the acute and chronic domains and then reported back to the assembled workshop composed of participants from all groups at OMERACT 9. At the General Assembly plenary session each domain proposed as essential was voted upon. The OMERACT convention had required that 70% of participants vote in favor of a particular domain for it to be retained.
Results
Seventy-seven attendees voted on the proposed domains. The breakouts had discussed and proposed some revision to the domains. Five domains were voted as essential for acute gout and 7 for chronic gout (Table 1). Based on consensus from discussions in the breakouts and in the assembled workshop minor clarifications were suggested. The term “activities limitation” was preferred over “functional disability”9. For chronic gout, serum uric acid was noted as an essential but surrogate domain that has yet to be proven to coincide with outcomes of concern to patients. The term “acute gout attacks” was preferred over “flares,” since translation of “flare” into some non-English languages was thought to be problematic. Figures 1 and 2 illustrate the results of voting to identify essential domains in the inner circle, or ovals, with these minor revisions. Outer ovals include those domains receiving < 70% of votes as well as domains from the previous Delphi exercise, which had not received consideration as essential in the voting. These outer domains were felt to merit consideration for inclusion in selected clinical trials.
Acute gout studies. Proposed outcome domains in studies of acute gout (domains in the inner oval are mandatory, in the outer oval, discretionary).
Chronic gout studies. Proposed outcome domains in studies of chronic gout (domains in the inner circle are mandatory; in the next oval, discretionary; and in the outer oval, for research).
Plenary voting (n = 77) for proposed core (inner circle) domains for gout.
Discussion
A multistage process with gout experts and OMERACT 9 participants has been included in the discussion at a special interest group, a formal Delphi process between OMERACT meetings, and a small group/plenary discussion that concluded with plenary voting at OMERACT 9. This led to identification of the listed core domains for outcome measurement in clinical studies of acute and chronic gout.
Information concerning patients’ perspective on what is important to them was not presented in plenary sessions at OMERACT because of timetable restrictions, but this was discussed at a meeting of the gout group, which was also attended by 3 patient partners with gout. Data from semi-structured interviews with gout patients in Barcelona, Spain (n = 31) (Diaz-Torne, personal communication); and Gainesville, FL (n = 30) and Cincinnati, OH (n = 49) (Edwards, McTigue, Khanna, Ginsberg, personal communication) showed that the principal concerns of patients with gout were loss of mobility, pain, emotional stress, sleep interference, fear of medication side effects, work and social limitations, joint swelling and deformities, dietary restrictions, and dependency upon others. The most frequently prioritized concerns were pain and mobility problems. These concerns were mostly represented in the proposed core outcome domains and were strongly endorsed by the patient partners present during the group discussion.
An additional means of obtaining the perspective of patients was represented by the International Classification of Functioning, Disability and Health (ICF) core-sets approach, in which categories of the impact of disease were selected for special relevance to a particular disease. The process by which core sets were developed includes patients’ perspectives gathered by a standardized quantitative and qualitative methodology10. This work has not been accomplished for gout specifically, but an ICF core-set was developed for acute inflammatory arthritis, which explicitly included crystal-associated disease11. The ICF Brief Core Set for Body Functions, Body Structures, Activities, Participation and Environmental Factors included 40 ICF categories listed in Table 2. Many of these categories may not be relevant to acute gout, and others do not clearly fall within the domains selected by the OMERACT process. Further work is required to resolve any important omissions from the OMERACT domains highlighted by the ICF Brief Core Set.
The International Classification of Functioning, Disability and Health (ICF) brief core set for acute inflammatory arthritis.
The possible importance of developing a responder index or indices was introduced and will be one area for further investigation. For acute gout, pain was identified as the most important domain and it would thus need to carry increased weight in any index. A 10-point Likert scale was generally favored for measuring pain, but the adequacy of instruments for measuring in other domains is an area for further development. For various measures at joints, the question whether we should measure a target joint or all joints still needs to be resolved. Progress in validation of measurement instruments is the subject of a companion paper12.
