{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T06:02:22Z","timestamp":1765605742710,"version":"3.48.0"},"reference-count":27,"publisher":"BMJ","issue":"9","funder":[{"DOI":"10.13039\/100001275","name":"Oak Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2016,8,30]]},"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Gout is the most common inflammatory arthritis in men over 40\u2005years of age. Long-term urate-lowering therapy is considered a key strategy for effective gout management. The primary outcome measure for efficacy in clinical trials of urate-lowering therapy is serum urate levels, effectively acting as a surrogate for patient-centred outcomes such as frequency of gout attacks or pain. Yet it is not clearly demonstrated that the strength of the relationship between serum urate and clinically relevant outcomes is sufficiently strong for serum urate to be considered an adequate surrogate. Our objective is to investigate the strength of the relationship between changes in serum urate in randomised controlled trials and changes in clinically relevant outcomes according to the \u2018Biomarker-Surrogacy Evaluation Schema version 3\u2019 (BSES3), documenting the validity of selected instruments by applying the \u2018OMERACT Filter 2.0\u2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>A systematic review described in terms of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will identify all relevant studies. Standardised data elements will be extracted from each study by 2 independent reviewers and disagreements are resolved by discussion. The data will be analysed by meta-regression of the between-arm differences in the change in serum urate level (independent variable) from baseline to 3\u2005months (or 6 and 12\u2005months if 3-month values are not available) against flare rate, tophus size and number and pain at the final study visit (dependent variables).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study will not require specific ethics approval since it is based on analysis of published (aggregated) data. The intended audience will include healthcare researchers, policymakers and clinicians. Results of the study will be disseminated by peer-reviewed publications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>CRD42016026991.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2016-012026","type":"journal-article","created":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T22:48:51Z","timestamp":1474411731000},"page":"e012026","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Using serum urate as a validated surrogate end point for flares in patients with gout: protocol for a systematic review and meta-regression analysis"],"prefix":"10.1136","volume":"6","author":[{"given":"Melanie B","family":"Morillon","sequence":"first","affiliation":[{"name":"Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Frederiksberg, Denmark"},{"name":"Department of Rheumatology, Odense University Hospital, Svendborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Stamp","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Otago, Christchurch, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Otago, Wellington, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaap","family":"Fransen","sequence":"additional","affiliation":[{"name":"JF Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Dalbeth","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Auckland, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasvinder A","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham & Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6600-0631","authenticated-orcid":false,"given":"Robin","family":"Christensen","sequence":"additional","affiliation":[{"name":"Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Frederiksberg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marissa","family":"Lassere","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, St George Hospital, University of NSW, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2016,9,20]]},"reference":[{"key":"2025121221574551000_6.9.e012026.1","unstructured":"Temple R . Clinical measurement in drug evaluation. In: Nimmo W , Tucker G, eds . A regulatory authority's opinion about surrogate endpoints. 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