Morillon Melanie B, Stamp Lisa, Taylor William, Fransen Jaap, Dalbeth Nicola, Singh Jasvinder A, Christensen Robin, Lassere Marissa
Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Frederiksberg, Denmark Department of Rheumatology, Odense University Hospital, Svendborg, Denmark.
Department of Medicine, University of Otago, Christchurch, New Zealand.
BMJ Open. 2016 Sep 20;6(9):e012026. doi: 10.1136/bmjopen-2016-012026.
Gout is the most common inflammatory arthritis in men over 40 years 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 'Biomarker-Surrogacy Evaluation Schema version 3' (BSES3), documenting the validity of selected instruments by applying the 'OMERACT Filter 2.0'.
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 months (or 6 and 12 months if 3-month values are not available) against flare rate, tophus size and number and pain at the final study visit (dependent variables).
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.
CRD42016026991.
痛风是40岁以上男性中最常见的炎性关节炎。长期降尿酸治疗被认为是有效管理痛风的关键策略。降尿酸治疗临床试验中疗效的主要结局指标是血清尿酸水平，它有效地充当了以患者为中心的结局（如痛风发作频率或疼痛）的替代指标。然而，血清尿酸与临床相关结局之间关系的强度是否足够强到可以将血清尿酸视为充分的替代指标，这一点尚未得到明确证实。我们的目标是根据“生物标志物替代评估方案第3版”（BSES3），研究随机对照试验中血清尿酸变化与临床相关结局变化之间关系的强度，并通过应用“渥太华共识标准2.0”记录所选指标的有效性。
按照系统评价和Meta分析的首选报告项目（PRISMA）报告指南进行的系统评价将识别所有相关研究。由2名独立审阅者从每项研究中提取标准化数据元素，分歧通过讨论解决。将血清尿酸水平从基线到3个月（如果没有3个月的值，则为6个月和12个月）变化的组间差异（自变量）与最终研究访视时的发作率、痛风石大小和数量以及疼痛（因变量）进行Meta回归分析数据。
本研究不需要特定的伦理批准，因为它基于对已发表（汇总）数据的分析。目标受众将包括医疗保健研究人员、政策制定者和临床医生。研究结果将通过同行评审出版物传播。
CRD42016026991。
