Planning for a Trial of Comparative Effectiveness of Gout Management Strategies

痛风是最常见的炎症性关节炎，影响着大约900万美国人。这是一种慢性病 以尿酸一钠(MSU)结晶沉积在关节和其他部位为特征的代谢性疾病。 痛风通过代表最常见原因的急性致残性关节炎发作而导致其主要疾病 美国急诊科的关节炎就诊人数最多；痛风还会导致痛风、骨侵蚀和慢性 关节病伴有关节损害，并与心血管代谢并发症有关。急性痛风发作 可以用抗炎药物有效治疗。当耀斑频繁且负担过重时， 降尿酸治疗(ULT)可以减少频率，减少TOHI，并防止其他 并发症。使用ULT将血清尿酸(SU)水平降至6.0 mg/dL以下(低于MSU饱和点) 应该溶解MSU晶体，这可能是痛风爆发的罪魁祸首，并减轻其他并发症。这是一种“款待 “靶向”血尿酸(TTT-SU)方法已被风湿科医生倡导。然而，大多数痛风患者 病例出现在初级保健中，许多风湿科医生担心初级保健对痛风的管理 攻击性不够强，启动ULT的门槛太高，使用ULT的剂量不足 “目标”。痛风治疗不足可能导致患者功能受损，原因是频繁的痛风发作和 伴有关节损害的慢性顶骨关节病。然而，TTT-SU管理痛风的方法在很大程度上 基于病理生理学原理，而不是临床试验。最近对美国人进行的一项系统评估 美国医师学会(ACP)临床指南委员会确认抗炎有效 痛风发作的药物，以及ULT降低急性发作风险的有效性，但承认， “尚未对特定目标水平的治疗进行测试”和“…我们仍然不确定这种款待的价值- 以目标为目标的策略与基于症状最小化的治疗强度的策略进行比较。机场核心计划 痛风管理指南既没有为ULT的启动设定特定的阈值，也没有推荐特定的SU 治疗目标。风湿病界对ACP指南的反应负面，主要关注的是 这可能会使初级保健中已经不太理想的痛风管理情况变得更糟。试图解决这个问题 争议，我们于2018年春季在波士顿召开了一次由NIH资助的会议，其中包括关键的利益相关者 在痛风护理中心。本次会议的共识是，痛风治疗策略的比较有效性试验 管理层将是以循证方式解决争议的最佳方式。因此，我们的 总体目标是设计一项试验，填补关键证据空白，并直接告知当前的做法。在这 申请，我们建议以下目标来计划这样的试验：1)进行Delphi Panel过程以确定 建议试验的最优设计和参数。2)准备试验细节，包括U01方案 (将在规划期的第二年期间提交)，以及研究方案、培训文件、 操作程序手册、同意书和调查员手册，并进行模拟招聘。

Gout is the most common inflammatory arthritis, affecting approximately 9 million Americans. It is a chronic metabolic disease characterized by monosodium urate (MSU) crystal deposition in the joints and elsewhere. Gout causes its major morbidity through acute disabling arthritis flares that represent the most common cause of arthritis visits to US emergency departments; gout can also cause tophi, bone erosions, and a chronic arthropathy with joint damage, and is associated with cardiovascular-metabolic complications. Acute gout flares can be treated effectively with anti-inflammatory medications. When flares are frequent and burdensome enough, urate lowering therapy (ULT) can be administered to reduce the frequency, reduce tophi, and prevent other complications. Using ULT to reduce serum urate (SU) levels below 6.0 mg/dL (below the MSU saturation point) should dissolve MSU crystals, the likely culprit of gout flares, and mitigate other complications. This “treat to target” serum urate (TTT-SU) approach has been advocated by rheumatologists. However, the majority of gout cases are seen in primary care and many rheumatologists have concerns that primary care management of gout is not aggressive enough, with too high a threshold to initiate ULT, and use of insufficient doses of ULT to achieve the “target.” Under-treatment of gout may lead to impairments in patient function due to frequent flares and chronic tophaceous arthropathy with joint damage. However, the TTT-SU approach to manage gout is largely based on pathophysiologic rationale, rather than clinical trials. A recent systematic review for the American College of Physicians' (ACP) Clinical Guidelines Committee confirmed the effectiveness of anti-inflammatory medications for gout flares, and effectiveness of ULT for lowering the risk of acute attacks, but acknowledged, “treatment to a specific target level has not been tested” and “…we remain uncertain about the value of a treat- to-target strategy compared with a strategy of basing treatment intensity on minimizing symptoms.” The ACP gout management guideline neither recommended a specific threshold for the initiation of ULT, nor a specific SU treatment target. The rheumatology community reacted negatively to the ACP guideline, with the main concern being it might worsen the already suboptimal management of gout in primary care. To attempt to resolve this controversy, we convened an NIH-funded meeting in Boston in the Spring of 2018 that included key stakeholders in gout care. The consensus of this meeting was that a comparative effectiveness trial of strategies of gout management would be the best way to resolve the controversy in an evidence-based manner. Thus, our overarching goal is to design a trial that will fill critical evidence gaps and directly inform current practice. In this application, we propose the following aims to plan such a trial: 1) to conduct a Delphi Panel process to determine the optimal design and parameters for the proposed trial. 2) to prepare trial details, including the U01 proposal (which will be submitted during year two of the planning period) with a study protocol, training documents, manual of operating procedures, consent form, and investigator brochure, and perform a mock recruitment.