Planning for a Trial of Comparative Effectiveness of Gout Management Strategies

痛风是最常见的炎症性关节炎，影响约900万美国人。它是一种慢性 以关节和其他部位的尿酸盐（MSU）晶体沉积为特征的代谢性疾病。 痛风的原因，其主要发病率通过急性致残性关节炎耀斑，代表最常见的原因 关节炎访问美国急诊科;痛风也可导致痛风石，骨侵蚀，和慢性 伴有关节损伤的关节病，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。当耀斑足够频繁和沉重时， 可以施用降低尿酸盐治疗（UREA）以降低频率，减少痛风石，并预防其他 并发症使用降尿酸盐将血清尿酸盐（SU）水平降至6.0 mg/dL以下（低于MSU饱和点） 应该溶解MSU晶体（痛风发作的可能罪魁祸首）并减轻其他并发症。这种“对待 靶向”血清尿酸盐（TTT-SU）方法已被风湿病学家所提倡。然而，大多数痛风 病例见于初级保健，许多风湿病学家担心痛风的初级保健管理 没有足够的侵略性，启动的阈值太高，使用的剂量不足，以实现 的“目标”。痛风治疗不足可能会导致患者功能受损，因为频繁发作， 慢性痛风性关节病伴关节损伤。然而，TTT-SU治疗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。最近一项针对美国 医师学院（ACP）临床指南委员会证实了抗炎的有效性 痛风发作的药物，以及降低急性发作风险的有效性，但承认， “尚未测试达到特定目标水平的治疗”和“.我们仍然不确定治疗的价值- 目标策略与基于最小化症状的治疗强度策略相比。非加太 痛风管理指南既没有推荐一个特定的阈值，也没有具体的SU启动 治疗目标流变学界对ACP指南反应消极，主要关注的是 因为它可能会使初级保健中已经不太理想的痛风治疗恶化。为了解决这个问题 为了解决争议，我们于2018年春季在波士顿召开了一次由NIH资助的会议，其中包括主要利益相关者 在痛风治疗中。这次会议的共识是，痛风治疗策略的比较有效性试验 管理将是以循证方式解决争议的最佳途径。所以我们 总体目标是设计一项试验，填补关键证据空白，并直接为当前实践提供信息。在这 应用程序，我们提出了以下目标来计划这样的试验：1）进行德尔菲小组的过程，以确定 最佳的设计和参数，为拟议的审判。2)准备试验细节，包括U 01提案 （将在计划期的第二年提交），并附有研究方案、培训文件， 操作程序手册、同意书和研究者手册，并进行模拟招募。

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.