1 Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
2 Division of Cardiology and Duke Clinical Research Institute, Duke University, Durham, NC, USA.
Clin Trials. 2019 Feb;16(1):90-97. doi: 10.1177/1740774518812776. Epub 2018 Nov 16.
The US Food and Drug Administration's Sentinel Initiative is well positioned to support pragmatic clinical trials. FDA-Catalyst combines direct contact with health plan members and/or providers with data in the Sentinel infrastructure. Here, we describe the rationale, feasibility analyses, and lessons learned from the planning phase of the first large pragmatic trial conducted using the Sentinel Initiative's delivery system capabilities-IMplementation of a randomized controlled trial to imProve treatment with oral AntiCoagulanTs in patients with Atrial Fibrillation (the IMPACT-AFib trial).
During the planning phase, we convened representatives from five commercial health plans, FDA, study coordinating centers, and a patient representative for protocol development, institutional review board preparation, and other activities. Administrative claims data from the plans were included in a retrospective cohort analysis to assess sample size for the trial. Members ≥30 years old with ≥365 days of medical/pharmacy coverage, ≥2 diagnosis codes for atrial fibrillation, a guideline-based indication for oral anticoagulant use for stroke prevention, and no evidence of oral anticoagulant use in the 365 days prior to the index atrial fibrillation diagnosis in 2013 were included. Exclusions for the analysis included other conditions requiring anticoagulation, history of intracranial hemorrhage, and gastrointestinal bleed. We calculated rates of oral anticoagulant use, transient ischemic attack or stroke, and bleeding in the 365 days following the index atrial fibrillation diagnosis.
A total of 44,786 members with atrial fibrillation with no evidence of recent oral anticoagulant use were identified. In total, 87% (n = 38,759) were classified as having a guideline-based indication for oral anticoagulants. Of those, 33% (n = 12,867) had a new oral anticoagulant dispensed during the following year, 15% (n = 5917) were hospitalized for stroke or transient ischemic attack, and 9% (n = 3469) for bleeding events. This information was used to develop the trial protocol including sample size, power calculations, and level of randomization.
Sentinel infrastructure generated preliminary data that supported planning and implementation of a large pragmatic trial embedded in health plans. This planning identified unanticipated challenges that must be addressed in similar trials.
美国食品和药物管理局的监测倡议(Sentinel Initiative)非常适合支持务实的临床试验。FDA-Catalyst 将与健康计划成员和/或提供者的直接联系与 Sentinel 基础设施中的数据相结合。在这里，我们描述了使用 Sentinel Initiative 交付系统功能进行的第一个大型务实试验的规划阶段的基本原理、可行性分析和经验教训-实施一项随机对照试验，以改善心房颤动患者的口服抗凝治疗(IMPACT-AFib 试验)。
在规划阶段，我们召集了来自五家商业健康计划、FDA、研究协调中心和一名患者代表的代表，共同制定方案、准备机构审查委员会和开展其他活动。计划中的行政索赔数据被纳入回顾性队列分析，以评估试验的样本量。纳入标准为：年龄≥30 岁、医疗/药房覆盖≥365 天、≥2 个心房颤动诊断代码、有基于指南的口服抗凝剂用于预防中风的指征、且在 2013 年索引心房颤动诊断前的 365 天内无口服抗凝剂使用证据。分析排除了需要抗凝的其他疾病、颅内出血史和胃肠道出血史。我们计算了索引心房颤动诊断后 365 天内口服抗凝剂使用、短暂性脑缺血发作或中风和出血的发生率。
共确定了 44786 名无近期口服抗凝剂使用证据的心房颤动患者。共有 87%(n=38759)被归类为有基于指南的口服抗凝剂指征。其中，33%(n=12867)在接下来的一年中开了新的口服抗凝剂，15%(n=5917)因中风或短暂性脑缺血发作住院，9%(n=3469)因出血事件住院。这些信息被用于制定试验方案，包括样本量、功效计算和随机化水平。
Sentinel 基础设施生成的初步数据支持了在健康计划中嵌入的大型务实试验的规划和实施。该规划确定了类似试验中必须解决的意外挑战。
