PREVENTABLE Vanguard Phase

Vanguard阶段对于早期证明成功招募和保留受试者、提供研究干预以及确定主要和次要结局至关重要。先锋阶段的主要目标是实施、审查和完善试验流程，确保成功入组，以满足NIH的预期，并确认试验的计划成功。这项试验将确定中等强度他汀类药物在预防痴呆（包括阿尔茨海默病和阿尔茨海默病相关痴呆）和延长75岁及以上无临床明显冠心病患者（包括虚弱、身体功能受损、轻度认知障碍、多药和多发病患者）的无残疾生存期方面的作用。在研究开始时，PCORnet的目标>90%和VA中心的目标>80%将准备好随机化，其余中心将在此后不久准备好随机化。我们将跟踪招募和留住代表可用人群的参与者的能力。我们将根据SPRINT、ADAPTABLE、雅阁、WHIMS和LIFE等试验进行培训和监测，以确保干预措施的成功实施。特别关注的是邮购药房、霍桑效应和视频同意过程的运营指标。我们将确定和/或裁定CV死亡和HFpEF验证研究支持的结局。在此阶段，PREVENTABLE还将仔细跟踪早期失访、从数据集市和医疗保险中获得的诊断以及交叉率，并改进流程以最大限度地降低研究风险并通知任何修改。先锋阶段核心将在DCRI的Karen亚历山大博士和WFSM的Jeff威廉姆森博士的领导下。在此阶段，我们将仔细跟踪早期失访率和交叉率，并在可能的情况下优化流程以最大限度地减少这些情况，并对研究程序进行任何必要的修改。我们预计在先锋阶段有7,000例随机化（5,250例随机化是75%的里程碑）。网站启动以及征聘和保留基准对于指导早期工作也至关重要。Vanguard阶段有以下具体目标：目的1：证明招募和保留可预防参与者的能力，这些参与者代表年龄≥75岁且无CVD或痴呆的患者。AIM 2.证明有能力提供干预措施，并以高度的准确性确定结果。目的3：根据观察到的失访率和交叉率证明保留功效。

The Vanguard phase is critical to early demonstration of successful recruitment and retention of participants, delivery of the study intervention, and ascertainment of the primary and secondary outcomes. The primary goal of the Vanguard Phase is to implement, review and refine trial processes and ensure successful enrollment to meet NIH expectations and confirm programmatic success of the trial. This trial will determine the role of a moderate-intensity statin in preventing dementia, including Alzheimer’s disease and Alzheimer’s disease-related dementias, and prolonging disability-free survival in patients 75 years and older without clinically evident coronary heart disease, including those with frailty, impaired physical function, mild cognitive impairment, polypharmacy, and multi-morbidity. A target of >90% of PCORnet and >80% of VA sites will be ready to randomize at study start with the remaining sites ready to randomize shortly thereafter. We will track the ability to recruit and retain participants who are representative of the available population. We will implement training and monitoring adapted from trials such as SPRINT, ADAPTABLE, ACCORD, WHIMS, and LIFE, to ensure successful delivery of the intervention. Of particular focus will be the operational metrics for the mail-order pharmacy, Hawthorne Effect, and video consent process. We will ascertain and/or adjudicate outcomes supported by validation studies for CV death and HFpEF. During this phase, PREVENTABLE will also carefully track early loss to follow-up, obtainable diagnoses from data marts and Medicare, and crossover rates, and refine processes to minimize risks to the study and inform any modifications. The Vanguard Phase Core will be under the leadership of Drs. Karen Alexander of DCRI and Jeff Williamson of WFSM. During this phase, we will carefully track early loss to follow-up and cross-over rates and refine processes for minimizing these when possible and make any needed modifications to the study procedures. We project 7,000 randomizations during the Vanguard phase (5,250 randomizations is the 75% milestone). Site activation and recruitment and retention benchmarks will also be vital for directing early efforts. The Vanguard phase has the following specific aims: AIM 1: Demonstrate the ability to recruit and retain participants in PREVENTABLE representative of those age≥75 years of age without CVD or dementia. AIM 2. Demonstrate the ability to deliver the intervention and ascertain outcomes with a high degree of accuracy. AIM 3: Demonstrate preserved power based on observed lost to follow up and cross over rates.