Fixed Dose Intervention Trial of New England Enhancing Survival in SMI Patients

描述(申请人提供)：严重精神疾病(SMI)患者比普通人群更早死亡。SMI患者的大部分超额死亡率可归因于心血管疾病，并因第二代抗精神病药物(2GA)的治疗而加剧。尽管心血管风险众所周知，而且存在安全、有效的治疗方法，但很少有SMI患者接受心血管预防药物。护理服务分散和患者依从性差是降低SMI患者心血管风险的核心问题。为了解决这些问题，我们建议进行一项多点、开放标签、随机对照试验，比较精神卫生诊所内提供的两种免费、固定剂量的非专利心血管预防药物(他汀类药物和血管紧张素药物)与常规治疗的初始治疗策略。这项研究将包括600名患有精神分裂症、分裂情感障碍或双相情感障碍的成年患者(18岁以上，每臂300人)，他们在波士顿地区的四家精神卫生诊所接受2GA治疗。我们有三个目标：1)比较每组中接受心血管药物治疗并在12个月的随访中坚持治疗的受试者的比例；2)使用意向治疗(ITT)方法比较综合(例如，Framingham评分)和个人(例如，血脂水平)心血管风险因素水平的变化；以及3)比较风险因素水平，使用因果推断技术来估计干预的每一项方案的效果，以说明坚持治疗随时间的变化。因此，我们的三个目标是检验这种低成本、简化的治疗策略是否增加了接受心血管预防治疗的受试者数量，并改善了心血管风险水平。由于患者的依从性是这一临床领域的一个主要问题，我们将通过使用边缘结构模型等技术来补充ITT对风险水平的评估，这些技术具有反向概率权重，以解释随时间变化的依从性。我们将跟踪受试者长达12个月，收集基线、3个月、6个月、9个月和12个月的访谈和生物统计数据，并用现有信息的其他来源补充这些数据，例如，来自电子健康记录和州所有付款人索赔数据库。这种以人群为基础的初步治疗策略可能是克服SMI人群中心血管疾病预防的传统障碍的有效和高效的方法。这项研究的结果将为改善护理和预后以及提高严重精神疾病患者的存活率的努力提供参考。

DESCRIPTION (provided by applicant): Patients with severe mental illness (SMI) die younger than persons in the general population. Much of the excess mortality for SMI patients is attributable to cardiovascular disease, and is exacerbated by treatment with second-generation antipsychotics (2GAs). Although the cardiovascular risks are well-known, and safe, efficacious therapy exists, few SMI patients receive cardiovascular prevention drugs. Care delivery fragmentation and poor patient adherence are central problems to reducing cardiovascular risks for patients with SMI. To address these problems, we propose to conduct a multi-site, open-label, randomized controlled trial comparing an initial treatment strategy of free, fixed-doses of two generic, cardiovascular prevention drugs (statins and angiotensin drugs) delivered within mental health clinics versus usual treatment. The study will include 600 adult patients (18+ years old; 300 per arm) with schizophrenia, schizoaffective disorder, or bipolar disorder who are receiving 2GAs within four mental health clinics in the Boston area. We have three aims: 1) to compare the proportions of subjects in each arm who are receiving cardiovascular drug treatment and are adherent to therapy during 12-months of follow-up; 2) to compare changes in composite (e.g., Framingham scores) and individual (e.g., lipid levels) cardiovascular risk factor levels using an intent-to-treat (ITT) approach; and 3) to compare risk factor levels, accounting for variation in adherence over time, using causal inference techniques to estimate the per-protocol effect of the intervention. Thus, our three aims examine whether this low cost, streamlined treatment strategy increases the numbers of subjects receiving cardiovascular prevention therapy and improves cardiovascular risk levels. Because patient adherence is a major concern in this clinical area, we will supplement the ITT assessment of risk levels by using techniques such as marginal structural models with inverse probability weighting to account for time-varying adherence. We will follow subjects for up to 12 months, and collect interview and biometric data at baseline, 3-, 6-, 9-, and 12-months, and supplement these data with other sources of existing information, e.g., from electronic health records and the state All Payer Claims Database. This population-based initial treatment strategy could be an effective and efficient approach for overcoming traditional barriers to cardiovascular disease prevention within the SMI population. Findings from this study will inform efforts to improve care and outcomes, and to enhance survival for patients with severe mental illness.