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

描述（由申请人提供）：重度精神疾病（SMI）患者的死亡时间比一般人群短。重度精神障碍患者的大部分超额死亡率可归因于心血管疾病，并因使用第二代抗精神病药物（2GAs）而加剧。虽然心血管风险是众所周知的，并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。护理服务的碎片化和患者依从性差是降低重度精神分裂症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地点、开放标签、随机对照试验，比较精神卫生诊所提供的两种非专利心血管预防药物（他汀类药物和血管紧张素药物）的免费、固定剂量的初始治疗策略与常规治疗。该研究将包括600名患有精神分裂症、分裂情感性障碍或双相情感障碍的成年患者（18岁以上，每组300人），他们在波士顿地区的四家精神卫生诊所接受2GAs治疗。我们有三个目的：1)比较每组接受心血管药物治疗并在12个月随访期间坚持治疗的受试者比例；2)使用意向治疗（ITT）方法比较复合（如Framingham评分）和个体（如脂质水平）心血管危险因素水平的变化；3)比较风险因素水平，考虑依从性随时间的变化，使用因果推理技术来估计干预的每协议效果。因此，我们的三个目的是研究这种低成本、简化的治疗策略是否会增加接受心血管预防治疗的受试者数量，并提高心血管风险水平。由于患者的依从性是该临床领域的主要关注点，我们将通过使用具有逆概率加权的边际结构模型等技术来补充ITT对风险水平的评估，以解释时变的依从性。我们将对受试者进行长达12个月的随访，并在基线、3个月、6个月、9个月和12个月时收集访谈和生物特征数据，并用其他现有信息来源（例如电子健康记录和国家所有付款人索赔数据库）补充这些数据。这种以人群为基础的初始治疗策略可能是一种有效和高效的方法，可以克服在重度精神障碍人群中预防心血管疾病的传统障碍。这项研究的结果将为改善护理和结果以及提高严重精神疾病患者的生存率提供信息。

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.