Identifying Best Practices for Medication-Based Suicide Prevention Strategies to Minimize the Risk of Medically-Serious Adverse Events

背景：锂(Li)和氯氮平(ClOZ)是预防死亡的最循证药物 和非致命的自杀行为(SB)。不幸的是，这两种药物也会在医学上造成许多 严重副作用(SSE)。退伍军人管理局正在进行一项大型的LI for SB和VA计划的随机试验 各办公室正在考虑鼓励更多地使用LI和CLOZ。这项研究的特点是有一个全面的数据库 分析和全国调查收集数据，以最大限度地成功扩大LI和CLOZ的使用。 具体目标：1)快速评估LI和CLOZ目前的安全性，并确定扩大使用的机会； 2)完善关于SSE风险的时间安排和对临床护理的影响的知识；3)检查使用情况 跨提供商&确定LI和CLOZ使用的感知障碍/促进者；以及4)整合结果和 制定政策建议、提供商指南和沟通工具。 意义：这项研究将显著提高人们对如何安全使用LI和CLOZ的认识。这些 改进将包括确定最安全的人群作为扩大使用的目标，以及如何最好地管理 患者一旦开始使用LI和CLOZ。将了解除SSE之外可能存在的障碍 这将阻碍LI和CLOZ的更广泛使用，并将从供应商那里获得关于如何克服这些障碍的投入。 调查结果将以几种方式结合起来，包括将其综合成一个有用的指南和交流工具。 优先领域(S)：自杀预防、心理与行为健康和预测分析。 独特性：之前没有研究将LI或CLOZ的SSE作为全面的、评估的预防措施进行检查 以及彻底的治疗策略，或将其调查结果浓缩为提供者和患者的工具。 方法：目标1：采用COX回归和倾向性评分分层的方法，以促进快速 对具有可信的SSE风险因素的患者组中关联的风险的估计(例如，特定的医疗， 精神疾病或药物使用诊断)。目标2：使用边际结构模型进行COX回归评估 随着时间的推移，风险的出现和发展，寻求确定临床上有用的“决策点”，以及 发病率将被计算出来，以促进关于SSE的患者与提供者的沟通。调查：简要介绍 全国范围内心理健康处方调查的重点是锂的使用障碍和促进者。打开 响应调查组件将有助于确保LI或CLOZ使用的任何意外障碍或促进者 很可能会被识别出来。全因死亡率分析和实例预测模型将有助于整合 结果，咨询委员会也会这样做。一种用户友好的提供者指南和患者-提供者沟通工具 将会被开发出来。 预期结果：对于LI和CLOZ，我们预计会发现某些患者组的SSE风险低于其他患者组 (例如，男性患者发生肾脏影响的风险可能较低)。我们还预计立即释放李某 与肾脏风险较低有关。对于CLOZ，我们预计在启动时对体重或代谢风险的治疗将是 有益的。我们还预计会找到一个“试行窗口”，在此期间，上证综指的风险可以忽略不计，这可能 增加患者尝试LI或CLOZ的意愿。我们预计这项调查将发现，上交所被视为 使用障碍，但也有其他障碍(例如，偏爱没有监测要求的药物)。 下一步：预计这项研究将立即产生政策建议(例如，针对或 不是在任何处方倡议中)和有价值的工具，因为结果可以直接转移到患者护理中。 下一步可能包括项目办公室立即努力扩大LI或CLOZ的使用。或者，一个 可以启动实施试验或交错实施。实时风险计算器的试点测试或 也可以对患者、提供者或其他关键告密者对LI和CLOZ的态度进行定性研究。 其他领域：这项研究还将支持这些独特价值的药物在非自杀疾病中的安全使用 病人。调查结果将提供可能为未来的提供者行为干预提供信息的数据。

Background: Lithium (LI) and clozapine (CLOZ) are the most evidence-based medications for preventing fatal and nonfatal suicidal behavior (SB). Unfortunately, both medications also can cause numerous medically serious side effects (SSEs). The VA is conducting a large randomized trial of LI for SB, and VA program offices are considering encouraging greater LI and CLOZ use. This study features a comprehensive database analysis and national survey to gather data to maximize the success of any effort to expand LI and CLOZ use. Specific Aims: 1) Rapidly Assess the Current Safety of LI & CLOZ & Identify Opportunities for Expanded Use; 2) Refine Knowledge about the Timing of SSE Risks and the Implications for Clinical Care; 3) Examine Use Across Providers & Identify Perceived Barriers / Facilitators to LI and CLOZ use; and 4) Integrate Results & Develop Policy Recommendations, Provider Guide, & Communication Tool. Significance: This study will markedly advance knowledge about how to safely use LI and CLOZ. These advances will include identifying the safest populations to target for expanded use, and how to best manage patients once LI and CLOZ are started. Understanding will be obtained about barriers besides SSEs that may impede wider LI and CLOZ use, and input will be obtained from providers on how to surmount these barriers. Findings will be integrated in several ways, including synthesis into a useful guide and communication tool. Priority Area(s): Suicide Prevention, Mental & Behavioral Health, and Predictive Analytics. Uniqueness: No prior study has examined the SSEs of LI or CLOZ as comprehensively, evaluated prevention and treatment strategies as thoroughly, or condensed its findings into tools for providers and patients. Methodology: Aim 1: Cox Regressions with Propensity Scores stratification will be used to facilitate the rapid estimation of risks associated in patient groups possessing plausible SSE risks factors (e.g., particular medical, psychiatric, or substance use diagnoses). Aim 2: Cox regression with marginal structural models will evaluate the emergence and development of risks over time, seeking to identify clinically-useful “Decision Points”, and incidence rates will be derived to promote patient-provider communication regarding SSEs. Survey: A brief nationwide mental health prescriber survey focused on Barriers and Facilitators to Lithium use. Open response survey components will help ensure that any unanticipated barriers or facilitators to LI or CLOZ use will likely be identified. An all-cause mortality analysis and an example Predictive Model will help integrate results, as will an Advisory Board. A user-friendly Provider Guide and Patient-Provider Communication Tool will be developed. Expected Results: For LI and CLOZ, we expect to find some patient groups at lower risk than others for SSEs (e.g., male patients may be at lower risk for renal effects). We also expect immediate release LI to be associated with less renal risk. For CLOZ, we expect treatment of weight or metabolic risks at initiation to be beneficial. We also expect to find a “trial window” during which risks of SSEs are fairly negligible, which may increase the willingness of patients to try LI or CLOZ. We expect the survey to find that SSEs are perceived as barriers to use, but also other barriers (e.g. a preference for medications without monitoring requirements). Next Steps: The study is expected to yield immediate policy recommendations (e.g., patient groups to target or not in any prescribing initiative) and valuable tools, since results are so directly transferable to patient care. Next steps might include immediate efforts by program offices to expand Li or CLOZ use. Alternatively, an implementation trial or staggered implementation could be initiated. Pilot testing of real-time risk calculators or qualitative studies of patient, provider or other key informant attitudes towards LI and CLOZ could also occur. Other Areas: This study will also support the safe use of these uniquely-valuable medications in non-suicidal patients. The survey findings will provide data that may inform future Provider Behavior interventions.