Comparative Safety and Effectiveness of Antipsychotics

描述(申请人提供)：近年来，非典型抗精神病药物(AAP)在各个年龄段的使用急剧增加和扩大，包括非标签适应症的广泛使用。然而，关于这些药物的相对安全性和有效性，特别是在脆弱的儿童和老年人中，重要的基本问题仍然没有得到回答。我们将为参加医疗补助的人解决这些问题，医疗补助是最严重精神病患者的主要精神卫生保健支付者。我们将联合来自三个地点的专业知识和资源，以应对医疗补助和医疗保险受益人和其他利益攸关方面临的这一重大公共卫生挑战。组织该项目联合体的目的是在CERTS网络内最强大的现有工作范围和相关方法专门知识的基础上，以及在可支持从授权期开始就开始工作的强大的现有合并数据集的基础上，以便利用这些资源形成一个更大、更强大的整体。个别研究将针对以下目标： 1.对于老年疗养院(NH)居民，利用由精神健康CERT开发的独特的链接数据集，该数据集将索赔中的药物/诊断信息与对居民的前瞻性、结构化的临床评估相结合，以评估个人抗精神病药物在大量普通护理人群中的相对有效性和安全性。检查的重要临床结果包括死亡率；心血管、脑血管、代谢、感染和其他医学结果；以及包括行为症状和认知功能在内的功能和临床结果。 2.评估大量儿童和普通护理人群中抗精神病药物治疗的临床结果 青少年。我们将对新开始的AP疗法在诊断为ADHD或行为或情绪障碍的年轻人(2-20岁)中的重要临床结果和相对安全性进行队列研究，并与其他治疗方式的倾向分数匹配的儿童队列进行比较。分析将首先在田纳西州医疗补助进行，可以使用电子/纸质医疗记录来验证研究变量/终点，并使用经过验证的定义，扩展到全国医疗补助青年人口，以增加检查相对安全性的能力。在被诊断为精神分裂症的青少年中，我们还将检查个别药物的疗效标志，包括停药和精神科住院。 3.对于所有非制度化AP用户的更广泛人群，利用50个州的医疗补助数据来确定个别AP在重要AP风险方面是否存在差异，包括催乳素瘤(所有年龄段)、糖尿病或高脂血症事件(成人)和各种原因死亡(老年人)。 使用强大的现有合并数据集，我们可以在项目开始时启动实质性分析。在项目初期，我们将实施更多的联系，并将现有的8个州的数据集扩大到全国范围，提供评估药物和重要亚群的相对安全性和有效性所需的更大能力。新的联系包括对照医疗图表验证基于索赔的不良影响措施，行政和电子病历数据之间的联系，以及扩大关于疗养院人口的独特的现有合并数据集。这项研究将把田纳西州医疗补助人口中的分析与多个州的医疗补助数据结合起来，这些数据为相对安全性和有效性研究提供了强大的动力。它将建立在过去CERT的投资、卓越的方法学领袖的专业知识以及关于这三个地点抗精神病药物使用和结果的重要先前研究成果的基础上，实施一系列严格的研究，旨在提供指导弱势人群最佳临床使用抗精神病药物所急需的证据。

DESCRIPTION (provided by applicant): Recent years have seen sharply increased and broadened use of atypical antipsychotic medications (AAPs) across the age spectrum including extensive use for non-labeled indications. Yet important basic questions remain unanswered concerning comparative safety and effectiveness of these medications, especially among vulnerable children and elderly. We will address these questions for enrollees in Medicaid, the primary mental health care payer for the most seriously mental ill. We will unite expertise and resources from three sites to address this critical public health challenge for Medicaid and Medicare beneficiaries and other stakeholders. The project consortium was organized to build on the strongest existing lines of work and relevant methodological expertise within the CERTs network, and on powerful existing merged datasets that could support the initiation of work from the start of the grant period, in order to leverage these resources into a larger and more powerful whole. Individual studies will address the following aims: 1. For elderly nursing home (NH) residents, utilize a unique linked dataset developed by the mental health CERT that merges medication/diagnostic information from claims with a prospective, structured clinical assessment of residents to evaluate comparative effectiveness and safety of individual antipsychotic drugs in large usual-care populations. Important clinical outcomes examined include mortality; cardiovascular, cerebrovascular, metabolic, infectious, and other medical outcomes; and functional and clinical outcomes including behavioral symptoms and cognitive function. 2. Assess clinical outcomes of antipsychotic therapy in large usual-care populations of children and adolescents. We will conduct a cohort study of important clinical outcomes and comparative safety of newly initiated AP therapy in youth (2-20 years of age) with diagnoses consistent with ADHD or behavioral or mood disorders, compared with a propensity-score-matched cohort of children with other treatment modalities. Analyses will be initially conducted in Tennessee Medicaid, with access to both electronic/paper medical records for validation of study variables/endpoints, and, using the validated definitions, extended to a national Medicaid population of youth to increase power to examine comparative safety. Among youth diagnosed with schizophrenia, we will also examine markers of effectiveness across individual drugs including drug discontinuation and psychiatric hospitalization. 3. For the broader population of all non-institutionalized AP users, utilize 50-state Medicaid data to determine if individual APs vary with regard to important AP risks, including prolactinomas (all ages), incident diabetes mellitus or hyperlipidemia (adults), and all-cause mortality (elderly). Using powerful existing merged datasets, we can initiate substantive analyses at the start of the project. Early in the project period, we will implement additional linkages and expand an existing 8-state dataset to national scope, providing enhanced power needed to assess comparative safety and effectiveness across drugs and important subpopulations. New linkages include validation of claims-based measures of adverse effects against medical charts, links between administrative and electronic medical record data, and expansion of a unique existing merged dataset on the nursing home population. The study will integrate analyses in the well established Tennessee Medicaid population with multistate Medicaid data that offer great power for comparative safety and effectiveness research. It will build on past CERTs investments, the expertise of preeminent methodological leaders, and important prior lines of research on antipsychotic use and outcomes at the three sites to implement a rigorous set of studies aimed at providing evidence that is critically needed to guide optimal clinical use of antipsychotic drugs for vulnerable populations.