Improved methods to assess the comparative safety of new psychiatric medications

描述(由申请人提供)：我是布里格姆妇女医院药物流行病学和药物经济学分部的流行病学家和初级教员，哈佛医学院的医学讲师。我的长期目标是在精神病学药物流行病学领域建立一名独立研究员的职业生涯。随着新的精神健康产品从高度受控的上市前环境进入临床实践，需要比较的安全性和有效性信息来指导最佳处方和政策决策。第三阶段试验通常不提供足够的证据来为这些决定提供信息，因为它们相对较窄地关注被定义为统计优于安慰剂的疗效。使用电子医疗数据的观察性研究在常规护理中产生比较信息方面发挥着关键作用，但通常在药物进入市场很长一段时间后才进行，因此可能无法在早期营销经验中发现严重的安全问题。从进入市场时开始对医疗产品进行前瞻性监测，为尽早发现关切提供了一种有希望的补充办法。开发用于心理健康应用的前瞻性监测框架的方法在很大程度上是未知的领域。拟议研究的目标是开发更好的方法来了解新的精神药物的相对安全性和有效性，并与NIMH战略计划中的战略目标3的优先事项保持一致。除了通过课程作业、实践经验和精神病学家的密切指导进行心理健康培训外，我还将追求以下研究目标：目标1：实施我们现有的监测系统原型，并使用实证例子研究其对精神疾病患者使用的处方药的特殊特征的适用性。目的2：针对心理健康比较研究所特有的方法学挑战，特别是研究药物与药物的相互作用，以及使用疾病风险评分和工具变量来缓解因可测量和不可测量的因素造成的混淆，定制监测系统。目标3：探讨使用电子病历和自然语言处理分析的可行性，以更好地捕捉使用行政数据代码特别难识别的精神健康结果，并 完善混杂治理。目的4：实施新的定制系统，并随着数据的实时积累，前瞻性地监测在筹资期间新上市的选定精神健康治疗的安全性。在精神健康药物生命周期的早期更好地检测安全问题具有非常重要的公共卫生意义，因为这可能会加快药物审批，并通过提供持续的上市后安全监测机制使处方者更放心地使用新药。它还将改善心理健康提供者的证据基础，并有助于遏制风险与利益关系较差的药物的使用。

DESCRIPTION (provided by applicant): I am an epidemiologist and junior faculty member in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham & Women's Hospital, and Instructor in Medicine at Harvard Medical School. My long term goal is to establish a career as an independent investigator in psychiatric pharmacoepidemiology. As new mental health products move from the highly-controlled pre-marketing setting into clinical practice, comparative safety and effectiveness information is required to inform optimal prescribing and policy decisions. Phase 3 trials usually do not provide sufficient evidence to inform these decisions due to their relatively narrow focus on efficacy defined as statistical superiority over placebo. Observational studies using electronic health- care data play a critical role in generating comparative information in routine care, but are typically conducted long after a drug has entered the market, and therefore can fail to identify serious safety issues in the early marketing experience. Prospective monitoring of medical products starting at the time of market entry offers a promising complementary approach to detect concerns as early as possible. Development of methods for use in a prospective monitoring framework for mental health applications is largely uncharted territory. The goal of the proposed research is to develop improved methods for understanding the comparative safety and effectiveness of new psychiatric medications, and is aligned with the priorities of Strategic Objective 3 in the NIMH Strategic Plan. In addition to pursuing training in mental health through coursework, hands-on experience, and close mentoring by a psychiatrist, I will pursue the following research aims: Aim 1: To implement our available monitoring system prototype, and study its applicability to the special characteristics of prescription drugs used in patients with psychiatric illness, using empirical examples. Aim 2: To customize the monitoring system to the methodological challenges that are specific to comparative research in mental health, in particular the study of drug-drug interactions and the use of disease risk scores and instrumental variables to mitigate confounding by measured and unmeasured factors. Aim 3: To explore the feasibility of using electronic medical records and natural language processing analysis to better capture mental health outcomes which are particularly difficult to identify using administrative data codes and to improve confounding control. Aim 4: To implement the new customized system and prospectively monitor the safety of selected mental health treatments newly marketed during the funding period as data accumulate in ear-real-time. Better detection of safety concerns early in the life cycle of mental health drugs is of great public health importance as it may expedite drug approval and make prescribers more comfortable using new drugs by providing a mechanism for ongoing post-marketing safety monitoring. It will also improve the evidence base for mental health providers, and help to contain use of medications with less favorable risk-benefit relations.