Improved methods to assess the comparative safety of new psychiatric medications

简介（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部门的流行病学家和初级教员，哈佛医学院医学讲师。我的长期目标是成为精神病学药物流行病学的独立研究者。随着新的精神卫生产品从高度控制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，以便为最佳处方和政策决策提供信息。3期试验通常不能提供足够的证据来支持这些决定，因为它们对疗效的关注相对狭窄，被定义为优于安慰剂的统计优势。使用电子卫生保健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，但通常是在药物进入市场很久之后进行的，因此可能无法在早期营销经验中识别严重的安全问题。从进入市场时开始对医疗产品进行前瞻性监测，为尽早发现问题提供了一种有希望的补充方法。制定用于精神卫生应用的前瞻性监测框架的方法在很大程度上是一个未知领域。拟议研究的目标是开发改进的方法，以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。除了通过课程学习、实践经验和精神科医生的密切指导来追求心理健康方面的培训外，我将追求以下研究目标：目标1：实现我们现有的监测系统原型，并通过实证例子研究其对精神疾病患者使用处方药的特殊性的适用性。目标2：定制监测系统，以应对心理健康比较研究特有的方法学挑战，特别是药物-药物相互作用的研究，以及使用疾病风险评分和工具变量来减轻测量和未测量因素的混淆。目标3：探索利用电子病历和自然语言处理分析来更好地捕捉特别难以使用行政数据代码识别的精神健康结果的可行性

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.