Active Surveillance of the Safety of Antipsychotic Medications in Pregnancy

妊娠期抗精神病药物安全性的主动监测

• 批准号: 10391510
• 负责人: Krista F Huybrechts
• 金额: $ 53.22万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-12 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10391510
• 关键词: Accounting; Adverse effects; Age; Animals; Antipsychotic Agents; Area; Bipolar Disorder; Centers for Disease Control and Prevention (U.S.); Clinical; Cohort Studies; Congenital Abnormality; Counseling; Data; Data Sources; Databases; Diagnosis; Discipline of obstetrics; Disease; Equilibrium; Etiology; Evaluation; Feeds; Fetus; Health Personnel; Human; Individual; Lead; Marketing; Mental Health; Mental disorders; Methods; Mothers; Neonatal; Newborn Infant; Outcome; Patients; Perinatal; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Population; Postpartum Women; Pregnancy; Pregnant Women; Process; Psychiatric therapeutic procedure; Psychiatry; Public Health; Registries; Reporting; Research Personnel; Risk; Safety; Scanning; Schizophrenia; Signal Transduction; System; Teratogens; Testing; Therapeutic Clinical Trial; Time; Tissues; Trees; Woman; adverse maternal outcomes; adverse outcome; adverse pregnancy outcome; base; case control; cohort; comparative; design; detection method; drug structure function; evidence base; fetal; health care service utilization; interest; maternal outcome; maternal risk; medication safety; member; neonatal outcome; novel; novel strategies; offspring; prospective; relapse risk; reproductive; screening; teratogenesis; topiramate; treatment risk; vaccine safety; venlafaxine

Mental health conditions are common among pregnant and postpartum women as well as non-pregnant women of reproductive age. While many patients require pharmacologic treatment, the safety of psychotropic medications in pregnancy is an area with large evidence gaps. Historically, spontaneous reports, pregnancy exposure registries, and case-control designs were the main approaches used to evaluate the safety of psychotropic medications in pregnancy, all of which have well-known limitations. In recent years, the field has gained much expertise with the conduct of cohort studies nested in large healthcare utilization data. Across all these designs, studies tend to focus on a single or a few selected adverse pregnancy outcomes, and they are performed at a single time point many years after the drug has entered the market and has been used by many pregnant women. To avoid unnecessary exposure of mother and fetus to harmful medications or to avoid women being unnecessarily deprived of treatments for psychiatric disorders when no harmful effects exist, a new and systematic approach is needed to generate timely evidence on the safety of psychotropic medications in pregnancy with respect to all relevant maternal and fetal outcomes. We will develop and implement a TreeScan based approach to conduct active surveillance of antipsychotic medication safety in pregnancy. TreeScan is a novel method for drug safety surveillance, which scans hierarchical trees of specific outcomes as well as groups of clinically related outcomes for associations with the treatment of interest, while accounting for multiple testing of correlated hypotheses. We will first develop hierarchical trees for congenital malformations, maternal and other neonatal outcomes based on shared underlying disease processes, and modify the TreeScan approach to accommodate the unique challenges of drug safety evaluation in the context of pregnancy. Use of hierarchical trees increases power to detect clinically related outcomes, which would not be feasible by evaluating individual diagnoses only. We will then implement TreeScan to evaluate the risks of a broad range of adverse maternal and neonatal outcomes associated with antipsychotic medications. Antipsychotics are the mainstay of treatment for women with schizophrenia and bipolar disorder, but little is known regarding their safety profile in pregnancy, especially for the newer antipsychotics. We will use nationwide cohorts of over 3.5 million publicly and privately insured pregnancies in the US, nested in healthcare utilization databases that contain rich information on confounders. In the final aim, we will extend the approach to conduct near real-time prospective, sequential surveillance of newly approved antipsychotic and other psychotropic medications in order to detect potential safety signals as early as possible after approval. By providing the necessary information for healthcare providers to make evidence-based prescribing decisions and to counsel women about the use of specific antipsychotics during pregnancy, the proposed studies will have an immediate public health impact within the field of perinatal psychiatry.

心理健康问题在孕妇、产后妇女以及非孕妇中很常见 育龄妇女。虽然许多患者需要药物治疗，但精神药物的安全性 怀孕期间的药物治疗是一个存在很大证据差距的领域。从历史上看，自发报告、怀孕 暴露登记和病例对照设计是用于评估安全性的主要方法 怀孕期间的精神药物，所有这些药物都有众所周知的局限性。近年来，该领域已 通过开展基于大型医疗保健利用数据的队列研究，获得了丰富的专业知识。跨越所有 在这些设计中，研究往往集中于单个或几个选定的不良妊娠结局，并且它们是 在药物进入市场并被许多人使用多年后的单一时间点进行 孕妇。避免母亲和胎儿不必要地接触有害药物或避免 在不存在有害影响的情况下，妇女被不必要地剥夺了对精神疾病的治疗， 需要新的系统方法来及时生成有关精神药物安全性的证据 怀孕期间所有相关的孕产妇和胎儿结局。 我们将开发并实施基于 TreeScan 的方法来对抗精神病药物进行主动监测 妊娠期用药安全。 TreeScan 是一种药物安全监测的新方法，它可以扫描 特定结果的分层树以及与临床相关的结果组 处理兴趣，同时考虑相关假设的多重检验。我们首先会开发 基于共享的先天畸形、孕产妇和其他新生儿结局的分层树 潜在的疾病过程，并修改 TreeScan 方法以适应以下疾病的独特挑战： 妊娠期药物安全性评价。分层树的使用增强了临床检测的能力 相关的结果，仅通过评估个体诊断是不可行的。然后我们将实施 TreeScan 用于评估与相关的各种不良孕产妇和新生儿结局的风险 抗精神病药物。抗精神病药物是治疗女性精神分裂症的主要药物 双相情感障碍，但对其在怀孕期间的安全性知之甚少，尤其是对于较新的患者 抗精神病药。我们将在全国范围内使用超过 350 万公共和私人保险怀孕的人群 美国，嵌套在医疗保健利用数据库中，其中包含有关混杂因素的丰富信息。在最终目标中， 我们将扩展该方法，对新批准的药物进行近乎实时的前瞻性连续监测 抗精神病药物和其他精神药物，以便尽早发现潜在的安全信号 批准后。通过为医疗保健提供者提供必要的信息来做出基于证据的 就怀孕期间特定抗精神病药物的使用做出决定并为妇女提供咨询， 拟议的研究将对围产期精神病学领域的公共卫生产生直接影响。