Real-world patient responsiveness & safety of long-acting beta agonists in asthma

真实世界的患者反应

• 批准号: 8641889
• 负责人: PINGSHENG WU
• 金额: $ 97.1万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2016-04-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8641889
• 关键词: Real; world; patient; responsiveness; safety

Significance. The comparative effectiveness of long-acting beta agonists (LABA) in asthma management with other controller medicines has not been established. Although LABA monotherapy increases the risk of serious adverse events (AEs) and is recommended to be used in combination with inhaled corticosteroids (ICS), the safety of combination therapy is not known. Also not known, and clinically important to understand, is how, why and to whom LABAs and/or combination therapy are associated with increased risk of serious AEs. Specific Aims. To address the comparative effectiveness and safety concerns of the combination therapy (ICS + LABA), as well as to understand the profile of those who experience AE, and the profile of those who benefit most from the combination therapy, we will (1) determine the effectiveness of LABA-containing therapies in comparison with other available controller regimens in persistent asthma disease management; (2) determine if LABA-containing therapies are associated with an increased risk of asthma-related serious AEs and all-cause mortality; and (3) determine the characteristics of patients who clinically respond to, or have AEs attributable to, LABA-containing therapies. Research Design. In Aim 1, we will conduct a population based cohort study of subjects with persistent asthma. The effect of LABA-containing therapies in the real-world setting will be measured and compared with other asthma controller therapies on asthma control and exacerbation prevention from 1998-2010. This period allows for the study of LABAs during use of LABA monotherapy, and during a period prior to AE recognition and the FDA black box warning. The study will be done in diverse populations of nearly 664,000 asthmatics which we have assembled, including a state Medicaid population, four HMO research populations, and a Department of Defense population. In Aim 2, we will conduct a nested case-control study to evaluate the risk of serious asthma-related AEs with the use of LABA-containing therapies. Asthma-related and all-cause death will be studied separately. In Aim 3, patient characteristics associated with both response to, and serious AEs related to, LABA-containing therapies will be assessed, including patient demographics, disease severity, underlying asthma control, medication utilization patterns, adherence, and definable asthma phenotypes using multivariable regression modeling. For each aim, various subgroup analyses, sensitivity analyses and simulation studies will be performed to provide robust results and to evaluate the accuracy of the estimates. Impact. This project is of critical importance as it addresses comparative effectiveness and safety concerns in asthma pharmacotherapy. It will inform and empower physicians, patients, and healthcare policy makers providing timely knowledge in how, when, and to whom to provide or avoid LABA containing therapies. Such knowledge will have widespread public health impact in asthma disease management.

意义。长效β受体激动剂（LABA）与其他药物治疗哮喘的疗效比较 其他控制药物尚未确定。尽管 LABA 单一疗法会增加严重的风险 不良事件（AE），建议与吸入皮质类固醇（ICS）联合使用， 联合治疗的安全性尚不清楚。同样不为人所知但在临床上理解这一点很重要的是如何、为什么 LABA 和/或联合治疗与严重 AE 风险增加相关。 具体目标。解决联合疗法的相对有效性和安全性问题 （ICS + LABA），以及了解经历过 AE 的人的概况，以及经历过 AE 的人的概况 从联合治疗中获益最多，我们将 (1) 确定含有 LABA 的有效性 与其他可用的控制方案在持续性哮喘疾病管理中的比较； (2) 确定含 LABA 的疗法是否与哮喘相关严重 AE 的风险增加有关 和全因死亡率； (3) 确定有临床反应或出现 AE 的患者的特征 归因于含有 LABA 的疗法。 研究设计。在目标 1 中，我们将对患有持续性抑郁症的受试者进行一项基于人群的队列研究。 哮喘。含有 LABA 的疗法在现实世界中的效果将被测量并与 1998 年至 2010 年期间用于控制哮喘和预防哮喘恶化的其他哮喘控制疗法。这个时期 允许在使用 LABA 单一疗法期间以及 AE 识别之前的一段时间内研究 LABA 以及 FDA 黑框警告。该研究将在近 664,000 名哮喘患者的不同人群中进行 我们已经收集了这些人群，包括一个州医疗补助人群、四个 HMO 研究人群和一个 国防部人口。在目标 2 中，我们将进行一项巢式病例对照研究，以评估以下风险： 使用含 LABA 的疗法会导致严重的哮喘相关 AE。哮喘相关死亡和全因死亡 将单独研究。在目标 3 中，与对严重 AE 的反应相关的患者特征 将评估含 LABA 的疗法，包括患者人口统计数据、疾病严重程度、 潜在的哮喘控制、药物使用模式、依从性和可定义的哮喘表型 多变量回归建模。对于每个目标，各种亚组分析、敏感性分析和 将进行模拟研究以提供可靠的结果并评估估计的准确性。 影响。该项目至关重要，因为它解决了以下领域的相对有效性和安全问题： 哮喘药物治疗。它将为医生、患者和医疗保健决策者提供信息并赋予他们权力 及时了解如何、何时以及向谁提供或避免含有 LABA 的治疗。这样的 知识将对哮喘疾病管理产生广泛的公共卫生影响。