Li Xiaojuan, Singh Sonal, Rasouli Bahareh, Lyons Jennifer, Cocoros Noelle M, Platt Richard, Abi-Elias Ivan, Gurwitz Jerry H
Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute Boston Massachusetts USA.
Division of Health Systems Science UMass Chan Medical School Worcester Massachusetts USA.
Alzheimers Dement (N Y). 2025 Apr 15;11(2):e70080. doi: 10.1002/trc2.70080. eCollection 2025 Apr-Jun.
Anti-amyloid beta monoclonal antibodies (anti-Aβ mAbs) have received approval from the US Food and Drug Administration for the treatment of patients with mild cognitive impairment or mild dementia due to Alzheimer's disease (collectively known as early AD) based on evidence from clinical trials. However, whether findings from these trials are generalizable to the real world is uncertain. We need reliable evidence on the real-world safety of these treatments to inform decision making for clinicians, patients, and caregivers. Using lecanemab as an exemplar, we outline the key considerations in designing and implementing an observational study on safety and utilization outcomes using established administrative healthcare claims data sources with the target trial emulation framework. The target trial emulation framework is a rigorous causal inference framework that minimizes common biases in observational studies. The approach proposed here can be applied to evaluation of additional mAbs as they become available.
Little is known about real-world safety of anti-amyloid beta monoclonal antibodies for early Alzheimer's disease.Existing real-world data can support studies of their safety and utilization outcomes.Target trial emulation can guide the design of these studies while minimizing bias.We provide key design and analytical considerations for future studies.
基于临床试验证据，抗淀粉样β单克隆抗体（抗Aβ mAbs）已获得美国食品药品监督管理局批准，用于治疗因阿尔茨海默病导致的轻度认知障碍或轻度痴呆患者（统称为早期AD）。然而，这些试验的结果是否能推广到现实世界尚不确定。我们需要关于这些治疗方法在现实世界中安全性的可靠证据，以为临床医生、患者和护理人员的决策提供依据。以lecanemab为例，我们概述了使用既定的行政医疗保健索赔数据源和目标试验模拟框架设计和实施一项关于安全性和使用结果的观察性研究的关键考虑因素。目标试验模拟框架是一个严格的因果推断框架，可将观察性研究中的常见偏倚降至最低。这里提出的方法可应用于评估其他可用的单克隆抗体。
对于早期阿尔茨海默病的抗淀粉样β单克隆抗体在现实世界中的安全性知之甚少。现有的现实世界数据可以支持对其安全性和使用结果的研究。目标试验模拟可以指导这些研究的设计，同时最大限度地减少偏倚。我们为未来的研究提供了关键的设计和分析考虑因素。
