Generating Real-World Evidence in Early Alzheimer's Disease: Considerations for Applying the Target Trial Emulation Framework to Study the Safety of Anti-Amyloid Therapies

Authors

Xiaojuan Li, Harvard Medical School
Sonal Singh, UMass Chan Medical School
Bahareh Rasouli, Harvard Medical School
Jennifer Lyons, Harvard Medical School
Noelle M. Cocoros, Harvard Medical School
Richard Platt, Harvard Medical School
Ivan Abi-Elias, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
Jerry H. Gurwitz, UMass Chan Medical School

ORCID

0000-0002-9306-7487 (Elias)

Document Type

Article

Publication Date

2025

DOI

10.1002/trc2.70080

Volume

11

Issue

2

Pages

e70080 (1-11)

Abstract

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.

Rights

© 2025 The Authors.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Original Publication Citation

Li, X., Singh, S., Rasouli, B., Lyons, J., Cocoros, N. M., Platt, R., Abi-Elias, I., & Gurwitz, J. H. (2025). Generating real-world evidence in early Alzheimer's disease: Considerations for applying the target trial emulation framework to study the safety of anti-amyloid therapies. Alzheimers & Dementia, 11(2), 1-11, Article e70080. https://doi.org/10.1002/trc2.70080

Repository Citation

Li, X., Singh, S., Rasouli, B., Lyons, J., Cocoros, N. M., Platt, R., Abi-Elias, I., & Gurwitz, J. H. (2025). Generating real-world evidence in early Alzheimer's disease: Considerations for applying the target trial emulation framework to study the safety of anti-amyloid therapies. Alzheimers & Dementia, 11(2), 1-11, Article e70080. https://doi.org/10.1002/trc2.70080