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
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 clinic...
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| Format: | Article |
| Language: | English |
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Wiley
2025-04-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
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| Online Access: | https://doi.org/10.1002/trc2.70080 |
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| author | Xiaojuan Li Sonal Singh Bahareh Rasouli Jennifer Lyons Noelle M. Cocoros Richard Platt Ivan Abi‐Elias Jerry H. Gurwitz |
| author_facet | Xiaojuan Li Sonal Singh Bahareh Rasouli Jennifer Lyons Noelle M. Cocoros Richard Platt Ivan Abi‐Elias Jerry H. Gurwitz |
| author_sort | Xiaojuan Li |
| collection | DOAJ |
| description | 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. Highlights 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. |
| format | Article |
| id | doaj-art-0b82adafa97a41afaf4a57cbe154b9a1 |
| institution | OA Journals |
| issn | 2352-8737 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj-art-0b82adafa97a41afaf4a57cbe154b9a12025-08-20T02:22:09ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372025-04-01112n/an/a10.1002/trc2.70080Generating real‐world evidence in early Alzheimer's disease: Considerations for applying the target trial emulation framework to study the safety of anti‐amyloid therapiesXiaojuan Li0Sonal Singh1Bahareh Rasouli2Jennifer Lyons3Noelle M. Cocoros4Richard Platt5Ivan Abi‐Elias6Jerry H. Gurwitz7Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute Boston Massachusetts USADivision of Health Systems Science UMass Chan Medical School Worcester Massachusetts USADepartment of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute Boston Massachusetts USADepartment of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute Boston Massachusetts USADepartment of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute Boston Massachusetts USADepartment of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute Boston Massachusetts USADivision of Health Systems Science UMass Chan Medical School Worcester Massachusetts USADivision of Geriatric Medicine UMass Chan Medical School Worcester Massachusetts USAAbstract 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. Highlights 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.https://doi.org/10.1002/trc2.70080Alzheimer's diseaseanti‐amyloid beta monoclonal antibodiesreal‐world datareal‐world evidencetarget trial emulation |
| spellingShingle | Xiaojuan Li Sonal Singh Bahareh Rasouli Jennifer Lyons Noelle M. Cocoros Richard Platt Ivan Abi‐Elias Jerry H. Gurwitz 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 Alzheimer’s & Dementia: Translational Research & Clinical Interventions Alzheimer's disease anti‐amyloid beta monoclonal antibodies real‐world data real‐world evidence target trial emulation |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Alzheimer's disease anti‐amyloid beta monoclonal antibodies real‐world data real‐world evidence target trial emulation |
| url | https://doi.org/10.1002/trc2.70080 |
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