Liu, K.Y., Senn, S. and Howard, R. (2025) Avoiding causal fraud in the evaluation of clinical benefits of treatments for Alzheimer's disease. Alzheimer's & Dementia, 21 (2). e14457. ISSN 1552-5260
Abstract
Recent regulatory approvals of three amyloid-lowering monoclonal antibody therapies for the treatment of Alzheimer's disease (AD) have triggered a polarizing debate in the field on the clinical meaningfulness of their reported effects. The question of how to define clinical meaningfulness for any treatment that has a modest effect size is important and will likely be subject to influence from interested stakeholders. We warn of claims of evaluating meaningful within-individual change from randomized parallel-group trials of AD treatments, sometimes purportedly assessed by a commonly recognized “responder” analysis approach, and explain why it is likely to mislead and should simply be avoided. The average between-group difference in score change is where the debate and research efforts should be focused to contextualize and evaluate the clinical meaningfulness of the true treatment effect. The statistical and communication principles we consider and would recommend are applicable to the evaluation of most interventions in medicine.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Alzheimer's disease; clinically meaningful; minimal clinically important difference; responder analysis; trial; within‐individual change |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Feb 2025 14:39 |
Last Modified: | 12 Mar 2025 17:01 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/alz.14457 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:222805 |