ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Potential impact of unblinding on observed treatment effects in Alzheimer's disease trials.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer's disease.The Cochrane database of systematic reviews · 2026Pooled it
- Clinical Benefits and Risks of Antiamyloid Antibodies in Sporadic Alzheimer Disease: Systematic Review and Network Meta-Analysis With a Web Application.Journal of medical Internet research · 2025Pooled it
- Amyloid-beta-targeting monoclonal antibodies in early Alzheimer's disease: a cochrane review summary and appraisal for the neurological community.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Cost-Effectiveness of Donanemab for Early Alzheimer Disease in Australia.The Medical journal of Australia · 2026Article
- Leveraging targeted kinase degradation as a novel therapeutic strategy for Alzheimer's disease.RSC medicinal chemistry · 2025Review
- Key questions for the future of amyloid research in dementia: a framework for integrating complex datasets.Molecular psychiatry · 2025Review
- Targeting Tau Protein with Proximity Inducing Modulators: A New Frontier to Combat Tauopathies.ACS pharmacology & translational science · 2025Review
- Considering challenges for the new Alzheimer's drugs: Clinical, population, and health system perspectives.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Are lecanemab and donanemab disease-modifying therapies?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Potential impact of unblinding on observed treatment effects in Alzheimer's disease trials.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
introductionAdverse effects of monoclonal antibodies against amyloid beta are common, and may affect validity of randomized controlled trials (RCTs) through unblinding of participants.
methodsWe used observations from published phase 3 RCTs in Alzheimer's disease to calculate the magnitude of unblinding effects on cognition that would be required to explain observed cognitive benefits in RCTs.
resultsIn trials of lecanemab, aducanumab, and donanemab, incidence of amyloid-related imaging abnormalities with active treatment ranged from 22% to 44%, the vast majority of which presumably led to unblinding. Effects of unblinding on the Clinical Dementia Rating Sum of Boxes required to fully explain observed drug effects ranged from 1.1 point (95% confidence interval: 0.2-2.0) with aducanumab, to 3.3 points (2.1-4.4) with donanemab and 3.7 points (2.0-5.6) with lecanemab. Infusion-related reactions were common, with potential unblinding effects particularly for lecanemab. Similar patterns were observed for the Alzheimer's Disease Assessment Scale Cognitive subscale. DISCUSSION: Psychological treatment effects due to unblinding may explain a substantial share of observed treatment effects in RCTs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.